Cowzer Darren, Soares Kevin, Walch Henry, Gönen Mithat, Boucher Taryn M, Do Richard K G, Harding James J, Varghese Anna M, Reidy-Lagunes Diane, Saltz Leonard, Connell Louise C, Abou-Alfa Ghassan K, Wei Alice C, Schultz Nikolaus, Kingham T Peter, D'Angelica Michael I, Drebin Jeffrey A, Balachandran Vinod, Sanchez-Vega Francisco, Kemeny Nancy E, Jarnagin William R, Cercek Andrea
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
J Natl Cancer Inst. 2025 Feb 1;117(2):279-286. doi: 10.1093/jnci/djae202.
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.
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.
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.
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.
肝动脉灌注化疗已显示出对肝内胆管癌的疾病控制作用，并提示可改善总生存期。我们在此报告一项肝动脉灌注化疗联合全身化疗的II期临床试验的长期结果及分子改变的作用，该研究纳入了纪念斯隆凯特琳癌症中心接受肝动脉灌注治疗的患者回顾性队列。
这是一项对单一机构的II期试验及不可切除肝内胆管癌回顾性队列的二次分析，这些患者接受了氟尿苷肝动脉灌注联合吉西他滨和奥沙利铂全身化疗。主要目的是评估长期肿瘤学结局。对一个亚组进行了基于组织的基因组测序，并将分子改变与无进展生存期（PFS）和总生存期相关联。
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了丝裂霉素C肝动脉灌注，客观缓解率为44%，中位PFS为3.93个月（95%CI=2.33个月至未达到）。共有170例未参加该临床试验的患者纳入回顾性分析。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，TP53和细胞周期途径的改变对基于肝动脉灌注的治疗的PFS更差。
在局部晚期肝内胆管癌中，氟尿苷肝动脉灌注联合全身治疗可实现长期持久的疾病控制。分子改变可能预测疗效。
