Archive for Cancer

The latest chapter in the seemingly never-ending saga of dichloroacetate as a cancer treatment

The road from an idea to a useful drug is a long one, and in cancer it is often particularly long. One reason is that to be able to tell whether a given treatment is effective against cancer often takes several years at a minimum, in order to determine if patients receiving the new treatment are surviving their disease longer than those who are not. Surrogate endpoints are usually not enough. Tumor shrinkage in response to a drug often does not correlate with prolongation of survival, although the converse (i.e., lack of tumor shrinkage in response to a new drug) does strongly correlate with failure of a treatment to prolong survival. In other words, effects observed on surrogate endpoints are not enough to judge whether a cancer therapy is working or not.

Three years ago, predating the existence of this blog by nearly a year, I became aware of a story that involved many of the issues in bringing a compound from the laboratory to the clinic. The case was unusual in that is is very rare to see the scientific process by which new drugs progress through the stages of cancer research, from concept to testing in cell culture to testing in animals to testing in humans challenged so strongly by patients themselves. The reason that this normally doesn’t occur is that new cancer treatments are almost always the product of either university-conducted research, pharmaceutical company-conducted research, or partnerships between the two. This case was markedly different in that it involved a chemical that was not only easy to synthesize, but cheap and long out of patent. Even more intriguing, it targeted a metabolic abnormality found in many cancer cells, an abnormality first described nearly 80 years before by Otto Warburg in 1928. This latter aspect of the drug gave it every appearance of a “rediscovery” of old wisdom that big pharma had ignored for 80 years, and that only added to its mystique.

The chemical was dichloroacetate (DCA), and three years ago it created a world-wide sensation. Last week, it created a sensation again, as breathless news reports once again overhyped its promise. Since I’ve been following the story since early 2007, I appear to be in as good a position as anyone to tell the story thus far and put the new findings into context. To begin that process, let’s head back to January 2007.

Posted in: Cancer, Clinical Trials, Health Fraud

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The 2008-2009 Report of the President’s Cancer Panel: Mostly good, some bad, and a little ugly

Mark Crislip is always a hard act to follow, particularly when he’s firing on all cylinders, as he was last Friday. Although I can sometimes match him (and, on rare occasions, even surpass him) for amusing snark, this time around I’m going to remain mostly serious because that’s what the subject matter requires. I’ve said it before and I’ll say it again: I’m a bit of an odd bird in the world of cancer in that I’m both a surgeon and I run a lab. Sadly, there just aren’t very many surgeons doing basic and translational research these days, thanks to declining NIH funding, increasing clinical burden necessitated by declining reimbursements, and the increasing complexity of laboratory-based research. That’s not to say that there aren’t some surgeons out there doing excellent laboratory research, but sometimes I feel as though I’m part of an endangered species, particularly years like this when grants are running out and I need to renew my funding or secure new funding, the consequence of failure being the dissolution of my laboratory. It’s a tough world out there in biomedical research.

As tough as biomedical research is in cancer, to my mind far tougher is research trying to tease out the relationship between environmental exposures and cancer risk. If you want complicated, that’s complicated. For one thing, obtaining epidemiological data is incredibly labor- and cost-intensive, and rarely are the data clear cut. There’s always ambiguity, not to mention numerous confounding factors that conspire to exaggerate on the one hand or hide on the other hand correlations between environmental exposures and cancer. As a result, studies are often conflicting, and making sense of the morass of often contradictory studies can tax even the most skillful scientists and epidemiologists. Communicating the science and epidemiology linking environment and cancer to the public is even harder. What the lay person often sees is that one day a study is in the news telling him that X causes cancer and then a month later another study says that X doesn’t cause cancer. Is it any wonder that people are often confused over what is and is not dangerous? Add to this a distinct inability on the part of most people, even highly educated people, to weigh small risks against one another (an inability that has led to phenomena such as the anti-vaccine movement), and the task of trying to decide what is dangerous, what is not, how policy is formulated based on this science, and how to communicate the science and the policy derived from it to the public is truly Herculean.

