Part three 3 treatments: Tumor cell growth and radiation

Tumor cell growth is very important to understand. First, it is highly variable with the time required to double the number of cancer cells ranging from less than 24 hours to more than 300 days. Furthermore, cells in the center of a tumor mass may not even be alive if they have outstripped their blood supply and delivery of nutrients and oxygen. Thus, tumor growth depends on the number of cells dividing over time. Usually, the larger the tumor the smaller the percentage of dividing cells and the longer it takes cells to divide. There are elegant models; one of the most common is the Gompertzian model that I am discussing. Some general rules apply. Growth rate is most rapid and often exponential during the early days of a tumor. Thus instead of two cells going to four, then eight, then sixteen; two cells may go to four, then sixteen then two hundred fifty six. Therefore, the growth fraction or the number of cells dividing is high. The portion of tumor cells that are growing decreases as the tumor gets larger and often plateaus because of nutrient supply. This may help one to get a handle on these numbers. It takes one billion cells for just one gram (about 28 grams to an ounce) of tumor tissue. One gram is about the lowest level at which we can detect cancer. That is equal to about a 1 cm mass in a breast or 1 cm nodules on a chest x ray. One thousand and one million times that amount is about 2-20 pounds of cancer and usually results in severe organ damage and major medical problems and death.

Sadly, tumor cells have multiple mechanisms of innate or acquired resistance to chemotherapy. Tumor cells within a given cancer may have some diversity in this regard. Some tumor cells are naturally (innate) drug resistant and eventually become the predominant cell. This is particularly true if chemotherapy eliminates all the sensitive cells. A theory called the Goldie–Coldman hypothesis asserts that the probability of a tumor having resistant cells is proportional to tumor size. Thus, tumors can become more resistant to chemotherapy as they grow. However, chemotherapy makes some tumor cells quickly make enzymes or use other techniques to neutralize the drug. This is acquired resistance. Some tumor cells make substances in high concentration that not only lead to destruction of the chemotherapy drug but also quickly repair any DNA or other damage the chemotherapy drug may have caused.

DNA on chromosomes is tightly coiled. There are specific enzymes that let it uncoil so it can duplicate DNA for its children. Some chemotherapy drugs either try to inhibit the enzyme that allows the uncoiling or try to keep the DNA for the children cells stuck on the spindle on which this occurs. Once again, tumor cells can acquire resistance to this. Sometimes the mere exposure of a drug to a tumor cell prompts the tumor cell to make a transport protein to carry the drug actively out of the cell before it can do damage. Sometimes this tumor cell reaction leads to not just resistance to one chemotherapy drug but induces the tumor cell to make a multidrug resistance gene. A gene is a portion of a chromosome that carries the code for one specific message; typically, for a protein that has a very specific job. Human cells have tens of thousands of genes. The multidrug resistance gene helps the tumor cells create a very effective pump that pumps chemotherapy drugs out of the tumor cell before they can cause harm. There is more than one multidrug resistance gene and unfortunately, there has been only minimal success in blocking these genes actions. Many of the above reasons are why we use non-cross resistant chemotherapy to try to hit the tumor from multiple angles. The concept is similar to using a cocktail of drugs against the cancer cells that are sufficiently different so that we hit the tumor cells multiple ways.

Regarding how much chemotherapy is enough; more often than not, more is not better. Very high does, which only work for a few tumors, require the support of bone marrow transplants to rescue the patient from the damage the high dosages of drugs inflict on normal cells.

Thus, if caught early enough, a dozen or so of human tumors are clearly curable with chemotherapy alone. There are about seven or so that are very responsive but cure is not typical with drugs alone. There are many, depending on their stage, which are highly treatable for long durations. Then there are the groups of only occasional responders such as advanced melanoma, the common type of kidney cancer, many forms of brain cancer and advanced cancer of the bladder and pancreas.

We previously discussed adjuvant chemotherapy. This is treatment given after the primary removal of the tumor when there is no evidence of remaining tumor but there is a well-known risk of recurrence. The intent is to prevent recurrence. Adjuvant therapy of breast cancer is the model for this concept and changes the odds of survival for countless patients. Neoadjuvant chemotherapy refers to treatment  given before primary surgical removal of a tumor to ease the removal, make surgery less invasive and offer the benefit in some cancers of determining whether the drugs chosen are effective or not. Salvage chemotherapy refers to treatment given after failure of initial therapies. It is not synonymous with unsuccessful treatment as many patients see prolonged survival free of progression or recurrence while enjoying a good quality of life.

Most chemotherapy drugs can also be categorized based on how they work rather than just when. Thus, there are alkylating agents that target tumor DNA and try to bind to it thus disrupting a tumor cells ability to have offspring. Some are anti-metabolites. These drugs mimic small molecules the cancer cell needs to keep living. These function like a computer virus by not allowing the cell to proceed in cycles, as they are dysfunctional copies. There are anti tumor antibiotics, which generally are drugs derived from microorganisms and are usually not cell cycle specific. These are often useful in slow growing tumors. There are plant alkaloids that function by not letting the spindle we talked about earlier form and thus halt the tumor cells from dividing. These drugs may also make the spindles’ structure unstable.

Finally, as will be touched on somewhat in the section “The Future”, other agents exist that do not neatly fit any of these classes. These novel drugs may destroy essential enzymes or function as a hormone or hormone receptor manipulator necessary for tumor growth. If a receptor or keyhole needs to work for a tumor cell to grow, blocking the keyhole could be very effective. Some chemotherapy agents can be very disabling by affecting the ability of the tumor cell to eliminate harmful by-products it produces as it grows.

Some drugs interfere with molecules necessary for the tumor to grow. Some drugs are estrogens, anti-estrogens and anti-male androgens. An exciting relatively new and promising type of treatment is immunologic therapy and biologics. We will discuss this in more detail in “The Future. The earliest effective treatment of this type is interferon. There have also been attempts to “beef up” immune cells of the patient outside the body of the patient and re-inject them in hopes they will find the target tumor cell and help the immune system. Finally, there are agents that try to force tumor cells that are “stuck” in a primitive always “on and dividing” phase go through orderly controlled cell growth and life. These drugs are trying to make the rogue cancer cells grow up, mature, straighten out and become normal. These are known as differentiation agents and have met with some success in some forms of leukemia.

A very exciting breakthrough of only the last decade is not true chemotherapy to fight cancer but rather employing genetically engineered drugs to fight the effects of the cancer on you and your bone marrow. We make all of our blood cells in the marrow. There is a complex army of specialized white blood cells to fight infection and red cells to carry oxygen. There are now genetically engineered drugs routinely available that largely are identical to your body’s normal molecules that stimulate red and white blood cell production. Anemia and dangerously low white blood cell levels can occur either from the therapy, the presence of the tumor or both. Enormous fatigue and poor quality of life is associated with anemia and infections which can be life threatening are more common with low infection fighting white blood cells. Both are now very effectively treated. There is also a genetically engineered product to help your body make platelets (which help blood clot). It is not as effective as the other two.

Thus, these hematopoietic (blood) growth factors have had an enormous impact on the ability to both fight, defray and hasten recovery from chemotherapy induced low blood counts and the secondary risks of infection and fatigue. These little miracle molecules are precise genetic replicates of your body’s’ own growth factors that can now be mass-produced by recombinant genetic engineering. Furthermore, longer acting versions are now available through manipulating the molecules and thus decreasing the frequency of injections. Thus, we are more effectively fighting fatigue, avoiding transfusions and decreasing the risk and expense of infection. Furthermore, oncologists are more frequently able to deliver full doses of chemotherapy on time in cases where cure and benefit depends on that.

The first widely used genetically engineered product was the red blood cell growth factor called Erythropoietin. This can improve the anemia and fatigue of many cancer patients if needed. This is an injection, similar to an insulin injection, self administered by the patient as infrequently as every 1-3 weeks in some cases. The other wonder drug, billion dollar sellers are G–CSF and GM-CSF, which like the red cell drug are administered sub-cutaneously. They support white blood cell counts ( infection fighting)  There are both daily and with every 2-3 week forms available. These have changed the practice of Oncology. These two drugs alone have markedly improved the quality of life for millions of cancer patients.

In summary, not all tumors are the same in terms of chemotherapy sensitivity. We design drugs to exploit unique cancer cell weaknesses and take advantage of their usual higher rate of growth. There are numerous ways to attack the malignant cells. These cancer cells are clever, adaptive, enemies that may be quick to find a way around our armamentarium. Wonderful new therapies exist to support patients undergoing some of the toxicities of therapy. As will be discussed in “The Future”, exciting and novel treatment approaches have arrived. Thus, the sooner we get to the cancer the better, the more we can do to prevent it the better and the more patients we can get on well designed clinical trials, the faster we will conquer this frequently devastating disease.


Radiation Therapy


Radiation therapy uses high-energy radiation to kill cancer cells by damaging their DNA. Radiation therapy can damage normal cells as well as cancer cells. Therefore, treatment must be carefully planned to minimize side effects. The radiation used for cancer treatment may come from a machine outside the body, or it may come from radioactive material placed in the body near tumor cells or injected into the bloodstream A patient may receive radiation therapy before, during, or after surgery, depending on the type of cancer being treated. Some patients receive radiation therapy alone, and some receive radiation therapy in combination with chemotherapy.

The care of the oncology patient must be multidisciplinary. Pathologists, radiologists, clinical laboratory physicians and immunobiologists are crucial members that render the correct diagnosis. In many cases, a team comprising the medical oncologist, surgeon or surgical oncologist and radiation therapist assess what treatment techniques are needed. Finally, there are chemotherapy nurses, technicians, and social workers rounding out an integrated team.

Radiation oncology is a clinical discipline devoted to the use of ionizing radiation for patients with cancer as well as some other diseases. We give radiation alone or in combination. The goal is to deliver the maximum lethal dose to the tumor and minimize any toxicity to surrounding normal tissues in hopes of eradicating the tumor while maintaining a high quality of life. Radiation therapy may also have a role in treating or preventing symptoms. This includes pain, restoring the opening of blocked airways, helping prevent bone fractures owing to tumor having spread to them and other organ function while again trying to minimize suffering. Just as the medical oncologist, the radiation oncologist must assess all the factors relevant to the patient’s situation and determine whether more radiation is safe and beneficial.

Many types of radiation are used. The most common kind is external beam irradiation using photons or electrons. Photons are x rays or gamma rays and may be considered as bundles of energy that deposit a damaging dose to the tissue as they pass through it. These beams are carefully shaped with shielding of the normal surrounding tissue. Depending on the voltage used, which can vary a million fold, these x rays may travel barely a millimeter to a depth of 3-4 cm with techniques used to spare the overlying skin. Radioactive isotopes create Gamma rays, the most common of which is Cobalt 60. Most facilities no longer use gamma rays because of the need to replace and frequently recalculate dosages due to the natural radioactive decay of the isotope. The gamma knife is an exception that radiates brain tumors with precise accuracy and employs up to 201 Cobalt 60 sources.

Other sources of external beam radiation are protons and neutrons. Protons are positively charged particles that have the advantage of depositing dose at a constant rate over the majority of the beam with most of it at the end of the beam. Protons, unlike photons, fall off quickly in their ability to do damage beyond the target. Although this vastly limits damage to normal tissue, the enormous expense in generating these rays has limited their use to only a handful of centers in the Unites States. Neutrons are uncharged heavy particles that are produced a number of ways. Neutrons collide with protons in the tumor cell nucleus and can be very effective. Experience with these units is limited again because of enormous cost and clinical trials are under way comparing all these types of radiation.

Brachytherapy is a physically different way of delivering ionizing radiation. In this technique, the physician places or implants sealed or unsealed radioactive sources very close to the target. Since the dose of radiation falls off very rapidly as distance increases, this is one technique to deliver higher doses of radiation to the target than external beam in most cases. The dose is generally delivered over days and is seen in use in some cervical, prostate and breast cancers. Various radioactive substances are used as the radiation-emitting source.

Radiation therapy may be intended to be curative or rather simply for symptom control. Cooperation of all members of the team is essential to achieve these goals. Furthermore, tumors have highly variable sensitivity to radiation doses. Importantly, normal tissues have maximum doses that can be tolerated after which severe damage can occur. Thus, as is true for chemotherapy, the probable benefit of radiation must be weighed on a careful case-by-case benefit against the probability of damage to normal tissue in the way of or near the beam. This is not a simple business and extremely close coordination with the physicist, dosimetrist (physicist who calculates the right dose), and treatment planning staff is standard.

So why does radiation work? First, one can kill just about anything with enough radiation; the issue is that you cannot safely give enough. High doses may be irritating or lethal depending on the tissue radiated. Thus, so called dose response curves exist for all tumors. These tell us the correct dose to get the desired effects of killing tumor cells. These curves also exist for each type of normal tissue, e.g. bone, brain, nerves, bone marrow, intestines, mouth, etc. Furthermore, the sheer bulk or lack thereof of the tumor will also play a pivotal role in the maximal tolerated dose or the necessary dose.

You may hear the term “Boost Volume” which is used to describe the residual tumor volume receiving the highest doses of irradiation. This is often necessary in larger tumors where a higher dose is delivered to where viable tumor cells may well be and would then, unchecked, multiply and grow. In addition, since radiation works better with plenty of oxygen and many of these cells are at the oxygen poor core of the tumor, the boost is helpful.

Molecular oxygen must be present at the time of irradiation for maximal tumor cell killing. The probable mechanism is that the radiation creates free radicals that are very damaging to tumor DNA. Nearly all cell death from radiation results from disruption of cancer cell division and the new tumor cell formation process. Thus, tumor cell death in non-dividing radiated cancer cells is uncommon. It is also true that apoptosis, which is the name for the phenomenon that all cells are pre-programmed to eventually die from “old age”, appears to occur at an accelerated rate once cells are radiated. It ‘ages’ the cancer cells. Cancer cells attempt repair of non-lethal and potentially lethal cellular damage from radiation. This occurs within about 5-6 hours and is probably never complete. Although human cells have a narrow range of tolerance, compared to tumor cells they have a more efficient repair and recovery processes. We try to exploit this phenomenon by the daily or twice daily treatment or fractionation scheme of most radiation.

As one would imagine, there is clearly an array of adverse effects from radiation depending on dose and intervals as well as type and duration. Three-dimensional planning is the biggest advance as regards not only focusing the beam precisely but also avoiding damage to normal tissue. In this technique, similar to a hologram, the radiation team can predict how much beam is going where. Nonetheless, there are both early and late radiation induced reactions. The early reactions occur during or immediately following treatment and are usually self-limiting, although they may last for a few weeks. These may be local or systemic and include loss of appetite, nausea, fatigue, inflammation of the esophagus, diarrhea, (if the G.I. tract is in the beam), skin reactions (redness and peeling), inflammation of the lining of the mouth, loss of hair and low blood counts. The basic mechanism is damage to rapidly dividing cells. These symptoms can be modestly treated and usually resolve well.

Late radiation induced reactions can be clinically important and may be apparent months to years later. They are often progressive and not self limiting. These are typically local and include inflammation of nerves, death of bone, tightening of bowels, scarring of the lung, loss of skin, kidney damage and heart damage. These are usually very infrequent owing to the careful planning discussed earlier. Since these late effects are usually irreversible, careful planning towards prevention is pivotal.

As one would expect, the side effects of radiation therapy influence other treatment methods and vice versa. Certain chemotherapy agents can greatly accentuate skin inflammation during radiation and thus we avoid simultaneous administration. Some may even create a radiation recall effect long after the chemotherapy is over. This is when after the administration of particular types of chemotherapy a previously radiated area may inflame even though the radiation was delivered quite some time previously. Prior abdominal surgery may accentuate both acute and late radiation induced bowel damage if it places bowels in the path or radiation. Radiation can damage small blood vessels and thus may impair healing after surgery. Finally, a more recently recognized complication of radiation is the risk of bone marrow and blood disorders as well as acute leukemia years after the therapy.

The key is teamwork and careful planning. As with any therapy, one must always weigh the goods against the harms while remembering the immense harm of not treating the tumor at all or inadequately. The techniques of radiation are becoming more refined. The field of radiation sensitizers that may increase the vulnerability of tumor cells relative to normal cells is growing. Radiation will continue to have a prominent role not only for symptom control but also as an integral portion of a comprehensive approach to the treatment of many human malignancies as seen in cancers of the lung, colon/rectum, breast and Hodgkin’s disease.


Part Two Treatments of Cancer

As was presented earlier, before treatment and after initial diagnosis, staging is done. Considering signs, symptoms, cues, and clues so far and knowing the typical history of each disease, your oncologist will look where needed to assess the exact extent of the disease in exquisite detail. Some patients require bone marrow biopsies; some need scans of the brains, and so on. The goal, using internationally accepted conventions and definitions, is to stage the patient’s cancer in manner that anyone hearing the stage has an understanding of the most clinically relevant way of knowing where your tumor is and is apparently not. Thus, we can compare patients with the same stage, intelligently develop treatment regimens, and follow outcome not just for you but also for all patients with similar stages. Before we look into how we treat it, we must understand the how and why of knowing where it is as local vs. systemic therapy or some combination therein depends on that as well.

Staging gives us the extent, spread and severity of a patient’s disease. This allows a more accurate and comprehensive treatment plan and can even infer a pre treatment prognosis by comparing to others similarly staged. The systems for staging have evolved and the more we learn what really matters for each disease the more we add criteria. Staging is a living science whose goal is to have more patients living because of its work.

Typically the so called T, N, M staging rules are used ( tumor size, lymph node involvement and metastases) (spread) puts patients in various levels or sublevels of stages 0-4. Physical exam, physical condition, certain laboratory tests, imaging scans and microscopic pathology reports refine the system.

A clinically useful tumor classification would be able to compare similar cancers and similar patients. Such a schema must be tumor specific and reflect the natural history of the tumor as much as possible. A unified approach to the degree of spread and or severity of the tumor is crucial as prognosis, therapy, and the ability of scientists worldwide to talk to each other hinge on it. Thus, the staging classifications of the American Joint Committee on Cancer rely on the premise that thoroughly staged and described tumors will largely act similarly and have similar outcomes.

The T (Tumor size), N (presence or absence of lymph node involvement) and M (evidence of metastasis or spread) system attempts to organize our understanding of tumors. The system is dynamic and living and evolves with our knowledge of increasingly relevant prognostic factors. If the world categorizes tumors in detail in exactly the same way, there is no Tower of Babel effect where no single scientific language exists and is universally accepted. The problems that can occur when different languages are used disappear and physicians then pave the road for rapid accumulation of information about highly similar tumors in highly similar situations. That information leads to clinical trials. Clinical trials lead to the future of better and evolving cancer care. Thus, precise tumor staging is crucial.

The most common mistake regarding staging that I see is that patients do not understand the implications of their stage and thus labor under erroneous conclusions. A frequent misconception is demonstrated when listening to how most patients describe their cancer. There is a tendency to name the cancer according to where it has spread, rather than where it came from. This is not correct.

Let us look at a mythical explanation using the United States as our body. We name terrorists for the land they came from. They have a native culture, character and craft of terrorism they conduct. Whether they are in California or Maine, we name them from their country of origin. Where they have spread to is crucial but only tells us how advanced their spread is. A real world example of this in cancer medicine is demonstrated when patients with breast cancer that has spread to bone state they have bone cancer. This is incorrect.  They have breast cancer that has spread to bone. This is not mere semantics. There are enormous differences in treatment and prognosis between breast cancer that has spread to bone and bone cancer.

The TNM classification is also identical to the Union Against Cancer schema (UICC).They both have clinical and pathologic staging. Simply put, pathologic staging is determined when a tumor is physically seen and biopsied. The site of origin determines the T stage and refers largely to the size of the primary tumor at that site. The N refers to proven evidence of lymph node spread and the M refers to proven evidence of distant spread or metastasis. Clinical staging employs multiple different non-surgical techniques such as X rays or CAT scans, MRI, ultrasounds or PET scans that may image or demonstrate findings that are extremely suggestive of spread.

Thus, clinical staging relies on what we can see and pathologic staging relies on what we can feel or have touched as a result of tissue biopsy. In some cases, biopsy may be required to confirm suspicions of the presumed clinical stage as frequently the impact of incorrect assumptions of the degree of advance can have enormous consequences. Of course, we cannot biopsy all tumors that we see. They must be safely accessible. In addition, in many cases such as breast cancer, biopsy of nearby draining regional nodes is routine. Immense knowledge is gained by systematically finding and assessing for cancer in what we call the sentinel lymph nodes regionally draining the primary cancer.

Stage grouping refers to when we combine the clinical or pathologic stage information, i.e. the T, N and M information and group them into larger numeric stages of usually 1-4 with occasional subsets. Stage 1 is the most limited and Stage 4 usually refers to being widespread. Different combinations of TNM can be in the same stage group such as a large tumor with no involved lymph nodes or a small tumor with a few involved nodes. All stage grouping is specific for each tumor. These numeric groups are not for convenience; rather they reflect the spread of the disease and have enormous influence on prognosis and therapy.

