Tor Magnus Smedman

Pushing to resect colorectal liver metastases: rethinking surgical strategy in colorectal liver metastases with extrahepatic spread

Background: The incidence of colorectal cancer is increasing, and the liver remains the predominant site for metastases. Whereas liver resection is the standard treatment for colorectal liver metastases (CRLMs), liver transplantation (LT) has re-emerged as a viable option for selected patients. The aim of this study was to investigate whether tumour volume and changes in tumour volume during chemotherapy before transplantation predict overall survival. Methods: Patients who underwent LT for CRLMs between November 2006 and August 2020 were included. Tumour volumes were measured via manual segmentation on computerized tomography scans at baseline, at maximum tumour volume, and immediately before LT. Response to chemotherapy was assessed using Response Evaluation Criteria in Solid Tumours (RECIST) criteria, and the heterogeneous response was noted to investigate whether this subgroup performs differently. Receiver operating characteristic analysis was conducted to determine a tumour volume cut-off value for predicting overall survival. Overall survival between groups was compared using Kaplan–Meier curves and log rank test. Results: Fifty-nine patients who underwent LT for CRLMs were analysed retrospectively. Receiver operating characteristic analysis revealed that final tumour volume at time of LT was a strong predictor of 5-year overall survival (area under the curve= 0.789), with a 35 mL cut-off providing optimal clinical discrimination. Patients achieving a final tumour volume below 35 mL, either consistently or via downstaging, demonstrated significantly improved survival compared with those with persistently high tumour volumes (4.54 years versus 2.17 years; P < 0.001). Heterogeneous responses to chemotherapy were associated with poorer prognosis with no patients surviving beyond 2.16 years (P < 0.001). Conclusion: Dynamic tumour assessment, particularly measuring tumour volume to below 35 mL, is an important prognostic marker in LT for CRLMs.

Colorectal cancer (CRC) is a leading cause of cancer mortality in Norway, with liver metastases being the most frequent manifestation. Liver transplantation (LT) has shown promise as a treatment for colorectal liver metastases (CRLM), with recent studies reporting improved 5-year overall survival (OS) rates ranging from 60% to 83%. However, the scarcity of available donor organs poses a significant challenge. Living donor liver transplantation (LDLT) utilizing segments 2+3 grafts by the RAPID technique (Resection and Partial Liver Transplantation with Delayed Hepatectomy) has been explored as a potential solution. This study aimed to assess the attitudes and considerations of next of kin toward living liver donation for patients with CRC. A survey was administered to three cohorts: next of kin to patients who underwent LT for CRLM, next of kin to patients with metastatic CRC ineligible for LT or liver resection, and healthcare workers with a healthy next of kin. The results showed that all respondents were willing to donate a portion of their liver if it could extend the recipient's survival. A significant majority (78%) expressed willingness to donate if it could extend survival by 6 months to 1 year. Children, siblings, or parents were more likely to find a survival benefit of 1 year or less acceptable compared to spouses or partners. The findings suggest that securing living familial donors for CRLM patients in Norway is feasible.

Colorectal cancer is the second most common cause of cancer-related death worldwide, and liver metastases are the leading cause of mortality in these patients. Surgical innovations combined with modern systemic chemotherapy have improved 5-year overall survival rates. This review aims to equip non-hepatobiliary surgeons with a comprehensive toolbox for the diagnosis and management of colorectal liver metastases. It covers the current landscape of diagnostic workup, including imaging modalities and biomarkers, and reviews the surgical and nonsurgical treatment options. This guide attempts to enhance multidisciplinary care for patients with colorectal liver metastases by integrating evidence-based practices with innovative strategies, which can improve outcomes and survival.

The objective of the study was to determine the impact of PET uptake on liver metastases on overall survival (OS) after resection of pulmonary metastases in patients who had received liver transplantation (LT) due to unresectable colorectal liver-only metastases. Resection of pulmonary colorectal metastases is controversial. Some hospitals offer this treatment to selected patients, whereas other hospitals do not perform the procedure in colorectal cancer patients who develop pulmonary metastases. All patients included in the LT studies who developed pulmonary metastases as first site of relapse, and had resection of these as first treatment, were included in this report. Metabolic tumor volume (MTV) in liver was derived from the pre-transplant PET examinations. OS from time of resection was calculated by the Kaplan–Meier method. Patients with low MTV (70 cm³). Patients with low MTV in the liver had 10-year OS from time of pulmonary resections of 86%. Liver MTV values from pre-transplant PET examinations may predict long OS in colorectal cancer patients with a resection of pulmonary metastases developing after LT. Thus, in selected colorectal cancer patients developing pulmonary metastases resection of these metastases should be the treatment of choice.

