Concurrent Systemic Therapy Intensity and Metabolic Response in Carbon-Ion Radiotherapy for Locally Advanced Pancreatic Cancer.

PURPOSE: Carbon-ion radiotherapy (CIRT) provides effective local control for locally advanced pancreatic cancer (LAPC), but the optimal integration of systemic therapy remains uncertain. We evaluated the associations of concurrent chemotherapy intensity and cumulative systemic therapy exposure with clinical outcomes and explored the prognostic value of metabolic versus morphologic response. METHODS AND MATERIALS: We retrospectively reviewed 96 patients with LAPC treated with CIRT and concurrent systemic therapy. Patients were stratified by concurrent chemotherapy intensity into single-agent, doublet, and triplet groups. An exploratory seven-month landmark analysis with endpoint-specific eligibility evaluated cumulative systemic therapy exposure. In the imaging sub-study, metabolic response was defined as ≥50% reduction in SUVmax or metabolic inactivation on post-treatment 18F-FDG PET (PET/CT or PET/MRI). RESULTS: No statistically significant differences in local failure-free survival (LFFS), distant metastasis-free survival (DMFS), or overall survival (OS) were observed across concurrent chemotherapy intensity groups. In the landmark analysis, standard-duration systemic therapy was not significantly associated with DMFS compared with suboptimal-duration therapy (HR 0.68, 95% CI 0.31-1.50). The adjusted estimate was similar but remained imprecise (HR 0.65, 95% CI 0.29-1.44). In the exploratory imaging sub-study, metabolic response was associated with improved local control (p=0.013), whereas morphologic response was not. Median OS for the overall cohort was 29.7 months. CONCLUSIONS: Concurrent chemotherapy intensity was not significantly associated with LFFS, DMFS, or OS in this retrospective cohort. Exploratory analyses provided no conclusive evidence that greater cumulative systemic therapy exposure improved clinical outcomes. These findings support prospective evaluation of risk-adapted concurrent systemic therapy during CIRT. 18F-FDG PET metabolic response showed potential prognostic value for local control, supporting its prospective validation as a response biomarker.