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Thursday, July 31, 2014





NEW YORK – Chronic myeloid leukemia (CML) patients can safely stop taking a tyrosine kinase inhibitor (TKI) if they participate in a clinical trial and hit certain predictors of remission, including a low SOKAL score and longer duration of TKI therapy, according to speakers who discussed the topic here at the Great Debates and Updates in Hematologic Malignancies meeting.


Yes, TKIs Can Be Stopped Safely

“Can we safely stop TKI therapy after achieving a complete molecular response (CMR) for more than two years? Sure, you can always restart TKI therapy if a relapse occurs,” said Michael Mauro, MD, Leader of the Myeloproliferative Neoplasms Program in the Leukemia Service at Memorial Sloan-Kettering Cancer Center.


CML is increasing in prevalence, he said: “We expect 10 times the number of cases in 2050. We now face a pharmaco-economic discussion on how to treat CML. Lifelong therapy with TKIs may not be feasible. Patients with copays are more likely to be non-adherent and to stop drug therapy due to the high costs.”  


He noted that in Mexico, the cost of a transplant is equal to three months of imatinib treatment. “Cost is a burden-- We need to try discontinuation.”


A growing number of CML patients are achieving CMR, Mauro said. About one-third of CML patients can expect to achieve treatment-free remission off-treatment, which is “quite reasonable.”


He pointed to several studies of imatinib discontinuation. For example, French researchers had CML patients with undetectable BCR-ABL stop therapy and observed them monthly. At 60 months, 61 percent of the patients relapsed, and the treatment-free remission was about 40 percent, he said, noting that the researchers estimated that the cost of imatinib would have been more than four billion Euros if the patients had stayed on therapy for the length of the trial.


In addition, in the TWISTER study, Australian researchers found a 43 percent success rate among patients who discontinued imatinib. “No patient progressed, and there was no development of mutations,” Mauro said. “There is consistent data. We can predict how many patients will be successful by discontinuing imatinib therapy.”


One predictor is to use the patient’s Sokal score (the system developed in 1984 by Joseph E. Sokal, MD). “At 60 months, 73 percent of patients with a high or intermediate score are at risk of relapse,” Mauro said. “This is a universal finding across studies,” he said. “Another predictor is imatinib duration. Those on imatinib therapy for longer are less likely to relapse and may be able to discontinue.”


Another study, A-STIM, he continued, found that half of CML patients with undetectable, intermediate transcripts not above threshold levels needed treatment. “Patients who lose major molecular response [MMR] should be considered in need of treatment for remission.” This study found that 60 percent of patient lost their CMR; stability did not have an impact on long-term success, he noted.


Discontinuation studies have also looked at second-generation TKIs. Another French group found a failure rate of 60 percent due to loss of major molecular response. “Patients in CMR may be defined as non-proliferative, rather than disease-free,” Mauro said. “They may not be different from patients with stable levels of undetectable disease. MMR loss may be a more pragmatic, accepted endpoint for failure and the need for treatment.


“I’m nervous about letting a patient who may have consistently undetectable disease rise to the level of MMR loss. We can’t predict the biology of these patients.”


In addition, slower-growing leukemia-initiating cells may remain even after imatinib treatment. A threshold of    molecular response (MR) 4.5 is most feasible, and treatment decrease after two years is now the standard, he said.   


Loss of MMR is a true sign of failure to get the patient back on treatment, but this should be done only in the context of a clinical trial, not in clinical practice.


The Euro-SKI discontinuation trial is going even further in using an MR 4 threshold, Mauro noted. The researchers will watch these patients for relapse and non-proliferative disease. So far, “it’s quite rare a patient needs retreatment,” he said.


In conclusion, Mauro said, “current approaches, even imatinib, offer the potential for treatment-free remission. Second-generation TKIs offer a greater opportunity. Treatment-free remission success can be predicted with old tools, such as Sokal score, and newer tools will give greater clarity.”


In addition, the need for retreatment of a TKI is nearly always evident within six months. “A non-proliferative state is likely a reality of treatment-free remission. Retreatment, by all reports in discontinuation studies, has been successful. Retreatment opportunities have increased with alternate TKIs, and will continue with experimental approaches, such as PD-1 and other immunotherapies.”  