Funding/Disclosure: Supported by Oslo University Hospital and the South-Eastern Norway Health Authority. The authors declare no conflicts of interest. Patients with colorectal cancer with unresectable liver metastases have an expected median overall survival of approximately 30 months with current standard treatment with palliative chemotherapy. Liver transplantation for these patients has showed encouraging results and has gained increased interest in recent years, currently being investigated in several clinical trials. We report a male patient who received liver transplantation due to non-resectable colorectal liver metastases. Shortly after the introduction of sirolimus the patient presented with severe pancytopenia with myelodysplastic syndrome-like bone marrow features, and was given a dismal prognosis. The condition was reversed when the immunosuppressive regimen was changed to cyclosporine. We cannot exclude the possibility of myelodysplastic syndrome in this case, but bone marrow failure with dysplastic features induced by immunosuppressant drugs in a patient who was previously treated by chemotherapy is a likely alternative explanation. This case illustrates the clinical relevance of sirolimus/tacrolimus induced pancytopenia, especially in patients treated with chemotherapy prior to transplantation. The bone marrow failure may be reversible with a change in the immunosuppressive regimen, as shown in this case. Abbreviations: CRC: Colorectal Cancer; OS; Overall Survival; LT: Liver Transplantation; PR: Partial Response; PD: Progressive Disease; WBC: White Blood Cell Count; ANC: Absolute Neutrophil Count; TRC: Thrombocytes; Hb: Hemoglobin; MDS: Myelodysplastic Syndrome; CHIP: Clonal Hematopoiesis Of Indeterminate Potential

Liver transplantation (LT) for patients with non-resectable colorectal liver metastases (CRLM) offers improved survival and has gained increased interest internationally the last years. The aim of this study was to describe the health-related quality of life (HRQoL) in patients with non-resectable CRLM receiving LT and how baseline HRQoL factors affect overall survival (OS). HRQoL data in the SECA (SEcondary CAncer) LT cohort was compared to data obtained from colorectal cancer patients starting first-line chemotherapy for metastatic disease in a clinical trial and data from a Norwegian normal population. HRQoL data from the QLQ-C30 questionnaire used in the SECA LT study and the NORDIC- VII study were reported. The relationship between patient-reported symptom burden at baseline and OS was investigated. In the SECA study longitudinal HRQoL assessment was used to describe the time until definitive deterioration as well as mean values at different time points. Patients in the SECA and NORDIC-VII studies reported similar baseline HRQoL. The median time until definitive deterioration in the transplanted patients was estimated to 36 months. In the SECA study appetite loss and pain at baseline had negative impact on OS (25.3 versus 71.7 months, p = 0.002 and 39.7 versus 71.7 months, p = 0.038, respectively). Despite a relapse in most of the LT patients the Global Health Score (GHS) remained good. Pain, and especially appetite loss at time of transplantation is associated with poor outcome after LT.

Liver transplantation (LT) in selected colorectal cancer (CRC) patients with nonresectable liver-only metastases may result in 5-year overall survival of up to about 70–100%. However, the majority will have recurrent disease. All patients included in this report were included in prospective studies. Forty-four out of 56 patients had a relapse, and all 44 patients received treatment for recurrent disease. The organ of the first relapse was lung metastases in 23 of the 44 patients. The first treatment modality of the relapse was the treatment with curative intent in 55.8% of the patients, and chemotherapy was the first treatment administered to 25.6% of the patients. Patients receiving surgery of lung metastases had a 5-year overall survival of 66.5% from the time of metastasectomy. Patients receiving treatment with curative intent for metastases to other organs had a 5-year overall survival of 24.8%. Nine of the 44 patients had no evidence of disease (NED) at the end of the follow-up. Median time of NED in these patients was 54.3 months, and median overall survival from the time of LT was 8.4 years. Because of the high incidence of recurrent disease, these patients should have a systematic long-term follow-up since many of the relapses may be treated with curative intent.

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.