Simple SummaryThe effectiveness of carbon-ion radiotherapy (CIRT) with systemic chemotherapy for locally advanced pancreatic cancer was examined retrospectively. Of the 44 patients receiving CIRT, 37 patients also received neoadjuvant chemotherapy, and all patients received concurrent and adjuvant chemotherapy. The median survival time of all patients was 34.5 months after the initial treatment and 29.6 months after the initial day of CIRT. The estimated two-year overall survival rate and local control after CIRT was 56.6% and 76.1%, respectively. Even in the era of multiagent chemotherapy, local treatment with CIRT has a survival benefit for local advanced unresectable pancreatic cancer.AbstractSystemic chemotherapy has significantly improved in recent years. In this study. the clinical impact of carbon-ion radiotherapy (CIRT) with concurrent chemotherapy for locally advanced unresectable pancreatic cancer (URPC) was evaluated. Methods: Patients with URPC who were treated with CIRT between January 2016 and December 2020 were prospectively registered and analyzed. The major criteria for registration were (1) diagnosed as URPC on imaging; (2) pathologically diagnosed adenocarcinoma; (3) no distant metastasis; (4) Eastern Cooperative Oncology Group performance status of 0–2; (5) tumors without gastrointestinal tract invasion; and (6) available for concurrent chemotherapy. Patients who received neoadjuvant chemotherapy (NAC) for more than one year prior to CIRT were excluded. Results: Forty-four patients met the inclusion criteria, and thirty-seven received NAC before CIRT. The median follow-up period of living patients was 26.0 (6.0–68.6) months after CIRT. The estimated two-year overall survival, local control, and progression-free survival rates after CIRT were 56.6%, 76.1%, and 29.0%, respectively. The median survival time of all patients was 29.6 months after CIRT and 34.5 months after the initial NAC. Conclusion: CIRT showed survival benefits for URPC even in the multiagent chemotherapy era.