No, We Need More Clinical Trials

Ellen K. Ritchie, MD, Associate Professor of Clinical Medicine at Cornell Weill Medical College, took the other side of the debate, saying: “No, we need more clinical trial data before we recommend stopping TKIs. It’s a gamble that is not ready for prime time. Be careful of doing this with an average CML patient.”


It’s true that several prospective studies, as well as retrospective studies from Japan and Korea, have demonstrated that TKI discontinuation is possible, she said. For example, the STIM trial enrolled 100 CML patients at an average age of 69, and followed them for a median of 24 months, assessing their CMR levels.


“A total of 61 percent of patients had a molecular relapse and were put back on imatinib. Molecular relapse-free survival was 45 percent at six months, 41 percent at 12 months, and 38 percent at 24 months. The majority of patients relapsed. Those who did well did well for a long time.”


The duration of imatinib therapy appears to be important, she said. After a median follow-up of 30 months, 61 percent of patients relapsed, most of them within seven months. Three patients relapsed at 19, 20, and 22 months.


The complete molecular response rate at both 24 and 36 months was 39 percent. “Patients who had an early restart regained CMR on imatinib,” she said, noting that patients who did not do well had high Sokal scores, which is “a significant predictor of prognosis.”


The TWISTER discontinuation trial included 40 chronic-phase CML patients. Of the 40 patients, 22 relapsed, 15 of them within six months. Five of 18 patients had detectable BCR-ABL transcripts without relapse. Treatment-free remission was 43 percent. All 22 patients who relapsed responded to retreatment with imatinib. Another 16 patients regained stable, undetectable minimal residual disease (MRD).


The predictors of success in this study, Ritchie said, are prior interferon therapy, the time to switch to imatinib, and Sokal score.


Still, even with these study results, discontinuation remains an ongoing gamble, she said. “From a patient perspective, is the patient willing to gamble that the CML will come back? A patient will consider this only if he thinks he can beat the odds.”


Patients may have many questions about discontinuing TKI therapy. These include: What is the chance of a sustained remission for five years or more? Will I need bone marrow biopsies? Will I need to see my doctor more? Will I need to have more blood taken? How likely am I to go into relapse again?


The probability of maintaining CMR off imatinib is about 39 percent, Ritchie said. “There are no data for more than 36 months. If a patient has a low Sokal score, the probability of CMR is 55 percent. With a high Sokal score, it’s unlikely a patient will be able to be maintained off drug.” She added that she would feel more comfortable if the patient had a longer duration of imatinib before discontinuing.


There is no need for more bone marrow biopsies, Ritchie said. “The TWISTER trial showed no benefit of ongoing bone marrow biopsies over peripheral blood monitoring. But patients will definitely have to see the doctor more and have more blood taken. I would tell patients: ‘Yes, you will see me more the first three years, and for the first three months you will see me a lot.’”


If a patient has molecular data that shows two positive samples in a row, then there is a concern for relapse. “To measure molecular relapse, we need to use real-time PCR from a high-quality laboratory,” she said. “We don’t have a great understanding of the mechanisms of relapse. Before stopping becomes widespread, we need to know how and why patients relapse.”


There are still unresolved issues with regard to measurement of major and complete molecular responses, she said.  “There is no single definition of CMR. Response is defined by an upper boundary, and the disease still may be detectable by real-time PCR or nested PCR at a lower level. There is substantial variation caused by technical differences across different laboratories, and it’s very difficult to standardize definitions of undetectable BCR-ABL.”


In addition, there is no evidence supporting the ability of TKIs to eliminate precursor stem cells. “We have no reliable method to measure CML stem cells,” Ritchie said, noting that the TWISTER trial measured BCR-ABL junctions from genomic DNA that characterized individual patient breakpoints to detect minimal residual disease. Factors other than the number of residual CML cells are important for a sustained CMR.


“Stopping should be done only in a clinical trial, and the trial should include peripheral blood monitoring for CMR off drug,” she said. “The patients need to be willing to come into the doctor’s office monthly for the first year for close monitoring to look for early molecular relapse.”


CML patients who are candidates for drug discontinuation are those who are not able to tolerate TKIs, are pregnant, or are otherwise unable to take the drugs.


In conclusion, Ritchie posed as a CML patient and asked, “Why should I stop taking my TKI? My insurance company pays for the drug. It took me three years to get in CMR. I might just barely be in CMR. Chances are I will relapse if I go off. I have to see the doctor more often and get more blood drawn. I am going to be really anxious the whole time, like I was when I was first diagnosed.”


