ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
This article is part of the Research TopicManagement of Localized Pancreatic CancerView all 3 articles
Proton Therapy for Pancreatic Cancer: Real-World Single-Center Experience of Efficacy, Toxicity, and Predictors of Outcome
Provisionally accepted
Philipp Lishewski1*
Zelal Geyik1Linda Agolli2Kerem Tuna Tas1
Houmam Anees2
Klemens Zink3Fabian Eberle1Anja Rinke1Hilke Vorwerk1Thomas Held4Daniel Habermehl2Sebastian Adeberg1Ahmed Gawish1- 1University of Marburg, Marburg, Germany
- 2Universitatsklinikum Giessen, Giessen, Germany
- 3Technische Hochschule Mittelhessen, Giessen, Germany
- 4Universitat Heidelberg Medizinische Fakultat Heidelberg, Heidelberg, Germany
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Background Pancreatic cancer has a poor prognosis, with five-year survival rates of 10-13%. Surgery, 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 nonsignificant 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.
Keywords: chemoradiation, chemotherapy, Image guided radiation therapy (IGRT), pancreas cancer, Proton therapy
Received: 22 Sep 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Lishewski, Geyik, Agolli, Tas, Anees, Zink, Eberle, Rinke, Vorwerk, Held, Habermehl, Adeberg and Gawish. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Philipp Lishewski
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