A Phase II Study of Short-Course Neoadjuvant Chemoradiotherapy with Gemcitabine, S-1, and Hypofractionated...

Neoadjuvant chemoradiotherapy (NACRT) is increasingly used for pancreatic ductal adenocarcinoma (PDAC), yet the optimal regimen remains unclear. This phase II trial evaluated the feasibility and efficacy of a short-course NACRT regimen comprising gemcitabine, S-1, and hypofractionated radiotherapy in patients with resectable (R) or borderline resectable (BR) PDAC.

Patients received NACRT with gemcitabine (1000 mg/m² on days 1 and 8), oral S-1 (60 mg/m²/day for 14 days), and hypofractionated radiotherapy (30 Gy in 10 fractions over 2 weeks). The primary endpoint was the R0 resection rate. Secondary endpoints included treatment completion, adverse events, tumor response, and survival.

In total, 54 patients were enrolled. Treatment completion ranged from 87 to 98%. Among 49 patients who underwent resection, 96% achieved R0 resection. A College of American Pathologists tumor regression score of 2 or lower was observed in 49% of tumors. Median follow-up was 24 months. In the intention-to-treat analysis, 1-, 3-, and 5-year overall survival rates were 78, 53, and 42%, respectively. Among resected patients, the median recurrence-free survival was 18 months. Patients with R-PDAC had survival comparable to those reported with longer NACRT regimens, while those with BR-PDAC had less favorable outcomes.

This short-course NACRT regimen was feasible and yielded favorable survival outcomes, achieving a high R0 resection rate in patients with R-PDAC. By contrast, patients with BR-PDAC may benefit from more intensive treatment, although this requires further validation. These findings support the clinical utility of short-course NACRT and highlight the importance of treatment stratification on the basis of resectability status.