Posted in: Cancer, Politics and Regulation, Public Health

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The complexity of cancer: A science-based view

Last week I participated in a panel discussion at NECSS with John Snyder, Kimball Atwood, and Steve Novella, who reported on the conference last Monday. What I mentioned to some of the attendees is that I had managed to combine NECSS with a yearly ritual that I seldom miss, namely the yearly meeting of the American Association for Cancer Research (AACR) meeting. There are two huge cancer meetings every year, AACR and the annual meeting of the American Society for Clinical Oncology (ASCO). AACR is the meeting dedicated to basic and translational research; ASCO, as the word “clinical” in its name implies, is devoted mainly to clinical research. Personally, being a translational researcher myself and a surgeon, I tend to prefer the AACR meeting over ASCO, not because ASCO isn’t valuable, but mainly because ASCO tends to be devoted mostly to medical oncology and chemotherapy, which are not what I do as a surgeon. Each meeting draws between 10,000 to 15,000 or even more clinicians and researchers dedicated to the eradication of cancer.

Having taken the Acela train from the NECSS meeting in New York straight to Washington, DC for the AACR meeting, I couldn’t help but think a bit about the juxtaposition of our discussion of the infiltration of quackademic medicine into medical academia with the hard core science being discussed at AACR. One session in particular at AACR highlighted what is one of the most significant differences between science-based medicine and the various forms of “alternative” medicine that we discuss here on SBM on such a regular basis. That difference, quite simply put, is the difference between the simple and the complex. “Alternative” medicine supporters often scoff at practitioners of science-based oncology, asking why we don’t have a “cure for cancer” yet—as if cancer were a single disease!—or why we haven’t made much more progress since President Richard Nixon declared “war on cancer” back in 1971. One part of the answer is that cancer is incredibly complicated. Not only is it not a single disease, but each variety of cancer is in and of itself incredibly complicated as well. To steal from Douglas Adams, cancer is complicated. You just won’t believe how vastly, hugely, mind-bogglingly complicated it is. I mean, you may think algebra is complicated, but that’s just peanuts to cancer.

Posted in: Cancer

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Chemotherapy versus death from cancer

Editor’s Note: Having pivoted immediately (and dizzyingly) from attending NECSS and participating with John Snyder, Kimball Atwood, and Steve Novella in a panel on the infiltration of quackery into academia to heading down to Washington, DC for the AACR meeting, I’ve neglected my SBM duties a bit this week. After a packed day of talks at the AACR meeting followed by spending an evening with a friend whom I haven’t seen for a long time (complete with a trip to The Brickskeller), there’s–gasp!–no new material today. Because for some reason a decision was apparently made to cut our panel very short in order to get the conference back on schedule, we were unable to answer anywhere near as many questions from the audience as we had originally hoped, I was thinking of doing a post trying to answer a couple of the questions asked by audience members who came up to me after the panel terminated prematurely, because one of them was a particularly dicey situation. Maybe later this week. In the meantime, here’s something that I wrote about a year ago, which I tweaked a bit. It’s a very serious topic, but I think it appropriate because it discusses exactly what science-based medicine tries to prevent using evidence and what “alternative medicine” claims it can prevent based on no evidence.

I’ve written before about the Daniel Hauser case, a 13 year old boy who last year refused chemotherapy for his Hodgkin’s lymphoma, necessitating the involvement of the legal system. Cases like that of Daniel Hauser reprsent supreme “teachable” moments that–fortunately–don’t come along that often. The antivaccine movement, for instance, will be with us always (or at least, I fear, as long as I still walk this earth and beyond), but cases like that of Daniel Hauser tend to pop up only once every couple of years or even less. As tragic as they are, they always bring up so many issues that I have a hard time leaving them alone.

