Liver transplantation for unresectable colorectal liver metastases in patients and donors with extended criteria (SECA-II arm D study).

BACKGROUND: Patients with metastatic colorectal cancer receiving palliative chemotherapy have a 5-year survival rate of approximately 10 per cent. Liver transplantation using strict selection criteria in patients with colorectal cancer and unresectable liver-only disease will result in a 5-year survival rate of 56-83 per cent. The aim of this study was to evaluate survival of patients with colorectal liver metastases (CRLM) after liver transplantation using extended criteria for both patients and donors. METHODS: This was a prospective single-arm study. Patients with synchronous unresectable CRLM who were not suitable for arms A, B or C of the SEcondary CAncer (SECA) II study who had undergone radical resection of the primary tumour and received chemotherapy were included; they underwent liver transplantation with extended criteria donor grafts. Patients who had resectable pulmonary metastases were eligible for inclusion. The main exclusion criteria were BMI above 30 kg/m2 and liver metastases larger than 10 cm. Survival was estimated using Kaplan-Meier analysis. RESULTS: Ten patients (median age 54 years; 3 women) were included. They had an extensive liver tumour load with a median of 20 (range 1-45) lesions; the median size of the largest lesion was 59 (range 15-94) mm. Eight patients had (y)pN2 disease, six had poorly differentiated or signet ring cell-differentiated primary tumours, and five had primary tumour in the ascending colon. The median Fong clinical risk score was 3 (range 2-5) and the median Oslo score was 1 (range 1-4). The median plasma carcinoembryonic antigen level was 4·3 (range 2-4346) µg/l. Median disease-free and overall survival was 4 and 18 months respectively. CONCLUSION: Patients with unresectable liver-only CRLM undergoing liver transplantation with extended patient and donor criteria have relatively short overall survival.

ANTECEDENTES: Los pacientes con cáncer colorrectal metastásico (metastatic colorectal c¡ncer, CRC) que reciben quimioterapia paliativa presentan aproximadamente una supervivencia a los 5 años del 10%. El trasplante de hígado utilizando criterios de selección estrictos en pacientes con CRC y enfermedad localizada hepática no resecable presenta una supervivencia a los 5 años del 56-83%. El objetivo de este estudio fue evaluar la supervivencia de pacientes con metástasis hepáticas CRC no resecables (non-resectable CRC liver metastases, CRLM) después del trasplante hepático utilizando criterios extendidos para pacientes y donantes. MÉTODOS: Se ha realizado un estudio prospectivo de un solo brazo. A los pacientes con CRLM sincrónicas no resecables que no eran adecuados para ser incluidos en los brazos A, B o C del estudio SECA-II, con resección quirúrgica radical previa del tumor primario y que recibieron quimioterapia, se les realizó un trasplante de hígado con injerto de donante con criterios extendidos. Los pacientes con metástasis pulmonares resecables también podían ser incluidos. Los principales criterios de exclusión principales fueron el índice de masa corporal > 30 y metástasis hepáticas > 10 cm. La supervivencia se estimó utilizando el método de Kaplan-Meier. RESULTADOS: Diez pacientes (mediana de edad de 54 años, 3 varones) incluidos en el estudio tenían una carga tumoral hepática extensa con una mediana de 20 lesiones (rango 1-45) y un tamaño mediano de la lesión más grande de 59 mm (rango 15-94 mm). Ocho pacientes tenían (y) pN2, seis tenían tumores primarios pobremente diferenciados/células de anillo de sello y cinco tenían tumor primario en colon ascendente. La mediana del Fong Clinical Risk Score fue 3 (rango 2-5). La mediana del Oslo Score fue 1 (rango 1-4). La mediana del nivel de CEA en plasma fue 4 µg/L (rango 2-4346). La mediana de supervivencia libre de enfermedad y supervivencia global fue de 4 y 18 meses, respectivamente. CONCLUSIÓN: Los pacientes con CRLM no resecables localizadas en el hígado que se someten a un trasplante de hígado con criterios extendidos de pacientes y donantes tienen una supervivencia global relativamente corta.

Growth rates of pulmonary metastases after liver transplantation for unresectable colorectal liver metastases.

BACKGROUND: The previously reported SECA study demonstrated a dramatic 5-year survival improvement in patients with unresectable colorectal liver metastases (CLM) treated with liver transplantation (LT) compared with chemotherapy. The objective of this study was to assess whether immunosuppressive therapy accelerates the growth of pulmonary metastases in patients transplanted for unresectable CLM. METHODS: Chest CT scans from 11 patients in the SECA study resected for 18 pulmonary metastases were reviewed retrospectively. Tumour diameter, volume and CT characteristics were registered and tumour volume doubling time was calculated. Findings in the SECA group were compared with those of a control group consisting of 12 patients with non-transplanted rectal cancer resected for 26 pulmonary metastases. Disease-free survival (DFS) and overall survival (OS) after first pulmonary resection were determined. RESULTS: Median doubling time based on tumour diameter and volume in the SECA and control groups were 125 and 130 days (P = 0·658) and 110 and 129 days (P = 0·632) respectively. The metastases in both groups were distributed to all lung lobes and were mostly peripheral. Median DFS after LT in the SECA group and after primary pelvic surgery in the control group was 17 (range 6-42) and 18 (2-57) months respectively (P = 0·532). In the SECA group, estimated 5-year DFS and OS rates after first pulmonary resection were 39 and 51 per cent respectively. CONCLUSION: Patients treated by LT for unresectable CLM have a good prognosis following resection of pulmonary metastases. Doubling time did not appear to be worse with the immunosuppression used after LT.