Neoadjuvant SBRT plus Elective Nodal Irradiation with Concurrent Capecitabine for Patients with Resectable Pancreatic Cancer: Survival Analysis of a Prospective Phase 1 Trial.

Abstract

Background and purpose: Elective nodal irradiation (ENI) in resectable pancreatic cancer remains undefined, though occult nodal disease is common. This study investigated the use of neoadjuvant stereotactic body radiation therapy (SBRT) to primary disease with ENI, with concurrent capecitabine. Safety data for this protocol were previously reported. In this report, we provide an updated survival analysis.

Materials and methods: This is a prospective, single institution, phase IA/B dose-escalation trial that enrolled patients with biopsy-proven, resectable, pancreatic adenocarcinoma between 2014 - 2019 (NCT1918644). Patients were enrolled into one of the 3 cohorts with escalating dose levels. Neoadjuvant SBRT to the primary tumor was delivered in 5 fractions of 5, 6, or 7 Gy with concomitant capecitabine (1650 mg/m2). All patients received ENI 5 Gy x 5 fractions. Our initial report found no dose-limiting toxicities. Clinicopathologic features were summarized using descriptive statistics. Kaplan-Meier (KM) curves were employed for survival analysis.

Results: Of 17 enrolled patients, 16 were evaluable (94.1%). Thirteen (76.5%) proceeded to surgery. Median follow up was 28.0 months (1.7 - 71.9). Four patients (25.0%) received neoadjuvant chemotherapy and six (37.5%) received adjuvant chemotherapy. Pathologic nodal involvement (69.2%) was associated with a higher risk of any relapse (p<0.01) and distant metastasis (p=0.02). Local failure occurred in 4 (25%) patients with 2/4 of those failures occurring partially within the 25 Gy elective nodal field and 1/4 occurred in the 25 Gy elective nodal field and partially within the 35 Gy tumor field. The median overall survival (OS) and disease-free survival (DFS) were 31.1 months (range, 2.3 - 73.6) and 12.0 months (range, 0.4 - 71.9), respectively. Three-year OS and DFS were 50% and 31.3% overall, and 61.5% and 38.5% for the surgical cohort. Patients with pN+ had worse median OS (23.9 vs 69.3 months; p=0.002) and DFS (9.9 vs 58.9 months; p=0.002). No further radiation related toxicities were noted since the prior report.

Conclusion: Neoadjuvant SBRT to the primary tumor with ENI and radiosensitizing chemotherapy is a feasible approach that may improve outcomes in patients with resectable and borderline pancreatic cancer, despite high rates of pathological nodal involvement. Further investigation of this strategy is warranted in a larger cohort.