The clinical stage guides therapy. The pathological stage determined after complete surgical removal of all visible disease can determine the need for further therapy even when no remaining tumor seems to exist. Both breast and colon cancer are excellent examples where the stage seen as a result of surgery predicts the risk of future relapse from microscopic tumor cells that may still be present. As mentioned in the Diagnosis chapter, adjuvant therapy refers to when we see no remaining tumor cells but history tells us, based on the tumor type and stage, that there is a meaningful risk that viable cancer cells remain undetected. The utility of such therapy is very specific for the type of tumor. Adjuvant therapy is wise if evidence suggests that it can help improve the odds of preventing recurrence, delaying recurrence or increasing the odds of survival. It is not wise for every tumor or every stage of any tumor. It is a very specific choice based on very specific clinical evidence; the benefit is very tumor and stage specific.

Therapeutic procedures, such as partial or total surgical removal, may alter a tumors’ stage and the life history of the cancer. Thus, we have the rTNM – restaging scheme, which yields different results than the original stage. Obviously, we use the rTNM for re-estimation of prognosis and guidance for further therapy after total or partial surgical removal. Whenever patients are compared or treated in clinical studies, physicians always use the pre therapy original stage of the tumor  so that  everyone is on equal footing and starting at the same place. Not all patients with any given tumor type or stage will or can have surgical removal. Comparison that is more accurate can occur among patients owing to this rationale.

There are exceptions to the TNM staging criteria and they usually include the so-called liquid tumors such as leukemia and lymphomas, etc. They do not lend themselves easily to the TNM system due to how patients with them typically present at diagnosis and their natural history. Thus, there are elegant detailed criteria for staging. In the case of most leukemia, physicians use lists of definitive factors to give a prognostic score. Thus, we can group these diseases into various stages that predict response to therapy and odds and duration of survival. These factors are constantly evolving as molecular and genetic tests and knowledge that goes far beyond simple laboratory tests develop.

The beauty of such staging schemes that are internationally accepted is that they allow us to compare therapies stage for stage and design clinical trials intelligently with high likelihood of answering an important question. The staging schemes help us decide what adequate therapy is and assists in further refining treatment approaches.

In most cases, staging relies on the anatomic extent of the malignancy. We know where the tumor has physically spread. However, sometimes the degree of aberrancy – the bizarreness and abnormality in the appearance of the tumor under the microscope (histological grade) and patient age can affect staging. Thus, two very similar tumors may have slightly different stages because the cancer cells are more primitive or angry in one case or the patients are different ages. The reason for the different stage is the same reasoning for staging. In the example above, we know that more angry cells or an older age impact the prognosis of otherwise similar patients thus we name the stage differently.

Although cancer cells mimic their normal cell counterpart as discussed in The Enemy, they often have very specific identifying fingerprints or products they produce. Increasingly, molecular markers, which are the presence of highly specific molecules that identify or mark the disease, specific genetic fingerprints or abnormal proteins on the cancer cell surface and other cancer specific characteristics and tumor produced products aid in staging and directing therapy. In some cases, the degree of bizarreness of the cancer cells may be the most important staging criteria of all.

The challenge for any staging system is that it must keep up with the diagnostic advances in oncology as we find newer valid and crucial prognostic variables. Thus, original and future stages of the seemingly same tumor may not be similar. There is no widely accepted detailed staging system yet for tumors of the central nervous system owing to inherent difficulties in defining landmarks, their significance and frequent lack of biopsy material.

In conclusion, it is imperative to have an extremely accurate staging of any tumor whether it is by anatomic site only, biochemical, genetic and molecular or immunologic measurements. Patients must be certain that their tumors are precisely staged and that they know what stage it is. As mentioned, we understand treatments and prognosis largely in terms of the stage of the disease at the time of the diagnosis. Individual treatment decisions require thorough staging.

Patients must remember that they are individuals and not a group. Although the study of groups of similar patients have taught us enormously what the odds are for response, duration of response, freedom from relapse and survival, patients experience their disease as individuals. Individuals may beat or, less happily, lose against the odds.




         The National Cancer Institute (NCI) has played an active role in the development of drugs for cancer treatment for over 50 years. This is reflected in the fact that approximately one-half of the chemotherapeutic drugs currently used by oncologists for cancer treatment were discovered and/or developed at NCI.

NCI’s Developmental Therapeutics Program (DTP) has over 400,000 drugs in its repository that have gone through some kind of screening process. About 80,000 compounds have been screened since 1990 using the current screening system. Compounds can enter at any stage of the development process with either very little or extensive prior testing. NCI supports about 1,500 clinical trials through a variety of programs. NCI researchers at the National Institutes of Health in Bethesda, Md., conduct some while others take place at cancer centers, hospitals, and community practices around the country.

It is far beyond the scope of this book to discuss in any depth all the nuances of the more than fifty common chemotherapy drugs available. Previously in the overview section we enumerated the major classes of drugs. Here we will delve a little more deeply into the how of the drugs we have as well as the most importance drug advances.

The first and most important concept is that typically, specific drugs work for specific tumors. However, this is this is changing as new combinations are tried. Secondly, drugs try to hit the Achilles heel(s) of the tumor. Yes, the majority of cancer cells have an Achilles heel, weak spots that theoretically drugs attempt to exploit. Although these drugs may damage normal cells in the process, such as the gastrointestinal tract, bone marrow and others, the bulk of the damage is intended to  affect the tumor because of its Achilles heel(s).

One particular area of concern is off-label use. Pharmaceutical companies initially apply to the FDA for approval of a new agent for a particular tumor in a particular setting. This requires an average of 6 years of development and more than five hundred million dollars. Becoming FDA approved means a drug is known to be safe and effective. It then receives approval for its use for a specifically tested indication. Once approved, hundreds of researchers and many patients with other tumors or different stages of the original tumor type compared to the original trials, participate in carefully designed phase I-IV clinical trials of the drug either alone or in combination with other drugs or radiation.

Remember, I am using a broad definition of drug to include novel immunologic agents, typical chemotherapy compounds, vaccines and many other varieties of substances given many different ways. In this way, researchers can develop numerous extremely important uses for the original drug that go beyond the original FDA approved use. After FDA approval, it is usually only a matter of time before we know, because of more trials, if the drug has additional uses. Typically, many do. Thus, patients need not be wary if the drug(s) they are treated with are off label.

Normal cells have a life cycle. The creation of new cells from a parent cell is a reasonably well understood process with numerous genetic and biochemical markers that tell us where the cells are in that process. The phases of the process have different names. One technique of developing a new drug is to target a potential vulnerability because of the phase a tumor cell may be in.

Cells that are resting are usually in a very chemotherapy resistant phase. In the next phase or interphase, cells become very active in making the building blocks that they need to live, maintain the household and prepare to divide and have children.

The genetic material of all cells is contained in tightly coiled twisted ladders knows as chromosomes. Those ladders are made of DNA and the nucleus inside the cell is the headquarters or home for the chromosomes. This genetic material contains all the directions and all the blueprints for everything that cell is and can do. In the DNA synthesis phase, the amount of DNA doubles in preparation of the cell dividing. In the Gap 2 phases, a fine meshwork of scaffolding appears inside the cells like an old-fashioned bingo spindle. This mitotic spindle is necessary for the duplicated DNA in our chromosomes to move across the nucleus before the cell divides into two cells. In the final phase, the M phase (for mitotic) all the newly created and aggregated DNA material goes into the two daughter cells in identical amounts.

Chemotherapy drugs may be specific for a phase they affect the most. These drugs attempt to exploit the fact most, but not all cancers cells are more active than healthy cells and more prolific at having offspring. Some chemotherapy agents however are phase non-specific and kill non-dividing cells. Examples are the anti-tumor antibiotics, excepting Bleomycin. Some drugs are simply specific for the whole cycle and do not need a particular phase. Rather, these drugs require only that the tumor cell be going through the cycle of life, not just a particular phase. Thus, these drugs can inflict injury at any point along the cell cycle. Examples are the so-called alkylating agents. Generally, these types of drugs have a linear dose-response behavior in that the more you give the more tumor cells they should theoretically kill. Of course, two things limit this. One is the tolerance of normal cells (thus the patients’ body) and the other is the multiple clever ways tumor cells can either acquire or already have in-born resistance to the agent.

As mentioned above, there are phase specific drugs that are only effective if they are present during a particular phase of a tumor cell’s life cycle. This type of drug usually has a limit in cell killing ability. After a certain dose level, no further killing happens. However, if the drug is still present by the next time that specific phase occurs in a tumor cell’s life cycle more tumor cells theoretically may die.





Staging- Where Is It




Pathological Diagnosis

Treatment Modalities, Goals and Timing


Potions and Poisons -Chemotherapy and Other Potions MORE IN DEPTH

What is The Buzz-Radiation Therapy

A Chance to Cut – A Chance to Cure-Principles of Surgical Oncology






PHOTODYNAMIC THERAPY AND LASER SO MUCH MORE                                                             VARIATIONS ON A THEME







Example of Finding Just One Cancer Cell


What follows in this section is a much more advanced presentation of the major ways we treat patients such as radiation, chemotherapy and surgery as well as some of the newer therapies. There is sufficient depth here for one who wishes to have a broad overview of one way to embrace the basic science principles (about late high school level per se). There is also sufficient depth layered in that is more like a Discovery Channel or Nova overview of how all the material connects. Again, I encourage you to look it over and certainly use it as a reference to better understand your options and more so the world of those professionals who are treating you.

You will be both amazed and awe struck at how we are wondrously assembled and how incredibly ingenious cancer cells disassemble the norm to their survival advantage. The sheer genius of the design and the methodical cleverness of the treatments being developed by talented men and woman worldwide as they unravel the nature of the cancer may deeply move you. Thus, there is something here for the student of science as well as a wow factor for all as we look at these therapies and their rationale.

They are also included because it is patients such as yourself not only supporting this work through your taxes but by enrolling in clinical trials ( to be discussed later) that have brought us this far. Thank you, and I hope this walk through these wonders helps calm the anxiety and embolden your power to fight right along with your health care team and when appropriate, to cheer on that this new age of enlightened endeavors make the weapons in the oncologist’s armamentarium grow.

Let us first look at the rationale and principles of treating starting from the not so hypothetical situation of having tests that find only one or only a few cancer cells in the blood. Large tumors within the level of detection (0.5 cm) are self-apparent; something must be done. However, there is a lot to be learned by looking at where technology is taking us in terms of early detection. There is a lot to be learned in terms of when to treat and why. So with that in mind, let us spend a little time examining lessons learned from the perspective of finding  one or barely any malignant cells – what do we do and what do we think . How did it these cancer cells escape our own immune system, or did they?

Research at the cellular level looks for why does one cell and its progeny survive, escape surveillance and destruction by our immune system and grow beyond the limits of the normal counterpart cell that they mimic to some degree. Why do they spread, frequently homing in on  specific normal tissues, displacing and destroying them? How do they do it? We do not have all the whys but the quality of questions is growing with each high quality answer.

No one wants to treat everyone who is found to have random malignant cells found accidentally or by intentional search just because they are there. No one wishes to ignore these cells all the time either. The same thinking applies to when you think you have a complete remission. How do you know what is enough therapy. How do you know you have a durable remission or cure. Often we do not know, but our tests are growing in leaps and bounds in terms of cell specific or cancer specific signs, symptoms and clues that cue us in that there is disease remaining. Our trials are telling us when and what therapies work best alone or together and when it is time to either stop or offer highly experimental treatment since all conventional therapy has failed.

At the millennium, The National Cancer Institute established a goal of eliminating the suffering and death due to cancer by 2015. This was noble but unrealistic. Much research is aimed at finding both the primary tumor as well as any metastases (sites of tumor spread) at the earliest ( fewest cells) time. Exactly when, where, how and why a distant metastasis of a primary tumor occurs is not clear in many cancers. In addition, it most certainly varies within patients with the same type of cancer as well as among cancers. For solid tumors we have a lot of data collected, using both cellular based techniques and imaging of tumor lesions of over 0.5 cm ( our present most common detection threshold) that gives us general ideas of the personality of  both treated and non treated cancers  in terms of  the where and when of spreading.

Some cancers spread by direct invasion and may invade and spill over into lymphatic and vascular channels. Some not only seek out and seed into the blood, but actually home to predestined organs manipulating our own machinery and building cell sized canals to travel within as well as feed themselves by bringing them close to these new vessels.

A great deal of research has gone into detection beyond the level of the physical exam and human eye. We will delve a bit more deeply into this notion of applying critical thinking to observations made over the decades derived by pondering the exciting notion of trying to find just one cancer cell among billions.

Even if there is just one tumor cell found, is it clonagenic? This means can it and will it anchor in some organ, have just the right conditions for growth and have offspring. Will it survive long enough to have offspring before its own internal clock signals time to die? Will all the essential nutrient requirements be present? Can it evade assault by antibody and non antibody producing cells of your immune system before whatever clock internally it is under or whatever assault it is battered by ( immune system, oxygen content, acid base environment, and such do it in. Is finding it once in the circulating blood a marker that many malignant cells are circulating undetected.

Is finding it once a sufficient marker of high probability that among the other tumor cells that are facing the same challenges, at least one will succeed? Is there high certainty that blood involvement on this test seen once; is a marker for high likelihood of bone marrow involvement or brain as is the case with other cancers? Do cells in the blood constitute real and sufficient markers for patients to do poorly in some predictable way as is known for some solid (excluding primary hematologic) malignancies? When would we want to listen to the presence of one such cell in the blood?

Put another way, is the finding of one test, or whatever number you have showing cells of the tumor in the blood, of clinical relevance? If so what is it relevant to; total tumor burden, response rate, disease progression, overall survival and so on. Or as the title of the book implies, is this ( the positive circulating blood results) a rumor  that does  not imply serious consequences and underlying meanings as listed above or in fact is it the bell weather test that is saying where you see few, trust there are many?

In general, finding circulating leukemic cells in patients with acute leukemia must be taken in the context of where in the therapy you are. In chronic leukemia, the same concept is true, as, by definition, even stable disease and low-level disease will show the malignant cells. However, when so-called solid tumors cells are showing up in ever increasingly sophisticated assays of the blood, all the above big clinical questions arise.

Yes, the test is very important if a positive circulating malignant cell test means  that where there is few there is many, ( such as a positive bone marrow with malignant cells in it) The standard reasoning ( if the  realistic intent is cure and not palliation) is to treat the patient full dose on time initially with chemotherapy. Patients may not handle this as well and if you under treat the malignant cells will overgrow and resist the less than optimal dosing because of the probable marrow involvement. If you do not cleanse the marrow, the marrow may never recover and you  may end up with the horrific possibility of a packed bone marrow with increasingly resistant cancer cells from insufficient dose. You will also have dependency on blood products. All of this transpired because we believed finding one positive circulating cell in solid tumors means the bone marrow is involved and that warrants, if treating for cure, full dose on time therapy.

As our technology grows we need to understand what the implications of their sensitivities are. It is not yet standard of care in clinical staging of solid tumors to assess patients’ blood or bone marrow to see if there are any circulating cells from the original cancer present which are actively circulating. Similarly, if the test is done, I am not clear as to what to do with a negative result.

If the test is negative and the patient has widespread disease, I feel you have added nothing. If it is negative with otherwise limited early stage disease I would be hesitant to treat an otherwise low stage patient with therapy meant for high stage without either new data showing the original staging was wrong or published research telling us how specific and sensitive the test is for predicting it behaving like advanced disease. The point is to be careful of what tests you do if careful review of published experience shows you that it is not clear what one does with the answer.

Might it make a difference if we could find cells circulating in the blood that presumably might be markers for cells trying to set up shop in distant lands? Intuitively, yes but again unless you have the data or are collecting it in an organized manner with patient consent to use it to get information that helps tailor your treatment, I would stay away from asking question whose answer you do not know how to address. I do support aggressively finding out through trials

This is why a number of companies have embarked to see if they can find circulating solid tumor cells in the blood. In the case of colon, prostate breast and lung (and in the literature, many tumors) the answer is yes. However, it is not clear if such detection is meaningful in the setting of a complete remission elsewhere or in the setting of a partial response. What do you with that?

In the case of leukemia, a large portion of what you do is aimed to have eradication of all leukemic clones (cancer cells capable of dividing) using all the tests there are to find them. These include looking for cell specific staining techniques to finding very specific molecules in or around or through their cell surface marking them uniquely from their benign counterparts. It continues to be our hope that earlier detection, even detection at the single circulating malignant cell in the bloodstream, might confer a different prognosis that might then argue for various therapies and combinations of treatments. In leukemia the argument holds true as by definition the tumor is of the bone marrow and diagnoses depends upon specific bone marrow findings primarily.

However, for the so-called solid tumors, we just do not know what finding circulating cells really means. One promising technique employs monoclonal antibodies that are discussed later but in brief are manmade antibodies engineered to be specific for something on, in or associated intimately with the cancer cell. You can put a marker or florescent tag or isotope on the antibody and look for the light (radiation) these tags emit. Then one can count the cells in a fluorescent activated cell sorter channel through which the blood flows  learning how many cells were stained showing the presence of the marker. Of course, this requires both high specificity and sensitivity of the marker for the tumor cell associated antigen and strong binding affinity so that the monoclonal antibody does not easily fall off. Another recent style of detection is to have the antibodies have iron in them that then allows for an antibody iron bound complex if the antigen is present. Then when the cells are run through a sorter under a magnetic field, only the cells with the marker will stay on the magnet

So, all of this is to tell you that one should understand the natural history of the disease to which you are going to apply a test. Based on other results is it in the realm of possibility that cancer cells could be in the blood, what is the pre test probability? If it is profoundly low, you could be asking for confusion and having a result you have no use for except perhaps as research data. You would also want to know from prior controlled applications of the test in multiple scenarios and locations how sensitive (low false positive) and how specific (low false negative rate) the test was was when tested against known positive and negative controls, In other words how well is its yes correct and its no (tumor cells in blood) correct.

There may be a role for assays looking for single circulating cells in both seeming complete responders and major responders initially in collecting the data on all manners of patients to learn what the test can do, and in some cases directing further therapy as early as possible. The more we use the tool to collect that information, the more they can teach us.

It is not yet clear in which cancers ( other than most leukemias) this single cell detection really indentifies cells destined to survive in a new area and multiply. You cannot biopsy everywhere as you will usually be taking a sample.

Before you choose to take the test be sure you know how specific and sensitive a test is before using it and know whether there are any likely scenarios where the test results clearly changes prognosis.


Beyond Single Cell Detection


Our present conventional level of detection of internally seeing gross tumor is about 0.5 cm whether we use a CXR or Computed Axial Tomography (CAT scans are specialized X rays with computer assistance that bread-loafs slices images to 0.5 cm detail). Magnetic Resonance Imaging (MRI) (translates the movement of water under a massive magnetic force into images of incredible detail and again about 0.5 cm resolution.) These are frequently used to supplemental simple X rays, Ultrasound and various so-called nuclear medicine scans such as bone scan and PET scans. Ultrasound is good at looking at flow of fluids as well as densities and cavities and bone scan measures new bone being laid down in response to processes which ate away or destroyed prior bone such as fracture and repair, arthritis and in some classic patterns by tumor either of the bone or  which has spread to bone. PET scans elegantly track the metabolism of isotopes of simple sugars in the brain and can be useful in the evaluation of both primary brain cancers and tumor that have spread to the brain which then take up the simple sugar you gave it thinking it nourishment of a sort.

After initial responses to treatment, one will have a very difficult time knowing if therapy had a positive sustainable benefit if you cannot easily see the tumor(s) using the above tests. You also do not know how viable any residual disease is, whether you see it or not. A spot on film might now be residual scar.

Ascertaining function of the cancer cells as mimicking normal counterparts will not be easy as only a few malignancies readily do that such as some thyroid cancers. Our tools of detection are imperfect with limits stated above. There can be problems with sensitivity of our studies when size is small which means that there is a high false negative rate wherein the test says the cancer cells are not there but in fact, they are and are out of our range of detection. Assays can also have a problem of not being sufficiently specific and have a high rate of false positives wherein the test incorrectly claims benign tissue to be cancerous.

Thus, an enormous of amount of research is looking into minimal residual disease and tests done of various biopsy type specimens or body regions that try to inform the clinician as to whether cells are present with the ability to divide and have ‘children’. This is not an exact science. There are so many other factors occurring at the same time we are making these measurements; the clinical condition of the patient, prior therapies, the condition of the bone marrow and other organs abilities to tolerate further therapy, the order of therapy and so on. Thus the research which looks for detecting disease at its lowest level of tumor burden tries to understand how that translates into the risk of a local, regional or systemically advanced disease.

