Purpose FGFR genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with FGFR GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown. Patients and Methods Patients with CCA with FGFR GAs were identified using next-generation sequencing or fluorescence in situ hybridization from four tertiary cancer centers and compared with FGFR wild-type counterparts. Data reviewed included demographic, treatment, overall survival (OS), and GA data. Fisher’s exact test, Kaplan-Meier plots, and log-rank tests were used for statistical analysis. Results Three hundred seventy-seven patients with CCA were identified, and 95 had FGFR GAs. FGFR2 GA was most common (n = 74, with 63 fusions) and seen in intrahepatic CCA. In patients with CCA, FGFR GAs occurred more frequently in younger patients (≤ 40 years; 20%) compared with older patients (> 40 years; 6.7%; P < .001), presented at an earlier stage (TNM stage I/II v III/IV: 35.8% v 22%, respectively; P = .001), and were associated with a longer OS compared with patients without FGFR GAs (37 v 20 months, respectively; P < .001). This difference remained significant after excluding 36 patients treated with FGFR inhibitors. There was no OS difference ( P = .60) between CCA with FGFR2 fusions (n = 63) versus other FGFR GAs (n = 29). Patients with FGFR GAs had a better OS with FGFR-targeted therapy compared with standard treatment ( P = .01). BAP1 mutation was the most common coexisting mutation without prognostic impact, whereas TP53 ( P = .04) and CDKN2A/B ( P = .04) were correlated with a shorter OS. Conclusion CCA with FGFR GAs represents a unique subtype occurring in younger patients with an indolent disease course. FGFR-targeted therapy may have a positive impact on OS in this subgroup.

Background: Patients with solid organ transplants (SOTs) have been excluded from programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor clinical trials due to concern for allograft rejection. The use of immune checkpoint inhibitor therapy remains controversial in transplant patients. Methods: A retrospective pilot evaluation was conducted to assess the safety and efficacy of PD-1 inhibitors in patients with liver transplantation (LT). The primary endpoint was the rate of allograft rejection. Secondary endpoints included overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Translational objectives included evaluation of tumor PD-L1, tumor infiltrating lymphocytes (TILs) and allograft PD-L1 expression. Results: Seven metastatic cancer patients with a history of LT who received PD-1 inhibitor therapy were included [hepatocellular carcinoma (HCC), n=5; melanoma, n=2]. Rejection was observed in 2 of 7 patients. When rejection occurs it appears to be an early event with a median time to rejection of 24 days in our cohort. One patient achieved a complete response (CR), 3 patients had progressive disease (PD) and 3 patients discontinued therapy prior to restaging assessments. Two of five patients with available tissue had PD-L1 expression in the allograft and both developed rejection. One of five evaluable patients had abundant TILs. Two of five evaluable patients had PD-L1 tumor staining. The single patient with both abundant TILs and PD-L1 staining obtained a response. The median OS and PFS were 1.1 (0.3-21.1) and 1.8 (0.7-21.1) months, respectively. Conclusions: In this pilot evaluation both preliminary efficacy (1 of 4) and allograft rejection (2 of 7) were exhibited in evaluable patients. Larger, prospective trials are needed to elucidate optimal patient selection.

This study demonstrates that HBCa surveillance significantly improves outcomes, including survival, in patients with PSC. (Hepatology 2018;67:2338-2351).