For a concise covering of cancer.

I have rewritten the section on cancer based up discovering that cancer is dependent upon glucose, and therefore can be starved into remission or better.  Sadly, though I have been reading the technical journals and summation articles I hadn't discovered the Warburg Theory (1924) until 2016.  The science is solid; I have spent 6 months examining it.  As a consequence I have rewritten one of my 2 summation articles on cancer and its dietary fix.  What follows is that work.  I have left my older work up, much of its is valid.  I simply didn't want to spend the time on rewriting both.  I have other trees to chop.  

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This applies to 95% of all cancer patient, that chemotherapy cannot alter significantly the course of the disease--a few cancers it can. 

CHEMO THAT CAN’T CURE METASTATIC CANCER, THUS IT CAN’T CURE INDOLENT CANCER.  They are essentially the same but for the ability to fool the immune system. There is not an atypical positive response for a subgroup; those terminal patients have an indolent form of the cancer.  The term “Survival” applied to chemo means “delays death” a few months.  Like soldiers, doctors are believers, thus they sell their faith in chemo.

There is a sales pitch for chemotherapy based upon bad logic.  An example will make it clear.  The 2 year survival for untreated small cell lung cancer average is 9 month, with 95 dying within 2 years.  Chemo therapy adds to the bell curve 2 months.  Thus average survival is 11 months, and 95% die within 2 years 2 months.   Gertrude has small cell breast cancer, and would untreated live average of 9 months.  If she elects treatment, she will be dead in the 11^th month.  Treatment doesn’t place Gertrude in the fortunate group of living over 2 years. 

If, for example a  stage 3 breast cancer (65% chance that it is metastatic) turns out to be metastatic  the results is the same with chemo, only now that person lives 2 months longer.  Chemo doesn’t convert doesn’t change the course of events.  Metastatic cancer is like a time bomb, set to kill its host after so many months.  For those who have an indolent non-metastatic cancer, the operation entails they are a cancer survivor.  If she is a survivor without chemo, electing chemotherapy, she shortened her life by years.  I estimate at least 4.5 years.  Millions of people undergo pointless chemo that shortens their lives, and most of them falsely believe they are a survivor because of the chemo.     

CANCER basics & CHEMOTHERAPY– 13 pgs  --  10/18/13 

 1) While beyond the scope of this paper, it is essential to understand the inroads made upon medical science by corporate medicine.   Corporate medicine is market driven; medical science evidence driven.    These two approaches result in different explanations concerning cancer. The goal here is to understand the general basic biology of cancer and its treatment options based quality scientific evidence—without market considerations. What follows is based upon sound science with sources.  Marketing science is driven by profits, & thus promotes aggressive treatments.   Pharma’s marketing ploys confirms Harvard Prof. Dr. Marcia Angell’s  observation that we have “the worst system we could imagine.”  To learn more read Marketing Science and its links.

2)  The primary goal of this explanation of the biology concerning cancer is to understand the benefits and limitations of chemotherapy.   This requires an explanation of the biology of cancer, a topic I have long studied.[1]  Since cancer involves a broad group of diseases, the exceptions to the generalities are often excluded (the object is to understand what cancer is; thus not to bury the reader in details).  Cancer is a line of body cells that have through mutations and often stem cells developed the ability to spread rapidly. There are 7 essential types of mutations for turning a cell into a cancerous cell line, and they involve over a hundred biochemical cellular activities.  Most chemotherapies hinder one of these essential processes, and thus it must be applied short term—only a few chemotherapies are curative (see paragraph 16).  With corporate medicine, this treatment of cancer is sold as effective, but most aren’t.   Radiation and excision, by removing an indolent cancer, reduces the risk of mutating into metastatic cancer.   If the tumor is in fact a cancer and has already metastasized, the prognosis is very, very poor:  excision, radiation, and chemotherapy are ineffective at preventing the fatal outcome.  Metastatic cancer can be indolent and take years to be diagnosed.  Chemotherapy does not destroy either the indolent or aggressive cancers, though pharma and physicians will try to persuade you otherwise.  Chemotherapies shut temporarily off an essential bodily process, and thus effects also cancer cells.  Once therapy has been stopped, the essential process, such as making new capillaries, resumes.   Life extension from chemotherapy in terminal patient averages 2 to 3 months.  It is not a magic bullet that destroys cancer cells.[2]   It affect upon non-metastatic cancer is not worth the side effects.   Chemotherapy won’t prevent an indolent cancer from at some future date becoming metastatic.  It is all a matter of numbers, and clinical trials for FDA approval are on terminal cancer patients, and are barely better than a placebo (no treatment).  Once approved, they are marketed using tobacco science for all stages of cancer.  Pharma manipulation of the results,  is the norm because effective peer review is impossible.[3]  When administered in office, the oncologist receives a spread between what is billed insurance and their bulk price for the drugs, plus a fee for treatment.  For the reasons just stated early only excision and irradiating the cancer are effective.  This paper in it discussion of the biology cancer reveals why chemotherapy fails to cure.     

