First-line chemotherapy with selective internal radiation therapy for intrahepatic cholangiocarcinoma: The French ACABi GERCOR PRONOBIL cohort

Abstract

Background & Aims: Selective internal radiation therapy (SIRT) is a promising option for liver-only unresectable intrahepatic cholangiocarcinoma (iCCA). The Real-SIRTCCA study retrospectively assessed the benefit of adding SIRT to chemotherapy in this setting within the French nationwide observational cohort ACABi-GERCOR-PRONOBIL. Methods: Inclusion criteria were advanced iCCA with limited or no extrahepatic disease, treated with first-line gemcitabine plus platinum chemotherapy +/- concurrent SIRT. All patients treated with chemotherapy and concurrent SIRT were included. To ensure groups’ similarity, a rigorous selection was applied to the chemo-only group, with exclusion of patients with liver involvement >50% and extrahepatic metastases. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response rate (ORR) and tumor resection rate. Propensity score and inverse probability of treatment weighting (IPTW) propensity approaches were used to address confounding factors between groups. Results: Between July 2007 and December 2023, 277 patients met the Real-SIRTCCA inclusion criteria, with 88 in the chemo-SIRT group and 189 in chemo-only group. Chemo-SIRT was associated with longer PFS (median = 10.8 vs. 5.5 months, hazard ratio [HR] 0.54, 95% CI 0.41-0.71, p <0.0001), a trend for longer OS (median = 22.5 vs. 15.1 months, HR 0.76, 95% CI 0.57-1.01), higher ORR (58.3% vs. 28.5%, odds ratio [OR] 3.51, 95% CI 2.03-6.09, p <0.0001), and resection rate (18.7% vs. 8.8%, p = 0.0279) compared to chemo-alone. After IPTW, the superiority of chemo-SIRT was confirmed with better PFS (HR 0.55, 95% CI 0.45-0.66, p <0,0001), OS (HR 0.70, 95% CI 0.58-0.85, p = 0.0004), ORR (OR 3.17, 95% CI 2.18-4.49, p <0.0001) and resection rate (OR 2.94, 95% CI 1.71-5.03, p <0.0001). Conclusions: Adding SIRT to first-line chemotherapy significantly improved survival outcomes, ORR, and secondary tumor resection rates in locally advanced iCCA. Prospective randomized data are needed to confirm these results. Impact and implications:: Herein, we report the results of the Real-SIRTCCA study, comparing the efficacy of the gemcitabine-platinum systemic first-line chemotherapy with or without selective internal radiation therapy (SIRT) in 277 patients with locally advanced intrahepatic cholangiocarcinoma within the cohort ACABi-PRONOBIL. An improvement of progression-free survival, overall survival, tumor response and secondary surgical resection rate was observed in favor of chemo-SIRT, before adjustment and after inverse probability of treatment weighting propensity score analyses. Even though prospective randomized data would be needed to confirm these findings, we believe that this study constitutes new evidence of the potential benefit of combining SIRT with chemotherapy. The safety and efficacy of this strategy whether as a bridge to intent-to-cure strategies or in a palliative setting, should encourage its adoption in a larger panel of clinical centers, or at very least, prompt clinicians to refer their patients to centers where SIRT is performed. Clinical trial number: NCT04935853.

Keywords

• cholangiocarcinoma
• biliary tract cancer
• SIRT
• radioembolization
• CISGEM
• GEMOX