Patterns Of Failure Following Preoperative Chemotherapy And Stereotactic Body Radiation Therapy For Patients With Borderline Resectable Or Locally Advanced Pancreatic Cancer

Neoadjuvant stereotactic body radiation therapy (SBRT) has been associated with an elevated risk of locoregional recurrence (LRR) compared to conventional external beam radiation therapy for pancreatic cancer. The aim of this study is to report on treatment outcomes of patients with borderline resectable (BL) or locally advanced (LA) pancreatic cancer following preoperative chemotherapy and SBRT and to characterize patterns of failure. Between 2011-2019, 18 patients treated with neoadjuvant chemotherapy and SBRT for LA (n = 7) or BL (n = 11) pancreatic cancer followed by resection were eligible for inclusion. Patients received a median of 4 months (range 1-12 months) of neoadjuvant chemotherapy (FOLFIRINOX (n = 9), FOLFOX (n = 2), gemcitabine-abraxane (n = 2), and other combination (n = 5)). SBRT was prescribed to 30 Gy over 5 fractions to the pancreas planning tumor volume (PTV) and a simultaneous integrated boost was included in 9 patients to 35-45 Gy to the high risk vascular PTV. Surgery consisted of a Whipple procedure (n = 13), distal or subtotal pancreatectomy (n = 2), and total pancreatectomy (n = 3). Vascular reconstruction was required in 8 patients. Resectability and LRR were defined as per the Alliance A021501 trial. Overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) estimates were obtained using Kaplan-Meier analysis. Following neoadjuvant treatment, 5 patients (28%) had a pathologic complete response (pCR) or <5% viable cells on pathology. Surgical specimen tumor size ranged from microscopic disease to 7 cm. 7 patients (39%) had node positive disease. 12 patients (66%) had a margin negative pancreatic resection (82% for BL vs 43% for LA). At a median follow up of 24 months (range 10-98 months), no patients had an isolated LRR. 5 patients (28%) had concomitant LRR and distal recurrence, and 5 patients (28%) had a distal recurrence only. Of the patients with LRR, 3 patients had an infield recurrence, 1 patient in and out of field recurrence, and 1 patient had a recurrence outside of the PTV. There are no local failures in the patients who had a CR or near CR. For the entire cohort, 2-year LRC, PFS, and OS were 66%, 38%, and 58% respectively. For BL and LA cancers, 2-year LRC was 82% vs 32% (p = 0.13) respectively, 2-year PFS was 36% vs 46% (p = 0.57) respectively, and 2-year OS was 60%. Preoperative chemotherapy and SBRT for borderline resectable pancreatic cancers offers encouraging R0 resection rates and outcomes. While few out of field local failures were observed in the entire cohort, numerically higher R1 resection and associated in-field local failure rates were observed in locally advanced patients. Further study is necessary to define the optimal role for neoadjuvant SBRT.