With acute leukemia, the message is already clearly; kill every cell visible using all means of detection as just one cell could be clonal and lead to relapse. In solid tumors, this is not clear. No one wants to treat everyone who is found to have random malignant cells found after intentional search or just because they are there and no one wishes to ignore them out of hand. We must understand these delicate relationships before we miss an opportunity to improve therapy or choose wisely to stop when there is no proven disadvantage.

Breast cancer is a great example of how numerous factors mix in increasingly accurate mathematical prediction models to sort patients into risk groups and to define what groups will do best with which therapies. The hunt is on to add to the already considerable lists of factors we search for in every breast cancer patients and their cells. All of that informs us as to the risks and benefits of future therapy. This is poignantly true even though we do not see residual disease that in many is clearly there but not yet reliably detectable in most patients by any one particular assay.

Resolving benign Vs malignant is, in the case of breast cancer, the realm of the pathologist looking at tissue. There is usually no need for anything further to ascertain if breast biopsy cells are malignant. However, their personality and their likely future behavior can be ascertained with incredible detail and power by studying those specimens hormonally, genetically, biochemically, antigenically and immunologically. Some of these tests show either positive or negative, others give actual numbers of cells. Thus, we look for interior or surface of cell chemical binding sites which when present predict behavior.  One may be able to use various immunologic trackers (antibodies that bind to a very specific portion of molecules known as antigens that are substances capable of eliciting an immune response, such as but not only antibody production). With these techniques, one can find individual cells among millions. Similarly, secondary chemical reactions can be triggered by the presence and interaction of a target seen only on malignant cells. Likewise, measurement and location of radiation given off when  radio-immunocongjugates ( created by adding minuscule radiation to the binding antibody) prove the detection of a target protein seen in either only malignant cells or  the more angry and apt to spread cells.

Sometimes we find receptors for common substances present or absent in the cancer cells, such as the receptor (think biochemical mailbox) for estrogen and progesterone. In the case of breast cancer, their presence is better than their absence and their presence opens up a whole class of drugs that can powerfully suppress the spread and growth of the clones (daughter cells) of cells that have the markers. Early work is suggesting putting various toxins  or powerful radioisotopes  that can tag some breast cancer cells on the antibody and deliver a  toxic payload lethal to nearby cancer cells as well as those directly taking up or linking with this “ magic bullet “ antibody or antibody missile combination. Furthermore, you may see the breast cancer cells by looking for the radioactive light emitted by the injected isotope on targeted cancer cells.

I was fortunate to be on the first team to image breast cancer with a radiation labeled isotope monoclonal antibody showing not only where the bulk of tumor was but also finding previously undetected areas of spread by looking for the radioactive light. In addition, our team had humanized the antibody. Previously, a major obstacle was that the antibodies were largely from mouse origin and the human patient could react against them confounding their utility. This was a crucial first step to showing one could make and successfully use human antibodies (most previously were mouse), as human patients would reject mouse antibodies more often than not.

Thyroid cancer shows similar possibilities for diagnosis that also looks for protein production of the cells as well as uptake of building blocks for the protein as well. The cancer is an easy target for diagnostic uptake of radioisotopes At higher dose, therapeutic radiotherapy can target the tumor which absorbs it and thus receives a lethal dose to the cancer cells.

Thus, we are trying to exploit the fingerprint of the cell surface, or trans -membrane or cell body or nucleus or nucleus associated proteins, or genes and their products; anything the cancer cell possesses uniquely, or slightly aberrantly or in excess amount to its benign counterpart. This type of targeted therapy is a type of rational drug design; we sleuthed for vulnerabilities  using the intricacies of the cancer cell as opposed to its benign counterpart and built near targeted bullets for only our intended prey.

Diagnostically, the more we understand any of the physical, genetic, molecular or immunologic and antigenic unique fingerprints of cancer cells, the more we can develop tests that exploit those differences. We can then “find”, with perhaps tagged on chemical or radioactive dyes, depots of malignant cells at much higher resolution than other techniques.

Therapeutically, finding the cells when they are less in number not only means less tumor burden, but probably better penetration into tumor depots and higher ratios of killed cells to viable cells. The tempo of such targeted therapy and rational drug design submissions to the FDA continues to pick up as the possibilities rumor of some animal or plant kingdom wonder drug. Similarly, the pace of thoughtful laboratory rational drug design based on finding more Achilles heels that tumor cells have as opposed to their normal counterparts which leads to rationally built drugs is accelerating. The numbers are staggering. About 5000 or so ideas thought worthy of beginning the testing that starts with non human toxicity studies turns into just a handful thought suitable  for phased human toxicity studies and trials per year.  It costs around one-half to up to a billion dollars to develop a major new drug and typically 3-5 years. Patents are not lifelong and generic drugs do follow after reasonable times.

For those in the know, the FDA does more (and by extension the USA) of drug development and testing with amazing track records of accuracy than any other nation or consortium. Drug companies or big pharmacies are neither robber barons nor angels. Their profit margin, what they actually return after all costs, is not spectacular and they can go years working on reserves before the next great drug comes along. There has been no better system shown for providing mankind with safe and effective oncology medicines.

Some cancers treatments require the death or disabling of all cancer cells in the patient capable of dividing and growing and or spreading. Some treatment may not remove all viable cancer cells but remove the ability of those cells to repeat the havoc of what preceded treatment. As a result, patients are living longer and often with a better quality of life. In some types of cancer, it is becoming more of a chronic disease that must be managed and controlled over the course of many years and maintained until new discoveries in treatment are made.

For the last several decades, the common cancer treatment methods have been surgery, radiation, and chemotherapy. While these treatments are focused on destroying the tumor cells, they can damage normal cells in the process or may have significant treatment related toxicity.

The newest category of cancer treatments are targeted therapies that act in specialized ways to destroy or act against tumor cells, often not affecting normal cells. These are innovative therapies, many of which were scoffed at less than a couple decades ago but are now commercially available with bold new trials launching nearly weekly internationally. These therapies are based on discerning something unique about the cancer cell or some sort of potential Achilles heel that can be exploited while not harming normal tissue. As a result, patients may experience less severe side effects. The newer treatments can also be combined with older therapies to enhance anti-tumor effectiveness.

The bottom line is that although all therapy is not individualized and may never completely be, the distance from laboratory bench to patients’ bedside is shrinking. Soon therapies will exploit singular or multiple areas of tumor vulnerability at the molecular and even genetic level, all as a result of fundamental research your tax dollars (in large part) support. Soon therapies will be more patient specific.

Because of improved early detection and better cancer treatments, there are approximately 9.6 million cancer survivors alive today in the United States. This compares with only 3 million people with a history of cancer who were alive in 1971.

Another potent message is the marriage of technologies. As discussed a number of times, we are often marrying the anitigenicity or chemical reactivity or genetic fingerprinting of tumor cells with CAT scans and MRI. This is done to detect and then “see” both the primary tumor but hopefully early depots of spread and in the case of the marrow, presence even on the single cell level. The notion of intellectual partnership in medicine is crucial. In Oncology, our tools function best when in synergy ( where for example one plus one equals three);   Critical thinking and well constructed trials based on good science casts a long shadow



Cultural Differences

Focus on Symptomatic Relief

Introduction to Clinical Trials

Complementary And Alternative Medicines Overview

Media Matters

Antidotes For Anecdotes

Prognosis And The Future

Taking Your Time, Avoid Timelines

Second Opinions

The Contract

Autonomy; Everything Begins And Ends There

A Final Few Words

Cultural Differences


Doctors must pay attention to cultural differences. People from different backgrounds and parts of the world have very different ways of relating to the physician. This may range from deification, rarely some level of disdain and even total acquiescence and deference. Despite the variability, it always remains wise for doctors to engage their patients as the folks in charge and the doctor as the expert consultant who will not allow avoidable errors in decision-making. Patient autonomy is pivotal to a successful treatment road.        Providers must stress who is and is not God and make it clear that it is not the doctor. This is at times unnerving but usually surprisingly very well received.


Focus On Symptomatic Relief


A difficult scenario arises when in rendering the diagnosis it is also clear that only symptomatic or so-called palliative care is available. Sometimes diseases are so advanced or resistant to treatment that the discussion may need a predominant focus on relief of symptoms. Sometimes, the patients’ general medical condition makes it reasonable to have such a focus. On occasion, a well-informed, competent patient may choose only symptomatic relief for any number of reasons. Thus, discussing the option of symptomatic care is always germane.

`The patient and physician must be mutually clear as to what the odds are for a response, its duration, the odds and nature of relapse or progression and the costs- psychologically, physically and financially. The first step is making it clear that such care refers to improvements in symptoms, irrespective of temporary changes in blood tests or other diagnostic studies. Otherwise, expenses and anxiety can grow exponentially and perhaps unnecessarily while temporarily inflated hopes die on the rocks of reality.


Introducing Clinical Trials


Although I cover clinical trials separately later, the issues initially arise when explaining either the diagnosis or the rationale for proposed treatment. Trials are a perfect match for some personalities, but the whole idea of “experiment” or randomization (explained later), no matter how carefully couched, can be frightening. This is a major dilemma for medicine in general as clearly this is a major way in which treatments are developed yet less than 5% of all eligible patients enroll in clinical trials. This is particularly sad when considering that these trials are the only valid means of determining a treatment’s effectiveness.

When there is an opportunity to offer a patient a trial, it is wise to follow a common sense rule; be sure the patient knows exactly what is happening at all times and always provide a  copy to the patient, their primary care provider as well as place one in their chart. One cannot predict who will volunteer for trials. The ethical rule is straightforward as all ethical rules should be. Physicians should present the trial in terms of a balance of what other therapy is available with possible results, the goods that the trial may offer and the harms that the patient may experience from either the trial or other therapy. Secondly, the patient must give a fully informed consent after significant time to reflect and have their questions answered.

The trials have to go through all manner of review boards and must be among the next best questions to ask. Your credentialed physician or anywhere near you may not have a trial for which you are qualified. No worries, the issue is to receive at least the standard of care and happily essentially all U.S. trained U.S. board certified oncologists deliver it. Sadly, fewer than 15% of those who could be on a trial enroll but that is getting better. You get all manners of scrutiny from being on one for obvious reasons and if they are level three or higher you are guaranteed receiving a treatment as good as the standard of care. The trial is asking if there is something we can do better.




Introduction to Complementary and Alternative Medicine


It is imperative that physicians explain, using every form of metaphor, simile, parable, analogy or allegory, how medicine has learned what it has about a disease over the years and that this occurs usually because of carefully planned research. There are notable unplanned observations leading to breakthroughs, but in cancer care, they are the exception. Patients need to understand when there is certainty based on vast data versus when there is only suggestive information.  Successful clinical trials involved many patients and showed how groups similar to an individual patient fared. However, individual patients, although likely to behave like the ones in a similar group, are still individuals

Sadly, largely owing to desperation, non-approved (non-FDA, non-National Cancer Institute) treatment regimens can find an easy mark in the cancer patient owing to unscrupulous practitioners offering savory hints of wondrous results. Patients are often easy prey for quackery. That is why I have included a special section on Complementary and Alternative Medicine (CAM). Patients and families spend billions on unproven therapies every year. Significant portions of cancer patients try CAM while most at least listen to if not solicit information regarding it. There are rarely corroborated results of success that can withstand scientific scrutiny. The reason is simple. There is no financial or political-legal pressure to do so. The “claims” that do exist regarding wondrous results from CAM raise more questions than answers. The questions they raise are of massive importance. Each must be addressed at the time of rendering the diagnosis to a patient or shortly thereafter as the issue of trying CAM will undoubtedly arise.

Quackery always has a pitch which many cancer patients will struggle with if left on their own such as “ “medicine is hiding the real cure because of profit and bad pharmaceutical companies”; “we have the secret”; “you can do this only by fresh air, diet and exercise; there is no need for ‘bad’, nasty, poisonous medicine or radiation. That is sheer nonsense if one calmly walks through this both in this section and the one that follows. I also refer the reader to the NCI site, Mayo clinic’s cancer site and .

The major issues CAM raises are these. How do we know if responses that are real are due to the alleged CAM therapy? How do we know if these alleged responses are durable and are reproducible in most patients and can be applied to a given patients’ situation? What monitoring is necessary? What are the toxicities of these therapies and are they compatible with conventional therapy? How do these CAM therapies truly compare to conventional therapy? Head to head well-done comparisons are rare.

At the very least, I recommend knowledge of everything that enters a patients’ body. Although I stand firm as regards the right of a patient to autonomy, I believe the right of these purveyors of unproven potions to hawk their wares must remain under constant scrutiny. I sometimes simply refuse therapy and state it must be one or the other and patients must chose. Although the patient may abandon conventional therapy, the physician should give assurances that they will not abandon the patient. The best way to fight quackery is with facts and calm, critical thinking. It is sometimes an uphill battle in appearing as physicians protecting their own turf. So be it.

There is little complimentary (with an “I”) to say about complementary and alternative medicine in patients with diagnosed malignancy. Level heads with tens of years of experience cannot say, I know this cannot harm you. Proponents also cannot say I know this is safe and effective to take against your cancer. They cannot say they know the exact ingredients in their concoction. Supporters of CAM may not even know the purity, other ingredients, and effects from processing (since none of this is required) and they do not know how it interacts with all other chemotherapy drugs as tested under the rigors of clinical trials. Wake up, hear the call of your anxiety and stop the craziness. CAM adherents cannot tell you any of those things because they do not know them.

Sellers of CAM routinely do not do any testing except making sure your credit cards and checks are good. Harsh? Not harsh enough. With rare exception, you will not see them go through complete scrutiny of the FDA. At best, they will get FDA statements of purity of ingredients but that is all. One hundred percent of nothing that works is not necessarily nothing. Fact is, it may be something that hurts you and unless the FDA has thoroughly investigated them and stated they are safe and effective, beware.

Be aware that once a drug is proven safe and effective by the FDA for one indication it is not illegal to use it as doctors see fit to use it for other off label uses based on well-scrutinized peer reviewed literature. This has lead to well reasoned application of drugs off label. This is not wrong and you will find these are all building blocks for the most part of intelligent studies showing their benefit.

When some substance looks promising from the plant and animal kingdom it is tested, not held back by some evil conspiracy. Think about how self-defeating that is. If it is sufficiently non toxic and has some mechanisms of action that make sense and some minimal response rate, it will find its way into early level trials described later. A number of our front line drugs exists today from the plant and animal kingdom. However this is after extensive years of testing. Ignore the shaman and the gurus hawking claims they may really believe as they have no high quality data nor relevant training. If what they had worked, it would not be complementary medicine, it would be front line.

There is also no rational reason to support any of the nonsense that “the man” or “Big Pharma” or whatever is holding CAM back. Ridiculous! Capitalism is doing just what one wants it to do; reward the real deal that will go the distance and not kill people or usurp their hope and resources. The system is not perfect but it is, without any equivocation, the best in the world for declaring a new drug as safe and effective. Moreover, our system does the right thing by limiting patents, expediting highly promising drugs and creating special tracks for enormously promising ones. The “Man” or “Big Pharma” would be idiots and bankrupt to proceed in any other way.

Furthermore, those of you who know how to read an annual report or balance sheet should ponder this. It takes almost 7 years for a new drug to go to marketing as safe and effective and over $600 million dollars. Consider how much is spent on non-winners. Profit margins, not profits but the real numbers  such as how much is finally left after everything is paid for range from negative 7-10% in bad years and 5-20% in good and overall about  average 6-9%. Nobody is routinely getting ripped off.

The cost in lives, pain and suffering, manpower, health care cost dollars wasted and clogging up the system because of CAM barkers and naive folks exercising their admittedly free choice is outrageous. Many put it as a ratio of one out of every 6 dollars is wasted in Oncology by the pursuit of, application of, and costs from using complementary or alternative medicine.


Media Matters


Beware mass media, they are often hit and run news du jour artists without the time, temperament or talent to clearly put any news or breakthroughs in perspective let alone in individualized terms . Sometimes they get a lot right, especially when they are fact based stories and not predominantly emotional content. Some incredible network as well as cable television shows highlight the exception of a bad physician and run the story without comments of the overwhelmingly good data out there when it comes to the constancy and quality of Oncology care.

Yes, the media have a crucial and welcome role to help watch, encourage and support and in a sense, police the field for the betterment of all. But remember their job is not meet you in the E.R., take your calls at three a.m., work with other consultants, calculate your chemotherapy, talk with the family and be the responsible individual from rumor to tumor to treat and beyond.


Antidotes For Anecdotes


One of the biggest poisons in our field is the anecdote. It is the irresponsible presentation without hard verified, in-context data of some patient response or treatment with an against all odds outcome or surprise ending ( such things happen rarely) that the storyteller or listeners then wrong headedly thinks present new rules and lessons to all broadly or especially to them.

Anecdotal medicine frequently causes suffering and in oncology where margins are slimmer, it can cause death.

For example- all seem to think if you flip a penny ten times and get 3 heads and then 7 tails in a row that tails is favored. No, not even if you got the same ratio doing it again.


Prognosis and the Future


It may or may not be premature to discuss prognosis early on. This is a case-by-case situation. It can be very confusing at first to present to individuals how groups have handled highly similar situations. Using comparative hypothetical or historical groups to predict an individual’s prognosis can be relevant and helpful but it is not a crystal ball into the individual patients’ future. No one is to be hopeless. I have seen enough surprise turns to the positive to jewel a crown with joy rather than be jaded by some anchor around my heart. Odds are things patients’ beat from time to time.

Oncologists and patients would be wise to outline and explain the potentially long list of experts needed in future care early in the journey. The list may be long, confusing and frightening. It may include ostomy nurses and physicians needed to perform further biopsies, diagnostic tests or radiation. Oncologists must prepare their patients for the entourage in their service; rather than position patients for a frightening flood of new doctors and procedures.

Take the Time and Avoid Timelines


Most importantly and least easily done, rendering the diagnosis takes time. The vagaries of managed care and reimbursement issues have private oncologists seeing enormous numbers of patients per day. This can be insane and inhumane. It is easy and understandable to state that there simply is not the time. Somehow, some way, there must be. In the end, spending the time will eventually save time. After all, it may be all the doctor has to give at some point.

Oncologists must not give Hollywood time lines. The best approach is to refer to the literature and the ranges that a patient most likely fits while stressing once again that patients are individuals, not statistics. Patients and providers should avoid attempting to quote dates or make dramatic pronouncements. That is pandering to fear and fatalism.

Odds should be explained, both as relative and absolute odds. As an example of this explanation, I will relate what I do to illuminate these crucial concepts to the patient. I take out a dime, a penny, and a one and ten dollar bill in front of the patient. The difference between the penny and the dime in “relative” value is that the penny is one tenth of the dime. The same is true for one and ten dollars. The one dollar is one tenth of the ten dollars. However, the difference between the “absolute” amount of ten cents and one cent is nine cents. The difference in absolute terms between the ten dollars and one dollar is nine dollars. Nine dollars is absolutely much larger than nine cents yet nine cents is 90%, relatively speaking, of ten cents as nine dollars in 90%, relatively speaking, is of ten dollars. However, the absolute difference between nine cents and nine dollars is absolutely quite large.

Why care? A ten percent improvement in survival or response or duration of response can vary greatly depending on what odds you started with. This concept is crucial when discussing adjuvant therapy. This is treatment given when statistics say there are high odds of recurrence of unseen lurking disease after apparent removal of the primary cancer and no visible evidence of cancer cells remaining anywhere. If adjuvant therapy is given, it is because it has a certain relative and absolute risk of preventing recurrence at some future point in time.

Oncologists offer many breast cancer patients adjuvant therapy, treatment after the primary surgery to kill hidden distant disease. The concepts of absolute and relative risk play a large role in this decision. It is crucial to know what the real difference, the absolute difference is between those treated adjuvantly and those not. A ten percent improvement in the odds of recurrence, when the odds of recurrence are only ten percent, is just an improvement from ten to eleven percent. However, a ten percent improvement of odds of recurrence when the odds of recurrence were eighty percent is the difference between eight and eighty-eight. That is eight percent. That is eight more people potentially alive out of one hundred.

Understanding basic statistical language does not end there and the education to build understanding begins at the time of giving the diagnosis. Patients must be able to understand what the percent improvement stated above really refer. Is it an improvement in the odds of response to therapy or the risk of recurrence? Does it translate into a ten percent improvement in the time to recurrence? Is it referring to a ten percent improvement in the odds of survival? Does it translate into how long one lives before eventually dying from the disease? On the other hand, and as is commonly the case, does the ten percent apply to some, but not all, of these very different notions? These are all very large, quality of life, practical issues and they are very different concepts.


Remember Statistics Can Be Your Friends


Statistics tell us number needed to treat to tell you if a study had any ability or power to tell you anything.

Statistics also give us wondrous definitions like the level of power ( predicting the truth) of published studies. They tell you if you can definitely say yes or no is true with some degree of certainty and if the type of study is rock solid and the evidence for it.

They tell you if you can know the odds of an outcome by others are likely or not for you.

They are so important they are discussed in multiple areas of the book.


