The War On Cancer

Peter Attia:

… I don’t need to say much about cancer that you don’t already know. You probably know that about one in three Americans will develop cancer in their lifetime, and you probably know that about half of them will succumb to the disease. What you may not know, however, is that we have made virtually no progress in extending survival for patients with metastatic solid organ tumors since the “War on Cancer” was declared over 40 years ago. In other words, when a solid organ tumor (e.g., breast, colon, pancreatic) spreads to distant sites, the likelihood of surviving today is about what it was 40 years ago with rare exceptions. We may extend survival by a few months, but not long-term (i.e., overall) survival.

We screen better today for sure, but subtracting lead-time bias, it’s not clear this extends overall survival. We’ve had success in treating and even curing hematologic cancers (e.g., some forms of leukemia and lymphoma). Certainly testicular cancer patients (especially seminomatous) are better off today and those with GI stromal tumors (GIST), too. Surgical control of cancer is much better today and some local treatments (e.g., specific radiation), too. But for the most part, when a patient has metastatic cancer today, the likelihood of living 10 more years is virtually unchanged from 40 years ago.

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Ketogenic diet slows the progression of cancer

Ketogenic diet slows the progression of cancer:
"Targeting insulin inhibition as a metabolic therapy in advanced cancer: A pilot safety and feasibility dietary trial in 10 patients", Eugene J. Fine et al., Nutrition, 1028-1035,2012

The Heretic has this comment:

It is interesting to note that, contrary to a myth about keto diets being supposedly harmful for kidneys,  not only it did not worsen the markers, but improved kidney filtration of one of the patients!

It is important to keep in mind that stopping of a disease progression is not the same as curing it. Ketogenic diet seems to help but I do not consider it to be a universal cure for cancer (it does however cure t2 diabetes!).

Caveat: It was only 9 patients, and it helped only 5 of them.

Money and Fraud

Too little money for research, and you get fraud as a result. Though too much money seems to be a problem as well:

Texas's $3 billion [per 10 years] cancer research agency is in trouble again: Its peer review system appears to have come apart. The entire eight-member scientific review council of the Cancer Prevention Research Institute of Texas (CPRIT) is stepping down, with most citing concerns about the integrity of the agency's peer review process. Many members of CPRIT's 100-strong roster of peer reviewers have begun to follow.

Looks like the NCI isn't the only one that got a little bit sloppy with billions from the "war on cancer".

Misidentified and contaminated cell lines lead to faulty cancer science

Misidentified and contaminated cell lines lead to faulty cancer science

AURORA, Colo. (June 20, 2012) -AURORA, COLO (June 20, 2012) -- Modern cancer therapies start in cells – researchers compare cancer samples to healthy cells to discover how cancer is genetically different, and use cell lines to test promising new drugs. However, a University of Colorado Cancer Center study published this week in the journal Gynecologic Oncology shows that due to a high rate of contamination, misidentification and redundancy in widely available cell lines, researchers may be drawing faulty conclusions.

"I've seen faculty and graduate students leave my lab in tears when we discovered the cells on the label weren't the cells they were actually experimenting on," says Christopher Korch, PhD, investigator at the CU Cancer Center and director of the center's DNA Sequencing and Analysis Service, the paper's co-first author. "When you get a cell line, you have to look that gift horse in the mouth – there's up to a 40 percent chance it's a Trojan horse, not what it says it is."

For example, the cell line known as HES has been widely used as a "normal" model of endometrial cells since its development in 1989. There are literally hundreds of papers that, for example, look for differences between endometrial cancer cells and these supposedly normal HES endometrial cells. Unfortunately, HES is not, in fact, an endometrial cell line. It's another cell line known as HeLa which was first derived from cervical cancer.
…

"I see two people working with different cultures in the same hood, or using the same growth medium for the same cultures with the same pipette," Korch says. "And especially HeLa is superwoman – it can fly." HeLa cells can travel in aerosols and once they land where they shouldn't, they're so adaptive and aggressive that they tend to out compete other cell lines wherever they land – contamination leads to a quick HeLa takeover and perhaps a vial labeled HES when in fact it's HeLa.

…

40 Years War On Cancer

Has the NCI achieved much with its billions? I mean, besides faking XMRV research?

