Adaptive Salvage Stereotactic Radiation for Locoregional Recurrence of Pancreatic Adenocarcinoma After Surgery

Isolated locoregional recurrence of pancreatic adenocarcinoma occurs in 25% to 50% of cases after surgical resection and has limited treatment options. Data on ablative stereotactic body radiation therapy (SBRT) with daily online adaptation for this condition are limited. Our objective was to illustrate the efficacy and safety of adaptive radiation for isolated locoregional recurrences of pancreatic adenocarcinoma.

This was a retrospective cohort study of 46 patients treated with adaptive 5-fraction SBRT for isolated locoregional recurrence of pancreatic adenocarcinoma after surgical resection between 2015 and 2024. Kaplan-Meier curves with log-rank analysis and Cox regression were conducted to assess oncologic outcomes, including locoregional recurrence-free survival, distant metastasis-free survival, and overall survival. Variables of clinical significance, including biologically effective dose, planning target volume, and receipt of salvage chemotherapy in conjunction with salvage radiation, were assessed. Local failure was defined by response evaluation criteria in solid tumors. Toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 criteria.

Radiation dose median was 50 Gy in 5 fractions. Seven patients had received prior radiation, and 27 patients received chemotherapy as part of their salvage treatment. The median duration of chemotherapy was 3.9 months. Forty-six patients were treated with a median age of 65 years; the majority were White and male. Median time to local recurrence from initial diagnosis was 20 months. Online adaptation was performed for 91% of fractions. Median follow-up from recurrent diagnosis and end of salvage radiation was 14 and 10.4 months, respectively. One-year local control was 73%, and 1- and 2-year overall survival were 69% and 42%, respectively. Chemotherapy had a statistically significant effect on progression-free survival (HR, 0.45; 95% confidence interval, 0.23-0.89; P = .02). No acute grade 3+ toxicities occurred, but 3 late grade 3+ toxicities were documented.

Adaptive SBRT permits a high biologically effective dose in 5 fractions and results in local control concordant with conventionally fractionated salvage radiation for locoregionally recurrent pancreatic ductal adenocarcinoma after definitive surgery, even after prior radiation with a reasonable toxicity profile. Future work may combine adaptive radiation with coverage of extrapancreatic neural tract anatomy and additional chemotherapy to improve outcomes.