Second Opinions


I address second opinions in the legal section in detail but a few points are germane when initially discussing the diagnosis. They should be encouraged for all patients and families who broach the subject. A word to the wise; such second opinions may be for therapy that is either far more or less aggressive than what was originally offered. Even more rarely, some who render second opinions may libel or slander the primary physician to the family and not condone what the primary doctor has done so far. Therefore, prudence, candor and pre planning is wise when assisting the patient obtain second opinions or commenting on them. The only significant problems I have ever encountered in this regard were when complementary or alternative medicine practitioners get into the mix. This dilemma is addressed more fully in a later chapter.


The Contract


Although stated later in the legal section, it bears mentioning here that patients are expecting a contract and the list of what is required is long: They expect doctors to listen, to teach, to be available, and to address pain (almost all pain can be effectively treated), get help with sleep and bowel habits and prevent nausea, and vomiting. Patients need to hear that we now have medications that may increase appetite and stamina. Providers must tell the truth and be clear on the schedule of progress reports. An often-overlooked area is the golden rule that doctors must never “keep secrets” from the patient no matter what the significant other or family says. Patients must always be clear on what their policy is regarding messages and answering machines and receivers of physician calls who are other than the patient.


Remember Autonomy – It Begins And Ends There


Will the real patient stand up? It is you but you are not your disease. YOU must have a relationship with your disease built on knowledge to lower your burden. There is immense power in the gift of autonomy as described earlier in the book. Go back and read the first few chapters again and remember this is your journey and you call the steps.



A Final Few Words


One of the deadliest weapons both against the cancer and unwittingly against the patient and family is not chemotherapy; it is the physicians’ mouth. The clinician must not only think about what they are about to say, but say only what they are thinking-no more and no less.  For example, more than once, I have heard stories of the devastating blow caused by an answering machine message thoughtlessly left for all to hear and often misunderstand.

In sum, this chapter is simply saying that the tongue, as well as the cancer, can be the “enemy of the neck” or the liberator of the patient’s autonomous license to engage fully and vigorously in their treatments.





Psychological Issues

Sex and Significant Others


Role Of Family

Teach Your Children Well


Psychological Issues


We all bring our own set of coping and interpreting skills, or lack thereof, to the diagnosis. These may or may not mature and evolve in time. The oncologist needs to sort these out straightaway. Moreover, pre-existent psychological issues will come into play at this time and clinicians need to be exquisitely sensitive to this. These can become intensified in general or even “telescoped” and directed largely on their health care team. Although the experience of a cancer diagnosis may have permanent personality altering effects, it is silliness to expect all patients to instantly mature or evolve into an enormously effective coping style. People will do what they do, not what one may wish them to do. Furthermore, if patients are not being real  and genuinely themselves when initially dealing with the disease, they may never be able to evolve into a more effective coping style . One can lose more than time running away from  a diagnosis.

The losses patients feel are both real and perceived and even if not shattering they may be life altering. Issues such as whether there will be a loss of health and physical integrity, a loss of friends and loved ones through rejection, and an inability to perform the duties of daily living, hobbies, and self-care, will arise. The very important impacts on job and finances, self-esteem and the all too pervasive guilt of “what did I do to deserve this”, may come flooding at the patient. The loss of control can be overwhelming

Fundamental initial emotional reactions are actually quite reproducible and common in our culture. After decades of practice, I have observed that anxiety, rarely veiled as hostility and anger, leads the pack.

The oncologist may see sleep problems, compulsive behavior and inability to concentrate. Guilt and petulance may follow with “what could I have done or should have done”. An entitlement based demanding demeanor may rarely arise. Once again, the goal is to impart knowledge that can bring the patient towards informed and willing choices and compliance with what is known to be true. Teamwork is then possible.

There are two “D’s” worth mentioning which some patients may fall into; depression and dependency. I am not referring to the clinical diagnosis of major depression, although certainly cancer patients may experience this. I am referring to a reactive, transient depression. A newly diagnosed patient may experience blunted emotions, insomnia, and lack of appetite, withdrawal and literal slowing down. Depression can often be mistaken for dementia, thus establishing the diagnosis expertly is crucial.

Dependency can be particularly severe. Although it is uncommon, I have seen patients immobilized in advanced cases of dependency. This is as simple as it sounds. The patient surrenders all sense of autonomy and self initiated behavior with also handing over control of their life to someone else. This is typically some family member but I have had a few patients wish to pass it all to the savior in the white coat with MD after their name. As dependency and depression in this setting are both reactive phenomena, it is critical to know the patients temperament and level of functioning before the diagnosis. Treatment, including medications and talk therapy, can be extremely effective and most patients respond.

This is not to say that patients with unrealistic post diagnosis behaviors cannot respond as well without them. They can, but it poorly prepares the patient for the reality of making future decisions as well as encouraging a realistic aggressive approach to rehabilitation. Regain of physical as well as psychological and emotional strength when doing so will be the hallmark of return to normalcy.

Some physicians, usually unwittingly and often as a reflection of their own underlying personality, elicit and reward the dependency of patients. This is obviously not wise as no one’s shoulders are that broad or strong to carry the burdens of others cares in crisis. Less commonly, in my opinion, some oncologists are very passive about patients’ non-engagement and seeming willingness to go along with whatever is offered without question . As mentioned, this could be fear and undo or misplaced respect for the physician or echoing of their pre treatment personality. I have seen such individuals who were hiding and cowering under the tyranny of “what if, maybe, so what, who cares, if only I had…” also do quite well.

The personality, per se, of the patient is not deterministic of survival and oncologists are not in the business of personality diagnosis or changing, even if such changes were in their little black bag of wonders. Rather, the journey will elicit prior coping skills and they must be recognized and if problematic, they must be dealt with by the entire team as they do affect the treatment team on some level.

Positive interactions are more honest and revealing as silent suffering is often reduced. The notion of a positive outcome from a “pay it forward” attitude and seeking and finding joy in the teeth of suffering and despair is not hogwash or Hollywood pabulum. It does make a material difference on life’s quality. It can also be breathtakingly beautiful to be touched by patients who find this path.

Facing your mortality can either serve the team well or if not, sentence one inappropriately to some sort of hell that simply need not be. Fear and anxiety driven bad behaviors and ‘stinking thinking’ cannibalizes hope. Although past behaviors will not guarantee future responses, they are often a clue. Thus, physicians must welcome input and insight into how patients have handled prior stresses. Oncologists must also look for coexistent stresses and be especially attentive to the behavior of the patients’ loved ones.

Although possible, blind denial of the diagnosis, severity or probable prognosis by patient and family is rare. It is usually transient and recognizable early. Once again, information, sympathy and emotional engagement are highly effective ways one breaks through. More severe, disabling and dangerous denial is actually quite rare. Patients and families virtually always want to know what is happening and what may transpire. I have had only two patients severely injure themselves because of complete withdrawal from reality after diagnosis.

The exceptionally quiet patient can be vexing. This may be a manifestation of outright denial or stoicism. It will slowly kill the family. It may be depression, or rarely some manner of spiritual acceptance from the start. When it happens it requires either prior experience or carefully matched counselors to help manage when the line the patient straddles moves from seeming acceptance to acquiescence. I have seen this with not only treatable but curable diseases. It happens that the rare patient gives up even before they get in the starting blocks.

The patient is the one with the disease; not a well meaning loved one. It is rarely acceptable to fail to divulge to the patient all information because of questioning the patients’ ability to cope with the revelation of the diagnosis. In such rare cases, one must always seek professional and documented psychiatric opinion. Incompetent patients are rare and they are virtually the only situation where the rule of total confidentiality and total disclosure to the patient do not apply. Families may oppose complete revelation. I have seen that happen. However, the rule is sacred. Failure to obey it is a sure road to disaster and creates emotionally impotent patients and emotionally paralyzed loved ones.


Sex and Significant Others


Oncologists are often amazed that they need to stress that cancer is not contagious and sexual activities are helpful, not harmful. I have some great anecdotes of this. Patients and their lovers need intimate contact. Patients may feel they are no longer desirable and lovers may fear to cause harm. Physicians should address this basic and essential means of human expression and contact and encourage it. One must look to the healthy spouse for veiled depression and exhaustion through a misplaced sense of self-mortifying duty. The data on spouses of those diagnosed with cancer suffering strokes and heart attacks in the heat of the battle against their beloveds’ cancer is very clear; they are at high risk to fall ill themselves.




Spirituality is a very real issue and comes to the fore at the time of diagnosis. Spirituality, religion and theology are not synonymous. We humans are more than mere flesh. A soul can and does ache deeply as cancer burrows into our lives. Existential is not a fancy word one bandies about in sophomore college classes or self-help books. The diagnosis of cancer evokes thoughts, feelings, ideas, dreams, experiences, and aspirations that are crucial in shaping individual destiny and vital to the form, texture and flavor of a patients’ self-chosen style of existence and their personal stance. The experience of cancer is fundamentally on an existential level.

Doctors do not have to evangelize but they do have to inquire and find the appropriate level of assistance. Personal touch is also an important issue at the time of the diagnosis. All patients want some level from a mere handshake to an embrace or a good cry . All patients have their boundaries and it is wise for providers to seek them out and meet them there. Touch is not just physical but emotional, spiritual and intellectual. It may simply be the providers’ body language and words, but I implore physicians, touch your patient; it could well be you some day.

This is time to solidify faith and not question it. The answer to the question of your shaking faith is believe. You already know the why me question is not answerable. It is not a fair world and cancer is no respecter of persons. Disease is unimpressed for the most part by us, although maintaining your health helps enormously, but never enough. You came in alone you will leave alone but you are not alone now.

Hear me when I tell you faith can move mountains. It may be the healing of personal emotions and family emotions. I think believing in miracles is miraculous enough and I never go looking for them however I have seen the unexplainable twice in thirty years.

The one mountain top experience we must claim together with the patient is Mt Understanding. We are not in this alone to live on Mt Solitude where the torrent of tears flood down and fear erodes hope.

Read, Listen, Learn and reach out. Let this be a season where the weightiness of worry is diminished as we engage as a team.


The Role of the Family


Family conferences are wise as families usually wish to be involved. Oncologists must ally with them but the patient must always be the center of everything. Family leaders will evolve. It will be clear soon enough whom the family leaders are. However, knowledge of state laws regarding next of kin is essential.

When it becomes necessary, families can have an immense burden lifted by recognizing and understanding the fundamental right of patient autonomy. Families should learn that when asked to make serious decisions on behalf of the loved one who can no longer decide for themselves they are being asked to be the patient, not themselves in the patient’s shoes. This is so called substituted judgment.

When patients cannot speak for themselves or when family conflict arises there should be a spokesperson armed with a pencil and paper. A spokesperson can be a great help to avoid painful and time wasting repeated conversations. I do the following. I try to get a note taker assigned right from the start. Often this is the patient or their spouse. They decide. I encourage recordings but first prefer practicing the more active role of note taking. After the first meeting I generally ask the note taker to relay the gist, the big picture of what they heard. This can save a great deal of heartache and save the day. As a practical issue, patients and families’ need plenty of paper and encouragement to interrupt and ask questions. I often tell them they can bring a tape recorder if it would help them although I usually do not do that in families who will rely only on that and thus not as fully engage. It is a judgment call with the goal being everyone  on the same page.

As is practicable, I try to schedule family conferences in advance. If families wish to record a conversation, I simply turn on my own pocket digital recorder for the obvious legal documentation reasons. It only takes a few seconds to download it onto a PC in a secure manner.

Patients need a realistic sense of control as soon as possible in the process of receiving the diagnosis. Thus, this is not a time for tap dancing around issues. Everyone must strive to reach a working, mutually understood grasp of the diagnosis and its implications. As with all active listening, everyone must check in with each other so that all are mutually clear. I have known clinicians (myself included) to leave a room, swelled with pride and comfort that they, the great communicator, had done a marvelous job. In some cases, that is far from true. It is not about fault. It is about everyone working hard to get the facts in the open, be clear on what they mean and how they relate in an understandable manner to the patient so the patient can make informed decisions.

Patients can be victims of some families and some patient’s care can suffer owing to satisfying the guilt or panic of such families. I have more than once facilitated the patient taking charge and telling such non-helpful members to “cut the crap”. Those are times to have a recorder running. Disagreements will come and this is not a contest. The goal is everyone being on the same team and the patient winning, especially as the definition of a win may change over time from cure to quality of life issues or smaller specific bucket list goals.

The common family conflicts are usually variations on a theme. A common example is the themes where one family member wants the patient left alone to “die with dignity” while others want to fight to the end. In such cases the mantra that the patient is the one with the disease has been left at the wayside. Family members might be more working out their own issues of redemption, salvation or resurrection of old hurts now again made acute by the present crisis and possible impending loss of second chance.  Once again, the key is communication.  Everyone must discuss all the reasonable options while making it clear that it is the patients’ final decision. Having reached a decision, everybody needs to get on board or get out of the boat. It really is as simple as that. It is imperative that patients state their wishes to clearly worded questions in the presence of the family while both the doctor and family, other than asking appropriate questions and assuring clarity, hold their tongue.

There should never be private conferences with individual family members or groups of family to the exclusion of others. Dogmatism is a another disaster waiting to happen. Physicians are neither God’s messenger nor the patients’ messiah. Another admonition is that patients and doctors can be sure that engaging in historical criticisms of past providers will not rewrite history and may incite hysteria. It is far wiser for oncologists to reassure about past care and when unsure, simply say nothing and urge a focus on the present.

The difficult family is another breed entirely. There are usually private agendas riddled with guilt and fear that will color all interactions. There is the translator from hell phenomenon where what the oncologist clearly means is not getting across. There are occasionally family members that are inappropriately demanding of time to suit their convenience. They may also be individuals whose overpowering fear or need to control simply prevents them from assuming the role of student who without bias accurately  would otherwise transmit and not translates information.

Disease is not convenient and does not keep a punch clock; clinicians will have to help such individuals face that. Doctors must also look out for those family members who flatter inappropriately and criticize former physicians. This is invariably an alligator pit. Typically, such folks will in time demand excessive consultations and question every treatment method. Once limits are set, clinicians sadly must be ready for accusations of insensitivity to outright litigation. Thus, it is wise to invest a reasonable amount of time in the beginning to build and buttress a bridge for the enormously difficult canyon cancer patients and their families must cross.



Teach Your Children Well




It is my opinion that families should keep the younger members of the family informed. Families usually have a realistic idea, on an objective level, of what each child can comprehend. The error, if made, tends to be in assuming what the child should comprehend. Remember, children may fantasize that they caused the illness, especially if kept away. In addition, children are not stupid. They know something is wrong and game playing is often transparent and misunderstood. It can potentially teach a very wrong lesson regarding how to face difficult times and the reality of pain and suffering in an unfair world. Emotional instability of the children may manifest as regressive behavior that ranges from infantile to greater dependency to even lack of toilet training. Most importantly, it is a dangerous thing to leave the child ill equipped to handle the trauma as well as kept away from a loved one that may be dying. This does not help the child and it damages both them and those who are suffering. Frequent hospital visits are important for both the child and the patient. If needed, the oncologist can assist the family with getting professional help for the children

Being told you have cancer




Opening Pitch

How you say it

Assessing Patient Goals

Lies, Damn Lies and Statistics

Listening For Those Whispering In The Patent’s Ear

Preconceived Ideas

Assess Patient’s Goals


Psychological Issues

Sex and Significant Others


Role Of Family

Teach Your Children Well



Cultural Differences

Focus on Symptomatic Relief

Introduction to Clinical Trials

Complementary And Alternative Medicines Overview

Media Matters

Antidotes For Anecdotes

Prognosis And The Future

Taking Your Time, Avoid Timelines

Second Opinions

The Contract

Autonomy; Everything Begins And Ends There

A Final Few Words





Opening Pitch

How you say it

Assessing Patient Goals

Lies, Damn Lies and Statistics

Listening For Those Whispering In The Patent’s Ear

Preconceived Ideas

Assess Patient’s Goals



The Opening Pitch


The actual or impending moment of rendering the diagnosis is a critical and unforgettable time for every patient. Physicians would be wise to know the personal space the patient needs and adhere to it. It is also wise to tune in to whom the patient wants to have there when the moment comes. The cancer team should be quick to evaluate the level of support available and offered by family, friends, church, social groups and employer. Patients must be oriented to reality to avoid “calamatizing” as soon as possible. Yes, this may or may not have been the worst that has happened to an individual, but it will not go away on its own and retreat is usually not a reasonable option. Your physician will be wise to use sympathetic listening coupled with a thorough emotional inventory to screen for any coexistent psychological disease such as depression or anxiety disorders as these will invariably not only need to be treated but will telescope under the duress of the cancer diagnosis. The more your doctor knows the more they can help.

Patients will often recall who were there, who said what and body positions, tone of voice and the like. Doctors must always place prime emphasis on patient autonomy. A doctor can lead a patient to intelligence but cannot make them think. It follows that the right of a patient to swing their proverbial fist ends just before the doctors’ nose. Those are key parts of the contract.

It should be stressed to patients that they can handle the journey as thousands before them have. Patients should hear their doctors telling them that intense feelings are the norm. Once again, anxiety is fear of the unknown and of what has not yet happened, only what may. It will paralyze. Fear of the known is that which most patients can handle remarkably well.

The key is to turn anxiety into fear through information, facts, and knowledge and kindness. Both can be destructive and are not in contest with each other as to which is worse. Fear will force responses or reaction to be sure and do so quickly in oncology as events will move rapidly. Anxiety, such as fear of recurrence, requires some acceptance as well as distraction and engagement in other activities until the anxiousness passes (such as major anniversaries being cancer free for example). Nonetheless, both are bears that can be battled appropriately. Time and events eventually eclipse anxiety wherein you have a choice of replacing them with healthier thoughts or not. Fear is present and real and one way or the other it will have its moment or engagement as it is fear of something real, not what may be.


How You Say It


Style of communication is critical. It is easy to fall into paternalism. This is where similar to the dad in “Leave It to Beaver”; the oncologist parses out packets of information regarding the diagnosis. That should stay in 1960’s TV land. Rather, the issue is for oncologists to individualize each “big talk”, as I call it, with each family. This is a sacred time and a private time.

There are practical concerns as well. The patient, and whomever they choose to be there with, must be able to hear and remain uninterrupted. Personal space and cultural and socioeconomic differences can be quite relevant. Delay and procrastination is an irreparable mistake. Once the diagnosis is certain or the urgency of the situation warrants, the talk occurs. Doctors must maintain and patients should demand personal eye contact. The greater the doctors’ candor, the more trust will be engendered. Attitude of the informing physician is immediately transparent to patients in fear and the doctors’ perceived attitude is enormously influential in how patients begin the journey. Our mothers were right; you get only one chance to make a first impression. The rest is gravy or damage repair. It is important that further staging procedures or consultations are seen as a positive approach to the disease rather than simply more physical or emotional experiences to be feared.

Lies, Damn Lies, And Statistics


Statistics are tools to describe populations of similar patients behavior based upon looking at how they did, not how you are doing, for the purpose of trying to predict and inform how you will do .You are a not a number, you are an individual. Understand that statistics try to inform you how patients sufficiently similar to you have fared.

Remember though, the answer that comes out of applying statistics will tell you with what degree of certainty groups of patients like each other in all relevant ways will likely perform with a certain level of certainty and not by chance. Although this is intended to be a guide for the individual , the statistics is still saying the odds of what or how an individual will do as a member of a group with a given stage and or treatment regime, they are not a magical prescription that cannot be avoided. People do beat the odds so to speak . It is the odds of beating them that we can calculate compared to the larger group if you are to be an exception.

Statistics is an elegant science where: (1) One can know the predictive powers of tests which is the ability of a tests’ yes to be yes and no to be no with great certainty (2) Whether you can compare two patients or two groups of patients with confidence that they are highly similar in all relevant ways and thus any difference in outcome is due largely to them being treated differently, (3) Whether you know an outcome was more by chance or (4) truly a prediction of what will happen almost always  while stating what almost always means. For example the odds of heads or tails is pretty much 50% with a penny but the odds of any particular dice number always coming up are no better than one in six (5) Statistics can tell you the number of patients needed to treat in a trial of a hypothesis to be able to even have a chance of knowing whether you can discern a true difference for one treatment to another. (6) They can tell you if trials of different treatments have the power to give you an answer before you run them and not just after they are done. Some studies have so few patients ( like too few flips of that penny) to have the power to ever give an answer with statistical certainty of any worth  to state that one treatment ( heads or tails) is more likely an outcome that the other (7) Statistics can tell you what factors are the most important individually or as a group in determining possible outcomes. For instance is it how high the penny is flipped, who flipped it, the temperature, any wind or the fact that the head weighs a tiny bit more that the tail side. (8) They can tell you crucially how powerful conclusions can or cannot be drawn when one groups multiple trials done at different times by different people on very similar patients. One may see very consistent messages and lessons, one may see conflict without clear reason. (9) Statistics can tell you how strong on a scale the evidence is for us to support one or more conclusions meaning a range from not only did the result not occur by chance but the odds are extremely high that you will get the same result nearly every  time to no more that the proverbial coin toss and mere chance. (10) They can tell you if there is no realistic way to know certain answers because of the nature of the factors that determine the outcome, such as when there is just not enough data at hand to make comparison or enough patients who have highly similar ways of describing them and their disease. (11) Statistics help sort out opinion versus heavily held opinion and can be, when understood, more powerful than a surgeon’s scalpel in cutting out truthful pieces of reality than presumed or hoped for ones.