 3)   “A benign tumor is a mass of cells (tumor) that lacks the ability to invade neighboring tissues or metastasize. These characteristics are required for a tumor to be defined as cancerous and therefore benign tumors are non-cancerous. Also, benign tumors generally have a slower growth rate than malignant tumors and the tumor cells are usually more differentiated (cells have normal features). [1][2][3]  Benign tumors are typically surrounded by an outer surface (fibrous sheath of connective tissue) or remain with the epithelium.[4]  Common examples of benign tumors include moles (nevi), colon polyps,[4] and uterine fibroids (leiomyomas).   Although benign tumors will not metastasize or locally invade tissues, some types may still produce negative health effects.  The growth of benign tumors produce a "mass effect" that can compress tissues and may cause nerve damage, reduction of blood to an area of the body (ischaemia), tissue death (necrosis) and organ damage.  The mass affect of tumors are more prominent if the tumor is within an enclosed space such as the cranium, respiratory tract, sinus or inside bones.  Tumors of endocrine tissues may overproduce certain hormones, especially when the cells are well differentiated.  Examples include thyroid adenomas  and  adrenocortical adenomas.[1]    Although most benign tumors are not life-threatening, many types of benign tumors can become malignant through a process known as tumor progression.[5]  For this reason and other possible negative health effects, some benign tumors are removed by surgery.[6]” Wiki.  Unfortunately pharma who profit from overtreatment of benign tumors, promotes guidelines that are contrary to the best interests of patients.  This practice has been exposed for the prostate, breast, thyroid,  cervix, uterus and ovaries, where studies have shown that aggressive treatment causes more harm than good—and undoubted for other tissues.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

4)   Cancer (malignant neoplasm) is a broad spectrum of diseases involving improperly regulated cell growth.  For that cell growth to become life-threatening it must be capable of sufficient reproduction so as to disrupt essential bodily processes.  Over 80% of fatal cancers spread to more distant part of the body through the lymphatic or blood systems—some such as cerebral cancer often don’t.  With the exception of blood and lymphatic cancers, they form hard tumors.  “One of the most important factors in classifying a tumor as benign or malignant is its invasive potential” Wiki.  “If a tumor lacks the ability to invade adjacent tissues or spread to distant sites by metastasizing then it is benign, whereas invasive or metastatic tumors are malignant.[1]  For this reason, benign tumors are not classed as cancer”[2] Wiki. The degree of dysplasia (abnormal development of tumor & it’s cells) does not make a tumor cancerous.   To be cancer it must be invasive.  “Not all tumors are cancerous, benign tumors do not invade neighboring tissues and do not metastasize” Wiki.  Unfortunately based on biopsy and microscopic examination of tissue and corporate medicine, many of these benign tumors are called cancerous.  The removal of a few benign tumors can be justified because of the high risk of becoming cancerous; however, in most cases low-risk benign tumors are removed.  Often both are mislabeled “carcinoma”.  Guideline then require excision (or irradiation) and chemotherapy.   A number of quality studies have shown that this aggressive approach does more harm than good.[5] The 800 pound gorilla (pharma), using marketing science, has worked the treatment-guideline committees, and thus compel physicians to treat tumors aggressively—compel though hospital administrators, and the risk of litigation based on failure to follow guidelines.      

