Survival outcomes in the modern era for localized pancreatic cancer with multi-agent chemotherapy and stereotactic body radiation therapy.
Authors: Sehgal Shuchi , Hill Colin , Fu Wei , Hu Chen , Hacker-Prietz Amy , Zheng Lei , Laheru Daniel A. , Herman Joseph M. , Narang Amol 
Published: January 2021

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Background: The benefit of stereotactic body radiation therapy (SBRT) in the neoadjuvant setting for patients with localized pancreatic adenocarcinoma (PDAC) remains an area of active investigation. Herein, we report on surgical, pathologic, and survival outcomes in a modern cohort of borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) patients (pts) who were treated at a high-volume institution with upfront chemotherapy (CTX) followed by SBRT. Methods: A prospectively collected institutional IRB-approved database was reviewed to identify PDAC pts diagnosed between 2015-2018. All pts were seen in our multidisciplinary clinic and treated with multiagent induction CTX followed by 5-fraction SBRT. In general, it was our institutional preference that ECOG 0-1 pts were recommended modified FOLFIRINOX (mFFX), whereas others were recommended gemcitabine/abraxane. Pathological outcomes by stage were characterized. Kaplan-Meier analysis was used to generate survival curves, and factors prognostic for survival were identified. Results: Our cohort consisted of 156 pts, including 92 LAPC pts (59%) and 63 BRPC pts (41%). Median follow-up from diagnosis was 21.0 months (range 4-49 mos). Of the entire cohort, 117 (75%) received mFFX and 37 (24%) received gemcitabine/abraxane. Median duration of upfront CTX before SBRT was 4.0 months, with 126 pts (80.8%) receiving greater than 4 months. After SBRT, 130 pts (84%) were surgically explored with 106 pts (68%) successfully resected. Of 106 pts who were resected, 97 pts (92%) achieved negative margins, 63 pts (59%) were node-negative, and eight pts (8%) achieved a pathological complete response (pCR). Among 63 BRPC pts, 49 pts (78%) underwent resection, of whom 47 pts (96%) achieved margin negative resection. Among 92 LAPC pts, 57 pts (62%) underwent resection, of whom 50 pts (88%) achieved margin negative resection. For the entire cohort, median overall survival (mOS) from diagnosis was 25.4 mos (95% CI: 22.2 to NR) and 17.6 mos from SBRT (95% CI: 16.1 to NR). ECOG 0-1, initial biopsy grade (well-to-moderately differentiated), duration of neaodjuvant CTX (≥ 4 mos), surgical resection, and receipt of adjuvant CTX were all associated with improved survival from diagnosis (all p < 0.05), but stage (BR vs. LAPC) was not ( p = 0.43). Conclusions: In a modern cohort of patients receiving mFFX (75%) followed by SBRT, a high proportion of pts were successfully resected with favorable pathologic outcomes. Interestingly, OS was not significantly different for BRPC vs LAPC. Factors that proved to be important with respect to OS included duration of neoaduvant CTX, performance status, initial biopsy grade, and receipt of adjuvant CTX, After maximal multiagent CTX, factors other than stage should be considered in determining which pts will benefit from SBRT and/or subsequent surgery.