Liver transplantation validated for select chemoradiation-treated cancer patients
MedWire News: Research supports the use of orthotopic liver transplantation after chemoradiation in select patients with unresectable perihilar cholangiocarcinoma.
"Our data serves to justify the use of scarce liver allografts for this otherwise lethal disease, as the unadjusted 5-year disease-free survival of 65% is not only similar to results from earlier single-center series but also similar to outcomes of liver transplantation for other malignant and non-malignant indications," say Julie Heimbach (Mayo Clinic, Rochester, Minnesota, USA) and co-authors.
The team examined the impact of the United Network of Organ Sharing (UNOS) decision to implement a standardized model of end-stage liver disease (MELD) exception approving liver transplantation for select patients with unresectable perihilar cholangiocarcinom who had completed a course of chemoradiation.
Data from 287 patients were collected between 1993 and 2010 from 12 US centers that treated three or more perihilar cholangiocarcinoma patients with neoadjuvant therapy followed by liver transplantation. Neoadjuvant therapy consisted of external radiation (99%), brachytherapy (75%), radio-sensitizing treatment (98%), and/or maintenance chemotherapy (65%).
As reported in Gastroenterology, 25% of patients dropped out after a median of 4.6 months, with an 11.5% decrease per 3-month period. The patients were followed up for a median of 2.5 years from time of listing for transplantation, with 43% dying after a median of 1.2 years, almost half of whom (49%) were pretransplant.
After transplantation, 20% of patients experienced recurrent cancer, and 22% died from recurrence, sepsis, multiorgan failure, liver failure, post-transplant lymphoproliferative disease, or other causes.
Intent-to-treat analysis gave 2- and 5-year survival rates of 68% and 53%, respectively. The rates of recurrence-free survival following transplantation were 78% and 65%, respectively.
Of note, patients who fell outside of the UNOS exception criteria - a tumor greater than 3 cm, metastatic disease at time of transplantation, direct tumor, biopsy - and those with a prior history of malignancy had significantly poorer survival rates than those who did not (hazard ratio=2.8). Mass size was the most significant predictor of recurrence-free survival, with 5-year rates of 32% and 69% for patients with tumors greater than 3 cm versus the smallest tumors.
Intraoperative staging did not significantly predict patient outcome. There was no significant difference in the survival of patients who did and did not receive brachytherapy in addition to chemoradiation treatment.
Heimbach et al conclude: "The central challenge for the future will be to gain a greater understanding of the tumor biology in order to reduce waitlist dropout and post-transplant recurrence, either by further refinements in patient selection or, ideally, by more effective chemoradiotherapy."
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