Salvage hepatic artery infusion chemotherapy after first-line systemic failure in patients with unresectable cholangiocarcinoma.
Authors: Nasar Naaz , Armstrong Misha , Chou Joanne F. , Gonen Mithat , Soares Kevin , Balachandran Vinod P. , Drebin Jeffrey A. , Kingham T. Peter , Wei Alice Chia-Chi , D'Angelica Michael Ian , Cercek Andrea , Harding James J. , O'Reilly Eileen Mary , Abou-Alfa Ghassan K. , Park Wungki , Connell Louise Catherine , Kemeny Nancy E. , Jarnagin William R. 
Published: January 2024

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Background: Unresectable intrahepatic cholangiocarcinoma (IHC) is associated with poor overall survival (OS). Prior studies have suggested improved outcomes with hepatic artery infusion chemotherapy (HAIC), with or without systemic (SYS) compared to SYS alone, but the role of HAIC continues to evolve. This study compares outcome of HAIC when used as 1st line treatment compared to 2nd line therapy in patients with advanced IHC. Methods: In this retrospective review, 722 consecutive biopsy-proven, liver limited IHC were evaluated from 2000-2018. Patients undergoing upfront surgery or those with metastatic disease beyond regional lymph nodes were excluded. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox regression model was used to examine the association of HAIC given at any time point with OS. To further dissect the timing of HAIC therapy (1st vs 2nd line) on OS, multi-state models using parametric Cox regression, as well as separate Cause-specific hazard model to intergrade the transition to 2nd line HAIC from the 1st line SYS state were used to estimate the mean survival time from diagnosis. Results: 336 patients eligible for HAIC were analyzed: 137 patients began treatment with 1st line HAIC (median age 63, 40% male) and 199 patients received 1st line SYS (median age 64, 46% male). Median time to first treatment initiation was 1.8 vs 1.2 months for 1st line HAIC and SYS, respectively. Median OS of all patients was 22 months (95% CI: 20-25 months), and HAIC given at any time was associated with reduced all-cause mortality by 34% (HR: 0.66, 95%CI: 0.52-0.84). Multi-states analyses revealed that patients who received 1st line HAIC had a mean OS of 33 months from disease diagnosis. Patients who transitioned to 2nd line HAIC after 1st line SYS had a mean OS of 36 months from diagnosis, while those who failed 1st line SYS and continued 2nd line SYS had a mean OS of 22 months from diagnosis. Patients who received no further treatment after 1st line SYS had a mean OS of 9 months. Median OS from the start of 2nd line for patients who received 2nd line HAIC was 18 months and 8 months for patients who started 2nd line SYS therapy. The sites of progression of disease (POD) in different treatment groups has been described in the Table. Conclusions: HAIC treatment of unresectable liver-dominant IHC at any time was associated with reduced mortality by 34%. Mean OS in patients treated with 2nd line HAIC did not appear to be significantly different than those receiving HAIC as 1st line therapy and both appeared to be superior to 2nd line SYS. The survival benefits of HAIC appear to be maintained after failure of 1st line systemic chemotherapy. [Table: see text]