Development of a treatment strategy for locally advanced pancreatic cancer using carbon-ion radiotherapy: Chemotherapy alone vs. induction chemotherapy followed by carbon-ion radiotherapy.

725 Background: The standard treatment for unresectable locally advanced pancreatic cancer (LAPC) is chemotherapy or chemoradiotherapy. However, the benefit of adding radiotherapy remains controversial. Carbon-ion radiotherapy (C-ion RT) offers superior dose localization and higher cytotoxicity compared to conventional X-ray therapy, enabling effective local control with minimal damage to surrounding tissues. Previous studies have demonstrated a survival advantage of C-ion RT over X-ray therapy. However, the survival benefit of adding C-ion RT to chemotherapy, as well as criteria for its indication and timing, remain unclear. This study aimed to compare outcomes between chemotherapy alone and induction chemotherapy followed by C-ion RT in LAPC patients, and to identify prognostic factors in the latter group. Methods: We retrospectively analyzed patients with histologically confirmed LAPC treated between April 2022 and March 2024. Seventy-two patients received C-ion RT at QST Hospital, and 36 patients received chemotherapy alone at Chiba University Hospital. The prescribed dose for C-ion RT was 55.2 Gy (RBE) in 12 fractions. Chemotherapy was continued after C-ion RT whenever feasible. Overall survival (OS) and prognostic factors were evaluated using the Kaplan–Meier method and Cox regression analysis. Results: Among the 72 patients in the C-ion RT group, 70 (97.2%) received induction chemotherapy. In the chemotherapy-alone group, 7 patients (19.4%) underwent conversion surgery due to marked tumor response. When OS was calculated from the start of each treatment modality, the 2-year OS rate was 68.1% (95% CI, 53%-80%) in the C-ion RT group and 48.6% (95% CI, 30%-67%) in the chemotherapy-alone group (p = 0.0657), showing a favorable trend for C-ion RT. When OS was calculated from the start of chemotherapy for all patients, the 2-year OS rate was 84.7% (95% CI, 74%-92%) in the C-ion RT group, significantly higher than the chemotherapy-alone group (p < 0.05). Grade 3 gastrointestinal toxicity was observed in 2 patients (2.8%) in the C-ion RT group, with no grade ≥4 non-hematologic toxicities. In univariate analysis, elevated pre-treatment CA19-9 levels were significantly associated with poor prognosis in the C-ion RT group. Conclusions: This study suggests that adding C-ion RT after induction chemotherapy may improve survival in LAPC. Administering C-ion RT during a favorable response to chemotherapy may contribute to better outcomes.