Background and Aims: In the last few years, there has been increasing interest in non-cancer medications and their potential anti-cancer activity. Data are not available in cholangiocarcinoma (CCA) patients. The aim of this study is to fill this gap by investigating the potential impact in terms of clinical outcome of the common non-cancer medications. Methods: All consecutive patients with CCAs were retrospectively identified from 7 Italian medical institutions. We investigated the role of intake of vitamin D, aspirin, metformin, statins, and diuretics. Results: A total of 537 patients with CCAs were identified; 197 patients undergoing surgery were evaluated for disease-free survival (DFS), and 509 patients with an advanced stage were evaluated for overall survival (OS). A longer DFS was found in patients with intake of vitamin D versus never users (HR 0.55, 95% CI 0.32–0.92, p = 0.02). In an advanced stage an association with OS was found in patients with intake of metformin versus never users (HR 0.70, 95% CI 0.52–0.93, p = 0.0162), and in patients who have started taking metformin after chemotherapy versus before chemotherapy and never users (HR 0.44, 95% CI 0.26–0.73, p = 0.0016). Conclusions: Our results highlighted that vitamin D intake improves DFS in patients undergoing surgery. Metformin intake after starting chemotherapy can improve the clinical outcome in advanced disease. These results could open up new therapeutic strategies in cholangiocarcinoma patients. We are planning to undertake a prospective study to validate these data.

Liver transplantation (LT) represents the primary curative option for HCC. Despite the extension of transplantation criteria and conversion with down-staging loco-regional treatments, transplantation is not always possible. The introduction of new standards of care in advanced HCC including a combination of immune checkpoint inhibitor-based therapies led to an improvement in response rates and could represent a promising strategy for down-staging the tumor burden. In this review, we identify reports and series, comprising a total of 43 patients who received immune checkpoint inhibitors as bridging or down-staging therapies prior to LT. Overall, treated patients registered an objective response rate of 21%, and 14 patients were reduced within the Milan criteria. Graft rejection was reported in seven patients, resulting in the death of four patients; in the remaining cases, LT was performed safely after immunotherapy. Further investigations are required to define the duration of immune checkpoint inhibitors, their minimum washout period and the LT long-term safety of this strategy. Some randomized clinical trials including immunotherapy combinations, loco-regional treatment and/or tyrosine kinase inhibitors are ongoing and will likely determine the appropriateness of immune checkpoint inhibitors’ administration before LT.

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In total 14/506 (2.7%) patients had some form of DPD deficiency. 8/14 patients went on to have 5FU-based chemotherapy. Five opted against treatment and one patient was found to have an alternative diagnosis and treated with non-5FU-based chemotherapy. Both commercial testing kits give recommendations for treatment dosing. Of the 8 we treated: one received the recommended reduced dose, 5 commenced at a lower dose (due to safety concerns) and 2 patients received higher than the recommended dose (due to result not being available before treatment started). One of these 2 patients, was de-escalated to the recommended dose. The other had retrospective testing at representation with metastases; she had previously received 1 cycle of adjuvant treatment at 100% of the dose (before routine testing), developed significant toxicity and stopped after cycle 1. 5/8 (62%) patients who received 5FU-based chemotherapy experienced grade 3 toxicities leading to cessation of 5FU-based chemo in 4/5 of the cases. The most common toxicities were: diarrhoea (5 patients e 1 grade 3 toxicity), nausea (5 patients e no grade 3 toxicities), fatigue (4 patients e all grade 1) and mucositis (3 patients e 1 grade 3 toxicity). Conclusion:Treatment decisions in colorectal oncology are often complex and it is clear that the presence of DPD deficiency adds further complexity to these situations. Patients with DPD deficiency can experience severe side effects when treated with fluoropyrimidines and clinicians fear harming patients. Decisions based on results showing DPD deficiency varied widely in our centre and we clearly need structured guidelines on how these results should influence our treatment decisions so as not to harm patients, but also to not exclude patients from potentially beneficial treatments.Acknowledgement: With thanks to the colo-rectal team at Weston Park Hospital.Legal entity responsible for the study: The authors.Funding: Biomnis provided free testing during the first three months and Weston Park Cancer Charity contributed apporoximately £200 to the processing fees during the first three months of testing. abstracts Annals of Oncology Volume 31 -Issue S3 -2020 S151