Radioterapia Integrada con Inmunoterapia-Quimioterapia para el Cáncer de Vías Biliares Irresecable: Un Estudio Piloto...

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

This retrospective analysis evaluated 497 participants with histopathologically confirmed unresectable BTC treated at two tertiary medical centers between January 2020 and August 2024. Participants were stratified into two treatment groups: radiotherapy combined with immuno-chemotherapy (RT+IO+CT) versus immuno-chemotherapy 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).

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; HR=0.58, P=0.0014) and PFS (10.0 vs 5.0 months; HR=0.56, P<0.001) versus the IO+CT group. Multivariate analysis identified non-intrahepatic metastasis, tumor size<5cm, baseline CA19-9 level<74 U/mL, first treatmentline 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=0.676). In the intrahepatic cholangiocarcinoma (ICC) subgroup (n=155), radiotherapy integration significantly improved both OS (HR=0.56, P=0.0025) and PFS (HR=0.54, P<0.001). Sequential radiotherapy demonstrated superior OS compared to IO + CT, whereas concurrent radiotherapy did not show a similar benefit.

The integration of radiotherapy 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.