Background: Although level 1 data supports the use of adjuvant chemotherapy (ACT) in resected pancreatic adenocarcinoma (PDAC), the role of adjuvant chemoradiation (ACRT) remains controversial. The objective of this study is to investigate the impact of adding ACRT to ACT on overall survival (OS), based on lymph node (LN) and margin status. Methods: Resected AJCC Stage I and II PDAC patients from 2004-2013 identified within the National Cancer Database were classified into groups based on treatment: surgery alone (SX), ACT alone, ACT+ACRT, and ACRT only. Kaplan-Meier analyses were performed to determine median OS. Multivariable (MV) Cox regression models with interactions of treatment with LN and margin status were constructed to examine the independent effects of ACT and ACT+ACRT in these subgroups. Results: Of 31,348 patients, 30% were treated with SX, 30% with ACT, 38% with ACT+ACRT, and 2% with ACRT alone. Median OS (mos.) for ACT (22.5, 95% CI 21.9-23.1) and ACT+ACRT (23.7, 23.3-24.2) were significantly longer than SX (14, 13.4-14.5) or ACRT (11.2, 9.8-12.9). MV analysis confirmed a significant OS benefit of both ACT and ACT+ACRT controlling for patient and tumor related factors. ACRT+ACT was associated with improved OS compared to ACT in patients with positive margins and/or LN. Those with negative margins and LN did not benefit from the additional use of ACRT (Table). Conclusions: This large hospital-based study demonstrates that ACT and ACRT are associated with improved OS when compared to SX. The addition of ACRT to ACT, however, was only beneficial in high-risk patients with positive margins and/or LN. ACT+ACRT in patients with both margin and LN negative disease may not be warranted. Future clinical trials should stratify patients based on LN and margin status in order to determine which patients are most likely to benefit from the use of ACRT.

(*Significant survival benefit)