Background: Population-based data on distal cholangiocarcinoma (DCC) from the Western world are not available, albeit essential to identify areas for improvement. This study investigated the incidence, treatment and outcomes, including time trends and predictors for survival, in a nationwide cohort of DCC. Methods: This is a retrospective cohort study of patients diagnosed with DCC (2009-2016) derived from the Netherlands Cancer Registry. Overall survival (OS) and its predictors were analyzed using Kaplan-Meier and Cox regression analysis. Time trends (2009-2012 versus 2013-2016) were assessed. Results: Overall, 1338 patients with DCC were included, with 1-, 3-and 5-year OS of 46%, 18%, and 11%. Incidence of DCC was 0.55-0.90 per 100.000 per year. Median OS was 10.4 months across all stages; 21.9 months for resected (n ¼ 620, 46.3%), 6.7 months for unresected nonmetastatic (n ¼ 445, 33.3%), and 3.6 months for metastatic DCC (n ¼ 273, 20.4%) (p < .001). After resection, 30-day mortality was 4.8% and 90-day mortality 7.7%. Patients with metastatic DCC who received chemotherapy (n ¼ 78, 28.6%) had a median OS of 8.2 versus 2.8 months for those not treated (p < .001). Over time, resection rates (53.6% to 61.7%, p ¼ .008) and use of palliative chemotherapy in metastatic DCC (22.3% to 32.9%, p ¼ .05) increased, without improvement in OS (10.3 vs 10.6 months, p ¼ .55). Independent poor prognostic factors for OS in resected disease were increasing age, pT3/T4 stage, higher lymph node ratio, poor differentiation, and R1 resection. Conclusions: In a nationwide cohort of DCC, resection rates and the use of chemotherapy increased whereas OS remained stable at 10.4 months.

Background No standard treatment is available for advanced biliary tract cancer (BTC) after first-line therapy with gemcitabine plus cisplatin (GEMCIS). The objective of this study was to evaluate safety and anti-tumour activity of fluorouracil, leucovorin, irinotecan plus oxaliplatin (FOLFIRINOX) as salvage treatment in patients with previously treated advanced BTC. Methods In this two-stage phase 2 study, patients with advanced BTC who had disease progression or unacceptable toxicity after ≥3 cycles of GEMCIS were eligible. Primary endpoints were safety and efficacy (defined as objective response rate, ORR). In stage one, ten patients were treated with FOLFIRINOX every 2 weeks. In stage two, an additional 20 patients were enrolled at a starting dose as defined in stage one, provided that in stage ≥1 objective response or ≥2 stable diseases were observed and ≤3 patients had serious adverse events (SAEs) within the first 6 weeks of treatment. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results Forty patients were screened for eligibility and 30 patients were enrolled. In stage one, one patient had a partial response and five patients had stable disease. One patient had a SAE during the first 6 weeks of treatment, and five patients required a dose reduction due to adverse events. The most common grade 3–4 adverse events in stage one were neutropaenia, mucositis and diarrhoea. Stage two was initiated with FOLFIRINOX in an adapted dose. In stage two, grade 3–4 neutropaenia, diarrhoea, nausea and vomiting were the most common adverse events. The ORR, median PFS and OS in all patients were 10%, 6.2 and 10.7 months, respectively. Conclusions In patients with advanced BTC who progressed after or were intolerant to GEMCIS, FOLFIRINOX can be administered safely and could be considered as an option for salvage treatment in these patients. Clinical trial registration ClinicalTrials.gov Identifier NCT02456714.

First-line gemcitabine and cisplatin is an effective and safe treatment for patients with unresectable BTC who do not meet the eligibility criteria for the ABC-02 trial. Median OS, PFS and treatment side effects were comparable between the patients who received chemotherapy (group I vs. group II).