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Chemotalk NewsletterChemotalk Newsletter, Vol. 80: December 1, 2014 End of the year, but the fight continues. STUDY POINTS TO OVERDIAGNOSIS OF THYROID CANCER BY Gina Kolata To the shock of many cancer experts, the most common cancer in South Korea is not lung or breast or colon or prostate. It is now THYROID CANCER, whose incidence has increased fifteenfold in the past two decades. "A tsunami of thyroid cancer", as one researcher puts it. Similar upward trends for thyroid cancer are found in the United States and Europe, although not to the same degree. The thyroid cancer rate in the United States has more than doubled since 1994. Cancer experts agree that the reason for the situation in South Korea and elsewhere is not a real increase in the disease. Instead, it is down to screening, which is finding tiny and harmless tumors that are better left undisturbed, but that are being treated aggressively. South Koreans embraced screening about 15 years ago when the government started a national program for a variety of cancers -- BREAST, CERVIX, COLON, STOMACH and LIVER. Doctors and hospitals often included ultrasound scans for thyroid cancer for an additional fee of $30 to $50. In the United States and Europe, where there are no formal widespread screening programs for thyroid cancer scans for other conditions, like ultrasound exams of the carotid artery in the neck or CT scans of the chest, are finding tiny thyroid tumors Although more and more small thyroid cancers are being found, however, the death rate has remained rock steady, and low. If early detection were saving lives, death rates should have come down. The pattern -- more cancers detected and treated but no change in the death rate -- tells researchers that many of the cancers they are finding and treating were not dangerous. It is a phenomenon that researchers call overdiagnosis, finding cancers that did not need treatment because they were growing very slowly or not at all. Left alone, they would probably never cause problems. Overdiagnosis is difficult to combat. Pathologists cannot tell which small tumors are dangerous, and most people hear the word "cancer" and do not want to take a chance. They want the cancer gone. But cancer experts said the situation in South Korea should be a message to the rest of the world about the serious consequences that large-scale screening or healthy people can have. "It's a warning to us in the U.S. that we need to be very careful in our advocacy of screening" said Dr. Otis W Brawley, chief medical officer at the American Cancer Society. "We need to be very specific about where we have good data that it saves lives." Colon cancer screening wins Dr. Brawley's unqualified endorsement. Breast cancer screening saves lives, he said, and he advocates doing it, but he said it could also result in overdiagnosis. Even lung cancer screening can be susceptible to overdiagosis with as many as 18% of patients treated when they did not need to be, Dr. Brawley said. The soaring increase in thyroid cancers in South Korea is documented in a paper published in the New England Journal of Medicine. The authors report not only that the number of diagnosis escalated as screening because popular, but also that the newly detected cancers were almost all very tiny ones. These tiny cancers called papillary thyroid cancers, are the most common kind and are the sort typically found with screening. They are known to be the least aggressive. The epidemic was not caused by an environmental toxin or infectious agent, said Dr. H. Gilbert Welch of Dartmouth, an author of the paper. "An epidemic of real disease would be expected to produce a dramatic rise in the number of deaths from disease," he said. "Instead we see an epidemic of diagnosis, a dramatic rise in diagnosis and no change in death." Cancer experts stress that some thyroid cancers are deadly -- usually they are the larger ones. And they say, if a person notices symptoms like a lump on the neck or hoarseness, they should not be ignored. "But there is a real difference between not ignoring something obvious and telling the population to try really hard to find something wrong," Dr. Welch said. Thyroid cancer tends to be particularly indolent. On autopsy, as many as a third of people have tiny thyroid cancers that went undetected in their lifetime. Once a cancer is found, though, treatment is onerous and involves removing the thyroid. Patients must then take thyroid hormones for the rest of their lives. For some, Dr. Brawley said, the replacement hormones are not completely effective, and they end up with chronically low thyroid hormone levels, feeling depressed and sluggish as a result. In a small percentage of those having thyroid surgery, surgeons