Objective Epidemiological data on synchronous and metachronous lung metastases from colorectal cancer are scarce. The aim of this study was to determine trends in the incidence, treatment and survival in colorectal cancer with lung metastases in the general population. Design and patients All cases of lung metastases from colorectal cancer registered in the Burgundy digestive cancer registry between 1976 and 2005 were included. Trends in the incidence of synchronous colorectal cancer lung metastases were estimated. A Cox model was used to analyse the risk of developing a metachronous metastasis. Multivariate analyses were performed using a relative survival model with proportional hazard applied to the net survival by interval. Results Overall, 11.0% of patients had synchronous lung metastases. The frequency of synchronous lung metastases significantly increased for both sexes over time, with a nearly threefold increase between the periods 1976–1985 and 1996–2005. The overall 5-year cumulative risk of developing metachronous lung metastases was 5.8%. It did not significantly vary with time. Compared to colon cancer, rectal cancers had a higher risk of developing synchronous (OR: 2.80 (1.65–4.76)) and metachronous (OR: 2.63 (1.69–4.08)) lung metastases. Overall, 4.1% of synchronous lung metastases and 14.3% of metachronous lung metastases were resected for cure. The 3-year relative survival was 11.3% for synchronous lung metastases and 13.8% for metachronous lung metastases. It was, respectively, 53.0% and 59.2% after resection for cure. In multivariate analysis, the relative risk of death for the 1996–2005 period was about one fifth of that for the 1976–1985 period. Conclusions The incidence of synchronous lung metastases increased over time, whereas the incidence of metachronous lung metastases remained stable. Lung metastases were more frequent in rectal cancer than in colon cancer. Unless surgical resection is possible, the prognosis for lung metastases remains very poor.

Importance Patients with unresectable intrahepatic cholangiocarcinoma (ICC) have a poor prognosis. Selective internal radiotherapy (SIRT) is a promising treatment option for hepatic tumors, but no prospective studies of combination SIRT with chemotherapy have been published to our knowledge. Objective To determine the response rate after SIRT combined with chemotherapy in patients with unresectable ICC. Design, Setting, and Participants This phase 2 clinical trial, the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) trial, included patients with unresectable ICC who have never received chemotherapy or intra-arterial therapy and were treated at 7 centers which had experience with SIRT between November 12, 2013, and June 21, 2016. Statistical analysis was performed from March 31, 2017, to June 17, 2019. Interventions Concomitant first-line chemotherapy with cisplatin, 25 mg/m², and gemcitabine, 1000 mg/m²(gemcitabine reduced to 300 mg/m²for the cycles just before and after SIRT), on days 1 and 8 of a 21-day cycle for 8 cycles. Selective internal radiotherapy was administered during cycle 1 (1 hemiliver disease) or cycles 1 and 3 (disease involving both hemilivers) using glass Y⁹⁰microspheres. Main Outcomes and Measures Response rate at 3 months according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary end points were toxic effects, progression-free survival, overall survival, disease control rate, and response rate according to Choi criteria. Results Of 41 patients included in the study, 26 (63%) were male, with a mean (SD) age of 64.0 (10.7) years. Response rate according to RECIST was 39% (90% CI, 26%-53%) at 3 months according to local review and was confirmed at 41% as best response by central review; disease control rate was 98%. According to Choi criteria, the response rate was 93%. After a median follow-up of 36 months (95% CI, 26-52 months), median progression-free survival was 14 months (95% CI, 8-17 months), with progression-free survival rates of 55% at 12 months and 30% at 24 months. Median overall survival was 22 months (95% CI, 14-52 months), with overall survival rates of 75% at 12 months and 45% at 24 months. Of 41 patients, 29 (71%) had grades 3 to 4 toxic effects; 9 patients (22%) could be downstaged to surgical intervention, with 8 (20%) achieving R0 (microscopic-free margins) surgical resection. After a median of 46 months (95% CI, 31 months to not reached) after surgery, median relapse-free survival was not reached among patients who underwent resection. Conclusions and Relevance Combination chemotherapy and SIRT had antitumor activity as first-line treatment of unresectable ICC, and a significant proportion of patients were downstaged to surgical intervention. A phase 3 trial is ongoing.

Background: Adipose tissue releases angiogenic factors that may promote tumour growth. Objective: To determine whether body mass index (BMI), subcutaneous fat area (SFA) and visceral fat area (VFA) are associated with outcomes in patients given first-line bevacizumab-based treatment for metastatic colorectal cancer (MCC). Patients: CT was used to measure SFA and VFA in 120 patients with MCC who received bevacizumab-based treatment (bevacizumab group, n=80) or chemotherapy alone (chemotherapy group, n=40) as first-line treatment. Associations linking BMI, SFA and VFA to tumour response, time-to-progression (TTP) and overall survival (OS) were evaluated. Results: In the bevacizumab group, median follow-up lasted for 24 months (3–70). BMI, SFA and VFA values above the median (ie, high BMI, high VFA and high SFA) were significantly associated with absence of a response. TTP was shorter in patients with high BMI (9 vs 12 months; p=0.01) or high VFA (9 vs 14 months; p=0.0008). High VFA was associated with shorter OS (p=0.0493). By multivariate analysis, high VFA was independently associated with response, TTP and OS (HR=7.18, p=0.008, HR=5.79, p = 0.005 and HR=2.88, p = 0.027, respectively). In the chemotherapy group, median follow-up lasted for 30 months (4–84). BMI, SFA and VFA were not associated with response, TTP or OS. In the whole population, interaction between VFA and bevacizumab administration was significant for response (OR=3.31, p=0.005) and TTP (HR=1.64, p=0.022), thereby confirming the results. Conclusion: This study provides the first evidence that high VFA independently predicts a poorer outcome in patients given first-line bevacizumab-based treatment for MCC. However, this predictive biomarker needs to be validated in a different dataset.