Background Hepatic artery infusion of chemotherapy has demonstrated disease control and suggested improvement in overall survival in intrahepatic cholangiocarcinoma. We report herein the long-term results and role of molecular alterations of a phase II clinical trial of hepatic artery infusion chemotherapy plus systemic chemotherapy, with a retrospective cohort of patients treated with hepatic artery infusion at Memorial Sloan Kettering Cancer Center. Methods This is a secondary analysis of a single-institution, phase II trial, and retrospective cohort of unresectable intrahepatic cholangiocarcinoma treated with hepatic artery infusion floxuridine 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 overall survival. Results A total of 38 patients were treated on trial with a median follow-up of 76.9 months. Median PFS was 11.8 months (95% confidence interval [CI] = 11 to 15.1 months). The median overall survival was 26.8 months (95% CI = 20.9 to 40.6 months). The 1-, 2-, and 5-year overall survival rate was 89.5%, 55%, and 21%, respectively. Nine (24%) patients received hepatic artery infusion with mitomycin C post-floxuridine progression with an objective response rate of 44% and a median PFS of 3.93 months (95% CI = 2.33 months to not reached). A total of 170 patients not treated on the clinical trial were included in a retrospective analysis. Median PFS and overall survival were 7.93 months (95% CI = 7.27 to 10.07 months) and 22.5 months (95% CI = 19.5 to 28.3 months), respectively. Alterations in the TP53 and cell-cycle pathway had a worse PFS to hepatic artery infusion–based therapy compared with wild-type disease. Conclusion In locally advanced intrahepatic cholangiocarcinoma, hepatic artery infusion with floxuridine in combination with systemic therapy can offer long-term durable disease control. Molecular alterations may predict for response.

中文翻译：

---

接受肝动脉灌注化疗的晚期肝内胆管癌患者的远期结局


背景 肝动脉输注化疗已证明疾病得到控制，并表明肝内胆管癌的总生存期有所改善。我们在此报告了肝动脉输注化疗加全身化疗的 II 期临床试验的长期结果和分子改变的作用，回顾性队列是在纪念斯隆凯特琳癌症中心接受肝动脉输注治疗的患者。方法 这是对肝动脉输注氟尿苷加全身性吉西他滨和奥沙利铂治疗的不可切除肝内胆管癌的单机构、II 期试验和回顾性队列的二次分析。主要目的是评估长期肿瘤学结局。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） 和总生存期相关。结果 共有 38 例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% 置信区间 [CI] = 11 至 15.1 个月）。中位总生存期为 26.8 个月 （95% CI = 20.9 至 40.6 个月）。1 年、 2 年和 5 年总生存率分别为 89.5% 、 55% 和 21%。9 例 （24%） 患者在氟尿苷进展后接受肝动脉输注丝裂霉素 C，客观缓解率为 44%，中位 PFS 为 3.93 个月 （95% CI = 2.33 个月未达到）。共有 170 名未接受临床试验治疗的患者被纳入回顾性分析。中位 PFS 和总生存期分别为 7.93 个月 （95% CI = 7.27 至 10.07 个月） 和 22.5 个月 （95% CI = 19.5 至 28.3 个月）。 与野生型疾病相比，基于肝动脉输注的治疗的 TP53 和细胞周期通路的改变 PFS 更差。结论 在局部晚期肝内胆管癌中，肝动脉输注氟尿苷联合全身治疗可提供长期持久的疾病控制。分子改变可以预测反应。