This time around, I wanted to touch on an issue that has come up frequently in the discussions of this case, and that’s the issue of chemotherapy. Specifically, it’s the issue of how horrible chemotherapy can be. Again, make no mistake about it, chemotherapy can be rough. Very rough. But what is often forgotten is that it can also be life-saving, particularly in the case of hematologic malignancies, where it is the primary therapy. What is also often forgotten or intentionally ignored by promoters of unscientific medicine is that doctors don’t use chemotherapy because they have some perverted love of “torturing” patients, because they’re in the pockets of big pharma and looking for cash, or because they are too lazy to find another way. They do it because, at least right now, it’s the best therapy science-based medicine has to offer, and in the case of Hodgkin’s lymphoma, for example, it’s life-saving. You can be sure that if a less harsh way were found to achieve the same results, physicians would jump all over it. Indeed, a major focuse of oncology research these days is to find less brutal regimens and improve the quality of life of cancer patients while still giving them the best shot at survival.

Posted in: Cancer, Pharmaceuticals

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Taking Control of Death

Science isn’t the only game in town. Literature can teach us things about the world that science can’t. It can give us vicarious experience and insight into other minds. Two recently published novels illuminate why perfectly rational people might reject the help of scientific medicine and prefer to die a little sooner but to die on their own terms. (more…)

Posted in: Book & movie reviews, Cancer, Medical Ethics

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Biologie Totale and other bastard offspring of Ryke Geerd Hamer’s German New Medicine

A few months ago, I wrote about a particularly nasty form of cancer quackery known as the “German New Medicine” or Die Germanische Neue Medizin in German. As you may recall, the German New Medicine is based on the nonsensical idea that cancer arises from an internal emotional conflict. This conflict then results in what is called the “Dirk Hamer Syndrome” (DHS) or “Dirk Hamer focus” in the brain, named after Dr. Ryke Geerd Hamer‘s son Dirk, who was tragically shot in his sleep by Vittorio Emanuel, the last crown prince of Italy. After a prolonged course requiring multiple operations, Dirk succumbed to his wounds and died. Three years later, Dr. Hamer developed testicular cancer, and, in a perfect case of post hoc ergo propter hoc, Hamer decided that it was the psychic shock of his son’s death that had caused his cancer. Thus was born Die Germanische Neue Medizin, which, according to Hamer, promises a 95% or more chance of curing any cancer, no matter how advanced. Never mind that Hamer apparently underwent a combination of surgery and other “conventional therapies for his testicular cancer. Also never mind that these “Dirk Hamer Focus” to which Hamer pointed on CT scans of the brain appeared, more than anything else, to be artifacts of the imaging process and nothing real.

As I described in my previous post in October, the German New Medicine is a seriously dangerous form of cancer quackery that is not only worthless but in many cases blames the patient for having developed cancer. Evidence can be found in this video, where a proponent of German New Medicine gives as examples of psychic stress a “cancer blow” that comes from menopause, in which loss of estrogen supposedly leads women to feel that they “aren’t the woman they used to be” and that that conflict is manifest in the bone or an athlete’s anger because of an injury that screws up his ability to perform leading to an osteosarcoma of extremity.

Unfortunately, cancer quackery frequently evolves under the selective pressure of competition with other cancer quackeries and based on the unique environments in which various forms of quackery come to land. Since I first wrote my post about Die Germanische Neue Medizin, I’ve been meaning to address one of its offshoots. The particular offshoot that I plan to address is, in essence, the French cousin of Die Germanische Neue Medizin, and it’s called Biologie Totale, or Total Biology (Claude Sabbah’s official site is here, but it’s all in French). I first became aware of Biologie Totale about a year and a half ago through this news story:

Posted in: Cancer, Health Fraud

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Questioning Colonoscopy

Everybody knows that colonoscopy is the best test to screen for colorectal cancer and that colonoscopies save lives. Everybody may be wrong. Colonoscopy is increasingly viewed as the gold standard for colorectal cancer screening, but its reputation is not based on solid evidence. In reality,  it is not yet known for certain whether colonoscopy can help reduce the number of deaths from colorectal cancer. Screening with fecal occult blood testing (FOBT) and flexible sigmoidoscopy are supported by better evidence, but questions remain.  It seems our zeal for screening tests has outstripped the evidence. 