The Psychosomatic Modell of Cancer: Bullshit or Bullshit?

The paper makes the case that sexual frustration can result in genetic mutation but fails to provide any evidence to support the claim. The paper is a perfect case study of how not to do science.

That leaves only one question: Should adherents of psychosomatic model of illness be shot before or after they graduate?

Could Milk and Dairy cause Cancer?

Here is an heretic idea: Could the consumption of (pasteurized) cow milk and dairy cause some forms of cancer? Specifically: breast cancer?

Well, this is pure speculation – yet an epidemiologist worth his/her salary should have no problem confirming or refuting this idea.

I just leave this idea here, so I can say in 30 years: "Told you so."

"Folate Status Linked to [Prostate] Cancer Cell Proliferation"

Folate Status Linked to Cancer Cell Proliferation

While folate is essential for one-carbon metabolism and biological methylation reactions, some evidence suggests that folic acid supplementation may increase cancer risk. In a cross-sectional analysis, Tomaszewski and colleagues investigated serum and tissue folate in prostate cancer patients and cancer-free controls. Interestingly, serum and tissue folate levels were higher in men with prostate cancer versus levels of cancer-free controls. Unlike the controls, the cancer patients’ serum folate positively correlated with prostate tissue folate content. In patients with Gleason 7 disease, those with the highest serum folate also had the highest level of proliferation markers in cancer tissue. These findings suggest a positive relationship between folate status and the proliferation of prostate tumors, although it is unclear how dietary and supplemental folic acid and folate metabolism are involved.

Remember, correlation is not causation.

Scientific process: Useless treatments found to be useless (2)

Last month [August 2009], a major study whose results had been anticipated by the alt-med community, as well as those of us who consider it to be highly unethical pseudoscience, were reported. However, they were reported without fanfare, without press releases, without any sort of publicity whatsoever. Only a handful of bloggers who have paid attention to the issue (myself included) even noticed, and even I wouldn't have noticed if someone hadn't forwarded the journal article to me and asked me what I thought of it. So under the radar is this important paper that not a single alt-med website that I've been able to find has commented on it, even nearly four weeks after its release.

I wonder why.

I suspect that you'll soon understand why. The study is of an "alternative" medical therapy for pancreatic cancer, one of the most lethal, if not the most lethal, cancer there is. There are several reasons for the lethality of pancreatic cancer. …

Because the outlook for pancreatic cancer, particularly unresectable pancreatic cancer is so grim (the median survival has barely budged from less than six months for decades. Median survival for untreated metastatic pancreatic cancer is on the order of 3-4 months, although gemcitabine chemotherapy regimens combined with radiation) can result in median survivals of six months or more. For locally advanced pancreatic cancer that cannot be resected but has not metastasized, the median survival is on the order of 6-12 months depending on the study. Thus, we can rightly say that pancreatic cancer is one of those cancers for which science-based medicine has frustratingly little to offer that can cure it. That's not to say that science-based medicine doesn't have a lot to offer for palliation, but no one wants just palliation. We all want to live to a ripe old age, not just have our pain and nausea palliated for a few months before cancer claims us. Even scarier is that pancreatic cancer usually produces few or no symptoms until it is fairly advanced. Usual symptoms include vague upper abdominal discomfort, loss of appetite, and post-prandial nausea from intermittent gastric outlet obstruction, you know, the sorts of symptoms that nearly of us have from time to time and that primary care doctors see in their practice every day. By the time a pancreatic cancer causes severe pain or obstructs the bile duct leading to jaunice, it's usually unresectable or metastatic. (Often the reason it causes such severe pain is because it invades a plexus of nerves just posterior to the pancreas.)

It is the very deadliness of pancreatic cancer and the lack of effective life-saving or life-prolonging treatments for it that make pancreatic cancer a ripe condition for quackery. Rising above most other quackeries to attract a lot of attention about a decade ago is a quackery known as the Gonzalez protocol. It is described on Dr. Nicholas Gonzalez's website as involving dietary changes, supplements, the replenishment of pancreatic proteolytic enzymes, and "detoxification," including coffee enemas. It is not an easy therapy to undergo.