Voting and Q&A

According to the vote by the audience, the debate was a draw. An equal number of “Undecided” voters switched their votes to each position presented.


In the question-and-answer period, an audience member asked how much the decision as to stop TKIs is due to cost concerns? Ritchie answered: “Cost is the driver if we look at developing countries and the U.S. About 12 percent of the U.S. population is over age 80. We have a revolutionary expansion of the population who are using more drugs. We need to learn how to use new therapies to manage costs in the interests of every government and health care paying entity.”


Thursday, July 31, 2014




WASHINGTON—Patient advocacy groups such as the National Coalition for Cancer Survivorship have praised the Affordable Care Act (ACA) for provisions that protect cancer patients from health insurance discrimination due to a pre-existing condition, expand insurance coverage, and other benefits. Data from many sources, including the American Cancer Society, show that uninsured cancer patients fare far worse than cancer patients with health insurance.


Now early data from the Urban Institute presented at a news briefing here on the ACA’s net effects on America’s uninsured population show that after a rocky start consumers were signing up for health insurance plans under the ACA’s marketplace open enrollment in higher numbers. Overall, eight million more American adults obtained health insurance coverage between September 2013 and June 2014, according to the Urban Institute’s Heath Reform Monitoring Survey (HRMS) data.


The greatest gains were among low-income and middle-income adults – the groups specifically targeted by the ACA’s new Medicaid and marketplace provisions. Enrollment gains were greater in states that implemented the ACA’s Medicaid expansion provision, where those without health insurance dropped by 37.7 percent.


“The Medicaid piece of this is very important… I think the first year is pretty much of a success,” said Stephen Zuckerman, PhD, Urban Institute Senior Fellow and Co-Director of its Health Policy Center.


Despite initial ACA website glitches and crashes, frustration, and acrimony, “it really is an impressive rollout--not perfect, but good,” agreed Sharon Long, PhD, a Senior Fellow in the Urban Institute’s Health Policy Center.


But the data also show that persistent health insurance enrollment problems remain, especially among Hispanics; Americans with low health literacy and less than a high school education; and among those who believe they cannot afford health insurance even with new provisions in the ACA. And even after enrollment in health plans, many Americans are confused by the complexity of health insurance plans and by unfamiliar terms such as “deductibles” and “co-pays,” and are not sure what they have actually purchased.


Some people don’t understand the concept of co-pays, believing that a health insurance should cover everything,” Long said. “People don’t quite know what kind of insurance they have--we see those confusions in the data.” She noted that America’s Health Insurance Plans (AHIP), a national organization representing approximately 1,300 member companies, has expressed concern, for example, about Americans who purchased high-deductible health plans don’t understand (see box).


Other Findings

Early data on health insurance under the ACA released at the briefing also show that:

  • The estimated rate for American adults without health insurance fell from 17.9 percent to 13.9 percent between September 2013 and June 2014;
  • Men and women, young and old, and all races and ethnicities benefited from the ACA’s coverage expansions, with the largest gains for population groups that have historically had high uninsurance rates: young, male, and minority adults;
  • Compared with the uninsured population in September 2013, uninsured adults were more concentrated in Medicaid non-expansion states in June 2014;
  • Two-thirds of uninsured adults in June 2014 had family incomes at or below 138 percent of the federal poverty level, and two-fifths were both low-income and lived in states that had not expanded Medicaid under the ACA;
  • Three out of five uninsured adults in June 2014 had heard some or a lot about the new ACA health insurance marketplaces and the individual insurance mandate, but fewer than two out of five had heard about the marketplace subsidies; and
  • Most uninsured adults in June 2014 said they were uninsured for financial reasons, despite new provisions in the ACA, and seven in 10 adults who remain uninsured even after spending time looking for information on health insurance cited financial barriers as a reason for not signing up for coverage. Part of the perceived financial barriers may be living in a state without Medicaid expansion. Some may even be living with debt. In fact, another new Urban Institute report shows that 77 million Americans (35 percent of US adults with a credit file) have a report of debt in collections, with an average debt of $5,178. (Debt in collections is a non-mortgage bill such as a credit card balance or medical or utility bill that is more than 180 days past due).