5)  “Cancer cells are cells that grow and divide at an unregulated,[6] quickened pace.  Although cancer cells can be quite common in a person they are only malignant when the other cells (particularly natural killer cells, cytotoxic lymphocytes) fail to recognize and/or destroy them.[1]  The failure to recognize cancer cells is caused by the lack of particular co-stimulated molecules that aid in the way antigens react with lymphocytes.[2]  Other factors pay a role including viruses, immune system issues, genetics, environmental pollutants including radiation which promote random mutations of the DNA code, age, and too much of SP2 protein which may turn stem cells into cancer cells” Wiki.  “Genetic and epigenetic[7] changes can occur at many levels, from gain or loss of entire chromosomes, to a mutation affecting a single DNA nucleotide, or to silencing or activating a microRNA that controls expression of 100 to 500 genes.[4][5] 

6)  “Oncogenesis (carcinogenesis): is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells. It is characterized by a progression of changes at the cellular genetic and epigenetic that ultimately reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.  Cell division is a physiological process that occurs in almost all tissues and under many circumstances.  Under normal circumstances, the balance between proliferation and programmed cell death, usually in the form of apoptosis, is maintained by tightly regulating both processes to ensure the integrity of organs and tissues. Only certain mutations and epimutations [genes that regulate the expression of other genes[8]] in DNA that disrupt the orderly process can lead to cancer.  These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations. The majority of potential mutations and epimutations will have no bearing on cancer” Wiki.

7)   “A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression. The resultant protein may be termed an oncoprotein.[10]  Proto-oncogenes code for proteins that help to regulate cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through their protein products. Upon activation, a proto-oncogene (or its product) becomes a tumor-inducing agent, an oncogene.[11]   The proto-oncogene can become an oncogene by a relatively small modification of its original function” Wiki.

8)  Stem cells

Stem cells are undifferentiated biological cells, that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells.  In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts,[1]  and adult stem cells, which are found in various tissues.  In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. Stem cells maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.  Stem cells possess two properties:  self renewal (to maintain through cell division the undifferentiated state) and potency (to give rise to any mature cell type).   For example, the defining test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency.[2]   Stem cells can also be isolated by their possession of a distinctive set of cell surface markers.  Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, dental pulp stem cell, etc.).[28][29]  Induced pluripotent, these are not adult stem cells, but rather adult cells (e.g. epithelial cells) reprogrammed to give rise to pluripotent capabilities. Using genetic reprogramming with protein transcription factors, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue.[53][54][55]   Adult stem cells (somatic stem cells)

9)  A progenitor cell is a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell. The most important difference between stem cells and progenitor cells is that stem cells can replicate indefinitely, whereas progenitor cells can divide only a limited number of times.  The majority of progenitor cells lie dormant or possess little activity in the tissue in which they reside. They exhibit slow growth and their main role is to replace cells lost by normal attrition. In case of tissue injury, damaged or dead cells, progenitor cells can be activated. Growth factors or cytokines are two substances that trigger the progenitors to mobilize toward the damaged tissue. At the same time, they start to differentiate into the target cells. “Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential” Wiki.

10)  A transcription-n factor (sometimes called a sequence-specific DNA-binding factor) is a protein that binds to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to messenger RNA.[1][2]  Transcription factors perform this function alone or with other proteins in a complex, by promoting (as an activator), or blocking (as a repressor) the recruitment of RNA polymerase(the enzyme that performs the transcription of genetic information from DNA to RNA) to specific genes^.[3][4][5] A defining feature of transcription factors is that they contain one or more DNA-binding domains(DBDs), which attach to specific sequences of DNA adjacent to the genes that they regulate.[6][7] Additional proteins such as coactivators, chromatin remodelers, histone acetylases, deacetylases, kinases, and methylases, while also playing crucial roles in gene regulation, lack DNA-binding domains, and, therefore, are not classified as transcription factors.[8]  Many transcription factors are either tumor suppressors or oncogenes, and, thus, mutations or aberrant regulation of them is associated with cancer. Three groups of transcription factors are known to be important in human cancer: (1) the NF-kappaB andAP-1 families, (2) the STAT family and (3) the steroid receptors.[73] 

