Final results of a phase II trial on the role of intraoperative radiotherapy in reducing local recurrence risk in resectable pancreatic cancer with low-energy X-rays

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) has a high propensity for locoregional recurrence despite curative surgery. We designed a phase II study to evaluate locoregional recurrence and mortality in patients with resectable pancreatic cancer (RPC) treated with intraoperative radiotherapy (IORT) using a 50-kV low-energy X-ray source. This report presents the final results. Methods: In a prospective single-institution phase II trial, the efficacy of IORT using a 50-kV low-energy X-ray source in resectable PDAC was evaluated. Thirty-eight patients underwent curative pancreatectomy followed by IORT delivering 10 Gy at 5-mm depth (approximate to 16 Gy on the surface). Gemcitabine-based chemotherapy was administered postoperatively in most cases. The primary endpoint was the 2-year local recurrence rate, and the secondary endpoints were recurrence-free survival (RFS) and overall survival (OS). Cox regression was used to identify the prognostic factors. Results: The 1-and 2-year local recurrence rates were 33.2% and 57.7%, respectively. The median local RFS was 19 months, and the median OS was 43 months. Multivariate analysis identified perineural invasion (PNI) and margin status (R1 vs. R0) as significant predictors of local recurrence, whereas lymphovascular invasion (LVI) and tumor-vessel contact >= 90 degrees were associated with poor OS. Conclusions: Low-energy X-ray IORT was feasible and well tolerated, showing a potential benefit in local control, particularly for patients with microscopic residual disease (R1 resection). PNI, LVI, and tumor-vessel interactions emerged as important prognostic factors. Larger multicenter randomized trials are warranted to confirm these findings.