Statistics show that the life-time risk for an adult American to develop colorectal cancer (CRC) is approximately 6%. Colorectal cancer is the second leading cause of cancer deaths in the United States. In the US there are currently 146,970 new cases   and 50,630 deaths each year. Between 1973 and 1995, mortality from CRC declined by 20.5%, and incidence declined by 7.4% in the United States.  

The US Preventive Services Task Force (USPSTF) recommends screening for colorectal cancer (CRC) using fecal occult blood testing, sigmoidoscopy, or colonoscopy, in adults, beginning at age 50 years and continuing until age 75 years.   (more…)

Posted in: Cancer

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Abortion and breast cancer: The manufactroversy that won’t die

Editor’s note: Given the controversial nature of the topic, I think it’s a good time to point out my disclaimer before this post. Not that it’ll prevent any heated arguments or anything…

The Science-Based Medicine blog was started slightly over two years ago, and this is a post I’ve wanted to do since the very beginning. However, since January 2008, each and every time I approached this topic I chickened out. After all, the topic of abortion is such a hot button issue that I seriously questioned whether the grief it would be likely to cause is worth it. (Take the heat generated any time circumcision is discussed here and ramp it up by a factor of 10.) On the other hand, there is so much misinformation out there claiming a link between abortion and the subsequent development of breast cancer when the data simply don’t support such a link, and the name of this blog is Science-Based Medicine. Why should I continue to shy away from a topic just because it’s so religiously charged? More importantly, in my discussion how can I focus attention on the science rather than letting the discussion degenerate into the typical flamefest that any discussion of abortion on the Internet (or anywhere else, for that matter) will almost inevitably degenerate into. Indeed, such discussions have a depressing near-inevitability of validating Godwin’s law not once but many times — usually within mere hours, if not minutes.

My strategy to try to keep the discussion focused on the science will be to stay silent about my own personal opinions regarding abortion and, other than using it to introduce my trepidation about discussing the topic, the religious and moral arguments that fuel the controversy. That’s because the question of whether abortion is the murder of a human being, merely the removal of a lump of tissue, or somewhere in between is a moral issue that, at least as far as I’m concerned, can’t ever be definitively answered by science. That is why it is not my purpose to sway readers towards any specific opinion regarding the morality of abortion. Indeed, I highly doubt that any of our readers care much about my opinions on the matter. On the other hand, I would hope that I’ve built up enough trust over the last two years that our readers will be interested in my analysis of the existing data regarding something another related issue. It is my purpose to try to dispel a myth that is not supported by science, specifically the claim that elective abortion is causes breast cancer or is a very strong risk factor for its subsequent development. That is a claim that can be answered by science and, for the most part, has been answered by science with a fairly high degree of certainty. Despite the science against it, the medical myth that abortion causes breast cancer or vastly increases the risk of it is, like the myth that vaccines cause autism, a manufactroversy that won’t die, mainly because it is largely fueled by religious beliefs that are every bit as immune to science as the ideological beliefs that drive the antivaccine movement.

Posted in: Cancer, Obstetrics & gynecology, Religion, Surgical Procedures

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Radiation from medical imaging and cancer risk

