Utilization of the Triangle Volume in Patients with Localized PDAC Undergoing Pre-Operative SBRT: Report of Early Outcomes

Abstract

In patients with borderline resectable or locally advanced pancreatic adenocarcinoma (BRPC/LAPC), advances in neoadjuvant therapy have led to an increased proportion of patients undergoing margin negative resection. Nevertheless, locoregional recurrence rates remain high. We have previously reported that the location of locoregional recurrences in this setting map to the "Triangle Volume (TV)," the anatomical space between the celiac artery, superior mesenteric artery, common hepatic artery, and portal vein, which is enriched in extrapancreatic perineural tracts at risk for microscopic residual disease after resection. At the beginning of 2021, we systematically changed our target volume to include the TV, in addition to gross disease and involved vasculature. Herein, we report early locoregional failure outcomes after resection in the setting of BRPC or LAPC treated with pre-operative stereotactic body radiation therapy (SBRT) to the TV, as compared to historical rates. Patients who received a diagnosis of BRPC or LAPC and who were treated at our institution with neoadjuvant chemotherapy (CTX) and SBRT between 2016 and 2022 were retrospectively reviewed. Between 2016 and 2020, the SBRT clinical tumor volume (CTV) included gross disease and full circumference of involved vasculature at the level of involvement. From 2021 onward, the CTV also included the TV. Survival was estimated using the Kaplan-Meier method. Statistical analyses were performed using scientific 2-D graphing and statistics software. From January 2016 to December 2022, 204 patients with localized PDAC underwent neoadjuvant CTX followed by SBRT. After completion of SBRT, all patients proceeded with surgical exploration. Of these patients, 111 (54%) had LAPC and 92 (45%) had BRPC disease. All patients were treated with induction CTX, mostly commonly with FOLFIRINOX (N = 166, 81%). Following CTX, the most frequently used SBRT regimen was 33 Gy in 5 fractions (N = 191, 94%). 155 (67%) patients were treated between 2016 and 2020 to the traditional CTV, while 49 (24%) patients were treated after 2020 to a CTV that included the TV. The 2-year local progression free survival rate of patients treated with SBRT using the TV was 77.6% as compared to 47.5% in patients treated with the traditional CTV. Over a median follow up of 15.7 months (range: 1 to 78.2 months), 47% (N = 73 out of 155) of patients who underwent SBRT with the traditional CTV developed locoregional recurrence, but only 12% (N = 6 out of 49) treated with SBRT to the TV have thus far developed locoregional recurrence (p<0.0001). In patients with localized PDAC who undergo pre-operative SBRT for BRPC/LAPC, targeting the TV may help reduce locoregional recurrence. More data and longer follow-up are needed to verify these findings and inform whether the TV may serve as a new standard for target volume delineation in this setting.