The Optimal Timing of Surgery Following Stereotactic Body Radiation Therapy for Borderline Resectable or Locally Advanced Pancreatic Cancer

Abstract

<h3>Purpose/Objective(s)</h3> In patients undergoing pre-operative stereotactic body radiotherapy (SBRT) for borderline resectable or locally advanced pancreatic adenocarcinoma (BRPC/LAPC), the optimal timing of surgery following SBRT is unknown. We aimed to assess the impact of time from SBRT to surgery on outcomes in this setting. <h3>Materials/Methods</h3> Patients treated at a single institution with BRPC/LAPC, who underwent neoadjuvant multi-agent chemotherapy followed by SBRT, and then surgical resection, were included in this analysis. Covariates were stratified by time from SBRT to surgery. Pearson's Chi-squared test was used to compare cohorts by time from SBRT to surgery with respect to baseline and treatment characteristics. A Cox regression model was used to identify variables associated with survival outcomes, with statistically significant covariates in univariable analysis included in multivariable modeling. <h3>Results</h3> One hundred seventy-one patients were ultimately included for analysis. The median time from SBRT to surgery was 6.4 weeks (range: 2.7 – 25.3, IQR 2.7 weeks). There was no statistically significant difference in age, sex, tumor location, neoadjuvant chemotherapy type (FOLFIRINOX vs gemcitabine/nab-paclitaxel) or chemotherapy duration >4 months, pathologic complete response (pCR) rates, or R0 resection rates by time from SBRT to surgery, using a 6-week cutoff. Local progression-free survival (LPFS) was higher in patients for whom time from SBRT to surgery was >6 weeks (1-yr LPFS 81.5% vs 70.2%, median LPFS 12.1 vs 10.8 months, log-rank P=.039). No difference in distant metastases-free survival or overall survival was detected. In univariable Cox regression, age, SBRT dose, neoadjuvant chemotherapy duration/type, tumor location, presence of pCR, and surgical margin status were not associated with LPFS, but time from SBRT to surgery less than 6 weeks (P=.042; HR 1.84 95% CI 1.02 – 3.30) and baseline elevated CA19-9 >200 U/mL (P=.018; HR 2.09, 95%CI 1.14 – 3.84) were significantly associated with reduced LPFS. In multivariable analysis, time from SBRT to surgery < 6 weeks (P=.011; HR 2.18, 95% CI 1.19 – 3.97) and baseline elevated CA19-9 (P=.006; HR 2.38, 95% CI 1.28 – 4.42) remained independently associated with reduced LPFS. Sensitivity analysis was performed excluding patients who had surgical resection >15 weeks after completion of SBRT (n=4). Time from SBRT to surgery <6 weeks and elevated baseline CA19-9 remained independently associated with reduced LPFS. <h3>Conclusion</h3> Prolongation of time from SBRT to surgery may be associated with improved local progression free survival. Further study is warranted to understand the factors that may contribute to differential local control rates based on time from SBRT to surgery.