accidentally damage the nearby vocal chords -- that happened to the 2% of South Korean patients who ended up with vocal cord paralysis. Or they damage the parathyroid glands, tiny yellow glands just behind the thyroid that control calcium levels in the body. When the parathyroids are damaged, as happened in 11% of patients in South Korea, patients get hypoparathyroidism, a difficult condition to treat. In South Korea, some doctors, including Dr. Hyeong Sik Ahn of the College of Medicine at Korea University in Seoul, the first author of the new paper, have called the thyroid cancer screenings to be banned. But their calls were mostly ignored. Dr. Ahn explained in an email. "Most thyroid doctors, especially surgeons, deny or minimize harms." Thyroid experts in the United States are calling the restraint in diagnosis and treating tiny tumors. A few places, like Memorial Sloan-Kettering Cancer Center in Manhattan, offer patients with small tumors the option of simply waiting and having regular scans to see if the tumor grows. But few patients have joined the program. "Once we have made a diagnosis of cancer it is difficult to say 'Don't do anything,'" said Dr. Ashok R. Shaha, a thyroid cancer surgeon at Memorial Sloan-Kettering, who is concerned about the zeal to diagnosis and treat tiny tumors. Doctors as well as patients can be wary, he said, "In the U.S. we have a fear that if we miss a cancer the patient will sue." Dr. R. Michael Tuttle, who runs the wait-and-see program at Memorial Sloan-Kettering, said the best way to encourage observation of very low-risk thyroid cancer instead of aggressive treatment was to "stop the diagnosis." That means, he said, "decrease screening and decrease F.N.A.," meaning fine needle aspiration, which is used to examine thyroid lumps noticed coincidentally. And the lesson from South Korea should be heeded, said Dr. Barnett S. Kramer, director of the division of cancer prevention at the National Cancer Institute. "The message for so long is that early detection is always good for you," he said. But this stark tale of screening gone wrong "should acutely raise awareness of the consequences of acting on the intuition that all screening must be of benefit and all diagnoses at an early stage are of benefit." * * *
COLORECTAL CANCER IN THE YOUNG Incidences of COLORECTAL CANCER have been decreasing by about 1% a year since the mid-1980s, but incidences among people younger than 50 -- the recommended screening age -- have been increasing sharply, and these younger patients are more likely to present with advanced disease. The study, published in JAMA SURGERY, used a national database of 400,000 patients with colon or rectal cancer. Incidences decreased by about 1% a year over all but rose about people aged 20 to 34, with the largest increase -- 1.8% a year -- in disease that had progressed to other organs. Incidence rates today, per 100,000 people, are three for ages 20 to 34; 17 for ages 35 to 49; and 300 for people over 50. But by 2030, the researchers estimate one in 10 colon cancers and one in four rectal cancers will be in people under 50, and rates among those over 50 will be 175 per 100,000. The study draws no conclusions about whether screening should start younger. "There are always risks and unintended consequences of screening tests," said the senior author, Dr. George I Chang of the University of Texas. * * *
Scary stuff below: PRIVATE ONCOLOGISTS BEING FORCED OUT, LEAVING PATIENTS TO FACE HIGHER BILLS* By Gina Kolata When Dr. Jeffrey Ward, a CANCER specialist, and his partners sold their private practice to the Swedish Medical Center in Seattle, the hospital built them a new office suite 50 yards from the old place. The practice was bigger, but Dr. ward saw th same patients and provided CHEMOTHERAPY just like before. On the surface, nothing had changed but the setting. But there was one big difference. Treatments suddenly cost more, with higher bills for insurers. Because of quirks in the payment system, patients and their insurers pay hospitals and their doctors about twice what they pay independent oncologists for administering cancer treatments. There also was a hidden difference -- the money made from the drugs themselves. Cancer patients and their insurers buy chemotherapy drugs from their medical providers. Swedish Medical Cancer, like many others, participates in a federal program that lets it purchase these drugs for about half of what private practice doctors pay, greatly increasing profits. Oncologists like Dr. Ward say the reason they are being forced to sell or close their practices is because insurers have severely reduced payments to them and because the drugs they buy and sell to patients are now so expensive. Payments had gotten so low, Dr. Ward said, that the only way he