Prognostic factors of survival and recurrence after liver transplantation for unresectable colorectal liver metastases: Results from the TransMet trial.

Abstract

3561 Background: Liver transplantation (LT) has recently proved to improve the survival of selected patients with unresectable colorectal liver metastases (uCRLM) compared to chemotherapy (C) alone. However, recurrence rates remain high, stressing the need for a better patient selection. This exploratory study aimed to identify prognostic factors associated with recurrence and death in patients undergoing LT as part of the TransMet trial. Methods: Data from 36 patients of the LT+C arm (per protocol population) were analyzed including age, gender, TNM and RAS status of the primary tumor, characteristics of metastases at diagnosis and at LT, chemotherapy regimen, tumor response (RECIST), and timeframe from primary resection to LT. Associations with recurrence and death were explored. Variables with > 5 observations per group and p-values ≤ 0.10 in univariable analysis were included in multivariable models. Results: Among the 36 transplanted patients, 27 experienced recurrence and 9 died after 50-month follow-up. Recurrence: At univariable analysis two factors were associated to a higher risk: serum CEA levels > 5 ng/ml at time of LT (11/11 vs 11/18, p 0.01) and oxaliplatin-based first line chemotherapy (14/16 vs 13/20, p 0.04). Two other factors showed a trend toward statistical significance: Female sex (14/15 vs 13/21, p 0.10) and > 20 metastases at diagnosis (11/17 vs 16/19, p 0.09). At multivariable analysis, CEA levels at LT > 5 ng/ml (HR: 2.91; 95% CI: 1.0–8.2; p 0.04) emerged as an independent predictor of recurrence. Female sex (HR: 2.2; 95% CI: 0.8–5.3; p 0.08) and oxaliplatin-based first line chemotherapy (HR: 2.0; 95% CI: 0.8–4.8; p 0.13) were also associated with around 2-fold higher risk of recurrence, although not reaching statistical significance. Death : At univariable analysis,two factorswere significantly associated with a higher risk: female sex (7/15 vs 2/21 for male, p 0.03) and > 24 cycles of chemotherapy before LT (8/19 vs 1/15, p 0.05). Two other factors showed a trend toward higher mortality: no response to 1 st line chemotherapy (6/14 vs 3/22, p 0.06) and stable disease (vs partial response) before LT (8/22 vs 1/14, p 0.08). At multivariable analysis, female sex emerged as independent predictor of death (HR 5.1; 95% CI: 1.0-25.0; p = 0.04). More than 24 cycles of chemotherapy (HR 7.1; 95% CI: 0.9 – 51.0; p 0.07) and stable disease (vs partial response) at LT, showed an approximately 7-fold increase in the risk of mortality, although not reaching statistical significance. Conclusions: Within the limits of a reduced sample size, these results suggest that LT should be envisaged early in the history of potential candidates to LT to reduce the number of cycles of chemotherapy. Both morphological and biological tumor response, initially and at time of LT, are essential. The notable influence of female sex on post-LT outcome needs to be further explored. Clinical trial information: NCT02597348 .