e16267 Background: R1 margins after biliary tract cancer (BTC) resection are associated with high recurrence risk. The role of adjuvant radiotherapy and the impact of delayed adjuvant therapy remain incompletely known. We compared overall survival (OS) with adjuvant chemotherapy (AC) versus adjuvant chemoradiotherapy (ACRT) and evaluated whether treatment delay modifies outcomes in R1-resected BTC. Methods: We conducted a retrospective cohort study using the National Cancer Database, including adults (≥18y) with intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), or gallbladder cancer (GBC) diagnosed from 2011–2019 who underwent definitive surgery with R1 margins and received adjuvant therapy. Treatment was categorized as AC or ACRT and stratified by timing: timely ( < 60 days from surgery) versus delayed (≥60 days). Kaplan–Meier analyses compared OS across groups. The log-rank test was used to compare time-to-event outcomes between groups. Multivariable Cox regression adjusted for age, sex, race/ethnicity, facility type, Charlson–Deyo comorbidity score, and stage. Results: Among 87,340 BTC patients, 1,182 (1.4%) underwent R1 resection and received adjuvant therapy; 52.1% initiated adjuvant therapy timely, and 47.9% experienced a delay. Treatment distribution was: timely AC 29.6%, delayed AC 26.2%, timely ACRT 22.5%, delayed ACRT 21.7%. In the overall cohort, timely ACRT was associated with improved median OS compared with timely AC (25.2 vs 13.7 months; p < 0.001) and reduced mortality on multivariable analysis (HR 0.59, 95% CI 0.48–0.73; p < 0.001). In ECC, timely ACRT improved median OS compared with timely AC (28.7 vs 19.0 months; p = 0.03) and delayed AC (28.7 vs 25.1 months; p = 0.04), with reduced mortality risk (HR 0.61, 95% CI 0.42–0.88; p = 0.008). In GBC, delayed ACRT was associated with improved OS versus timely AC (22.7 vs 10.3 months; p < 0.001) and delayed AC (22.7 vs 14.7 months; p = 0.006), also demonstrating reduced mortality risk (HR 0.53, 95% CI 0.39–0.72; p < 0.001). In ICC, OS differences were not statistically significant (p = 0.46). Conclusions: In R1-resected BTC, ACRT was associated with improved OS compared with AC alone, particularly in ECC and GBC. In GBC, delayed ACRT remained associated with improved OS, suggesting radiotherapy may mitigate the adverse impact of delayed postoperative therapy in selected high-risk patients. Univariable and multivariable survival analysis of adjuvant chemoradiotherapy versus chemotherapy in R1-resected biliary tract cancers. Univariable Median OS (mo) Univariable p-value Multivariable* HR (95% CI) Overall Timely AC vs Timely ACRT 13.7 vs 25.2 <0.001 Ref vs 0.59 (0.48-0.73)<0.001 Gallbladder Adenocarcinoma Timely AC vs Delayed ACRT 10.3 vs 22.7 <0.001 Ref vs 0.53 (0.39-0.72)<0.001 Extrahepatic Cholangiocarcinoma Timely AC vs Timely ACRT 19.0 vs 28.7 0.03 Ref vs 0.61 (0.42-0.88)0.008
Özer et al. (Thu,) studied this question.