How tumors respond to treatment prior to liver transplants may be useful in selecting recipients

Liver transplantation is widely recognized as an effective treatment for early-stage hepatocellular carcinoma (HCC) and the size and number of tumors, known as the Milan criteria, are traditionally used to determine a patient's eligibility for a transplant. Treating tumors prior to transplant has been used as a strategy to bridge the waiting time before an organ becomes available, but little research has been conducted on whether pre-treatment may influence survival.

Led by Gerd Otto, M.D. of the Department of Transplantation and Hepatobiliopancreatic Surgery at Johannes Gutenberg University in Mainz, Germany, researchers selected 96 HCC patients between May 1996 and May 1998 for periodic transarterial chemoembolization (TACE) prior to liver transplantation. TACE is a treatment where agents designed to halt or reduce tumor growth are injected into the artery supplying the tumor. The treatment was repeated every six weeks and every time a CT scan was performed to assess tumor growth.

Of the 96 patients, some initially met the Milan criteria, which screens for smaller tumors and fewer lesions, and were immediately listed for transplant, while others exceeded the Milan criteria initially but responded to TACE and were subsequently listed, even though some of them ultimately had tumors that exceeded the criteria before receiving a transplant. Ultimately, 16 patients met the Milan criteria and were transplanted and another 34 exceeded the Milan criteria but received a transplant following TACE. Freedom from recurrence after five years was 94 percent in the first group and 75 percent in the second group.

Since freedom from recurrence was not significantly different in patients who met versus patients who exceeded the Milan criteria, the authors conclude that these criteria may not be crucial in predicting recurrence. “Our study suggests that oncological control reached by the scheduled TACE pretreatment during the waiting time is obviously of greater importance for the long-term prognosis than downstaging [reducing tumor size] itself,” the author state. “According to our data, favorable tumors seem to be selected with a much higher degree of reliability if the process of tumor control persists during the total waiting time.” They maintain that even large or multiple tumors can be successfully treated by liver transplant if they show a favorable response and remain stable during pretreatment with TACE. “This observation may form a basis of biologically more plausible selection criteria rather than simple tumor size or tumor number,” they conclude.

In an accompanying editorial in the same issue, Francis Y. Yao, M.D. of the Division of Gastroenterology at the University of California, San Francisco acknowledges that “this article raises the intriguing possibility of looking beyond tumor size and number in selecting patients with HCC for OLT [liver transplant], but without relying on information that requires biopsy of the tumor.” He adds that since no upper limits in tumor size and number were used to exclude patients from receiving transplants, one might conclude that all patients would be eligible for a transplant regardless of tumor size as long they responded to a local treatment such as TACE. However, other research contradicts this conclusion and it is likely that an upper limit in tumor size and number exists beyond which a transplant will most likely yield poor results, despite pretreatment. “While the authors advocate using response to TACE alone as a selection criterion for OLT in patients with HCC, questions still remain regarding the practicality of this approach,” the editorial states. He concludes that the study's findings support the basic principle behind reducing tumor size in HCC patients before transplant, because this may eliminate the most aggressive tumors. However, response to this type of treatment is probably not enough by itself. The author concludes: “Rather than replacing tumor size and number, response to TACE or other loco-regional therapy should be an important endpoint used in conjunction with an upper limit in tumor size and number in refining the existing selection criteria for OLT.”