ResearchBlogging.orgScience-based medicine consists of a balancing of risks and benefits for various interventions. This is sometimes a difficult topic for the lay public to understand, and sometimes physicians even forget it. My anecdotal experience suggests that probably surgeons are usually more aware of this basic fact because our interventions generally involve taking sharp objects to people’s bodies and using steel to remove or rearrange parts of people’s anatomy for (hopefully) therapeutic effect. Ditto oncologists, who prescribe highly toxic substances to treat cancer, the idea being that these substances are more toxic to the cancer than they are to the patient. Often they are only marginally more toxic to the cancer than to the patient. However, if there’s one area where even physicians tend to forget that there is potential risk involved, it’s the area of diagnostic tests, in particular radiological diagnostic tests, such as X-rays, fluoroscopy, computed tomography (CT) scans, and the variety of ever more powerful diagnostic studies that have proliferated over since CT scans first entered medical practice in the 1970s. Since then, the crude images that the first CT scans produced have evolved, thanks to technology and ever greater computing power, to breathtaking three dimensional-views of the internal organs. Indeed, just since I finished medical school back in the late 1980s, I’m continually amazed at what these new imaging modalities can accomplish.

The downside of these imaging modalities is that most of them require the use of X-rays to produce their images. True, over the last 15 years or so MRI, which uses very strong magnetic fields and radiofrequency radiation rather than ionizing radiation to produce its images, has become increasingly prevalent. MRI is great because it produces more contrast between different kinds of soft tissue than CT scans do. However, CT tends to be superior for examining calcified organs, such as bone. (The breast surgeon in me notes that breast MRI is pretty much useless for detecting microcalcifications, an important possible indicator for cancer.) Also, MRI scans require a prolonged period of laying still in a very tight tube, which is a problem for patients with any degree of claustrophobia, although “open” MRIs are becoming increasingly available. More importantly for the quality of images, because they require a patient to lie more still than a CT, MRIs tend to be prone to more motion artifacts, which is perhaps why CT is more frequently used to image the abdomen other than large solid organs such as the liver. The point is that, although MRI is becoming more prevalent, CT scans aren’t going away any time soon. They have different strengths and weaknesses as imaging modalities and are therefore best suited for different, albeit overlapping, sets of indications.

Posted in: Cancer, Public Health

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Another wrinkle to the USPSTF mammogram guidelines kerfuffle: What about African-American women?

A while back I wrote about rethinking how we screen for breast cancer using mammography. Basically, the USPSTF, an independent panel of physicians and health experts that makes nonbinding recommendations for the government on various health issues, reevaluated the evidence for routine screening mammography and concluded that for women at normal risk for breast cancer, mammography before age 50 should not be recommended routinely and should be ordered on an individualized basis, and that routine formalized breast self-examination (BSE) should also not be routinely recommended. In addition, for women over 50, it was recommended that they undergo mammography every other year, rather than every year. These recommendations were based on a review of the literature, including newer studies.

To say that these new recommendations caused a firestorm in the breast cancer world is an understatement. The USPSTF was accused of misogyny; opponents of health care reform leapt on them as evidence that President Obama really is preparing “death panels”; and HHS secretary Kathleen Sebelius couldn’t run away from the guidelines fast enough. Meanwhile, a society I belong to (the American Society of Breast Surgeons) issued a press release accusing the USPSTF of sending us back to the “pre-mammography” days when, presumably women only found breast cancer after it had grown to huge size (just like Europe and Canada, I guess, given that the recommendations for screening there closely mirrors those recommended by the USPSTF). Meanwhile, in the most blatant example of protecting its turf I’ve seen in a very long time, the American College of Radiology went full mental jacket with a press release that was as biased as it was insulting. Meanwhile some physicians even likened the recommendations to going back to being like Africa, Southeast Asia and China as far as breast screening goes in that he actually speculated that he’d now become very busy treating advanced, neglected breast cancers. Unfortunately, as Val pointed out, the communication of the USPSTF guidelines to the public was almost a perfect case study in how not to do it. Even though the science was in general sound and the USPSTF recommendations were in essence close to identical to what other industrialized nations do, they were communicated in just such a way as to produce maximum misunderstanding and misuse for political purposes.

Despite all the hysterical and in some cases disingenuous attacks on the new guidelines, there is one criticism that actually resonates with me because I work at a cancer center in a very urban environment with a large population of African-American women. Last week I heard on NPR this story:

Posted in: Cancer, Clinical Trials, Diagnostic tests & procedures, Public Health

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