11)  “Cancerous Stem Cells (CSCs):  The role of stems cells is complex, varied, only partially revealed, and very uncertain.  A number of factors support their role, but just what it is need elucidation.  A major problem consists of identification; viz., differentiating between stoma cells turned cancerous and that of stem cells turned cancerous.  A number of paths involving stem cells as the source of the malignant tumor, or as the driving force behind progenitor cells, or functioning in the healing process to stimulate the growth of benign tumors that emit an appropriate signal for this process.  Whatever way or ways, CSC would explain the variability of cell lines in cancerous tumors and their rapid growth.  A third issue clouding the research is that that only a small percentage of CSCs have the ability of generating a tumor.  “In human acute myeloid leukemia the frequency of these cells is less than 1 in 10,000[9].  Many tumors are very heterogeneous and contain multiple cell types native to the host organ. Heterogeneity is commonly retained by tumor metastases. This implies that the cell that produced them had the capacity to differentiate into multiple cell types. In other words, it possessed multi-differentiative potential, a classical hallmark of stem cells[9]  One important distinction that will often be raised is that the cell of origin for a tumor cannot be demonstrated using the cancer stem cell as a model. This is because cancer stem cells are isolated from end-stage tumors. Therefore, describing CSCs as a cell of origin is often an inaccurate claim, even though a cancer stem cell is capable of initiating new tumor formation.  Tissues with high rates of turnover, such as skin and colon are likely to involve CSCs, since they are more active in such tissues. Like normal stem cells, CSCs can have “the ability to form anchorage-independent spheres.”  Metastatic cancer stem cells:  Metastasis causes 80% of tumor lethality in patients.  Since cancerous tumors are made up of different cells (see illustration above), not every tumor cell has the ability to metastasize. This “potential depends on factors that determine  growth,  angiogenesis [growth of new blood vessels], invasion and other basic processes of tumor cells.  Many tumors are very heterogeneous and contain multiple cell types native to the host organ. Heterogeneity is commonly retained by tumor metastases. This implies that the cell that produced them had the capacity to generate multiple cell types. In other words, it possessed multi-differentiative potential, a classic hallmark of stem cells[9^]” Wiki.  “To date, researchers have reported findings evidence of cancerous stem cells in tumors of breast, brain, skin, colon prostate, pancreas, and liver, among others…. At least some cancers follow the stem cell model… Nor do researchers understand how cancer stem cells originate;, how often they derive from normal stem cells, or whether each tumor has just a few or many of the cells.  Some of the latest study results suggest that a complex mix of both the standard model [one cell line] and the cancer stem cell idea comes closest to elucidating how cancers form.”  Cassandra Willyard, Scientific American Aug, 2011, p. 34)

12) Mechanisms for preventing a cell line from becoming malignant: 

Cancer is the result of a series of mutations that confer on one cell line (from a single cell) a number of properties for which various biological constraints on proliferation have been modified.  In most cases the cell line continues to mutate rapidly and presents when examined presents significant variation in physical form, function, and mutations.  Nevertheless, the tissue from which the cancerous cell line is derived very significant effects prognosis.  Oncogenesis involves typically 7 basic families of changes (leukemia 4) which are governed by many genes.  Typical of most cancer cell lines is an oncogene failing to limit the rate of mutations thus causing an abnormally high rate of mutations.  This increases the probability of a lethal cancer.  Thus in addition to transformation into oncogenes, there are many other noncancerous mutations which affect the cancerous cell line.  Thus most tumors under the microscope show a high degree of abnormal cells (see illustration above).  A second key to malignancy is the involvement of stem cells.  A few stems cells are found in benign tumors, in metastatic, and in invasive cancers.  Their important roles have been an object of intensive research for over 3 decades (see section below).  While the tumor is small, most ultimately fatal cancers develop the ability to metastasize.  Nevertheless, an indolent invasive cancer as it ages can evolving into a fatal cancer.  Early detection has been oversold (a topic developed below with breast cancer used as an example), and the removal benign potentially cancerous tumors has for most tissues minimal effect upon lethality.  Such benign tumors are too often called stage I cancers.  Under 10% of all cancers involve an inherited genetic mutation disabling a gene which promotes the accurate reproduction of the DNA during mitosis, and thereby accelerating the rate of ocogenetic mutation and subsequent cancer.  Those with the inherited defect have a cellular mutation rate of around 10 fold that of the norm.  Another common way the rate of mutation accelerates is through the exposure of tissues to radiation or chemicals which promote mutations.  Tobacco smoke contains such chemicals, and increases the risk of cancer in most tissues; for example pancreatic cancer 250%.  Counting environment including infectious causes, they account for about 50% of all cancers; the rest are a matter of chance including the 10% inherited oncogenes.  There are 15 general types of functional alterations that contribute to turning a single cell line into a life-threatening cancer; however, not all 15 types of are essential. 

