Proton therapy for pancreatic cancer: real-world single-center experience of efficacy, toxicity, and predictors of outcome

Background: Pancreatic cancer has a poor prognosis, with five-year survival rates of 10-13%. Surgery is the only curative option, though not feasible for many patients. Radiation therapy is crucial but limited by surrounding radiosensitive organs. Proton therapy provides improved dose distribution and higher biological effectiveness; however, clinical data comparing it to conventional photon therapy remains scarce. Methods: We retrospectively analyzed 41 patients with unresectable or recurrent pancreatic cancer treated with curative-intent proton therapy at Marburg Ion Beam Treatment Center. Median patient age was 69.5 years; 58.5% were male, 70.8% had T3/4 tumors, and 73.2% presented at stage III. Median delivered dose was 54.0 GyE (median BED: 64.0 GyE) over 30 fractions. Most (95.1%) received proton therapy alone, 68.3% with concurrent chemotherapy. Outcomes evaluated included overall survival (OS), local recurrence-free survival (LRFS), progression-free survival (PFS), and CTCAE v5.0-assessed toxicities. Results: Proton therapy showed good tolerability with minimal toxicity (early grade ≥III: 2.4%; late grade III: 4.9%, no late grade IV/V). Local recurrence occurred in 13 patients (all within 6 months), and overall progression was noted in 33 patients (mostly within 1 year). Salvage RT correlated with worse PFS on univariate analysis (p=0.03), though non-significant in Cox regression (p=0.06). Adjuvant chemotherapy showed a non-significant trend toward improved OS (HR = 0.53, p=0.08). No dose-related factors influenced local recurrence. Conclusions: Proton therapy for pancreatic cancer was well tolerated, though outcomes remained modest compared to recent studies utilizing higher doses and optimized protocols. Low toxicity supports proton therapy's theoretical advantages. Dose escalation and protocol optimization may enhance outcomes. Prospective studies with larger cohorts are warranted.