Systematic review and pooled analysis of locoregional therapies in patients with intrahepatic cholangiocarcinoma

Background Locoregional treatments (LRT) including radioembolisation (SIRT), transarterial chemo-embolisation (TACE), hepatic arterial infusion (HAI) of chemotherapy, external beam radiotherapy (EBRT) and ablation, have been studied for the management of intrahepatic cholangiocarcinoma (iCC). The aim of this systematic review was to provide outcome benchmarks for clinical trial design. Methods Identification of studies reporting outcomes of patients treated with LRT for iCC was performed using PubMed and Embase. Pooled weighted means were calculated for progression-free survival (PFS) and overall survival (OS); meta-analysis of proportions was used for estimation of pooled response rate. Results 6325 entries were reviewed; 93 studies were eligible, representing 101 cohorts and a total of 3990 patients [15 cohorts (645 patients) for ablation, 18 cohorts (541 patients) for EBRT, 27 cohorts (1232 patients) for SIRT, 22 cohorts (1145 patients) for TACE, 16 cohorts (331 patients) for HAI and 3 cohorts (96 patients) not pooled]. 74% of the studies were retrospective, 93% non-randomised; and 19% were only available in abstract form. The pooled mean weighted OS was 30.2 months (95% confidence interval (CI): 21.8-38.6) for ablation, 18.9 (14.2-23.5) for EBRT, 14.1 (12.1-16.0) for SIRT, 15.9 (12.9-19.0) for TACE and 21.3 (15.4-27.1) for HAI. The pooled complete response rate was 93.9% for ablation. When analysed together, SIRT, TACE and HAI had a pooled mean weighted OS of 15.7 months (all patients) and 25.2 months for patients treated in first-line with concomitant systemic chemotherapy. Conclusions Available literature on LRT for iCC was heterogeneous and of insufficient quality to make strong recommendations. Ablation achieved satisfactory outcomes, and may be recommended when surgery is not feasible. Benchmark outcome estimates are provided to inform the design of phase III trials. Legal entity responsible for the study The authors. Funding Dr Angela Lamarca received funding from The Christie Charity and the European Union’s Horizon 2020 Research and Innovation Programme [grant number 825510, ESCALON]; she is a member of the COST Action European Cholangiocarcinoma Network, supported by COST (European Cooperation in Science and Technology; www.cost.eu), a funding agency for research and innovation networks. Disclosure J. Edeline: Research grant / Funding (institution): Beigene. A. Lamarca: Advisory / Consultancy: QED Speaker Bureau / Expert testimony: QED; Travel / Accommodation / Expenses: QED. D. Palmer: Advisory / Consultancy: Servier, Celgene. B. Guiu: Advisory / Consultancy: Boston Scientific. All authors have declared no conflicts of interest.