Physicians often use the acronym GIGO (garbage in garbage out). This is an important rule meaning the folly in trying to reach or give a conclusion if you have poor study design or a poorly constructed method to ask for odds of a patient taking one particular treatment ( or odds from not taking treatment ). Not only can good statistics point out that you have muddied the water in trying to come up with an answer, they can bring clarity as to how.

Think of it like this. Let us ask what is the best route to school ( the best therapy or treatment plan for you). To answer you need to be sure you know and keep constant everything that can affect the answer, such as time of day, weather, what vehicle, driver, air pressure in the tires, traffic, day of week and more before you run the test many times. If you have poor control of all the variables and put “garbage” into the study you will get garbage for answers. If however multiple studies have consistently shown a direction or choices for you to take and what the outcome for groups of similar patients have been, your physician can tell you that and do so with some degree of certainty or define the lack of certainty.

Finally, statistics can tell you if there are biases in the treatment studies  that can inappropriately influence the results. For e.g.,  when asking a new question of one treatment versus another in highly similar patients, it is important that we know pre treatment that either treatment may work with the same degree of chance.

The bottom line is that physicians will be offering treatments to patients based on either many or few experiences of similar patients and because of the elegant and competent statistical analysis done on them they offer treatments that are indeed at least the standard of care. Statistics, properly used and understood can highly inform intelligent choices taken not by mere chance.


Listening for Those Whispering in the Patient’s Ear


Physicians must first listen to what their patients think they know. What do the patients know, fear, suspect, have heard or God forbid, overheard, as is all too common. What do they have in their head about cancer and what does the diagnosis mean to them? Only then, can physicians understand where the patient is starting both emotionally and intellectually. This also clears the air and affords the doctor an excellent opportunity to customize the game plan of imparting information to the individual. We experience cancer        individually. One size does not fit all.

It is imperative to realize that none of us arrives at the diagnosis of “cancer” without morbid, pre-conceived ideas. Then there is the insufferable onslaught of the media, the assemblage of well-intentioned relatives and thoughtless, groundless declarations from well-meaning, often-misguided friends.

Frequently in life, whenever it hits the proverbial fan, newly minted experts fly off the fan blades. These are folks, good intentions aside, who act as if they have graduate training in advanced cancer care and are all too eager to deluge you with their newfound genius. Articles, media and all manner of experts who seem to explode out of the woodwork may soon be assailing the newly diagnosed patient and family. Family and friends may seem to ooze from every nook and cranny with some anecdote of a friend with “cancer” (frequently not even the same disease) and will recommend some wild remedies.

The best approach is to deal with these head on and use the Physicians’ Desk Reference (PDR) and web sites discussed later as a guide about various potions and pills and always tell everything to your physician. If you feel you cannot, tell them and share it with the family member who you know would “take over” if you could not speak for yourself. If that trust is still not there, get another physician and explain why tactfully.

The cancer team should take a polite stand and not denigrate or humiliate when perhaps well meaning others light upon vulnerable prey. There is usually no shortage of well-meant and outrageous advice and stories seeking to compare your unique situation to all others. This is dangerous stuff and the best advice is to focus on mastering facts first. Get data, turn it into information and knowledge and then, with the help of your cancer care team, go to reputable outside sources – gain wisdom.

The next bane or boon can be the media. Despite the harm they do with half stories and hype, let us remember that enormous harm to society caused by censorship and restraint is far more insidious, permanent and broad sweeping.

The vast majority of accurate and personally relevant knowledge of a medical illness for most people comes strictly from a physician. Thus, it is up to physicians to have their facts straight as well as very up to date. Physicians need to be aware of what patients can find on the web, from rumors mills, blogs and irresponsible inside scoop publications and other less reputable sources. Physicians should become familiar with some of the superb web sites for cancer patients that do exist starting with the one your taxes pays for at the National Cancer Institute A well-informed patient is indeed a frequently much healthier patient. Certainly, family group involvement in reading, perhaps starting with this book, should be encouraged.

A medical journalist’s job is not to be a doctor but rather write the news as best as is provided to them. We have a saying in the military that one of the most dangerous weapons is a brand spanking new second lieutenant with a pencil. The point is that the journalists may journal or write well, but they are not a clinician and even while many understand that, the holes in their coverage reinforce the risks of simple reading and believing. They also write for the masses. You are not the masses and the you that is not in their article is the one with your disease and all its unique characteristics.

Patients are usually not critical readers and should practice checking out the latest breakthrough against what their physician tells them. The sheer ignorance and frank misuse of medical vocabulary and grammar that leads to wildly erroneous conclusions is amazing. Using one instance that seems related to you to more deeply understand your situation and prognosis has profound limits. All the time spent guiding patients to reputable sources to develop a bond of honest and patient communication is always worth it.

There is also an enormous temptation of non-reputable sources that make outrageous unsubstantiated claims to generalize. It is often difficult for a patient to grasp that they are an individual and that the articles they read are not  necessarily specifically about them. Furthermore, patients should beware the frequent whiff of sensationalism about a new technology that may have little or no bearing on their situation.

Also beware the media junkie who might as well be sitting on the medical or research campus stoops or hanging about biotech cafeterias. These are folks addicted to “breakthrough” technology and they sing its praises every time the slightest whiff of something new is in the air. Remember, there is distance and time from bench (laboratory) to your bedside and thank God for it. It is there for patient safety. News is often mistaken for information and the starter gun to begin therapy, which it usually is not. Even when it opens new and wonderful avenues of investigation and perhaps trials of treatments, let the system do what is does and is profoundly motivated to do; prove if it is safe and effective and how it compares in all manners to other patients with the  disease. The devil is always in the details as whether every new glove is a handy right fit for you.

There are breakthroughs. Some do apply to large groups and they are glorious. However, nothing comes easy. Nonetheless, with uncommon exception, when patients gain access just in time to some new highly promising treatment we must remember the rules about nothing being a payment free cure. It may be only (and I use that word with caution) a psychological or financial wild mouse ride since it is new, with no knowledge of just how durable responses or remissions may be. Our bodies usually do not easily fly into a fairyland where all are cured and none fall sick to “other” effects of the new breakthrough. Although exceptions are uncommon they have happened such as the superbly well tolerated and revolutionary Gleevec in Chronic Myelogenous Leukemia.

Finally, patients should never be embarrassed if they do not know of the latest heralded wonder treatment that hits the streets. Physicians should be honest, lending their critical mind but not necessarily vote of credibility when new miraculous cures are brought into the discussion.

Preconceived Ideas


They are unavoidable, have variable life spans and are frequently  dangerous.  Get the facts, read this book and numerous other sources and give yourself a break from preconceived ideas. Do not try to build bulwarks around preconceived ideas to authenticate them as powerful when in fact they are biases and opinion that are not necessarily true. Do not buy batteries for the Boogie Man. Rather, introduce these ogres of your imagination to your team without prejudice or embarrassment and let your team help you with sorting fact from fiction. Even if all is true, turning on the lights and swinging at those bats in the belfry of your unfound biases, especially when not alone and in the light of the physician’s office is often wise.

Never preconceive how weak your will is for the journey. Of course, you are afraid but trust me, you are amazing. Cowardice or sheer inability to handle the diagnosis and treatment is rare. People are remarkably brave. Your oncologist and their team as well as survivors and in-treatment supporters whom you will be immediately pointed towards as well as in-treatment professionally moderated groups can all help. There are many resources and the best is guaranteed to be the shortest distance away, yourself.

Use When Tumor Is the Rumor… to fuel your hopes that you too can excel in the journey no matter where the fight may lead. You will be deeply touched and will touch in return. Become informed and fully engaged, a never ending process in the journey.

In life we are rarely assaulted by true emergencies, the sort of thing for which instant action is the only thing possible. Think about it, they are not that common. I am an Oncologist and a retired Colonel telling you it is so.  Your team is where you place your confidence and pledge your allegiance to reflection and response, not just react. I assure you your cancer hates the measured coordinated comprehensive response, never having enough time to regroup. Your health team will flourish with it.

Information and a competent team who view teaching you as one of the many first steps to action is what you need. If you do not see that, speak up. If they do not hear you, go elsewhere quickly. When selecting therapy with your team place high value in high-level trials supported by the National Institutes of Health and major cancer centers in large major cooperative groups. This is how we know so much today and such therapies are often available with non academic physicians as well. Chances are high that treatments as part of a national protocol known to be a good standard are being compared to others also known to be a standard. Ask about that after reading the clinical trials section.

Assess Patient Goals



















As said in the true short stories “The Enemy” and was reiterated later in “The Telling”, few things can take a patient on a psychological and emotional rollercoaster from conjuring fear and loathing as well as becoming embraced in love, deep understanding and insights than the diagnosis and treatment of cancer.

Each of the major steps of the journey of when tumor is the rumor until cancer is the answer will hold this to be true.  The lymph node found on physical exam, the new skin growth, the time when the not so routine clinical complaint; and the everyday “oh it’s nothing”“becomes something and with it comes anxiety. For millions each year, the words are said and the stage is set that something needs further examination, eventually some type of biopsy for tissue will be needed and in short time your nothing may be the something that puts your heart in your hand and a lump in your throat on the journey to the oncologist.

The oncologist may first enter the picture when the diagnosis is suspect but not confirmed. This is a tricky situation and dealt with case by case on the fly, in a careful manner customized for the individual patient and family. To be sure, there are some fundamental and universal ground rules when approaching that point where suspicions of a cancer diagnosis are dismissed or founded. Perhaps the most important of rules is the time proven adage “Although Tumor Is the Rumor and Cancer May Be the Answer, Tissue Is the Issue and No Meat, No Treat”. Yes, it is crude, but right on target.

Oncologists never, ever, label a patient with a diagnosis of malignancy without absolute certainty and as much evidence as time and safety allow. They always have tissue confirmation from a biopsy of some manner unless it is simply too dangerous or not possible to get to the area of concern. Usually, the broad array of tools and superb clinical skills make obtaining tissue usually safe and quick with little lasting discomfort. It logically follows that one never pronounces a recurrence without the same degree of certainty. It is important to note, however, that not all recurrences require or can be biopsied.

In most situations the notion of a clinical presentation consistent with recurrence by the patient with known malignancy being very apparent is common and not requiring invasive techniques. Nonetheless, when the odds of recurrence are low owing to the typical personality or original early stage of the primary tumor or the long time since treatment or a remission, biopsy may be needed. Rarely, in some cancers, a second biopsy is needed because some cancers actually change, needing a different approach than the original treatment.

When we suspect the diagnosis, oncologists often have to work quickly behind the scenes. Not only do we not wish to step on the toes of the primary physician while nonetheless guiding the primary physician as to what the best diagnostic route may be for those for whom tumor is the rumor, but we want to avoid missteps or statements by those who go before us. Thus a delicate balance must be struck as the entrance of the oncologist prior to the diagnosis being certain can understandably be quite evocative of enormous anxiety for the patient and family. Thus, it is essential for the primary, or soon to be referring physician, to identify for the patient and family what roles the many future consultants have. An individual who serves as the “quarterback” must be identified quickly with full consensus and understanding of their role by all.

This concept of focusing the attention on the right professionals applies to the family as well. It is the patient, not the family, who has the disease. The role of the family is enormously important. However, family and friends, the Internet and media as well as other health care providers, frequently inadvertently or overtly inundate the patient with stories that are either inappropriate or way off base. Their influence must be anticipated and never underestimated.

This is a time of reinforcing the message of the autonomy and individual nature of the patient. A good analogy is the vehicle identification number of cars of the same make and model. Theses vehicle may have enormous similarities but run differently based on age and other factors. This is precisely the situation with each patient. Patients are individuals with a disease and they are not their diseases. It is never just another case of non-small cell lung cancer. The philosophic point raised above has enormous practical applications. Oncology is not a one size fits all endeavor.

The health care team must decide early if the oncologist leads or is initially behind the scenes. Sometimes the oncologist does not take over until there is definitive diagnosis or a diagnostic dilemma evolves at which point they step forward. Once again, one must never underestimate the importance of timing the oncologists’ entrance into the world of the patient and family. The comfort zone of the referring provider, of course, will largely affect this. There is great variability in this regard. Some primary referring providers remain very involved and others wish to pass the reins on to the oncologist as rapidly as possible.

Once it is clear that sufficient information exists that it is time to state the diagnosis and begin to put anti anxiety lassos around the beast, here are some insights that may be enormously helpful for patients and their supporters:

    • The first few days being a daze is to be expected. Confusion, upheaval, immense sadness and disbelief, anger and crisis of faith that can be challenged and thought lost or in some cases, galvanized.
    • A powerful sense of loss of control and even greater fear of that ensuing is common place. This is something Oncologists may assume up front and address directly with the facts as they become evident and their reasoning behind diagnostic or treatment algorithms in advance of crossing those bridges.
    • Empathy builds trust and greater patient engagement in the process. It must real, not feigned and not dispensed off to clinical staff (the norm) as the emotional bond of therapeutic alliance is best with the physician as well as the treatment administering oncology nurses. Patients trust less empathetic providers less and not being capable of being their own doctor they can be left to themselves; not a satisfactory situation for anyone.
    • Patients may think it is the worst thing to have ever happened to them. It may not be. But anxiety paralyzing you from action would be the worst. It is very therapeutic to have anger and it is very therapeutic to fight. However, it is soul sucking to roll over before fully informed and well-reasoned decisions can be made. Patients would be wise to transform anxiety into fear, fear of the known through knowledge and never stop learning all they can, as that knowledge is power in your fight. God has hard wired you for heroics; unbelievably so as it may seem. I have not seen a cowering cancer patient yet who totally collapsed refusing to being informed when it was offered to them.
    • It is a myth that in life or oncology any meaningful portion of your decision must be made spontaneously with no time for reasoned reflection and rational thought.
    • It is not a myth that it is unhealthy to rant, rave and react angrily. I see plenty of reason to be very angry whether it be at altered life’s plans, unhealthy personal behaviors leading to this or sheer damn bad luck as in “why me?” You have my permission, and I am confident God’s, to be simply initially angry.
    • It is very real to be shocked and when smacked in the face, reeling from the blow is natural, normal, and expected. Retreating from life or retreating from the fight before all the information needed to make wise decisions once calm, or just giving up the ghost is not O.K. Your life is your own and your anxiety is to be honored, not discarded when frightened most. Even if you seem most alone, and rarely anyone is, let knowledge be your friend and counsel. You also must eat, exercise if possible and attend to the activities of daily living as you are very much alive and the journey has barely begun. You need not go right back to work unless you know you cannot; there is no rule. If you need a little time, take it. If you need family, get them involved right away and if you need alone time, take it.
    • Own the disease and your reaction. Do not become the caretaker of others who swoon or swing into inappropriate and certainly not helpful reactions over your news. This is your news and your life. This is your trauma and trek; own it. For now, you are the star of this show. Believe me as to the necessity of my stressing this. You do not live or die for others. If you want to handle all communications with others, fine. If you wish to delegate, fine as well. It is your call. This is a time in your life where the most frightening of all scenarios dropped on your doorstep. For the moment, you are not as in control of your destiny as you were before. Understand and fight the overwhelming panic of the diagnosis and your morbid imagination trying to rip the helm from your hands. You have barely set sail and your disease is not, and shall not be you. Your diagnosis may try to direct the show. You must not rest until you wrest from every opportunity the control God intended you to have over these moments. Get knowledge. Demand information and experience your feelings but do not let them define you. This book will help, I promise.
  • You have heard the theme before, the next step is knowledge. It is the best anti-anxiety medicine in the world


    • Although knowledge will be your greatest pal, if you can, muster up an army of at least one other who forms an allegiance with you to conquer ignorance and face fear. There will be personal business issues needing attendance as well as the new administrative and secretarial assistance needed to stay on top of all the tests and appointments and their results and inevitable questions they will engender. I often encouraged that either a small hand held recording device or better yet a trusted friend or family member act as a scribe to objectively write what was said, not felt, and what needs remembering, not fearing. This is wise to do with every consultant, your primary Oncologist and of course, your original referring primary care provider if that is how all this started. Such a scribe must understand that this is not about their feelings or interpretations; they are a robotic scribe capturing all that was said in context and without error or asking from the source until it is correct. Even in our aggressive American culture, there is still too much reluctance of patients to take such an initiative.
    • Avoid blind trust. The relationship you want most, initially, is with the truth; the facts and figures expressed in as much detail in context and relationship to your diagnosis that help you understand what is your disease, what does that mean, what can be done and what decisions are next:
  • Never surrender autonomy. Your scribe is a partner there to assist you so that through the frenzied fog of anxiety you can muster yourself for the fight..and have your facts straight.
  • Author Jessie Gruyman, president of the Center for the Advancement of Health and survivor of many a life threatening diagnosis wrote “After shock: What To Do When The Doctor Gives You-Or Someone You Love- A devastating Diagnosis. She offers the concept of a contract of sorts with a partner. I support the notion as well as have used it in my practice for years. Key issues Jessie covers are for the partner to agree to attend appointments, confirm in advance of their attendance, always re evaluate and check in with the one diagnosed as to what role they have and should play and in detail address whether one is a passive listener or authorized to ask tough questions. Make sure the duties of scribe are clearly outlined from the practicalities of paper and pen or laptop all the way to details as to whether a summary transcript would be useful. The partner must always remember that the patient is the one with the disease as they become familiar with laws regarding privacy of medical information and learn to keep their opinions to themselves unless specifically asked. To those who understandably and naively feel this is a waste of precious time and too intense an endeavor, I say think again:
  • The anxiety mitigating impact alone on a now engaged and in control patient is God sent. The literature suggests the diminishing stress gained though being engaged may diminish overall suffering and positively impact quality of life. The more aware and in tune patient will bring in any new signs and symptoms to their team with greater precision and speed and that is always good.


  • Patient and health care team are enmeshed in an intricate and not always predictable dance. Suggesting the patient should have no record of emotions, moments, and meanings that give them context in the greater therapeutic meaning borders on cruelty. Listen, learn, engage, and if you cannot understand, bring in that specially selected scribe to help


The oncologist



This is Dr KEVIN Ryan MD MBA FACP and hematologist oncologist here, medical oncologist professor and retired colonel and cancer survivor and this is when tumor is the rumor and cancer is the answer. This show is Modeled after my nonprofit book of the same name available on the web site of the same name… you can find it on the web site and a lot more, interviews, films excerpts on the site and it is also available on Amazon in all formats All shows are also on my blog off the web site  same name  and on www.w4cs  and in a few days Iheart radio

Think of these next shows as a look into the mind of physicians and especially the oncologist How and why do they so the voodoo that they do




Why Oncology?



The roads chosen for a career in Oncology are diverse. Some choose research; some enjoy a mixture of the laboratory bench and bedside. Others choose full time private practice as opposed to academics while others go into the big business of biotechnology research and have a path marked by brilliant entrepreneurial zeal. Owing to the military paying for medical school, I had my road chosen for me as a largely clinical route with significant exposure to all of the others-especially clinical research and teaching.

While oncologists are not all the same, most cancer clinicians are quite similar in their heart of hearts, their thought processes and I think in many ways their spiritual view of all of this. I have found that most of my colleagues share an immense sense of purpose and meaning in their practices and research.

The most frequently asked question I have received from trainees and colleagues alike is “How can you do it, Why do you do it?” usually followed by “I could never do oncology”

This is the best answer I have been able to muster.

There is an indefinable but unmistakable nature to being human. It is unique to the species, reproducible and immensely sensitive. The human mind and heart connect as a somewhat huge spider web of the finest silken threads capturing and suspending every experience of life in the chambers of consciousness. Life-threatening situations, such as the diagnosis of cancer, pull upon all of those threads thus bringing ones’ world into unparalleled focus.

I have never seen this nature more vividly than when my patients faced the enormous fear malignancy evokes. I have seen the diagnosis cement the realization that we are all connected and, in a practical sense, underscore the insight that we are and always can be truly knowable. In the practice of oncology, patients and providers alike quickly accede to the marvelously hidden plot, the master illusion whereby we appear to differ.

Cancer respects no organ or person. Furthermore, the oncologist must have intimate knowledge of all the fields of medicine, radiology and pathology as well as a finger on the pulse of breakthroughs in basic science. They have an armamentarium of diagnostic tools unmatched in depth and elegance and the field is perhaps better organized than many internationally in terms of asking the next best clinical question through cooperative research and clinical trials.