“The elephant in the room is the [Medicaid] non-expansion states,” said Katherine Hempstead, PhD, a director of the Robert Wood Johnson Foundation and a coauthor of two of three new HRMS data reports released at the Urban Institute briefing. As of June 2014, Medicaid expansion had occurred in 25 states and the District of Columbia. New financial assistance for health insurance coverage through federal and state marketplaces had occurred in all states. (However, two recent conflicting court decisions now put the fate of health care subsidies under the ACA in doubt.)


“Some of the people who cite financial barriers are aware of the subsidies and some are not,” Hempstead said, adding that among some Americans who “live paycheck to paycheck,” the price of health insurance comes with “sticker shock” even under the ACA.


Zuckerman stressed that due to the complexity of the new health insurance provisions, many adults who enrolled gained health insurance coverage through the help of navigators, who can play an important facilitation role. He said there need to be continuing outreach and education efforts to reach Americans with low health literacy and low educational attainment to explain to them why health insurance is valuable and to walk them through the process of becoming enrolled.


For many consumers, health insurance is intangible, unlike “getting something delivered to your door in a nice Amazon box,” Zuckerman said. The data also show that some Americans need a non-website approach to health insurance information and education: “There’s a lot of complexity here… not always clicking on a screen is going to help them.”


Asked by OT who should bear the responsibility for consumer education on health insurance coverage under the ACA, Zuckerman said that in terms of getting people through the door and enrolled in health plans, the ACA health insurance exchanges bear the responsibility. Once people have enrolled, though, he said, “I do think the insurance carriers bear the responsibility for education.” 


Long noted that family and friends are currently a major source of education for consumers on new health insurance plans under the ACA, and Hempstead predicted that a kind of “organic outreach” on the part of enrolled Americans will take place to others who are not yet insured.  




ASCO’s Educational Efforts on the ACA

In late May, the American Society of Clinical Oncology launched an online ACA Resource Center to help patients and oncologists better understand the Affordable Care Act. Information on how patients can navigate the ACA is available at Cancer.Net, ASCO’s patient information website (, and resources for oncologists can be found at

Thursday, July 31, 2014


The U.S. Food and Drug Administration has issued a final guidance on the development, review, and approval or clearance of companion diagnostics used to detect some gene-based cancers. The FDA, consistent with the requirements of the Food and Drug Administration Safety and Innovation Act of 2012, is also notifying Congress of its intention to publish a proposed risk-based oversight framework for laboratory developed tests (LDTs), which are designed, manufactured, and used within a single laboratory, which include some genetic tests and tests that are used by health care professionals to guide medical treatment for their patients. [The FDA already oversees direct-to-consumer tests regardless of whether they are LDTs or traditional diagnostics.]


“Ensuring that doctors and patients have access to safe, accurate and reliable diagnostic tests to help guide treatment decisions is a priority for the FDA,” FDA Commissioner Margaret A. Hamburg, MD, said in a news release. “Inaccurate test results could cause patients to seek unnecessary treatment or delay and sometimes forgo treatment altogether. Today’s action demonstrates the agency’s commitment to personalized medicine, which depends on accurate and reliable tests to get the right treatment to the right patient.”


The new guidance for companion diagnostics is intended to help companies identify the need for such tests during the earliest stages of drug development and plan for the development of a drug and a companion test at the same time—the ultimate goal being to stimulate early collaborations resulting in faster access to new treatments for patients, the news release noted. The guidance is written taking into consideration public comments made on the 2011 draft guidance.


The FDA has historically exercised enforcement discretion over LDTs (generally not enforced applicable regulatory requirements), but today these tests may compete with FDA-approved tests without clinical studies to support their use. The LDT notification to Congress  provides the anticipated details of the draft guidance through which the agency would propose to establish an LDT oversight framework, including pre-market review for higher-risk LDTs, such as those that have the same intended use as FDA-approved or cleared companion diagnostics currently on the market. The draft guidance would also propose to phase in enforcement of pre-market review for other high risk and moderate risk LDTs over time.


“The FDA is seeking a better balanced approach for all diagnostics,” Jeffrey Shuren, MD, Director of the FDA’s Center for Devices and Radiological Health, said in the news release. “The agency’s oversight would be based on a test’s level of risk to patients, not on whether it is made by a conventional manufacturer or in a single laboratory, while still providing flexibility to encourage innovation that addresses unmet medical needs.”


