Association Between Cumulative Chemotherapy Exposure and Survival Outcomes in Advanced Biliary Tract Cancer

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Abstract
Background: This study evaluated the association between cumulative chemotherapy exposure and overall survival (OS) in patients with advanced biliary tract cancer (BTC) and explored baseline factors associated with prolonged treatment continuation. Methods: Patients with advanced BTC receiving systemic chemotherapy were stratified by cumulative chemotherapy exposure (p < 0.001). Multivariable logistic regression identified metastatic disease as an independent factor associated with a lower likelihood of receiving ≥8 cycles (OR 0.34, 95% CI 0.12–0.97, p = 0.044). In landmark-adjusted multivariable analysis (n = 66), receiving ≥8 chemotherapy cycles remained independently associated with longer OS (HR 0.46, 95% CI 0.22–0.96, p = 0.039). Restricted cubic spline analysis demonstrated progressive hazard reduction with increasing chemotherapy exposure, although the magnitude of reduction attenuated beyond approximately 8 cycles. Conclusion: Greater cumulative chemotherapy exposure was associated with prolonged OS in advanced BTC, with attenuation of the survival benefit beyond approximately 8 cycles. Sustained treatment exposure may partly reflect preserved physiological reserve and ability to maintain systemic therapy in real-world clinical practice.

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