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International Registry of Hepatic Tumors in Liver Transplantation
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Tumor Characteristics Impact on Outcome After Liver Transplantation for Hepatocellular Carcinoma: A Registry Report, American Surgical Association |
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Goran B. Klintmalm, M.D., Ph.D.
Liver replacement to treat patients with hepatic malignancy was conceived early in transplantation. It was soon discovered that recurrent disease marred the results. The transplant community has since worked to find the proper indication for liver replacement in tumor patients. No single center treats enough patients for a universally applicable evaluation.
As a result, an International Registry of Hepatic Tumors in Liver Transplantation was established in 1992. Once the patient is entered in the registry, he/she is followed every six months for the rest of his/her life. The registry provides data on demographics, tumor characteristics, treatments, time and location of recurrences and survival.
Currently 53 liver transplant centers from 21 countries have entered 553 patients into the registry. Of those patients, 410 have hepatocellular carcinoma and 12fibrilamellar (FLL-HCC). We were surprised to find that only 204 (49.8%) received adjunctive therapy. Thus, the registry is still too small for a valid analysis of the impact of adjunctive therapy on patient outcome.
HCC was the indication for transplantation in 240 patients (one missing). Secondary disease, including cirrhosis, was reported in 175 patients (47.8%). In 169 patients (41.3%), the tumor was defined as incidental which indicates it was found at surgery or in the pathology of the specimen.
As single lesion was found in 167 patients. Bilobar spread was seen in 109 patients (26.6% -- missing 101), multi-focal in 209 patients (51.0% - missing 34). Vascular invasion was seen in 71 patients (23.2% - missing 104). The tumor size was less than 5 cm in 267 patients (65.5%) and more than 5 cm in 104 patients (25.4%), size missing in 39 patients (9.5%). Only 24 patients (6%) were reported with positive nodes. Well differentiated tumors G1, were seen in 105 patients; moderately differentiated, G2, in 58 patients; poorly differentiated, G3, in 19 patients; and anaplastic, G4, in six patients. Grading was missing in 222 patients.
The overall patient survival rate at one-, three-, and five-year intervals was 71%, 52% and 44%. Of the deaths that occurred, 85 out of 182 (46.7% - 5 unknown) were reported to be tumor related. In comparison, the one-, three-, and five-year patient survival rates in the United States were 70%, 72% and 57% respectively (UNOS Annual Report, 1996)
Recurrence was reported in 114 patients (29.3% - 2 missing). The first site of recurrence for liver was 43.1%, lungs 27.5%, adrenal 5.5% and mediastinum 2.8%. Currently, 187 patients are alive free of tumor, 17 are alive with tumor, 91 died free of tumor, 89 died with tumor and five have unknown tumor status (21 missing).
A multivariate analysis for all HCC factors reported above shows that histologic grade G1 + 2 vs. 4 is the only independent variable predicting survival (p=0.0008). Since 222 (54.1%) of the patients lacked histologic grading, the Cox analysis rerun without histologic grade showed only vascular invasion related to patient survival (p=0.0043). Of particular interest was that for incidentally diagnosed tumors, only multi-focality predicted patient survival (p=0.0018).
Discussion: Results of liver transplantation in tumor patients is surprisingly successful when compared with non-tumor patients. When determining candidacy for liver replacement as part of the cancer treatment, pre-transplant histological grading seems to be the essential factor. Histology and other reported tumor criteria that influence the response to adjunctive therapy will hopefully be determined with the growth of the registry.
American Surgical Association, 1998
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