For example, Dr. Gonzalez states:

Overall, cancer patients will consume 130-175 capsules a day, including nutrients as well as enzymes. Non-cancer patients might consume in the range of 80-100 capsules a day, the exact number depending on their health status and medical problems.

I know of no science-based cancer protocol that requires a patient to consume 150 pills a day. There are also the dietary alterations that can be quite hard to follow, as well as the frequent coffee enemas. All in all, the Gonzalez protocol is an arduous regimen for a debilitated pancreatic cancer patient to follow. Still, for some reason, it gained some popularity in the "complementary and alternative medicine" (CAM) community, so much so that, based on poorly designed case series of eleven patients, Dr. Gonzalez managed to get a clinical trial funded by the NIH to study his method versus standard chemotherapy, a sordid story that Dr. Atwood has chronicled in detail in a long series of blog posts. That trial ended in 2005.

So why is it 2009 before we have the results of this trial, which show that the Gonzalez protocol is worse than useless? As Gollum would say, "It makes us wonder, yes it does." …

Sadly, the "scientific" rationale behind the Gonzalez protocol, with its megadoses of supplements and pancreatic enzymes plus "detoxification" by coffee enemas, is a perfect example of what Harriet Hall terms "Tooth Fairy science." The Gonzalez treatment is basically a modification of a protocol known as the Kelley Treatment, which in turn was very similar to the Gerson protocol. In any case, it's all an example of how alties have this conception that disease is caused by "toxins" and "contamination" that must somehow be purged in a religious ritual of colon cleansing. I've joked about this before as being an example of when mere regularity is not enough and mocking late night infomercials about colon cleanses, but, totally serious, Chabot writes in the introduction to this study:

The Scottish embryologist John Beard first proposed pancreatic proteolytic enzyme treatment in 1906 and soon after published a monograph, entitled The Enzyme Therapy of Cancer. In 1981, Nicholas Gonzalez began to evaluate the use of proteolytic enzyme therapy. Twelve years later, in 1993, he was invited to present a series of cases at the National Cancer Institute (NCI), which led him to undertake a case series of alternative medical therapy that included proteolytic enzymes, diet, nutritional supplements, and detoxification procedures. Among 11 patients with inoperable, biopsy-proven, stages II to IV pancreatic adenocarcinoma, he reported 81% survival at 1 year and 45% at 2 years. Four of the 11 patients survived for 3 years.

This is the very example of an implausible hypothesis. True, it's not as implausible as homeopathy (few hypotheses are), but it goes against everything we know about cancer in general and pancreatic cancer in particular. There is no evidence that pancreatic enzyme deficiency has anything to do with pancreatic cancer, for example. …

Here's the problem. These "toxins" are never identified, nor is there any evidence that the Gonzalez regimen actually removes them. It's not that environmental exposures don't have an effect on cancer susceptibility. Smoking can cause lung cancer and, ironically enough, increase the risk of pancreatic cancer as well. "Detoxification" quackery like the Gonzalez protocol takes science and turns it into Tooth Fairy science by giving near magical characteristics to these "toxins." In any case, cancer is primarily a genetic disease. Even heavy smokers who smoke for 50 years "only" have about a 25% lifetime risk of developing lung cancer, which means more smokers don't get lung cancer than do. In any case, think about it: Let's say there is this host of unnamed, undefined "toxins" that give you pancreatic cancer. Remember, the toxins from tobacco smoke that predispose to lung cancer are largely known and quantifiable. Why would one think that coffee enemas would remove those "toxins"? Certainly there is no scientific basis to think that the special diet, the dozens of capsules of supplements and pancreatic enzymes, or the other aspects of the regimen would "detoxify" anything. Basically, the Gonzalez protocol appears to derive from a prescientific notion of disease that is almost religious in its nature blaming "contamination" as the cause of all disease and that one must "purge oneself" of this "contamination" to cure the disease.

