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Liver transplantation is effective when liver metastases from neuroendocrine tumors are unresectable, according to a European Liver Transplant Registry study.
But transplant should be reserved for selected cases, when all other options have been exhausted, Dr. Yves Patrice Le Treut from Hopital de la Conception, Marseille, France told Reuters Health in an email.
Those cases include patients with "unresectable liver metastases, well differentiated neuroendocrine tumor (NET) and no need of extra hepatic resection at the time of (transplant)," he said.
Using data from the European Liver Transplant Registry, Dr. Le Treut and colleagues reviewed the short- and long-term outcomes of 213 patients who underwent liver transplantation for neuroendocrine tumors. They published their findings online March 25th in Annals of Surgery.
Mortality in the three months after transplantation was 10%, driven mostly by surgery-related complications. The median postoperative hospital stay was 25 days and the median ICU stay was 10 days. Twenty-four patients required retransplantation, including 16 within the first three months.
The mean follow-up overall was 56 months (range, 0-283 months). Among the 192 patients who survived at least three months after transplant, 103 died later. Eighty-six of these later deaths were due to recurrent disease; the remainder were due either to late postoperative complications (six patients), late retransplant complications (four patients), infectious complications (three patients), or other causes (four patients).
At the end of follow-up, 63 patients were alive without recurrence, and 26 were alive with recurrence. The median survival for patients who died without recurrent disease was eight months.
Median overall survival after liver transplantation was 67 months. Overall survival rates were 81% at one year, 65% at three years, and 52% at five years.
Five-year overall survival did not differ between patients whose primary tumor was undetected at the time of liver transplantation, those whose primary tumor was discovered and removed during or after liver transplantation, and those whose primary tumor was never identified.
Median disease-free survival was 24 months. Disease-free survival rates were 65% at one year, 40% at three years, and 30% at five years.
Independent predictors of poor prognosis included major resection in addition to liver transplantation, poor tumor differentiation, and hepatomegaly. Age over 45 years also independently predicted poor prognosis among patients treated since 2000.
"The most striking finding is that (the) overall survival rate in the whole series was more than 50% at five years, thus validating the use of liver transplantation for patients with cancer," the researchers note. "Despite this validation, the actual benefit of liver transplantation needs to be proven."
The timing of transplant in asymptomatic patients is very controversial, Dr. Le Treut noted. "This retrospective work cannot give any answer to this question," he said. "But my personal point of view is that liver transplantation must be indicated when asymptomatic patients present (with) a progressive tumor load (after a period of stable disease) that became refractory to all other treatments."
Dr. Mark Bloomston from The Ohio State University's Division of Surgical Oncology, Columbus, Ohio agreed. He told Reuters Health, "Given the scarcity of available livers, transplantation should still be reserved for patients proving to have indolent disease affecting only the liver. In other words, enough time must pass to prove the disease is not very aggressive but should not wait so long that the patient is in dire straits."
Dr. Bloomston added, "Evaluation for liver-directed therapies (including resection, transplantation, or chemoembolization) should take place early in disease course for metastatic NET, preferably when the disease is at its best (e.g., low volume, slow growth, or even stable disease). Liver-directed therapy should not be undertaken in desperation as it is doomed to failure and could be dangerous."
Dr. Gabriel Chan from the University of Montreal in Canada offered a somewhat different view. "I believe until there is further prospective evidence, liver transplantation should be reserved for patients who are symptomatic, with hepatic only, low grade NET," he said. "There is currently no proof that there is a survival benefit over the current treatments including arterial therapy, hormone therapy, and even no treatment in such patients."
Good prospective trials "are absolutely essential," Dr. Chan told Reuters Health, "and as a result of the rare situation where it is indicated, national and international cooperation is essential to provide the essential numbers and statistically significant evidence of benefit, either symptomatic or survival."
"The future may feature better situations where recurrence is diminished if the everolimus experience in metastatic NET expands over the next few years, and if the therapeutic ranges of the oncological and immunosuppressive modalities cross over," Dr. Chan concluded.


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