and his partners could have stayed independent was to work for free. When he sold his practice, Dr. Ward said, "The hospital was a refuge, not a culprit." When a doctor is affiliated with a hospital, though, patients end of paying, out of pocket, an average $134 more per does for the most commonly used cancer drugs, according to a report by IMS Health, a health care information company. And, the report notes, many cancer patients receive multiple drugs. "Say there was a Costco that had very good things at reasonable prices," said Dr. Barry Brooks, a Dallas oncologist in private practice. "Then a Neiman Marcus comes in and changes the sign on the door and starts billing twice as much for the same things." That, he saidm is what is happening in oncology. The situation is part of the unusual world of cancer medicine, where payment systems are unique and drive not just the price of care but what drugs patients may get and where they are treated. It raises questions about whether independent doctors, squeezed by finances, might be swayed to use drugs that give them greater profits or treat poorer patients differently than those who are better insured. But one thing is clear: The private practice oncologist is becoming a vanishing breed, driven away by the changing economics of cancer medicine. Practices are making the move across the nation. Reporting on the nation's 1,447 independent oncology practices, the Community Oncology Alliance, an advocacy grouip for independent practices, said that since 2008, 544 were purchased by or entered contractual relationships with hospitals, another 313 closed and 395 reported they were in tough financial straits. In western Washington, just one independent oncology group is left. Christian Downs, executive director of the Association of Community Cancer Centers, said that although there are no good data yet, he expected the Affordable Care Act was accelerating the trend. Many people bought inadequate insurance for the expensive cancer care they require. Community doctors have to buy the drugs ahead of time, placing a burden on them when patiets cannot pay. The act also requires documentation of efficiencies in medical care which can be expensive for doctors in private practice to provide. And it encourages the consolidation of medical practices. The American Hospital Association cites advantages for patients being treated by hospital doctors. "The hassle factor is reduced," said Erik Rasmussen, the association's vice president of legislative affairs. Patients can have scans, like CT and M.R.I., use a pharmacy and get lab tests all in one place instead of going from faculty to faculty, he said. And he added, there is a reason hospitals get higher fees for their services -- it compensates them for staying open 24 hours and caring for uninsured and underinsured patients. For doctors in private practice, providing chemotherapy to uninsured and Medicaid patients is a money loser. As a result, many, including Dr. Ward before he sold his practice, end up sending those patients to nearby hospitals for chemotherapy while keeping them as patients for office visits. "We hate doing it, I can't tell you how much we hate doing it," said Dr. Brooks, the Texas oncologist. "But I tell them, 'It will cost me $200 to give you this medicine in my office, so I am going to ask you to go to the hospital as an outpatient for infusions.'" Dr. Peter Eisenberg, is private practice in Marin County in Northern California, said: "The disgrace is that we have to treat people differently depending on how much money they've got. That we do diminishes me." Hospitals may be less personal and less efficient, said Dr. Richard Schilsky, chief medical officer at the American Society of Clinical Oncology. Many private practice oncology office, he said, "Run on time, they are efficient, you get in you get out, as opposed to academic medical centers where they may be an hour and a half wait." Dr. Ward and others in private practice said they tried for years to make a go of it but were finally defeated by what he described as "a series of cuts in oncology reimbursement under the guise of reform to which private practice is most vulnerable." Lower reimbursements have two effects. One is on overhead. Unlike other doctors, oncologists stock their own drugs, maintaining a sort of mini-pharmacy. If a patient gets too sick to receive a drug or dies, the doctor takes the loss. That used to be acceptable because insurers paid doctors at least twice the wholesale price of drugs. Now doctors are reimbursed for the average cost of the drug plus 4.3%, there are more and more drugs to stock, and drugs cost more. "The overhead is enormous," Dr. Schilsky said. "This is one of the reasons why many oncologists are becoming hospital-based." The second -- and bigger -- effect is less profit from selling drugs to patients. For years, the chemotherapy drugs provided a comfortable income. Those days are gone, doctors say. The finances are very different in hospitals, with their higher reimbursement rates for administering rugs, discounts for buying large quantities, and a special federal program that about 30% of hospitals qualify for. The program, to compensate research hospitals and hospitals serving poor people, lets hospitals buy chemotherapy drugs for all outpatients at about 50% discount. In addition, Dr. Schilskiy notes, cancer patients at hospitals use other services, like radiation therapy, imaging and surgery. "A cancer patient is going to generate a lot of revenue for a hospital," Dr. Schilsky said. Health care economists say they have little data on how the costs and profits from selling chemotherapy drugs are affecting patient care. Doctors are constantly reminded, though, of how much they can make if they guy more of a company's drug. Celgene, for example, in a recent email about its drug Abraxane, told one doctor who had bought 50 vials that he could get a rebate of $647.51 by buying 68 vials. If he bought 175 vials he'd get $1,831.93. This hidden profit possibility troubles Dr. Peter B. Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center. "When you walk into a doctor's office you don't know that in most cancer scenarios there are a range of therapeutic choices," Dr. Bach said. "Unless the doctor presents options, you assume there aren't any." While individual oncologists deny choosing treatments that provide them with the greatest profit, Dr. Kanti Rai, a cancer specialist at North Shore-Long Island Jewish Cancer Center, said it would be foolish to believe financial considerations never influence doctors' choices of drugs. "Sometimes hidden in such choices -- and many times not so hidden -- are considerations of what also might be financially more profitable," he said. * This article explains why my oncologist's practice was sold. It also compounds my fears. * * *
RESEARCHERS IDENTIFY NEW WAYS TO DRAIN CANCER'S 'FUEL TANK' Scientists at the University of Manchester have discovered a potential weakness in CANCER'S ability to return or become resistant to treatment, by targeting the 'fuel' part of stem cells which allows tumours to grow. Floating mammospheres containing breast cancer stem cells Cancer stem cells are particularly difficult to eradicate and are at the heart of why it is so hard to more effectively treat cancer patients, as the post-treatment survival of cancer stem cells drives tumour recurrence, the systemic spread of cancer and, ultimately, treatment failure. The researchers, based at the University's Institute of Cancer Sciences and the Cancer Research UK Manchester Institute both part of the Manchester Cancer Research Centre - investigated the role of mitochondria which produce and release energy within cells. In this context, the new Manchester Centre for Cellular Metabolism (MCCM) also played a critical role in these studies. By observing cancer stem cells in a lab setting, they discovered that mitochondria are especially important for the proliferative expansion and survival of cancer stem cells, also known as 'tumour initiating cells', which would then promote treatment resistance. The research was carried out in breast cancer stem cells grown in a lab, but the theory was also checked against human breast cancer cells from patients. In both cases, proteins within the cells were examined. Sixty-two mitochondrial-related proteins showed significantly increased levels. In particular, fuels such as ketone and L-lactate appeared to be critical, and in the past, they have been shown to accelerate the growth of tumours. Professor Michael P. Lisanti, director of the Breakthrough Breast Cancer Unit, who led the research, says, ''Essentially mitochondria are the ''engines'' of cancer stem cells and ketone and L-lactate are the high octane fuels, which promote cancer growth. This is one of the first times that the actions of mitochondria in cancer stem cells have been fully appreciated and the results suggest new ways in which we can drain the fuel tank restricting cancer's ability to come back after treatment.'' Trials run by Cancer Research UK are currently underway using MCT inhibitors, which also target the mitochondria in cancer cells and the researchers believe that this could, if successful, open up new avenues of treatment. Dr Federica Sotgia, a senior lecturer, who also led the study, says, ''Targeting the mitochondria is difficult because of potential side effects, but, if these trials prove successful, then it represents an exciting new way to treat a large number of different cancer types.'' According to Nell Barrie, senior