Once the team of caretakers and cared-for coalesces, a dance begins. It is a dance whose rhythm is the beat of the patients’ trek to garner knowledge and quell anxiety by doing so. It can be hero making.

Cancer unravels, mocks and challenges the norm more than any other malady. The wonderfully divine plan of human existence at the cellular level is never clearer than in the thick of the battle of fighting cells that mimic the norm.

When tumor is the rumor and cancer is the answer, the sweetness of the privilege of simply being alive is immediate. The solace and comfort offered by the health care team, family and loved ones is more pressing. In facing the possibility of premature death, the pulse and zeal for life as well as perhaps redefining it beats more soundly. What truly matters can become so transparent. There is also a sense of camaraderie in fighting a war of great and personal consequence and not having to do it alone with both people and science as allies. Oncologists have a ringside seat as the heroes and the health care team “box with God”. More than once, although frequently bruised, battered and stunned, the team wins a round, and with increasing frequency, the match. That is some of the  “Why Oncology”…for me.



MD – What Is In A Name?



Since the beginning of time, the world sets physicians apart as magnificent demagogues (MD) for many understandable reasons. I am not talking about arrogance, per se. The enormity of knowledge acquired, the responsibility, and immense emotions entailed leads to a very circumspect world for the physician. It is a world that patients really could not understand easily. Enhancing this is the reality that patients often lean more towards being a patient than a participant. Although understandable, other than when the competency of the patient is in question, it is best for all if the patient and family deeply participate in their cancer care. There is always a better outcome when the other “MD” is exposed- the Magic Decoder ring. Becoming the master of our journeys occurs when we all share in the secret handshakes of what initially is overwhelming information and in time everybody gets in the boat, grabs an oar and pulls hard.

However, many physicians are not that eager or aware of the necessity to crack the code and share the secret handshake. There is considerable variance in this regard depending upon medical specialty. It should come as no surprise that some fields attract abstract thinkers more than immediate-action, black and white problem solvers. Some fields of medicine attract urgent “fix it” types; some attract urgent “find it” types. Some medical specialties are appealing to “hand holders” and some physicians prefer a practice more removed from patient contact, let alone in depth emotional engagement.


What About Oncologists?


Oncology is a mixed bag. It tends to attract deep thinkers but certainly not to the exclusion of all other fields of medicine. Oncologists tend to be folks who like to box with God. They are intellectual problem solvers who love to master immense and diverse amounts of knowledge and who live to ask the next best question. Although it has improved and there are many notable exceptions, oncologists’ strongest suit tends not to be in depth personal emotional or spiritual engagement with their patients. Frequently, oncology support staff, nurses and front office alike soar like angels in this regard. By no means am I implying that oncologists do not feel deeply nor fail to understand the profound emotional aspects of their practice. In fact, I think they do. Rather, owing to time constraints, frequently pressing urgency in diagnosis and treatment, self-protection and an appropriate need to remain somewhat distant emotionally, in depth engagement of patients in manners discussed in this book are not overwhelmingly preeminent.  Furthermore, there is simply not enough time to do so.

Oncologists are not only not immune to stress, they are magnets for it, as are many other physicians. In oncology however, one faces terrorism of the highest and most clever degree every day as discussed in the chapter “The Enemy”. Accrual of new patients to an oncology practice is usually for ominous and frightening reasons. Patients do not become cancer patients for routine, typically reversible diagnoses. It is not largely about some surgical procedure or therapy where of course, “everyone always turns out just fine”. New patients become a lifelong affair and interactions with family and support systems are intense and long term. Loss of patients is often owing to death.  Fear, both physical and spiritual, is commonplace. Thus, stress is frequently a disease that affects the patient, their loved ones and supporters and the oncologist and their staff.

Let us just pull back the protective white coat on this phenomenon of stress for a moment. Hans Selye spent almost five decades studying stress since the 1930’s. A noted psychologist, Herman Feifel observed the intense enmity and perhaps fear physicians characteristically have of death. Sociologist Renee Fox’s work echoed similar conclusions when it focused on those physicians conducting pioneering work. As discussed in the section Clinical Trials, research and implementation of research results are the hallmark and mainstay of this field of medicine more routinely than many others. The tempo and intensity of moving information from the laboratory bench to the bedside is enormous.

Stress is essential for life. Without the eternal struggle between tension and release, joy is muted, passion subdued, biological and personal growth is stunted, and life is a bore. However, out of balance, stress can be damaging. Today’s oncologist must deal with insurance companies and HMO’s exerting various levels of control regarding patient treatments owing to reimbursement issues. Oncologists’ typically work very long hours and the demands for rigorous documentation can be pressing. Fortunately, technology is beginning to ease that burden with digital patients’ records. Compounding this is some natural professional disgust with the everyday business pressure foisted upon the oncologist unlike ever before.

Thus, there are sufficient ingredients in the mix that do not foster an environment allowing lengthy visits with patients. The sheer patient volume necessary to maintain a practice can be overwhelming simply not affording sufficient time to meet the entire emotional, psychological, spiritual and at times, educational needs of the patient and family. All the while, the oncologist is the authority, the mentor, the captain of the ship. To whom do they talk.? Other physicians? Not likely and what little data is out there confirms that.

The intellectual orientation of a physician starts to form early. Medical School is a culture that reinforces the concept of immensely delayed gratification. Loyalty to the guild takes on almost priest like proportions. The sheer level of physical and mental labors is staggering. Governance of the mind is often by way of an addictive technocracy whereby dependence on data, tests and technology tends to supplant other more creative and less didactic techniques of collecting information and solving problems. All of this combines seductively and may lead physicians in training to be unaware of and underestimating personal needs and the power and promise of human relationships. Medical school sentiments of privilege, honorable responsibility and excitement quickly mellow.

Although these notions have broad applicability among many physicians groups, a primary source of tension in oncology is the physicians’ changing role from “curer,” to “life-prolonging champion of the fight against the disease”; and to “sustainer,” when active therapy is no longer useful. This is difficult, heady stuff. Most surveys to date note that “not enough time” is right at the top of challenges and easily competes with the need to keep up with new medical information, dealing with difficult patients or family members, the number of patients who don’t get better, and the amount of paperwork.

In 1991, one survey reported “burnout” in over 50% of the more than 1000 long term clinical practice oncologists responding. The incidence of burnout was lower among university-based oncologists. University oncologists’ time is somewhat protected, their practice entails a large portion of teaching and competent residents and fellows often assist research and physician load. Three of the major stressors identified by the respondents were dealing with dying patients, reimbursement issues, and a heavy workload. The researchers suggested that the lack of preparation for dealing with the emotional aspects of oncology contributed to job stress and burnout.

In a subsequent similarly sized study of British oncologists, the prevalence of psychiatric disorders among this British sample was 28%. Clinicians who felt insufficiently trained in communication and management skills had significantly higher levels of stress than those who felt sufficiently trained. The authors concluded that improved training in communication skills might provide a useful tool to lessen the stress of practice.

As is intuitively obvious, being in the Captains’ chair and dealing with repetitive human suffering and frequent losses takes its toll. Just as one cannot deny their creativity, one cannot escape the pressure of simple human sorrow. The first response of oncologists is to detach in order to remain effective. However, too often this means to become disaffected, unengaged, and non-communicative as regards the issues addressed in this book. In time, everyone loses.

The solution of the physician to detach may lead to losing some of the comfort they sought out in pursuing a career in medicine. They may lose the quiet comfort of knowing they have been effective in alleviating suffering. One is on sacred ground when intimately involved with the sufferer and taking action to alleviate that suffering. Here is the rub. Chemotherapy, potions and pain meds may enormously mitigate distressing symptoms but anxiety and emotional anguish are insidious tormenters not as easily diagnosed or treated by formula. Physicians can have an enormous impact in these areas.

I am not inventing any new ideas. There are no truly new lessons to life or truly original emotions. There are variations on universal themes. Pain, whether it is psychic, emotional or physical, is the same in any language. Effective and broad reaching communication, sympathy and empathy, coupled with dispensation of in depth information are  benign opiates patients and families are happy on which to depend.

Studies have shown that a lack of formal training in communication skills heightens physician’s daily stress. Every day oncologists are bringing bad news, discussing prognosis, complicated therapies, treatments of pain and suffering and a dizzying array of future pitfalls and milestones. So what to do? It starts with enhancing communication skills to decrease stress for all. The key is to engage the patient and family. The time spent reaps immense rewards for all and, in effect maximizes not only the quality life for family and patient, but for the physician and staff. In the final analysis, it actually saves time to invest time.

However, enhancing these skills starts with dissecting and discovering all that needs talking about. Data are easy for the oncologist. It comes as quickly as does fear to patients and families. One first must know what to talk about before teaching how to talk about it. This book informs the patient and presents a wealth of information to help them participate more fully in the journey and perhaps more deeply develop appropriate relationships with their health care team..

Doctors are hard-wired to keep up with the latest advancements through reading, and continuing medical education. Perhaps many can view this book as a form of critical reading and continuing medical education. The syllabus was suggested by excellent experts; a few thousand patients.

Enormously successful politicians, pundits and prophets all know that we can enhance our sense of competence and lessen our feelings of anxiety when we feel understood and understand. The doctor must impart a wealth of information to their patients and families. In like manner, there is an enormous amount of needs and knowledge that the patient wants the doctor to address. What the patient does not know to ask yet can be a source of even greater anxiety.

Let us be reminded that it is hard to feel overwhelmed when you are in familiar territory. It is easy to be overwhelmed when you are on unfamiliar ground no one wants to traverse. This cuts both ways for patients, families and physicians. When there is a canyon of uncovered ground, conflicts and crisis can grow which sadly rarely are brought into the open, let alone the examining room. There are the usual culprits. Fear, time constraints, lack of information on the part of the patient and family and lack of eager engagement and pursuit of patient and family intellectual involvement by the health care team top the list.

Certainly, there is a wealth of information routinely disseminated by the health care team in most encounters. Rather, it is the depth, the intimacy, the focus and the scope that have the greatest positive impact. Granted, there is simply often not enough time to time to engage everything by even the most enterprising, experienced and engaging health care teams, and there are plenty. Thus, this book may help. Consider it a field manual, survival guide and reference.

Patients should never feel abandoned. However, abandonment usually carries a realistic component of personal responsibility. The traveler who refuses to seek direction, the motorist leaving for a journey low on gas, the camper without basic overnight survival gear and the homeowner who leaves the doors unlocked are inviting problems. Patients and families alike must minister somewhat to their own needs. Self-care begins with self-esteem. It is empowered by knowledge; knowledge of needs versus wants and knowledge of enemies versus allies. Patients must have knowledge of resources that are available and the lessons of history by those sufficiently similar to themselves that they may apply to themselves. Others have walked a similar road before and patients must know and truly understand that. Thus, this book.

The past generation has seen enormous advances in technology. Generic medical school training has continued to progress with more in depth education and attention to the nuances of patient and family communication. More attention to interfacing with those who are enormously frightened is the norm. Internal medicine residencies are also moving forward in this regard. Lastly, fellowship training in oncology has begun to pick up the cue of improved communication with families and patients as well as with oneself as the often captain of the health care team. But there is a lot of ground to cover. When one looks in the oncology world at all the presentations from the podium, abstracts presented and published, poster, plenary and “meet the professor” sessions and published articles, one finds a slowly growing but still small body of work such as this book.

So is this really such a big deal? Yes! Cancer is one of the great anathemas. Not too many utterances can whip up a faster frenzy of emotion, thought and agitation than “You have cancer”.  Knowledge is our greatest asset; patient knowledge.

Cancer is both incubus and pariah. The mere mention of the word strikes fear in the hearts, minds, and souls of millions of patients and families per year. These souls are awash in a tumultuous sea of blinding anxiety and pounding waves of enormous ignorance. The vast majority of non oncology providers avert from its care and quickly defer to the too few medical oncologists whose job it is to fight this sort of terrorism on its most personal and persistent level. The patients are not the only ones who carry a burden in the battle. Perhaps if we all understand this, we can pull the oars together and share the journey.


More nuts and Bolts of Cancer

June 27th

This is dr kevin ryanmd mba facp and hematologist oncologist here, medical oncologist professor and retired colonel and cancer survivor and this is when tumor is the rumor and cancer is the answer. This show is Modeled after my non profit book of the same name available on the web site of the same name… you can find it on the web site and a lot more, interviews, films excerpts on the site and it is also available on amazon in all formats All shows are also on my blog off the web site  say name  and on www.w4cs  and in a few days iheart radio

Think of these next two shows as a mixture of nova and the wonderful world of disney- and the end of the nuts and bolts of Oncology –what you need to know to get started at really diggin in Following this is an intriguing two part series into the mind and eart of the Oncologist Why do they do it

Scope of Adult Oncology Practice


Our patient population involves treatment of those over 18, with two thirds of patients being over 65. The diagnosis of a primary (first time) cancer process is usually initiated by the primary care physician. Often some radiographic study (plain film, chest x-ray, mammogram, etc.) is ordered to evaluate some symptom (pain in bone, cough, lump in breast, etc.) or abnormality found such as (lesion, “hole” in bone, mass in lung, microscopic calcifications on mammogram) etc. Tissue diagnosis is then made: radiologists may use fluoroscopic device to biopsy bone or needle localization to biopsy breast masses; pulmonologists may use fiber optic bronchoscopy to look into and biopsy in the lung. Then the pathologist reads the biopsy sample as: cancer, not cancer, or suspicious  and perhaps gives a level or grade of severity depending on the cancer type and then calls the physician that sent him biopsy tissue to inform them of the diagnosis. Special stains of cell tumor associated products or fingerprinting of the traits of the material follow.

These can include Her 2 neu , Estrogen and progesterone testing in breast cancer and many more immunologic, hormonal, or genetic markers or assays of the actual biopsy material AND THAT NUMBER OF PERSONALITY TRAITS SO TO SPEAK, THAT FORENSIC FINGER PRINTING IS INCREASING EVERY DAY. Thus getting enough tissue is crucial and also being sure to get clear margins is often very important, if not at the biopsy phase, later. There is a phrase, intended to be a bit rough that I drill into the heads of all of my students. It nonetheless makes a crucial point and completes the mantra of the title of the book… “ Although  tumor is the rumor and cancer is the answer, tissue is the issue,  no meat no treat.” Getting to the meat of a diagnosis requires specific and adequate tissue.

This is not said to be cute, it is said to be memorable. Meat means you need to be sure you have enough of the

    • Right specimen from the right spot ( often assisted in the O. R. by various scopes and scanners.
    • The right labeling of orientation ( where exactly was it).
    • Submitted in the right way, fresh Vs fixed in the right amount and most importantly.
    • Submitted by the right people who not only know all of this but do so as a team.
  • Discuss your case before biopsy and every decision step of the way in conference as a team.When there is a team approach:


  • Your pain and suffering is guaranteed to go down.
  • Your odds of remission , its quality and durability and even the chance of cure go way up.
  • You recuperation at home is much better.
  • Your family is closer and more supportive.
  • Your insights into the less than optimal management of the most frightening diagnoses are greater making your ability to take and give in support groups.
  • You will live and love more. If you read MY book, I guarantee with YOU at the helm, your odds are best. This time YOU means an ACRONYM for
  • YOUR ONCOLOGY UNIVERSE- THEY all orbit around you the patient!

Treatment setting


Patients are treated primarily in the outpatient clinic setting. There has been a large evolution from inpatient to the outpatient (clinic) setting largely pushed by medical advances and health care reform that has decreased inpatient stays. New drugs are introduced specifically for the clinic setting more often than not.

There are also oncologist reimbursement issues. Outpatient care is often more lucrative with occasional uncommon inpatient episodes as a consequence of treatment: e.g. immediate complications such as allergic reaction to chemotherapy during infusion or chemotherapy leakage out of veins into tissues causing tissue damage (necrosis) leaving skin ulcers. There are also delayed (days-weeks) complications: infections, which can be life-threatening, diarrhea with subsequent dehydration, nausea and vomiting which very uncommonly can be relentless and delayed (weeks to months), and neurological complications as well as blood counts requiring replacement blood products.






This book has a focus on those individuals that engage cancer when tumor is the rumor or cancer is the answer. Thus, the massive and crucial field of prevention, cancer surveillance and screening is intentionally not addressed in any depth.IT IS MANY BOKS IN ITSELF Nonetheless, this book is also designed as a reference that can be read in logical order from start to finish as well as each section being able to stand up on its own, complete unto itself for quick referral as needed. This means that there is background information about the nature of cancer that better prepares you to fully participate in your care and exercise your autonomy. Thus some comments about prevention and screening are included WHAT I GIVE YOU IS ALL THE INSIDE SCCOP THAT YOU HAVE TO KNOW AND SEPARATE MYTH FROM REALITY


, there is also aN understandable fascination with and attraction to the science of Oncology as it represents conditions that broadly encompasses all aspects of the human condition, psychosocial, ethereal and of the flesh. It does so as a mimic of the normal tissues on the most fundamental genetic and macro or gross anatomic level .REMEMBER, cancer is a respecter of no one. Its understanding and treatment more deeply involves all aspects of medicine that perhaps any other field. More research dollars are poured into it than perhaps even cardiovascular disease. More drugs are rationally screened and designed for its treatment and management each year than any other disease and discoveries in its basic science routinely open more doors into the nature of what is life and  the tools which tell us so. Invader of anywhere, its story is one of the stories of the progress of modern medicine in all of its aspects, drug therapy, radiation treatment and surgery with all its combinations.

Thus, we know some of its causes, but not nearly enough and we know some of how to screen for it, but nowhere near well enough to profoundly impact the disease yet (with some exceptions). Thus, physicians are responsible to counsel all patients and family members regarding what we do know about diet, alcohol, sexual behavior, obesity, exercise, self-examination, over exposure to sunlight, pap smears, mammograms, fecal occult blood, and sigmoidoscopy. There are numerous sources the physician can refer the patient to such as the American Cancer Society, The American College of Surgeons, The National Cancer Institute and many more. A simple call to 1- 800 –4- Cancer will do it all.

There is no proof yet that the patient without symptoms or JUST high risk factors NOT FINDINGS benefits from routine scans of the body (whole body CAT, MRI, Ultrasound and such).  As we will discuss later, avoid reasoning by the anecdote wherein  some singular episode of something occurring is incorrectly taken to mean those results apply to you and thus you should be tested despite neither signs nor symptoms of proven high risk factors. Tests cost money and emotions . Many  tests done in this screening manner are neither sensitive nor specific (no false positives or false negatives) and worth the test cost as well being safe and effective as a screen. Another exception is the patient with a clear family pedigree of a number of cancers such as breast, various colon cancers and other rare genetically based syndromes as well as clinical presentations highly suggestive of an underlying malignancy. In addition it has been shown that in right age groups, mammogram and colonoscopy performed in patients with no known risks does make sense. This is also true of routine pap smear with exam and possibly true for routine blood testing in specific age groups for a specific protein related to prostate cancer with a well done physical exam for prostate cancer.

An overview of the top five areas of progress from the standpoint of diet, nutrition and weight management and cancer were recently the subject of a poll of the American Institute of Cancer Research. They concluded: 1. Excess body fat is a major cause of cancer 2. The scientific study of who survives and why is now fully underway in our research and university centers 3. Technology is making the evidence on causes much clearer and out of the realm of unsubstantiated claims. 4. A growing connection between diet and genes seems to be taking shape and 5. The same is true between diet and cancer links in general.

However, once a cancer is clinically established, it is not clear that any radical change in diet will have a direct impact on that cancer while not removing the possibility that it may impact development of a second cancer which had not yet taken hold (this is theoretic and nearly impossible to prove). Mega diet changes or frankly any dietary change radically different from those recommend by the National Institutes of Health has simply not yet been shown to be capable of stopping tumor growth, cause sustained remissions or cures and  prevented spread once tumor  is clinically  visible with routine tools such as physical exam and scans.

Cancer prevention means taking active steps intended to decrease an individual’s, or a whole population’s, risk of developing cancer. Most cancers have environmental issues as causes (other than aging) and lifestyle issues at their core meaning to some degree that they may be controllable. Thus, there is some reality to stating that certain aspects of cancer can be considered a preventable disease. For example, lung cancer does occur in people with no risk factors, directly or otherwise but they are a small minority. Thus, never smoking or being around it (second hand smoke) or being chronically exposed to significant levels of radiation or certain chemicals and a few other lesser factors are steps one can take to markedly diminish but not totally remove the risk of developing lung cancer.

Most experts say that about 30% of cancer risk can be diminished  by improving exercise, decreasing alcohol intake, not being obese, avoiding tobacco products , inadequate diet, avoidance of sexually transmitted disease  and to a modest degree severe air pollution as well as exposure to naturally occurring background radiation.

Dietary recommendations that may decrease cancer risk are (1) reducing energy dense highly processed foods and high corn syrup sugary drinks (2) increasing plant origin foods (3) Decreasing processed meat and high proportion of red meats (4) limit consumption of alcohol and salt and mold-risky cereals.

