Introduction Hepatic artery infusion (HAI) of chemotherapy has demonstrated disease control and suggested improvement in overall survival (OS) in intrahepatic cholangiocarcinoma (IHC). We report herein the long-term results and role of molecular alterations of a phase II clinical trial of HAI chemotherapy plus systemic chemotherapy, with a retrospective cohort of patients treated with HAI at Memorial Sloan Kettering Cancer Center. Methods This secondary analysis of a single-institution, phase 2 trial and retrospective cohort of unresectable IHC treated with HAI floxuridine (FUDR) plus systemic gemcitabine and oxaliplatin. The primary aim was to assess long-term oncologic outcomes. A subset underwent tissue-based genomic sequencing, and molecular alterations were correlated with progression-free survival (PFS) and OS. Results Thirty-eight patients were treated on trial with a median follow up of 76.9 months. Median PFS was 11.8 months (95% CI11-15.1). The median OS was 26.8 months (95% CI20.9-40.6). The 1-, 2- and 5-year OS rate was 89.5%, 55%, and 21% respectively. Nine (24%) received HAI with mitomycin C post FUDR progression with an objective response rate of 44% and a median PFS of 3.93 (2.33-NR) months. One-hundred and seventy patients not treated on the clinical trial were included in a retrospective analysis. Median PFS and OS was 7.93 (95%CI: 7.27-10.07) and 22.5 (95%CI : 19.5-28.3) months, respectively. Alterations in the TP53 and cell-cycle pathway had a worse PFS to HAI based therapy compared to wildtype disease. Conclusion In locally advanced IHC, HAI with FUDR in combination with systemic therapy can offer long term durable disease control. Molecular alterations may predict for response.

中文翻译：

---

肝动脉灌注化疗治疗晚期肝内胆管癌患者的长期结果


简介 肝动脉灌注 (HAI) 化疗已证明可以控制疾病，并表明可以改善肝内胆管癌 (IHC) 的总生存期 (OS)。我们在此报告了 HAI 化疗加全身化疗的 II 期临床试验的长期结果和分子改变的作用，其中包括在纪念斯隆凯特琳癌症中心接受 HAI 治疗的患者的回顾性队列。方法 这是对使用 HAI 氟尿苷 (FUDR) 加全身吉西他滨和奥沙利铂治疗的不可切除 IHC 的单机构 2 期试验和回顾性队列进行的二次分析。主要目的是评估长期肿瘤学结果。一个子集接受了基于组织的基因组测序，分子改变与无进展生存期 (PFS) 和 OS 相关。结果 38 名患者接受了试验治疗，中位随访时间为 76.9 个月。中位 PFS 为 11.8 个月 (95% CI11-15.1)。中位 OS 为 26.8 个月 (95% CI20.9-40.6)。 1年、2年和5年OS率分别为89.5%、55%和21%。 9 名 (24%) 患者在 FUDR 进展后接受 HAI 联合丝裂霉素 C 治疗，客观缓解率为 44%，中位 PFS 为 3.93 (2.33-NR) 个月。回顾性分析中纳入了一百七十名未接受临床试验治疗的患者。中位 PFS 和 OS 分别为 7.93 (95% CI: 7.27-10.07) 和 22.5 (95% CI: 19.5-28.3) 个月。与野生型疾病相比，TP53 和细胞周期途径的改变导致基于 HAI 的治疗的 PFS 更差。结论 在局部晚期 IHC 中，HAI 联合 FUDR 与全身治疗相结合可以提供长期持久的疾病控制。分子改变可以预测反应。