13)  Changes: 

1.  Rapid cell division by turning on the chemical signals for mitosis and leaving it on.  VERY COMMON

2.   Angiogenesis: Stimulating the formation of new capillaries to assure adequate oxygen supply for continued growth of the abnormal cells. ESSENTIAL but for leukemia

3.   Limitless replication of one cell line by turning on telomerase, which adds telomeres to make the cell line immortal.  Cell divisions in normal cells are limited to about 50 replications.  ESSENTIAL

4.  Mutations affecting adhesiveness[1], to free the cells from the matrix which holds them in place. VERY COMMON

5.   Invade adjacent tissues:  Organs are enveloped in a membrane (muscle, intestine, lung, etc).  Most cancers fairly early develop the ability to grow through the membrane and invade adjacent tissues.  VERY COMMON

6.  Metastasize:  have microscopic colonies of the tumor relocate in other sites.  This involves mutations affecting the ability to enter capillaries, which thus permits single cells to migrate.  ESSENTIAL for the 80% that are metastatic cancers.

7.  Fool immune system for migration to distant tissues: change markers on the cell wall so cells do not appear as foreign to the immune system, which will destroy those cells.  Which tissues a cancer migrates to is highly dependent upon the markers.  ESSENTIAL for metastatic cancer.

8.  Being able to both enter and leave blood vessels like the way lymphocytes do by secreting a factor which allows them to enter a capillary and then at another site to pass out of the capillary again--a class of compounds known as SRC kinase. ESSENTIAL for metastatic cancer.

9.     Infection including oncovirus can increase risk of cancer.  The WHO estimates that 18% (1/6^th) of cancers have as a causal vector an infection, of which two thirds are viral.

10.  Some cancers have abnormal DNA due to gross changes in the chromosome that consist of translocation, duplication, deletion, or inversion.  This type of abnormality results in the imperfect expression of genes on that chromosome. MODERATELY COMMON

11. Environment causes, exposure to carcinogens and ionizing radiation by causing mutation—for a large population, a causal factor in about 30% of cancer.

12.   Disabling of the gene that check the accuracy of replication of DNA during mitosis, such as p53, BRAC1, BRAC2, etc. Given the number of mutations required for cancer, most cancerous cell lines have this system disable to some extent.  Not all mutations disable the checking process, thus the risk factor depends on the mutation.[2]  When a specific cancer runs in a family, the cause could be an inherited mutation. Of one of these genes.  COMMON

13.  Programmed cell death (apoptosis) is disabled.  Cancers are immortal:  not limited to about 50 cell division.  ESSENTIAL

14.  Heterogeneity results from the high rate of mutation in most cancers, “tumor population exhibit functional, and tumors are formed from cells with various proliferative and differentiate capacities” Wiki, and.[3]  VERY COMMON

15.  Excrete growth factors which enable the cancer to attract stem cells which then help support the growth of the tumor by stimulating the growth of capillaries and other structures needed to support a large tumor.  ESSENTIAL

16.  Natural selection favors the uncontrolled reproduction of the cancerous cell line.[4]

17.  Pluripotent cells created by action of stem cells create from stoma cells.  COMMON

This is a list of the key types of mutations On average, for example, “15 driver mutations" and 60 "passenger" mutations are found in colon cancers.^[2] Mutations in those certain types of genes that play vital roles in cell division, apoptosis (cell death), and mutations and epimutations (see article Genome instability) in DNA repair genes will cause a cell to lose control of its cell proliferation.  This mass alternation of genetic code in malignant tissue is essential to the understanding of why cancer can develop resistance to chemotherapy, and why invasive cancer given a couple of years has a guestimate 20% chance of becoming metastatic.  Natural selection favors the cell line which can resist chemotherapy and spread to distant organs. This raises the question against the backdrop of orderly low rate of mutation stoma cells[5] and while others form tumors that are quite indolent; why is there a modest percentage that are mutating at very high rates?  How is this possible?  One answer is mutations in genes which promote accurate replication of DNA.  Another is the involvement of stem cells.   Stems cells have the ability to convert stoma cells into progenitor cells as a way to promote re-growth are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues.

14.   Complexity—some examples

Chemical stimulation of angiogenesis is performed by various angiogenic proteins, including several growth factors.

Overview  http://en.wikipedia.org/wiki/Angiogenesis (genes involved in the production of new blood vessels): 

This table is illustrative of the number of orchestrated genes that are involved the production of new blood vessels.  Thus an epigenetic switch is responsible for angiogenesis.  That for most tumors this switch is off, then at some point turned is evidence for the role of stem cells.     