But, say Gonzalez supporters, what about the case series of 11 patients with stage II to IV pancreatic cancer from the 1990s reporting 81% survival at 1 year and 45% at 2 years, with 4 of the 11 patients surviving for 3 years? As Dr. Kimball Atwood pointed out, this was a nonconsecutive case series, a so-called "best case" series. Basically, it's a cherry-picked series, and I've criticized "best case" series before because they in essence intentionally look at outliers for whom the therapy may or may not have made a difference. …

So what was this trial? These were the objectives:

1. Compare the survival of patients with stage II, III, or IV adenocarcinoma of the pancreas treated with gemcitabine versus intensive proteolytic enzyme therapy and adjunctive dietary and nutritional support.
2. Compare the quality of life in patients treated with these regimens.

…
One serious problem with a nonrandomized design like this is the likelihood of selection bias. In this case, it would be "self-selection" bias in that investigators would have to worry whether patients who were either worse off or better off might opt preferentially for one arm of the trial over the other. I will address that point after we look at the results, which are quite striking:

In words:

At enrollment, the treatment groups had no statistically significant differences in patient characteristics, pathology, quality of life, or clinically meaningful laboratory values. … At 1 year, 56% of chemotherapy-group patients were alive, and 16% of enzyme-therapy patients were alive. The quality of life ratings were better in the chemotherapy group than in the enzyme-treated group (P <.01).

In all my years in medicine, surgery, and surgical oncology, I have never seen a study with such a striking difference in outcome between the two groups. No wonder the Office for Human Research Protections (OHRP) issued a determination letter stating that it was appropriate to terminate the study before the full 72 patients were enrolled due to the study having reached its "predetermined stopping point." These days, clinical trials are designed with periodic assessment of results and predetermined stopping points. These stopping points are invoked to shut down the trial in the event that one group is doing so significantly better than the other that enrolling the remaining patients could not possibly change the result. The purpose of such a stopping point is to protect clinical trial subjects from being enrolled in a study that no longer has clinical equipoise; i.e., the groups can no longer be predicted to have roughly equivalent outcomes based on what we know. Usually, it's the experimental group that does better than the control group. At least that's the intent. Sometimes, however, as in the case of the Gonzalez protocol, it's the experimental group that does much worse, so much so that the study has to be halted before reaching its full accrual.

But it's even worse than that.

Read it all!

The moral of the story: Even if evidence based science hasn't much to offer for your illness, you can be much worse off by trusting untested treatments.

… Given the striking difference between the two groups and the fact that the Gonzalez group did more poorly than historical controls, from this study we can confidently say that the Gonzalez protocol is almost certainly no better than no treatment.

In fact, it's probably worse. Go back to Dr. Atwood's post on this issue and consider the story of an unfortunate 40 year old man who enrolled in the trial and chose the Gonzalez protocol arm. This man was told to have his fillings removed and afterward tried as hard as he could to continue the regimen to the letter and suffered horribly as he did. At one point he was even told that increasing pain might be an indication that his tumors were "dissolving."

Oh, this reminds me of the "die off" myths with regards to antiviral and antibiotic drug (ab)use.

Finally, the most disturbing issue that this trial raises is the question of why it took nearly four years after the trial was stopped to publish the results. Dr. Atwood has speculated why this might be the case, namely to cover up the results that were unfavorable to Gonzalez. There is now no doubt that this trial was completely unethical right from the very beginning, but that lack of ethics was compounded by not having the results reported right away. In this, after having had a few days to think about it, I am going to have to strongly disagree with Dr. Atwood when he asserted, "A compelling argument can even be made that the JCO should not have published the report--as paradoxical as that sounds."
…

I can understand where he's coming from. This study clearly violates the Helsinki Declaration, to which JCO requires the clinical trials that it publishes to adhere. However, I find an it equally, if not more, compelling to take the view that the patients who suffered in the Gonzalez group will have suffered in vain if the results of this trial were not published. I also tend to take the view that shining a light on such a trial, in the form of publication, is a good thing in this particular case because it eliminates the uncertainty over whether the results were as bad as we know them to be. Let's put it this way: If the results were not published in a peer-reviewed journal but rather announced or mentioned in a report, they would seem less credible to shruggies. It is these people who need these bad results rubbed in their noses, the better to let the stench waft into their nasal passages and make them retch. When they ask, "What's the harm," we can tell them in no uncertain terms what the harm is. The same would apply if they were simply announced on ClinicalTrials.gov or mentioned in a report. It's just not the same as a peer-reviewed publication in one of the highest impact oncology journals there is. This is truly a case where the greater good can be served by disseminating this data far and wide as soon as possible by the most scientifically credible means necessary.