The data for each of these recommendations ranges from clear and strong to highly suggestive. Studies carefully looking at these observations show diminished colon cancer rates as well as pancreatic, stomach and breast cancer rates in populations of patients who markedly differ in these risk factors.

The notion that some form of medication readily available to all can limit our risk of all cancers is very attractive but unproven and often the source of great sorcery against unsuspecting patient’s souls and quackery. In certain circumstances there is some suggestive data. For example, aspirin has been found to reduce the risk of death from cancer overall but it is not a risk free drug. Teasing out how much of the effect is due to decreased cardiovascular disease is tough but the slight suggestion remains. Hormone blocking drugs tamoxifen or raloxifine can reduce the risk of developing breast cancer in high-risk women by 50%. Finasteride may decrease the risk of prostatic low grade cancers in men. Non steroidal anti inflammatory drugs celecoxib and a relative have shown in cases of familial adenomatosis polyposi  they may decrease risk of developing malignant polyps as well as possibly also in normal people ( with polyp tendency). However, this benefit comes at a price of increased cardiovascular risk.

Vitamins have not been found to be effective at preventing cancer, but low levels of Vitamin D is associated with increased risk-the nature of this observation is unclear. Beta carotene supplementation may actually minimally increase lung cancer risk and folic acid not only does not decrease colon polyps, it may increase them. Vitamin C definitely does not diminish cancer risk and it is dangerous, just as is Laetrile when given in large doses.

There are vaccines recently developed that prevent some infection by some viruses that are associated with cancer, and therapeutic vaccines are in development to boost our immune response against certain types of tumors. Two vaccines against certain strains of human pappiloma virus decrease later development of cervical cancer in infected patients that together cause 70% of cervical cancer. These vaccines also have a role in protection of males from later development of anal cancer in those chronically infected with HPV viruses.




Cancer screening involves efforts to detect cancer before it is noticeable in terms of signs or symptoms. Screens could be as simple as tests on stool for non-visible blood, to tests of the sputum, urine and multiple blood assays for proteins or blood markers associated with cancer and as well as various types of medical imaging.

Universal screening means applying the tests without disqualifiers to all people. Selective screening means limiting the test to specific people who for any number of reasons increase the odds of a true positive result and decrease the odds of a false negative result which is when we wrongly state all is well based on the test but in reality cancer is present.

One has to balance factors that affect test outcome before applying a screen in either case. There may be harms, clinically as well as psychologically from the test. There may be unnecessary radiation exposure or to dyes that might be allergic and so on. You only suggest a test with such risks when the risk of failure to screen a high risk patient is higher.

Sensitivity and specificity are covered a number of times in this book and it is well worth the time to have some basic grasp of the concepts. If a test is not sensitive, it will miss cancers when they are there. If it is not specific, it will wrongly claim it is there when it is not.

All tests can produce false positives and false negative with false positives being more commonly produced. Experts look at all of this and come up with the positive predictive value of a test which is a wise calculation based on collected data that a test claiming to show cancer in an individual has whatever power or accuracy to reveal people with true positive results.

If a cancer is rare, there is not much rationale for screening tests nor is it often helpful in young people as cancer is mostly found in people over the age of fifty. There are some exceptions but not many that stand up. There may be cultural differences where in the U.S. we screen for colon cancer far more than stomach cancer but in Japan stomach cancer screening is commonplace because the disease it is screening for is commonplace.

Positive screens may mean a lot more people undergoing invasive biopsies. If a test produces many false positives you may have bad outcomes if the biopsies hold some risk. The same holds true when screening for diseases for which treatment may not be suitable or available. If treatment is not available, then diagnosis of a fatal disease  may produce significant mental and emotional harms and must be weighed in an informed manner.

Even when treatment is available, finding cancer early may have no impact on outcome. The only thing then that screening does ( if positive) is make it appear the patient lived longer when in fact the added time was at discovery not at the end of their life. Furthermore, the only length of time increased is the patient knowing they had cancer for which there may or may not be effective therapy. This also IS true if the treatment result from screening is the same as without screening. All this is the notion of lead-time bias, where one knows the diagnosis earlier making it appear they lived longer.

A powerful screening program reduces years of potential life lost and disability adjusted lives (increases healthy lives). It truly catches diseases earlier where it made a difference doing so.

In our zeal as scientists, we can over diagnose. There are some cancers where no treatment may ever be necessary. One can see this in the elderly with slow growing cancers. Prostate cancers and hormonally receptive breast cancer in the elderly come to mind where perhaps no harm is done to watch and treat symptomatically in selected cases if and when therapy might be poorly tolerated and not affect quality of life or survival.

Remember, the patient is the one with the disease. Physicians and their patients should look at the logistical burdens the testing proposes and decide if it takes too much time for little reward.  If there is  or ARE cultural reasons, patients may not wish to participate. The law of patient autonomy must be respected.

Of course, there is the issue of the cost of screening. The US preventive task force recommendations ignored the issue of money. However, most good tests and studies that evaluated them include a cost effective analysis. Obviously, all else being equal, the less expensive test is the one supported. Such analyses do not just compare two tests to each other; they look at all the detailed costs associated with the test from development to interpretation and follow on biopsies. However, the costs to the individual are often hard to quantify and may not be done, such as time taken away from work.

The  U.S.  preventative Services Task Force ( USPSTF) recommends cervical cancer screening in women with a cervix and who are sexually active until age 65. They advise  annual stool blood testing and less frequent sigmoidoscopy or colonoscopy starting at age 50 until age 75 (every 5-1-5 to 10 years respectively) depending on which test was done. Routine screening for other cancers is not recommended. There is some disagreement regarding screening for prostate cancer. There is also some controversy by OR when to start mammograms in women with no family history. Presently the consensus is every two years for those 50-74 years of age. I DISAGREE Some researchers feel strongly that yearly mammography does more harm than good. As mentioned, Japan screens for gastric cancer and they use photofluorography to enhance sensitivity. (They use a dye to look for cell changes that assist the human eye.

Genetic testing for certain high risk patients is recommended as certain cancer syndromes are known to exist. The BRCA1 and BRCA2 genes are looked for in breast ovarian and pancreatic cancer. A number of other genetic tests are now suggested in certain GI and GU tumors from patients in families with multiple prior cancers. Patients showing as positive for these gene mutations then undergo more frequent other tests such as mammograms and various scopes and perhaps even preventative surgery or a trial at chemoprevention.

Again , the scope of this book is not screening. Far more detailed information can be found at the National Cancer Institute site for patients and at 1 800-4- CANCER





This is not a book centering on the cause of cancer, its prevention or survivorship. Those topics and perspectives are covered in droves. However, this work relates to the patient suspected of having cancer who is found in fact to have it and finds themselves awash in a sea of anxiety with almost no life buoys of knowledge to keep them and their families afloat until reaching a safer shore.

Entire careers have been devoted to the cause of cancer. For the perspective this book strives, it suffices to say that most cancers find their cause in an environmental basis. Large scale monozygotic ( identical) twin studies have shown that about (80%) of adult cancers are not primarily due to inheritance. You are not predestined to develop cancer with some notable exceptions of well-studied examples and family syndromes. Cancer is part of the aging process in many of us. For example, in time the majority of all elderly males will have often slow growing prostate cancer.

Malignant transformation and growth of a cancer is a genetic event but there must also be a breakdown, overwhelming or effective hiding from the patient’s immune surveillance system that accompanies the early malignant events allowing or facilitating their survival. Once again, this too is an acquired event and not something in-born  or pre programmed to happen (a common misconception). Of course, as we age, the constancy of spontaneous rising up of cells with malignant potential can eventually overload us as part of the normal process of aging. Nonetheless, it is not true that old age simply means you will definitely develop aggressive malignancy; it is more complex than that.

The cascade of events leading to the malignant transformation of cells and their subsequent ability or tendency to grow and spread is possibly the most active field of all clinical and basic cancer research. Your inherited genetic makeup does clearly have a role but it is not usually deterministic. There are unknown acquired genetic defects. Smoking is a major cause, high fat and low fiber diet, viruses such as is seen in AIDS and more rarely the virus of Mononucleosis and certainly alcohol and radiation exposure in excess increase risk.

The causes of cancer, while not a particular object of this SHOW, is nonetheless heavily related to our goal in that false beliefs in causes is often the battleground of numerous rumors where incorrect and damaging viewpoints and opinions can run amuck. For example, to some an honest answer regarding “why me” can seem flippant and almost irreverent because the response is; “why not”? Cancer is not a rare phenomenon and the longer you live the greater the odds. Of course, for some patients some strong singular risk factors are a familial relationship risk (in-born increased odds for a specific cancer). But to the largest extent  the answer is that it is a common disease whose risk increases with age and some lifestyle choice  factors and that there is no one single cause most of the time. For e.g. although cigarette smoking is a singular factor, the type of tobacco and the manner of the exposure is important and some (most) people escape development of both the small cell (solely related to tobacco products) and the more common non small cell cancers of the lung.

I will review the major categories of cause without delving into sophisticated data as that takes us off target too long and too far for too little reward.

It is usually impossible to prove exactly what caused a cancer in any individual, because most cancers have multiple possible causes. For example, if a person who uses tobacco heavily develops lung cancer, then it was very probably caused by the tobacco use. But since everyone has a small chance of developing lung cancer as a result of air pollution AND THAT DATA IS WEAK or radiation, there then is a tiny chance that the smoker’s lung cancer actually developed because of air pollution or radiation. In some cases we simply do not know why.

Cancers are primarily an environmental disease with 90-95% of cases attributed to environmental factors ( if we include age) and 5-10% due to genetics. Environmental means non-genetic causes. The common causative agents are tobacco  exposure 25%, obesity and diet 30%, types and chronic infections 30%, radiation meaning both non ionizing ( think suntans) and ionizing, (think radon), x rays 10%, lack of physical exercise and environmental pollutants. Stress is not clearly related to the cause of cancer in humans although this is chronically debated.

Lung cancers are highly related to tobacco smoking which has substances in it know as mutagens which cause DNA mutations which impact cell growth and increase the likelihood of metastasis. Mutagens that specifically cause cancer are known as carcinogens. Various carcinogens can cause various cancers, not just lung cancer such as cancers of the head and neck, bladder, esophagus, pancreas, larynx and kidney. Tobacco carcinogens are related to 90% of lung cancers and tobacco smoke contains over 50 carcinogens causing about a third of death in the developed world and one in five worldwide. Many mutagens are carcinogens but not all and not all carcinogens are mutagens. Alcohol is like that where about 10% of male cancers in Western Europe are related to alcohol whereas about 4 % of female cancers are.

Cancer related to one’s occupation may represent between 2–20% of all cases. Every year, at least 200,000 people die worldwide from cancer related to their workplace. Millions of workers run the risk of developing cancers such as lung cancer and mesothelioma from inhaling asbestos and leukemia from exposure to benzene in the workplace.

Diet, physical activity, obesity, and the overall adverse impact of obesity on immunity and the endocrine system play a cooperative role in many cancers. Poor diets low in balance of whole grains, fruits, physical activities and obesity are related to approximately 30–35% of cancer cases. In the United States, excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of all cancer deaths. Physical inactivity is believed to contribute to cancer risk not only through its effect on body weight but also through negative effects on immune system function and through the endocrine system.

Diets that are low in vegetables, fruits and whole grains, and high in processed or red meats are linked with a number of cancers that were previously discussed. In addition, a high   salt diet is linked to stomach cancer. The frequent third world food contaminate afaltoxin is associated with liver cancer and Betel nut chewing with oral cancer. Thus, you will see cultural differences that shift when populations move into a new country of residence and do or do not continue their diet or origin culture.

We previously discussed infection in cancer with perhaps as many as 18% of cancers worldwide being related to infections. These infections were largely previously addressed but it is worthy to note both viruses and bacteria have been implicated. Viruses that can cause cancer are called oncoviruses. There are also viruses that cause forms of rare leukemia. In polluted third world rivers, parasites such as schistosoma haematobium and the liver fluke opisthorchis can cause can cause bladder cancer and cancer of the gall balder and liver ducts. This is not an all inclusive list but rather stresses the point that chronic irritation from infectious causes can lead to malignancy.

Radiation can cause all types of cancer after typically long periods of exposure and duration of radiation. Large dose have effects more immediately while most exposure has a long latency period between total lifetime dose and the development of malignancy. The young are most vulnerable to the bone narrow toxicities of radiation and the elderly to skin cancer due to lifetimes of exposure. The jury is in on tanning beds, skin is damaged and the risks for all types of cancer are increased. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults are with radiation exposure before birth having ten times the effect. Ionizing radiation is not a particularly strong mutagen. Residential exposure to radon gas, for example, has similar cancer risks as second hand smoke.

Living near a nuclear power plant or power lines does not impact your cancer risk. The steps involved with chronic ionizing radiation in forming cancer are well known and are cumulative. Radiation is a more potent source of cancer when it is combined with other cancer-causing agents, such as radon gas exposure plus smoking tobacco.

The familial syndromes were briefly touched on previously. Members of these families can have increased risk of specific cancers such as breast, ovarian and colon as well as in general. Adding to the prior list are individuals who inherited a defective gene for repair of routine damage. The gene for controlling cell growth in these people is a mutation of gene p 53. They run the risk of a number of cancers, especially soft tissue and brain cancer. Mutations in the retinoblastoma gene defects  leads to the same named cancer in children. Those with well known genetic syndromes in general tend to have a generally increased risk of cancer, for example, Down’s syndrome where there are three copies of chromosome 21.

Some substances cause cancer primarily through their physical, rather than chemical, effects on cells. Asbestos exposure and other naturally occurring as well as industrial synthetic fibers can be inhalants leading to mesothelioma. Physical trauma as a cause of cancer has been debunked with the sole possible exception of chronically drinking scalding hot tea causing inflammatory defensive repairs similar to what is seen in people with chronic reflux of gastric contents . It is the repair, not the trauma that is the culprit.

Hormones were also previously addressed and the general mechanism is their stimulation of the growth of hormone dependent cells which may become uncontrolled and malignant.

Cancer is not a transmissible disease. It is not infectious with the rare possibility of transfer of cells during pregnancy and extremely rare transfer of cells during organ transplant, the most common of that rare event is melanoma

Chemotherapy What is it Part 1

This is dr kevin ryanmd mba facp and hematologist oncologist here, medical oncologist professor and retired colonel and cancer survivor and this is when tumor is the rumor and cancer is the answer. Modeled after my non profit book of the same name available on the web site of the same name you can find it on the web site and a lot more, interviews, films excerpts on the site and it is also available on amazon     in all formats it is also on my blog off the web site  say name  and on www.w4cs  and in a few days iheart radio

Think of this show as a mixture of nova and the wonderful world of disney- what is chemo and how does it work


For this show the word “chemotherapy” when used without any modifying terms, will refer to drugs used to fight malignant cells. Typically, these drugs are given in some kind of standardized regimen, either alone or in some well thought out rationally designed and previously tested and developed manner to fight cancer. We are not talking about immunotherapy and targeted molecular therapy although you can make an argument for the former being included

Sadly and fascinatingly, the field owes a lot to the observed effects and later understood chemistry of what lethal mustard gas was doing to humans in ww i. Without too profound a modification, so called nitrogen mustard became one of the first successful agents against human malignancy. Then the fda and national institutes of health and national cancer institute for all intents rose to master the how of safe and expedient new drug development and testing .

The noticing of the mustard gases’ affect on the bone marrow in patients with cancers of cells of part of the immune system, known as lymphomas, led in december 1942 to several patients with advanced  lymphomas getting the compound by vein with massive improvement that was dramatic but short lived. After the war records were declassified, the race to exploit what these drugs were doing and use of them against cancer was underway. Soon, mustine, the first chemotherapy drug, was developed. Since then, many other drugs were used in combination and remissions with cures of some lymphomas, one in particularly known as hodgkin’s disease or hodgkin’s lymphoma were being tentatively reported. After that, drug development has exploded into a multibillion-dollar industry, although the principles and limitations and rules of new chemotherapy development discovered by the early researchers still apply.

Cancer cells not only tend to divide and have children or daughter cells more often than their normal counterparts, they keep doing it, your liver does not keep growing, it knows when it has reached just right “liverness” and if the injury is not too bad it will regenerate right back, after some types of injuries, to just right “liverness”- no more no less. Not so with malignancy.

Chemotherapy can try to take advantage of that growth trait of cancer cells but this means one may see affects on other rapidly dividing cells such as bone marrow, digestive track, and hair follicles. Obviously, and particularly in the case of the bone marrow, decrease in normal marrow contents can occur known as “myelosupression”, this can be dangerous and require careful monitoring and support. This is when and if red cell counts fall with serious anemia, platelets fall increasing the risk of bleeding and certain types of white blood cells fall dramatically increasing the risk of infection.

Notionally, the overarching purpose of cancer chemotherapy may in some cases be expressed as palliative, which means there is no hope of cure. In such cases, the treatment is intended to alleviate symptoms and perhaps prolong life and do so in a manner the patient agrees was worth the effort as it is often not free from toxicities that must be weighed against benefit.

Then there is therapy clearly planned as a regimen intended for cure.  This is an all out attack against all the cancer cells with or without surgery or radiation or other therapies as part of the plan. Thus, the oncologist will tend to give doses known to have the power to kill cancer cells and support the patient through the dangers and toxicities possibly requiring hospitalizations or transfusions or other support, as the goal of cure is possible. Dosing at full dose and on time is a consistent theme.

Then there is the use of chemotherapy before a primary modality of therapy, which might be radiation or surgery, to reduce the burden of cancer cells and eradicate non-local metastasis or sites of spread as well as make surgery more feasible with a better result. This is called neoadjuvant chemotherapy and it may have cure as intent.

In contrast to neoadjuvant therapy, adjuvant chemotherapy is a post-primary treatment modality or given after primary treatment, typically radiation or surgery, to mop up supposed remaining local, as well as distant cancer cells. This therapy is done based on the understanding for a particular cancer that both local or especially distant development of cancer is at risk to occur post original therapy but may not ever or rather take a long symptom free time to do so with the adjuvant therapy being given after local therapy. It is done also because it is known to decrease the risk of relapse  especially when one looks at the original stage remember these are all individual decisions

           There are about 500 drugs approved and mainly used for the treatment of or directly in principal support of the treatment of human cancer. Broadly, chemotherapy is  the treatment of cancer with drugs that can destroy cancer cells by impeding their growth, reproduction and spread. Thus we can broadly classify drugs by names that are meaningless to many but will ring bells with anyone one who has taken a few chemistry courses.

Amazingly, many of these come from stumbled upon observations in the plant and animal kingdom. Others are products of so-called rational drug design. The national cancer institute (nci) and other nations institutes has played an active role in the development of drugs for cancer treatment with over half of those drugs currently used coming from the us national cancer institute (nci) drug development program. Consider this; over 400,000 compounds have gone through nci screening and are in its drug repository of which 80,000 have been screened since 1990. Drugs can enter any level of this program depending on how much  is already known regarding them. Thus, it is a system designed to not waste time. The nci supports the majority of clinical trials in the world with over 1500 ongoing at one time which have some major nci connection. Then there are some private foundation funded trials and university trials and other nations bringing the total to over 2000 ongoing per year in the u.s., representing well over 70% of all trials worldwide.

The sales of cancer drugs will grow at nearly double the rate of the global pharmaceutical market and may pass $150 billion by 2018, according to ims health, the leading provider of information services for the healthcare industry who covers markets in 100+ countries around the world. Expensive new treatments, an increasing number of patients on chemotherapy in major markets and evidence that more people in emerging markets are gaining access to modern targeted therapies will contribute to sales of cancer drugs growing at a compound rate of 12 to 15 percent, ims said.

In 2008, u.s. Sales of oncology products exceeded $50 billion. This comprises nearly 17 percent of all of worldwide pharmaceutical sales growth for that year. As techniques to diagnose disease earlier as well as detect spread or metastatic disease earlier develop and the understanding on a genetic and immunologic basis of each patient’s cancer cells abound, much more elegant and specific therapies will rapidly shuttle their way through the fda’s drug approval pipeline. This will not slow down.

In 2007, titus plattel, ims vice president for oncology showed laser accurate vision when correctly predicting that, “double-digit sales growth in oncology drugs (would be) fueled by increased use of targeted therapeutic agents introduced over the past 10 years… (in addition to ) first-time innovations coming to the market and longer treatment periods for growing numbers of patients,”  indeed, since 2007 over 60 new and important chemical entities were released as safe and effective either alone or in combination with other drugs or types of therapies contributing to the exploding cost of treatment.

The more we learn of the why of  the development of malignant cells that escape  or overcome immunologic surveillance and destruction and  the how of their potential and timing  for spread on a basic science , genetic and immunological and clinical level, the more that knowledge will be exploited. The distance from laboratory bench to patient’s bedside will continue to shrink as not only new drug classes with mechanisms of action helpful to many sufficiently similar patients will be proven safe and effective but the more so-called tailor made therapies for your specific cancer could become a reality.