17)  WHY MOST CHEMOTHERAPIES DO NOT AFFECT THE LETHALITY OF METASTATIC CANCER: The fundamental problem is how to poison or make dormant long-term, bodily cells that are malignant without also poisoning or making dormant normal bodily cells.  The difficulty arises because cancerous cells are nearly identical to normal cells.  There are a few very effective chemical therapies; most often in a tissue for which major damage is not life threaten, such as testicles.  A unique marker on the cell wall or a unique chemical process in that cell line can permit the development of a chemotherapy that will destroy the metastatic distant tumors without destroying the adjacent tissue.  For the other types of tissue where this is unlikely, pharma relies upon chemicals that are disrupting cell division (reproduction).  Most cancers divide rapidly.   “Thus chemotherapy also harms normal cells that divide rapidly in the bone marrow, digestive tract, and hair follicles, and to a lesser extent slow dividing cells.  This results in the most common side-effects of chemotherapy:  myelo-suppression (decreased production of blood cells, hence also immuno-suppression),  mucositis (inflammation of the lining of the digestive tract), and alopecia (hair loss).  Virtually all chemotherapeutic regimens can cause depression of the immune system, often by paralysing the bone marrow and leading to a decrease of white blood cells, red blood cells, and platelets” Wiki.   Indolent cancers tend to respond much more modestly to chemotherapy.  Causing damage and shut-down are why most chemotherapies are given short term.  Thus for aggressive cancers, the chemotherapy does not eliminate the cancer, but rather produces a short remission and thus prolongs life on average a few months.  

18)  PROBLEMS WITH RESEARCH, JOURNAL PUBLICATIONS, and AND GUIDELINES:  Drug companies push that everyone with cancer should be on chemotherapy at the greatest dose for the longest time, and they do the research to “prove” it (see Marketing Science and Side Effects).   Given that positive bias is the norm (average 32%), and guidelines heavily rely upon junk science, a starting point would be to look for published clinical trials show major advantages to the treated cohort, and remember that side effects are always under-reported, and long-term ones don‘t become statistically significant during the period of most studies and often are not within the study’s protocol.[1]     The standard testing for FDA patent of exclusivity is on terminal metastatic cancer patients, compared to a placebo generally after the standard chemotherapy’s temporary remission has ended and further chemotherapy is contra-indicated.  If there is an average life extension of a couple of months for the treated cohort, the FDA grants a patent of exclusivity.  And though the FDA receives the raw data during the approval process, they do not make it public, nor do they review for accuracy the journal articles published based these submissions.  The 32% bias referred to above was found in a study comparing the raw data submitted to the FDA compared to its journal publication (raw data obtained through the Freedom of Information Act).  Such short-term testing in terminal patients does not reveal most side effects.  Unfortunately the treatment is not tested on those mostly likely to receive it, Stage I-III cancers.  But should they, and how to decide?   Remember the marketing department of pharma is involved in all aspects of their clinical trials and they own the results.  Given this, major benefits must be demonstrated, as it is for the treatment of non-Hodgkin’s lymphoma.  Bias, junk science, junk guidelines, and junk continuing education of doctors are the norm. 

18)  SHOULD CHEMOTHERAPY BE GIVEN TO A STAGE I, II, OR III CANCER?  Except for the most lethal cancers, all too often the chemotherapy is life shortening, because of its side effects upon those who were cured through invasive treatment.  Aggressive treatment of stages I & II shorten life, for breast cancer an average of 2.5—and this is not taught oncologists in continuing education classes.  The journal article that documented this has been lost in the sea of time and pharma sponsored articles.  Besides most  doctors follow treatment guidelines even when skeptical of its application. 

Following radiation or surgery, how beneficial is adjunct chemotherapy, maintenance (long-term) chemotherapy, and neo-adjunct (prior to radiation/surgery)?   A combination of factors is germane:  1) the life expectancy of the patient following excision of the cancer.  2) The health consequences of the chemotherapy both on quality of life and duration.  3) The cost of the chemotherapy and the recommended subsequent drugs. 4) The effectiveness of the chemotherapy upon the indolent excised cancer with in vitro chemo-sensitivity testing.[2]  5) The effectiveness of the chemotherapy upon the malignant tissue found in adjacent lymph nodes.[3]  6) The result of study of a matching or placebo controlled study on the value of adjunct chemotherapy for stage I, II, III cancers.  Most studies are not placebo control, so duration of cancer growth suppression (termed “remission”) is the best substitute information.  Typically it averages the duration of the chemotherapy.  Since the manufacturer most likely funded the study the results are biased over 30%, thus increased survival needs to be adjusted.[4]   An informed choice is not easy, made more difficult by the system of corporate medicine and the vest interest the oncologist has in aggressive treatment.[5]  Serving the patient’s best interest is lost in the corporate system.  Thus for example chemotherapy as an adjunct treatment is pushed on patients without in vitro testing of the drugs.  There are more profits in treating everyone.  Moreover, the costs of treatment upon the healthcare system and the need for a better allocation of resources, this is not figured into the short-term maximization of corporate profits.  

