Integrated Radiation Therapy With Immune-Chemotherapy for Unresectable Biliary Tract Cancer: An Exploratory Pilot Study.

PURPOSE: Although immunotherapy-chemotherapy represents the latest first-line standard for unresectable biliary tract cancer (BTC), the survival outcome remains unsatisfactory. Radiation therapy exerts synergistic effects with immunotherapy and chemotherapy, generating potential survival benefit for patients with BTC.

METHODS AND MATERIALS: This retrospective analysis evaluated 497 participants with histopathologically confirmed unresectable BTC treated at 2 tertiary medical centers between January 2020 and August 2024. Participants were stratified into 2 treatment groups: radiation therapy combined with immunochemotherapy (RT + IO + CT) versus immunochemotherapy alone (IO + CT). Propensity score matching (PSM) was implemented to control for baseline covariates. Primary endpoints included overall survival (OS) and progression-free survival (PFS). Secondary endpoints comprised objective response rate (ORR), disease control rate (DCR), and treatment-emergent adverse events (TEAEs).

RESULT: Following 1:1 PSM, the analytical cohort comprised 210 patients: 105 undergoing RT + IO + CT and 105 receiving IO + CT alone. At a median follow-up of 23.0 months, the RT + IO + CT cohort demonstrated significantly superior OS (15.0 vs 9.0 months; hazard ratio (HR), 0.58; P = .0014) and PFS (10.0 vs 5.0 months; HR, 0.56; P < .001) versus the IO + CT group. Multivariate analysis identified nonintrahepatic metastasis, tumor size <5 cm, baseline CA19-9 level <74 U/mL, first treatment line and RT + IO + CT treatment as independent predictors of prolonged OS. No significant difference between groups was observed in grade ≥3 TEAEs incidence (58.1% vs 55.2%; P = .676). In the intrahepatic cholangiocarcinoma (ICC) subgroup (n = 155), radiation therapy integration significantly improved both OS (HR, 0.56; P = .0025) and PFS (HR, 0.54; P < .001). Sequential radiation therapy demonstrated superior OS compared with IO + CT, whereas concurrent radiation therapy did not show a similar benefit.

CONCLUSION

The integration of radiation therapy with immunotherapy-chemotherapy significantly enhances survival outcomes in unresectable BTC without increasing severe toxicities, particularly demonstrating pronounced benefit in ICC. However, its efficacy and generalizability require confirmation through randomized controlled trials.