“ten years ago it was all about chemo,” said dr. Kim lyerly, director of the duke university comprehensive cancer center at the 2007 american society of clinical oncology annual meeting (largest cancer care meeting in the world). “this time you walk down the convention center and it’s all about new targets. And we can get more mileage out of these drugs if we can predict who will respond.”

Here is a brief explanation of the how of present anti cancer chemotherapy therapy.

Chemotherapy is the use of powerful medicines to kill cancer cells. However, not all chemotherapy agents act the same way. Some of the newer therapy  is aimed at specific targets within cells and not principally at highly dividing ( multiplying) cells. Nonetheless, the idea is either to try to exploit some level of an achilles heel present in the malignant cell that is either absent or not as crucial for cell survival in healthy cells. This can be done directly or by means of a cascade of events.

Some chemotherapy drugs affect the behavior of cancer cells without directly attacking them and some directly attack the dna of the cells, preventing them from multiplying or by triggering their ultimate demise. Others do not act directly; they target the molecular abnormality in certain types of cancer. Depending on their biochemical mode of action, chemotherapy drugs (also called an antineoplastic or cytotoxic drug that means toxic to cells or cell killing) are grouped into different therapeutic classes i will mention you may find it useful to have a deeper understanding of just what drugs are being used and why. Feel free to talk with your treating physician regarding these drugs and their combinations. This may also be of great help when looking on the web for new clinical trials and treatments with different combinations than what you have seen. It will also help you understand the differing spectrum of toxicities that may occur with these drugs. By no means is this a chemistry course but it is a window of clever attacks by anticancer drugs

           Alkylating agents (also called dna damaging agents): alkylating agents form chemical bonds with the dna of cells of all kinds but more so with those that are more actively dividing (more target available). The drugs incorrectly link rungs on the ladder like structure that dna can be envisioned as; a ladder of two legs of what are called nucleotides that match up only one complementary or matching like a puzzle base pair at their ladder rungs. The pair called a always matches up with t and g always matches with c at the rung area. Then the whole ladder is twisted and folded. The explicit pattern of those “rung-connected pairs” with nonsense spaces and other fillers and such is your dna. That code, when read through unzipping and sending a messenger of the unsoiled code to   protein factories of the cell are instructions for proteins of all the functions of your body. If the  code is wrong or unreadable all manner of havoc can break loose in this intricate system. Alkylating agents can stop tumor growth and set the stage for tumor cell death directly or in time by creating cross links of chemical bonds in the ladder of the two complementary strands that should not be there. So linked, cells cannot go through the normal cycle of cell division, repair, and production of daughter cells  as they are unable to reproduce their dna, an essential step to cell division . Alkylating agents include several drugs, the most common are: cisplatin, carboplatin (paraplatin), ifosfamide, chlorambucil, busulfan, and thiotepa.

            Anti-metabolites: these anticancer agents work by inhibiting the synthesis of nucleic acids (dna, rna), which are essential in cell division and the making of daughter cells. So, while not making wrong chemical bonds as the drugs above, the outcome is very similar. Normal cells which divide rapidly will be adversely affected. The benefit comes from the fact that unless and until cancer cells show resistance specifically (unusually) or generally to these drugs, they are often initially more sensitive to the effects of these drugs than normal cells during the necessary processes of cell multiplication. In nature, cancer cells divide more frequently than normal cells; and therefore any halt in cell division affects cancer cells more than healthy cells.

The antimetabolites are among the oldest chemical agents used in chemotherapy and are broadly divided into three groups depending on their therapeutic action.

  • Pyrimidine analogues – those molecules are found mainly in nitrogen containing bases that mimic the essential building blocks, the nucleotide, of dna and rna that hold the source code the blueprint and further directions of everything in that cell and made by that cell. One of the anti pyrimidines agents is 5-fluorouracil (5fu), a drug used in the treatment of many cancers, principally colorectal cancer and pancreatic cancer.
  • Purine analogues – they are substances that inhibit enzymes that are crucial for the assembly, maintenance, and duplication and normal tying together of dna: dna polymerase, dna primase and dna ligase. One powerful common example is fludarabine, a chemotherapeutic drug used to treat chronic lymphocytic leukemia.
  • Antifolates – these are drugs that through direct competition interfere with a crucial vitamin used in many levels of mammalian cells, the synthesis of folate. One of the most common of antifolates is methotrexate; it acts by inhibiting dihydrofolate reductase, an enzyme essential for synthesis of purines and pyrimidines.
  • Plant alkaloids and terpenoids: alkaloids of vegetable origin that have therapeutic properties that are used to produce anti cancer drugs by preventing the formation of what is known as the spindle, an egg shaped structure like what is used to shake up dice in some betting games. During cell division, the spindles run the long axis of an egg shaped device and are what chromosomes needs to guide themselves along when the mother cell divides into two daughter cells and takes a full complement of chromosome to each of the two cells. Cancer cells are more sensitive, to a degree, than normal cells the process causes the cells to remain blocked at a stage of cell division and are then unable to divide and thus multiply in number. The most common alkaloids that affect the spindle like tracks include vincristine, vinblastine, vinorelbine, paclitaxel and docetaxel.
  • Taxanes: the taxanes also halt cell division and were originally found in the english yew tree. Many tumors find it difficult to grow with a taxane on board. Although they can be used in the treatment of many tumor types’ cancerous conditions, the taxanes are used mainly to treat advanced stages of breast cancer, lung cancer and metastatic ovarian cancers. The taxanes include paclitaxel and docetaxel. You may here them called taxol and taxotere
  • Topoisomerase inhibitors: wow, that’s a mouthful .dna topoisomerases are essential enzymes that maintain the highly specific and elegant coiling, twisting and orientation in three-dimensional space, of dna. This is not only not random but its integrity must be maintained for accurate functions such as copying, reading of the   dna code and then recombining when dna unzips , reads itself and makes perfect complementary strands of itself         for each daughter cell. Again remember we are talking in three dimensional space among this class of chemotherapy drugs include amsacrine, anthracyclines, camptothecin derivative (irinotecan), and epipodophyllotoxin derivatives (etoposide and teniposide). The topoisomerase inhibitors are used to treat several types of cancers.

           Antitumor antibiotics: antitumor antibiotics are a class of chemotherapy drugs used to treat many malignancies such as acute myeloid leukemia, breast cancer, and non-small cell lung cancer. These drugs act by preventing cell division in both cancerous cells and healthy cells that multiply rapidly so the therapeutic index or margin of safety between where they seriously impair normal cells versus irreversibly damage cancer cells is very narrow. The most common  antitumor antibiotics include :

·       Aclarubicin

·       Bleomycin

·       Dactinomycin

·       Daunorubicin

·       Doxorubicin

·       Epirubicin

·       Mythramycin

·       Mitomycin

·       Zorubicin.



              Hormones:  some cancers- especially breast and prostate are either hormone-dependent or hormone sensitive cancers this can be both a positive or negative effect and drugs are used to exploit this. Hormone therapy can be used to block hormonal stimulation by acting at various aspects of their metabolism, thus stopping or slowing tumor growth. For example, some drugs manipulate circulating testosterones affect on prostate cancer; other drugs interfere with hormone responsive breast cancer cells ability to reproduce and thrive in a progesterone or estrogen rich environment. Some drugs work at local cancer cell receptors and some work distantly in aspects of the endocrine system to include the brain in areas such as the pituitary gland and elsewhere. It is really rather marvelous the ways that these cells mimic and try to exploit the norm as well as the ways science has uncovered this and exploited them doing so.

                Monoclonal antibodies: these were a giant breakthough at the lab bench of the late eighties and are now expolding in medicine such as rheumatoid arthritis and psoriasis and more than just cancer all of us are equipped with an amazingly intricate immune surveillance system that has a liquid ( antibodies and cytokines and inter leukins and interferon and more) , and a cellular system somewhat analogous to a complete army of intelligence cells, short lived marines,  cannibalizing cells and a metaphor that really does go on and on. The immune system is wonderfully connected and communicates rapidly with all of its aspects. We fight bacteria, cancers, viruses, anything we sense as foreign, such as organ transplants and of course tumors. The noble prize in 1975 went to scientists who discovered we can engineer antibodies highly specific for just one foreign entity one single tiny foreign enitity as long as it can be recognized  and seen as foreign. One can then imagine how the race was on to make these antibodies against cancers and perhaps even attach payloads of radiation or biologic toxins and chemotherapy as well as to try to deliver cancer cell specific therapy .think of somewhat like a silver bullet in some cases, the antibody alone does the trick. The  whole point is specificity  leaving healthy tissues and cells alone while trying to target something very unique about the cancer cells thus addressing the achilles heel notion that was raised earlier.   This is now a multibillion-dollar industry and growing rapidly.

Of course, never underestimate the workarounds cancer cells already have or develop and they are many and can develop very quickly but overall, the direction of research and therapy with monoclonal antibodies is positive with this notional type of approach. A common bottom line of therapy is the antibody singles out the cancer cell and deprives them of something essential, blocks some important pathway or delivers a payload of something toxic. In many cases, it triggers the cancer cells to commit suicide by many different mecanisms. In the beginning, these antibodies used mouse cells to make the antibodies and humans reacted with anti-mouse human antibodies. I was on the first team to publish the building of techniques to humanize these antibodies. In so doing we “ saw”, by tacking radioactive light to the antibody, breast cancer metastasis in a patient which other scans could not see.i was on active duty then or otherwise i would be a very rich man today  oh well was not meant to be and it was exciting to be first in short order, a billion dollar industry was thriving principally involving non hodgkin’s lymphomas and soon other cancers on a large scale. Among drugs classed as monoclonal antibodies include:

·       Herceptin, used in the treatment of breast cancer.

·       Rituximab, used to treat lymphoma and other similar malignancies.

·       And many more.


              Podophyllotxin – podophyllotxin is a plant-derived  (american and endangered himalayan mayapple) compound  from which we get two drugs. These make cells get hung up and unable to proceed to multiply just before the life cycle phase called g    one. This is the starting of doubling up their dna prior to dividing . It also  blocks cells caught past g1 trying to actually make the double dna ( to give half to each daughter cell). We see what these drugs, etoposide and teniposide do but we still cannot clearly state exactly how. The mechanism of its action is not yet fully known. Owing to the rarity of their plant of origin scientists are trying to find the genes for the dna codes (just like forensic scientists do in crime solving) to be able in time make the chemicals in the lab by teaching certain cells to be factories for the chemical and they are  suceeding.

                Nanoparticles – now this sounds like science fiction picture this. These particles fall in the size between atoms and small molecules and can be designed to be identical to each other. They are finding increasing use in biomedicine. For example, some of our drugs are very insoluble using conventional techniques. By getting the essential active agents into the size of nanoparticles it allows a highly concentrated delivery of drugs. Here is one example of getting clever and combining breakthroughs nanoparticles made of magnetic material can be used to concentrate agents at tumor sites in the body that have been first identified with monoclonal antibodies with a few atoms of iron attached. You now have tumor sitting vulnerable to agents affiliated with external magnetic fields. This is a novel way to localize at the near atomic level a highly toxic therapy that might well leave other  wise non engaged ( magnetically speaking ) tissues alone. Think of as a  laser site whose focus is as tight as a few molecules on target.

               Electro chemotherapy: this is the idea of somehow giving a physical chemistry or immunologic or biochemical fingerprint to that which you want to singularly find and eliminate. Imagine injecting a chemotherapeutic drug that is then followed by application of high voltage electric pulses locally to the tumor that opens and facilitates the passage of some drugs that normally cannot get transported across the cancer cell wall defenses to it interior. Early work with the antitumor antibiotic bleomycin and the alkylating agent cisplatin is showing some benefit in combination for treatment of skin cancers or those just under the skin no matter what the original tumor type may be. Using this as a cue, endoscospists (clinicians using flexible fibreoptics scopes to look into tubular structures, such as the gi track) are combining these lessons to catch tumors at extremely early phases avoiding more invasive surgery later. The idea is to minimize impact on normal surrounding functioning cells, specifically target, and then eliminate the tumor cells because of either identifying them easily or using techniques to which they are uniquely vulnerable. This should result in an increased tumor kill and/or reduced toxicity.

Specially targeted delivery vehicles may be shown to have a differentially higher affinity for tumor cells by interacting with tumor-specific or tumor-associated antigens. In addition to their targeting component, they also carry a payload – whether this is a traditional chemotherapeutic agent, or a radioisotope or an immune stimulating factor.  These vehicles will vary in  stability, selectivity and targeting motif but they all have the same aim of increasing the maximum effective dose that can be delivered to the tumor cells.


The hope and some cases reality is that reduced systemic toxicity means that they can also be used in sicker patients, and that they can carry new chemotherapeutic agents that would have been far too toxic to deliver via traditional systemic approaches. Think of the drone technology we now have in warfare that is designed for the drone to single out a vehicle with a specific license plate or some other highly specific trait with laser accuracy and spares all non intended targets while delivering a payload.

More non dna or antigen targeted therapies


Some cancers, one in particular known as chronic myelogenous leukemia, has a well defined defect known as the philadelphia chromosome wherein in the malignant cells and all its children one portion of genes or dna material have a highly specific deletion and movement to other section of dna strands making a chromosome known as the philadelphia chromosome  ( named after the city it was discovered in …by a woman). This leads to the bone marrow cells getting a message to code for a category of gene family  known as a type of tyrosine kinase which leads to out of control, and overtime bone marrow activity. The disease was only curable by bone marrow transplant with highly matched donors and recipient. The death rate from therapy was high with more likely death rates if you wait too long to try the risky transplant. In time,  rational drug design and targeted drug therapy led to an almost non-toxic pill that blocks the aberrant type of tyrosine kinase the aberrant mimicking malignant kinase the philadelphia chromasome  in the cancer cells gave the instructions to make that is seen in the disease. Now most patients have high quality remissions if not cures.- from a highly non toxic pill with response rates of over 90% that are probably cures instead of waiting with the chroninc disease to convert  to acute leukemia and then a transplant being the only hope and a very very high mortality rate

             Other targeted therapies : in one form of acute leukemia a class of drugs known as the retinoids yes like the aniti acne family of drugs  were discovered to  force the arrested maturity of one type of adult leukemia into maturation and eventual control.  These retinoids drugs are  being looked at in multiple malignancies : bexarotene, isotretinoin, tretinoin and atra. In addition we now see exciting work with:

            Vaccines : the well known example is to prevent a large proportion of cervical cancers. And now hpv vaccination works

Also vaccine work is early but encourqaging with a modifiend virus vaccine in the most lethal from of brain cancer

  • Targeted therapies against cellular enzymes or products unique or essential to the cancer cell more than normal cells.
  • Genetic manipulation by inserting specific work horse pieces of dna that help single out malignant cells or programs them to self destruct selectively.this is just taking off and flying in the laboratory we are now looking at finding ealry recurrence or maybe even diagnose of malignancy by finding snippets of cancer specific gene products from cancer dna in the blood
  • High dose chemotherapy with stem cell rescue including auotologous (yourself) or allogeneic ( other humans) peripheral blood or bone marrow transplantation. Better techniques of support and combining this with other therapies and in particular anitbodies is adding months and perhaps years to some people with specific types of cancer
  • Biologic response modifiers: such as interferon and interleukins which use the body’s own immune system to fight cancer and to reduce treatment-related side effects.
  • Ultra sound and cryotherapy which use high frequency microwaves to try and break apart tumor cells or freezing them using inserted probes. Not proven to have more than limited use but some success has been reported
  • Radiation sensitizers: this is where drugs that can concentrate in cancer cells can increase the sensitivity to radiation of just those cells allowing for less damage to surrounding cells and more targeted treatment.
  • Anti angiogenesis angiogenesis means making new blood vessels ,,,,these inhibitors are ; drugs which when delivered block the tendency of some cancers to cause the blood vessel system to be stolen   in a manner that brings more nutrients to the cancer giving it a growth advantage as well as help it have highways that facilitate their ability to access more remote areas of the body. Amazing

In sum, the more we understand that which confers malignant behavior  to malignant cells as well as all the special tricks and traits malignant cells use, the more we single out those seeming advantages as targets for design of increasingly specific therapy with decreasing toxicity. The same holds true for finding the vulnerabilities some of these cancers have separately or in excess to their normal counterparts.

Thus, we see how the word chemotherapy is not only complex and colorful but not at all necessarily a bad thing. Furthermore, the search for new and more specific agents from the plant and animal kingdom for rational drug design and tailored therapy have brought us over 500 approved effective compounds. More on the types of therapy and beauty of the rationally designed clinical trials comes later.

So what is the scope of lay knowledge of malignancy

              Numerous studies have assessed in not only western nations but worldwide the extent of knowledge and understanding of cancer by the nonprofessional. It matters little if one is asking about the diagnosis, biological behaviors, types, effects, and benefits of therapies, causes or odds of response and long term effects; the fund of knowledge by the layman is abysmally low. Hearing this hopefully you see that all manner of research has and is going on and is very clever and building on itself this underscores the argument supporting the need for books such as mine abd this radio show as well as reminds us of the enormous power anxiety has in this disease due to lack of knowledge. The gap of fact versus fiction existing in the non-professional population is a mish mashed jumble with lack of clarity and discernment on all fronts. It is driven by fear …of the unknown.

              People in rich and poor nations alike have faulty understandings of the causes of cancer and need further education as to how to fend off the disease. Studies have shown that in all parts of the world there is a greater tendency to believe that factors out of our individual control as opposed to lifestyle choices are the main cause. The sentiment that we are tossed to the winds of fate or bad luck from genes is largely present and of course, wrong. After simply aging how we have lived is a major factor

A 2007 report, based on a survey sponsored by the international union against cancer (uicc) of nearly 30,000 people in 29 countries was released at the start of a four-day world cancer congress in geneva. In high-income countries like australia, britain, canada, greece, spain and the united states, as well as low-income nations the survey found refusal to recognize that alcohol consumption increases the cancer risk ran at 30-50 percent of the population. Of course, cancer risk rises as alcohol consumption rises.


There was overall denial that obesity is a cancer risk factor and a greater belief that fruits and vegetables consumption increasing in the standard western diet will have a more powerful impact that moderation of alcohol and cessation of smoking. This is of course, wrong.


Strikingly, there was an unfounded perception that stress posed an ominous proven danger as regards developing cancer similar to the common understanding of the credible data regarding stress as a contributing factor to heart disease.this too is wrong  just like living near high voltage power lines or using cell phones. There is a lot of crap out there


Air pollution was also incorrectly held as a major  remember we said major  cause of cancer. “in general, people in all countries are more ready to accept that things outside of their control might cause cancer, like air pollution, than things that are within their own control, such as  being overweight which is a well-established cancer risk factor,” declared the uicc.

           The survey showed that in low and middle-income countries, people were more pessimistic about the chances of treatment curing cancer.


In the poorest countries 48 percent felt not much could be done once the disease had taken hold. In middle-income countries, 39 percent had the same view, but in the richest countries, pessimists totaled only 17 percent. The problem with the fatalistic view, said the uicc, was that it could deter people not only from seeking treatment but also from participating in cancer screening programs that can save many lives.

This is only a snapshot of studies that echo the same point. The fund of knowledge what we think we know by non professionals and accuracy of that knowledge regarding causes, methods of diagnosis, treatment modalities and odds of response, morbidity of treatments and frankly most of the relevant aspects of human malignancy are archaic and a poor reflection of reality meaning of the truth why; because it is the very nature of a beast with so many  frightening faces.


Cancer is a disease not always externally seen that can affect anyone in any organ, spread at will causing all manners of havoc and whose therapies, without guidance and correct counseling are held by many to be worse than the disease. It is a disease that can cause inexplicable wasting and distant effects from only local tumors and alter quality of life in dizzying arrays. This is why the profound anxiety. Imagine a process wherein a few cells somehow imitate their benign counterpart organ on a genetic level. Then  add in their selective growth advantage ; not stopping, not staying put and then tricking and fooling the defenses of the body, escaping detection and eradication and using the body’s own building blocks to spread. Then they require typically difficult intense therapies to eradicate which may not be sufficiently cancer specific to spare normal functions and tissues so that not only the disease causes all manner of  impairment of health quality issues and risks, but so may the therapy. Imagine the problems that arise when the scope of accurate, sufficiently detailed knowledge of the enemy is sparse and largely incorrect. Thus again, the need for this show and my book.


Any more questions?????


This has ben dr kevin ryanmd mba facp and hematologist oncologist here, medical oncologist professor and retired colonel and cancer survivor and this has been when tumor is the rumor and cancer is the answer. Modeled after my non profit book of the same name available on the web site of the same name  you can find it on the web site and a lot more, interviews, films excerpts on the site and it is also available on amazon         in all formats i am signing off radio the cancer support radio program remind you the program is archived here and the iheart radio as well as the www.w4cs blog and myblog accessed easily from the web site