19)  Three special cases for chemotherapy:

1)       Salvage chemotherapy or palliative chemotherapy is given without curative intent, but simply to decrease tumor load and increase life expectancy. For these regimens, a better toxicity profile is generally expected. 

2)       Curative chemotherapy, such as for non-Hodgkin’s lymphoma and testicular cancer.

3)       Some newer anticancer drugs (for example, various monoclonal antibodies) are not indiscriminately cytotoxic, but rather target proteins that are abnormally expressed in cancer cells and that are essential for their growth.  Such treatments are often referred to as targeted therapy (as distinct from classic chemotherapy).   Their lower immediate and obvious side effects, doesn’t entail that there aren’t major long-term ones.  And being able to target the cancer does ipso facto make them curative.  Their use with traditional chemotherapy should be carefully evaluated to remove business bias. 

20)  Deciding what to do

Read Marketing Science then start with the journal literature, oncology textbooks, http://www.wikipedia.org/, https://www.worstpills.org/, http://www.rxlist.com, http://www.mayoclinic.com/, http://www.cochrane.org/, and the http://www.merckmanuals.com/.  Be skeptical of the advice given by the oncologist.  If you can’t find strong evidence of major advantage in all the articles for the chemotherapy than forgo such treatment.  Write out key point which promotes rational analysis rather than a decision by a gut feeling, for which social considerations play a major role.  Treatment choices ought to be solely based on the evidence.    

For the few patients who research the issues.  Learn to recognize the 1) unmerited positive enthusiasm in journal articles.    Bias is often found in the conclusion and abstract sections that does not follow from the results of the study.  Convert results to the number of patients that must be treated for 1 patient to show major life extension, Calculate the average life extension of treated group.  One common fallacy is to conclude that a 2) subgroup will benefit atypically from the chemotherapy and be cured or have a prolonged remission.  This is the result of a statistical fallacy:  by simple chance a few small groups will do better than the average (and a few will do worse).  Without clear proof, don’t assume that slowing down the rate of mitosis (cell division) for a few months will produce a cure for a subgroup of patients.     Look for 3) obvious issues that should be measured but aren’t; all too often they aren’t because the results aren’t in the interest of pharma.[6]  Most studies don’t follow long-term patients or list all causes of death because pharma doesn’t like those results.  It is very convenient that they use terminal patients, since side effects are very poorly reported and long-term ones don’t occur.   4) Pharma actively downplays and hides side effects.  After FDA approval for which pharma must submit the raw data, the subsequent marketing studies are of a significant lower standard since there is no review of the raw data.  Many of these studies are on non-metastatic cancer.  Don’t assume that there is an honest evaluation of side effects.   Most studies do not have a placebo group, which make evaluation of net benefit impossible.

Remember only those who are pharma “friendly” receive funds for research, and pharma’s marketing department is actively involved in all aspects of the project, and they often ghost write the journal articles. 5)  Don’t assume that there isn’t substantial favorable bias  for the reported benefits of chemotherapy.  There are many ways to create positive bias.  Remember that this is the way business is done.

Especially, search for articles by critics published in a major medical journal.  These articles often review the literature and perform a meta-study on the published clinical trials that meet a higher standard.  But they can’t rise above pharma’s hold upon research, favorable bias is the norm.  Sometimes an article will glean out of pharma funded studies the negative results. These critical articles meet a higher standard that marketing studies to be published in a major journal.   Also in general older wisdom is not false, especially when it stands in the way of profits for pharma.  For example in our article of natural estrogen there is listed 8 articles with links showing that estrogen lowers the risk of metastatic  breast cancer deaths, the incidents of breast cancer,  and the relapse.  Also shown is that using certain progestins in HRT the opposite consequences—with 4 links to journal articles.  The 800 pound gorilla has rewritten the book on HRT and breast cancer.   Question treatment guidelines, they are all pharma friendly.  Remember “The pharmaceutical industry is the most lucrative, the most cynical and the least ethical of all the industries.  It is like an octopus with tentacles that has infiltrated all the decision-making bodies:  world health organizations, government agencies, parliaments, high administrations in health and hospitals and the medical profession." Dr. Evan with Debre authors of Guide Des 4,000 Medicaments Sept. 2012.  There they list half the drugs that are useless and dangerous.   Population studies show that cancer, if it is metastatic, chemotherapy and regular checkups[7] make minor differences, not enough to justify chemotherapy or frequent follow-up examinations.   