The agency intends to propose continuing to exercise enforcement discretion for low-risk LDTs, LDTs for rare diseases, and, under certain circumstances, LDTs for which there is no FDA-approved or cleared test, according to the news release. The FDA also intends to publish a draft guidance outlining how laboratories can notify the FDA that they are currently manufacturing and using LDTs, how to provide information about their LDTs, and how they can comply with the medical device reporting requirements.


The FDA is required, based on a provision in FDASIA, to provide at least 60 days’ notice to Congress before the agency publishes for public comment any draft guidance on the regulation of LDTs. As such, the comment period will open at a later date when the draft guidances are published in the Federal Register and the public is alerted to the start of the comment period. The agency also intends to hold a public meeting during the comment period to collect additional input, the new release noted.

Tuesday, July 29, 2014


The U.S. Food and Drug Administration has expanded the approved use of Imbruvica (ibrutinib) for the treatment of patients with chronic lymphocytic leukemia (CLL) who carry a deletion in chromosome 17 (17p deletion). Having the mutation has been found to be associated with poor responses to standard treatments for CLL, and Imbruvica received a breakthrough therapy designation for this recently expanded use.


The breakthrough therapy designation, enacted as part of the FDA’s 2012 Safety and Innovation Act, was created to expedite the development and review time of a potential new drug for serious or life-threatening disease where early clinical evidence suggests the drug may demonstrate substantial improvement compared with existing therapies.


“We continue to see advances in the availability of therapies to treat chronic lymphocytic leukemia, especially for difficult-to-treat patient populations,” Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a news release. “Imbruvica is the fourth drug approved to treat CLL that received a breakthrough therapy designation, reflecting the promise of the breakthrough therapy designation program and demonstrating the FDA’s commitment to working cooperatively with companies to expedite the development, review and approval of these important new drugs.”


The FDA has also approved new labeling for Imbruvica to indicate that the drug’s clinical benefit in treating CLL has been verified. The drug had received accelerated approval for the treatment of CLL earlier this year based on its effect on overall response rate (OT 3/10/14 issue). New clinical trial results examining progress-free survival and overall survival have confirmed the drug’s clinical benefit.


Also approved by the FDA for the treatment of CLL in the past year are: Gazyva (obinutuzumab)(OT 12/10/13 issue), Arzerra (ofatumumab)(OT 5/10/14 issue), and Zydelig (idelalisib).


The latest actions for Imbruvica are based on a clinical study of 391 previously treated patients, 127 of whom had CLL with the 17p deletion. The patients were randomly assigned to receive Imbruvica or Arzerra until disease progression or side effects became intolerable. The trial was stopped early for efficacy after a pre-planned interim analysis showed a 78 percent reduction in risk of disease progression or death, as well as a 57 percent reduction in risk of death for patients treated with Imbruvica. Of the patients with the 17p deletion, those receiving Imbruvica had a 75 percent reduction in risk of disease progression or death.


The most common side effects observed in the trial were thrombocytopenia, neutropenia, diarrhea, anemia, fatigue, musculoskeletal pain, upper respiratory tract infection, rash, nausea, and pyrexia.


The drug’s new use has been approved more than two months ahead of its prescription drug user fee goal date (which was October 7, 2014). The FDA reviewed Imbruvica’s application for this new use under the agency’s priority review program, which provides for an expedited review of drugs that are intended to treat a serious disease or condition and, if approved, would offer significant improvement compared to marketed products.


Imbruvica is co-marketed by Pharmacyclics and Janssen Biotech.

Tuesday, July 29, 2014




BARCELONA, Spain -- At a meeting of primarily medical oncology presentations, a gastrointestinal surgeon had some positive news, and a message, for medical oncologists about treating pancreatic adenocarcinoma. “It should not be forgotten that the only cure for pancreatic cancer is offered by surgery,” said Markus Büchler, MD, PhD, Professor of Surgery and Surgeon-in-Chief at the University of Heidelberg and Director of the European Pancreas Center, speaking here at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer.


“And with increasing evidence on the surgical and perioperative aspects of pancreatic cancer therapy, the short-term and long-term outcomes of resectable and borderline resectable pancreatic cancer are improving,” he said in a session on surgical resection for pancreatic cancer.