science information manager at Cancer Research UK, ''Blocking cancer cells' ability to generate the energy they need to grow and divide is an exciting new avenue for future cancer treatments. This research suggests that MCT inhibitors may be particularly effective against breast cancer 'stem cells' that can resist other treatments, and could prevent the cancer from coming back but further work is needed to find out if these drugs can help patients. Cancer Research UK is funding trials of these drugs in a range of cancer types.'' Dr Matthew Lam, Senior Research Officer at Breakthrough Breast Cancer, says, ''Whilst further investigation beyond the lab is needed to test the validity of these findings, this is promising work because in effect the team used one of the unique properties that cancer stem cells have against them. ''Secondary breast cancer is responsible for all deaths from the disease and we know that cancer stem cells play an important role in its development. If we are going to out-smart cancer once and for all in the future, every step taken towards finding new ways to prevent it from spreading and becoming life-threatening will be an important one.'' * * * NERVOUS SYSTEM AY PLAY BIGGER PART IN INFECTIONS THAT PREVIOUSLY KNOWN The nervous system may play a bigger role in infections and autoimmune diseases than previously known. If researchers can learn more about that role, it could provide insight into diagnosing and treating everything from the stomach flu to RHEUMATOID ARTHRITIS. Researchers at St. Michael's Hospital in Toronto, in conjunction with the Feinstein Institute for Medical Research in Manhasset, N.Y., reviewed the latest, most vigorous pre-clinical trials on this topic in a commentary published in the New England Journal of Medicine. They noted that neurons of the peripheral nervous system - specialized nerve cells that transmit information throughout the body - are known to send information about local infections or inflammation to the central nervous system (the brain and spinal cord) so the CNS can co-ordinate the whole body response. Dr. Benjamin Steinberg, a post-doctoral fellow and an anesthesiology resident at St. Michael's, hypothesized that the neurons may be sending the CNS not just a general Danger Warning but specific information about whether the infection is caused by a virus or bacteria, the type of bacteria present or the nature of the auto-immune reaction. Basic science researchers are now trying to decipher that "neural code" of information being sent by neurons. "The blue sky idea is that if we know the language and can read the code, in theory we can engineer or write our own," said Dr. Steinberg, writing with coauthors Dr. Arthur Slutsky, vice-president of research at St. Michael's and Dr. Kevin Tracey, president of the Feinstein Institute. Since those messages are being sent from neurons to the CNS in real time, knowing what they're saying could speed diagnoses or prognostication, which would be especially important in pandemics or outbreaks of particularly contagious or deadly diseases, such as flu, Ebola or SARS. The current method for confirming infections is to test body fluids or tissues, sometimes using invasive techniques, a process that can take hours, days or even longer. Moreover, Dr Steinberg said researchers might even be able to tell how severe an infection is and how the illness is expected to progress without treatment. "Timely diagnosis and intervention are essential to minimize deaths and complications," said Dr. Steinberg. "If the neurons are reading this information from an infection in the blood or the liver and we can interrogate the nervous system, we can make a diagnosis in real time. For example, we could perhaps tell quickly whether someone has the flu virus or bacterial pneumonia, which would determine whether antibiotics would be appropriate. At the extreme, a patient in septic shock requires prompt administration of antibiotic agents since each hour of delay is associated with a 7.6 per cent increase in mortality, but physicians do not always know what bacterium they need to target. An inappropriately chosen antibiotic can have serious ramifications for patient well-being." It's already possible to intercept and change some messages being sent to the CNS using bioelectric therapy. When injured, pain receptors send messages to the CNS that are registered as pain. Bioelectric therapy relieves pain by interrupting pain signals before they reach the brain. It also prompts the body to produce endorphins, which help to relieve pain. * * * Happy New Year to all of you! And if you have any thoughts of how this newsletter could be improved, please email me directly, at Elaine@elainejesmer.com. Elaine Jesmer
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