21)  Atypical cures, Hope’s hypothesis:

Chemotherapy is sold on the hope that a few will undergo long-term remission. Case histories don’t prove that point, only large studies can show that a treatment works just for a few patients.  And that is because it is compared to a population who were given that chemotherapy.    It is Hope’s hypothesis to believe that the benefit for a few terminal patients who live much longer than the average, that it was because of treatment.  For terminal lung cancer if 90% of the placebo cohort survival averages 6 months and 10% live longer than 1 year, and the chemotherapy cohort lived an average of 3 months longer, the logical conclusion is that for each treated patient 3 moths is the benefit.  Thus a patient living 16 months, the logical conclusion is untreated death would come at 13 months..  There is no reason to assume atypical benefits, and if there are, then some had no benefits at all, thus giving the 3-motnh average.   Pharma often teases out of a trial a subgroup that benefits, and argues for approval from FDA on that basis when their drug’s results are the same as the placebo.  This is a statistical fallacy, especially in smaller trials.  Create sufficient subgroups and some will by chance come at better than the matching control group.   Repeat the trial, and different results will be obtained. 

The treatment of cancer has usually been aimed at destroying the primary tumor or at least in stopping its growth. Even though, major improvements in the methods of surgery, radiation and chemotherapy have taken place, often there have not been corresponding improvements in patient survival.[8] Treatment methods that focus on the primary cancer typically fall short in aiding the patient after the cancer has metastasized[1]” Wiki.  How can there be major improvements if it doesn’t result in a corresponding improvement in patient survival?  The razzle-dazzle has improved.  In other words, survival has been determined upon excision and radiation.  If the cancer has already metastasized, it is a leathel.  The chemotherapy won’t change the course, at best delay it.  Given this most chemotherapy are not worth the side effects. 

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^  Non-technical summation

Cancer is distinguished from a benign tumor by its ability to invade neighboring tissue and sometimes spread to distant tissues (metastasize).  Also benign tumors generally have a slower growth rate and are more differentiated (more normal cell features).  This is the first area where business has blurred the distinction between benign and malignant and thus aggressively treats with surgery and chemotherapy benign tumors, by calling them “carcinoma”.  Critics have pointed out the negative consequences from such treatment of benig tumors of the breast prostate, and thyroid cancers, and others by the adjunct chemotherapy following excision.  Benign breast tumors, called “cancer”, when treated shorten life over 2.6 years.  Another line crossed is to treat a stage I & II cancers aggressively where the risk for it being metastatic cancer is low and the chemotherapy offers minor benefit.  With a few exceptions, chemotherapy doesn’t cure cancer, but rather shuts down an essential biological process that affects the rate of cell reproduction, including the cancers’.  This toxicity entails a limit to the chemotherapy.  The average remission for such treatments is 3 months.  Both in the treated and untreated groups there will be people who last years past the average (they have indolent cancers); therefore consider only the average life extension.

Three special cases for chemotherapy:

1)       Salvage chemotherapy or palliative chemotherapy is given without curative intent, but simply to decrease tumor load and increase life expectancy. For these regimens, a better toxicity profile is generally expected. 

2)       Curative chemotherapy, such as for non-Hodgkin’s lymphoma and testicular cancer.  Only a few cell lines of metastatic cancers can be cured. By chemotherapy.  

3)      Some newer anticancer drugs (for example, various monoclonal antibodies) are not indiscriminately cytotoxic, but rather target proteins that are abnormally expressed in cancer cells and that are essential for their growth.  Such treatments are often referred to as targeted therapy (as distinct from classic chemotherapy).   But being able to target the cancer doesn’t make them curative. 

The choice of chemo and target therapy should be carefully evaluated to remove business bias and the oncologist sales pitch.  Oncologists make the spread between what they bill and the discount price.  Remember that excision produces over 95% of the cures for the common types of cancer.