"Breast cancer screening can no longer be justified"

Breast cancer screening can no longer be justified, because the harm to many women from needless diagnosis and damaging treatment outweighs the small number of lives saved, according to a book that accuses many in the scientific establishment of misconduct in their efforts to bury the evidence of critics and keep mammography alive.

I doubt very much that this will settle the debate, but we'll see. (via)

Does thinking make it so?

Does thinking make it so?

Causes of Death Among Patients With Chronic Fatigue Syndrome

Causes of Death Among Patients With Chronic Fatigue Syndrome
Leonard A Jason et al 2006

Chronic fatigue syndrome (CFS) is a debilitating illness affecting thousands of individuals. At the present time, there are few studies that have investigated causes of death for those with this syndrome. The authors analyzed a memorial list tabulated by the National CFIDS Foundation of 166 deceased individuals who had had CFS. There were approximately three times more women than men on the list. The three most prevalent causes of death were heart failure, suicide, and cancer, which accounted for 59.6% of all deaths. The mean age of those who died from cancer and suicide was 47.8 and 39.3 years, respectively, which is considerably younger than those who died from cancer and suicide in the general population.

Psychosomatic Model fails in Cancer

A recent study of cancer patients in Finland and Sweden found no association between survival rates and whether people were positive or negative in their outlook.

The study, in the American Journal Of Epidemiology, looked at 4,600 people with cancer over 30 years, and found that whether they were extrovert or neurotic, their attitude to life had no relationship with how long they survived their illness.

I will not deny that getting (or maintaining) a positive outlook despite having cancer can improve the quality of the life you can have until your body gives in to cancer – but thinking positive will not delay death.

When Science is marketed...

To achieve the 98 percent efficacy claim, Merck excluded from analysis anyone who “violated” the study protocol. In other words, all real-world problems that arose were excluded from analysis. Problems like girls who refused to take a second or third shot after they became sick and (correctly or incorrectly) blamed the vaccine. Or doctors who incorrectly gave the vaccine to someone who shouldn’t have received it. While it’s worth knowing how effective the vaccine is when it’s used exactly as it should be, for a public-health decision, it’s not as relevant as its real-world effectiveness.

To Merck’s credit, they reported that when all women in the study were analyzed, the vaccine’s efficacy dropped to 44 percent. Still, 44 percent might be considered a smashing success when you’re talking about saving lives. Except for one thing: the numbers get worse. The 44 percent benefit included only those women with the two specific cancer-causing HPV strains found in the vaccine. But when the researchers looked at negative cervical changes from any causes, they found that changes occurred in unvaccinated women at a rate of 1.5 events per 100 person-years, while vaccinated women had 1.3 events—dropping the benefit to 17 percent.

Moreover, most of the cervical changes tracked by the researchers weren’t even indicative of cervical cancer in the first place. Most were innocent cellular abnormalities that either disappear entirely on their own, or never progress to cancer. In fact, when they looked more closely at advanced cervical changes most likely to progress to cancer versus more innocent changes that go away spontaneously, it was the innocent changes that accounted for the decline.

Whether Gardasil will reduce cervical cancer deaths in real-world conditions has simply never been answered. It might—but that would take a long-term study, and one that should be done before it’s widely promoted.

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So how did the HPV vaccine become a multi-billion-dollar winner for Merck? Well you might not be surprised to hear that the company happily lavished money on doctors, professional societies, and over 100 legislators. Of course, there is no tie between the recipients of this largesse and their promotion of the vaccine, say beneficiaries like presidential candidate and current Texas governor Rick Perry. In 2007, Perry signed an executive decree mandating that all girls in Texas receive the vaccine. The $28,500 Perry received was minor compared to his other connection to Merck: Perry’s chief of staff, Mike Toomey, became a lobbyist for Merck, championing the HPV vaccine. Once in that position, announced his plans to raise over $50 million for Perry’s presidential campaign.

Low carbohydrate diets slow tumor growth and prevent cancer initiation

Low carbohydrate diets slow tumor growth and prevent cancer initiation

(via)