Most physicians still think pancreatic cancer cannot be cured and that patients die, but there are some patient groups that have much better survival rates than others, he said. “Studies show that surgery can offer a cure rate of 20 to 30 percent with a median survival after surgery of between 10 and 40 months, which should be compared to what medical oncology can offer--between six and nine months.” he said, citing as an example the following review article for which he was senior author: Hartwig W et al: Lancet Oncology 2013;14:e476-e485)


Among the recent studies he cited in surgical treatment of pancreatic cancer to support his optimistic outlook were the following, for which he is also senior author:

·    Research showing that the presence of one lymph node does not mean a worse outcome after surgery (Oliver Strobel et al, in press). “Patients with N0 stage have the same outcome as patients with N1,” Büchler said, emphasizing, though, that at least 24 lymph nodes have to be sent to the pathology department to be able to determine stage.

·    A single, local recurrence occurs in about 20 to 30 percent of patients after pancreatic cancer resection, and a purely local recurrence after pancreatic surgery is amenable to a second surgery in at least half of patients. “In patients who had a local recurrence where we did a second operation, when the local recurrence was removable, the patients had an median 26 months of additional survival,” he said (Werner  et al: Nature Reviews Clinical Oncology 2013;10:323-333).

·    Whether to do combined pancreatic resection with resection of one to three liver metastases is a very controversial issue, Büchler said, but the data show that pancreatic resections with M1 disease can be performed with acceptable safety in highly selected patients (Shrikhande et al: Annals of Surgical Oncology 2007;14:118-127). “In our series published in 2007, these patients did better when we removed the liver metastases together with the primary tumor, but that was only in 29 patients. We have updated the series to 144 patients with M1 disease and clearly resectable primary tumor, and found that when we do the surgery these patients do better long term as against the patients who undergo chemotherapy. But it's too early to conclude [definitively] -- it is still an open issue for the future.”

·     After neoadjuvant chemotherapy, about 30 percent of patients become resectable and have good outcomes. In adjuvant treatment, in the randomized controlled ESPAC-3 (European Study Group for Pancreatic Cancer) trial of 1,149 patients treated with adjuvant chemotherapy consisting of either fluorouracil plus folic acid or gemcitabine following pancreatic cancer resection, there was no difference between the two regimens (Neoptolemos et al: JAMA 2010;304:1073-1081).“This was an important message, because you were believing that gemcitabine was better, but the answer is that gemcitabine is only more expensive--not better; 5FU has the same effect in adjuvant treatment,” Büchler said. And in an ESPAC-3 update among patients with resected periampullary adenocarcinoma receiving either adjuvant chemotherapy or observation, the data clearly show a statistically significant survival benefit associated with adjuvant chemotherapy, he said (Neoptolemos et al: JAMA 2012;308:147-156).

·    ESPAC-3 data are also suggesting that adjuvant chemotherapy need not be started so soon after surgery (Valle et al: JCO 2014;32: 504-512). A 2014 report concluded that completion of all six cycles of planned adjuvant chemotherapy was an independent prognostic factor after resection for pancreatic adenocarcinoma, rather than early initiation, and there seemed to be no difference in outcome if chemotherapy is delayed up to 12 weeks. “You were told to start chemotherapy within four weeks after surgery, but the answer now is that you can easily start with very good results up to 12 weeks,” Büchler said. “This is good for the patients, because they can recover from the surgery.”

·    And according to research from ESPAC-3 on human equilibrative nucleoside transporter 1 (hENT1), levels of that biomarker in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection  (Greenhalf et al: JNCI 2014;106:djt347).


ESPAC Trials Continue Apace

Results from ESPAC-4, a Phase III trial with more than 1,000 patients testing adjuvant gemcitabine versus gemcitabine-capecitabine, will be available later in 2014, Büchler said.


And the Phase III ESPAC-5 trial has started, with four study arms: pancreatic adenocarcinoma treated with surgery alone; treatment with either of two arms of neoadjuvant chemotherapy; and treatment with neoadjuvant chemoradiotherapy.




Became a Surgeon Because…

In an online biography, Büchler said he became a surgeon because his father, a physician, “hated surgeons,” quoting his father as saying, “I put them in the hospital where the surgeons kill them.” He became a surgeon, Büchler said, to prove his father wrong.


Büchler concluded his presentation at the ESMO meeting by noting that surgeons in the University of Heidelberg's Department of General, Visceral and Transplantation Surgery perform approximately 800 pancreatic resections per year, with an overall mortality rate of only 3.5 percent.