Objective To determine overall survival and disease-free survival in selected patients with nonresectable liver-only colorectal cancer receiving liver transplantation. Background Patients with nonresectable colorectal cancer receiving palliative chemotherapy has a 5-year overall survival of about 10%. Liver transplantation provided an overall survival of 60% in a previous study (SECA-I). Risk factors for death were carcinoembryonic antigen (CEA) >80 μg/L, progressive disease on chemotherapy, size of largest lesion>5.5 cm, and less than 2 years from resection of the primary tumor to transplantation. Methods In this prospective (SECA-II) study, we included colorectal cancer patients with nonresectable liver-only metastases determined by computed tomography (CT)/magnetic resonance imaging/positron emission tomography scans and at least 10% response to chemotherapy. Time from diagnosis to liver transplant was required to be more than 1 year. Results At a median follow-up of 36 months, Kaplan-Meier overall survival at 1, 3, and 5 years were 100%, 83%, and 83%, respectively. Disease-free survival at 1, 2, and 3 years were 53%, 44%, and 35%, respectively. Overall survival from time of relapse at 1, 2, and 4 years were 100%, 73%, and 73%, respectively. Recurrence was mainly slow growing pulmonary metastases amenable to curative resection. Fong Clinical Risk Score of 1 to 2 at the time of diagnosis resulted in longer disease-free survival than score 3 to 4 (P = 0.044). Patients included in the present study had significantly better prognostic factors than the previous SECA-I study. Conclusion Liver transplantation provides the longest overall survival reported in colorectal cancer patient with nonresectable liver metastases. Improved selection criteria give patients with nonresectable colorectal liver metastases a 5-year overall survival comparable to other indications for liver transplantation.

Survival Following Liver Transplantation for Patients With Nonresectable Liver-only Colorectal Metastases.

Liver transplantation for non-resectable colorectal liver metastases: the International Hepato-Pancreato-Biliary Association consensus guidelines

Selection criteria related to long-term survival following liver transplantation for colorectal liver metastasis.

Background
Liver transplantation is considered the standard of care for patients with hepatocellular carcinoma (HCC) within the Milan criteria. Liver transplantation in patients with unresectable colorectal cancer with liver-only disease has been shown to be associated with a 5-year overall survival rate of 56 per cent, compared with 9 per cent in patients receiving standard palliative chemotherapy. The aim of the present study was to compare disease-free (DFS) and overall (OS) survival after liver transplantation in patients with HCC and those with colorectal metastases.

Methods
Data were collected from the SEcondary CAncer (SECA) study database and an institutional (national) database of patients undergoing liver transplantation for HCC; all liver-transplanted patients were included. Patients with colorectal metastases treated by liver transplantation were divided into high- and low-risk groups for mortality based on carcinoembryonic antigen levels, response to chemotherapy, largest lesion at time of transplantation and time from primary surgery to transplantation.

Results
Patients with colorectal metastases had a median of 8 lesions, compared with 1 in patients with HCC within the Milan criteria. DFS was shorter in both the high-risk and the low-risk colorectal cancer groups compared with that in patients with HCC. The 5-year OS rate in the low-risk colorectal cancer group was 75 per cent, compared with 76 per cent in patients with HCC within the Milan criteria. The 5-year OS rate in patients with HCC beyond the Milan criteria was 56 per cent.

Conclusion
The low-risk group of patients with colorectal cancer and unresectable liver-only disease had a 5-year OS rate following liver transplantation similar to that of patients with HCC with lesions within the Milan criteria.

Survival following liver transplantation for liver‐only colorectal metastases compared with hepatocellular carcinoma

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.

https://bjssjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/bjs5.50278

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

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.

/pdf/growth-rates-of-pulmonary-metastases-after-liver-2g1psa2tm0.pdf

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

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