Reirradiation With Proton Therapy Using Hypofractionated Schedules: A Systematic Review of the Literature.

Authors

Daniela Alterio, Vanessa Eleonora Pierini, Stefania Volpe, Maria Giulia Vincini, Mattia Zaffaroni, Annamaria Ferrari, Marvaso Giulia, Federico Mastroleo, Nicolaus Andratschke, Matthias Guckenberger, Jiri Kubeš, Icro Meattini, Carsten Nieder, Yvette van der Linden, Giuseppe Petralia, Roberto Orecchia, Barbara Alicja Jereczek-Fossa

Published in

International journal of particle therapy. Volume 22. Pages 101963. Epub Sep 14, 2026.

Abstract

Re-irradiation (re-RT) with hypofractionated proton therapy (PT) may be a treatment option in selected cases. Aim is to provide a critical overview of the state of the art.
PRISMA-compliant systematic review was performed on 2nd October 2025. All tumor sites were considered, provided that re-RT was performed with dose/fraction>2Gy(RBE) in adults. Oncological and toxicity outcomes were retrieved.
Twelve original research works were identified. The total number of patients treated with hypofractionated PT re-RT was 478. The majority of patients were treated for recurrent tumors of either the gastrointestinal (GI) region (n = 143) or the lung (n = 123). The majority of the published series refers to data derived from retrospective and monoinstitutional experiences. Most patients were treated for recurrent tumors of either the gastrointestinal (GI) region (n = 143) or the lung (n = 123). Median sample size was 32 (interquartile range: 26-46, range: 14-83). Moderate hypofractionation (< 5 Gy(RBE)/fraction) was the most frequent schedule. All included studies had a radical intent. Overall, 2 year overall survival ranged from 8.4% (head & neck) to 87.5% (liver). The rate of severe side effects remained relevant. Of note, clinical outcomes and toxicity profiles were highly heterogeneous among the different tumor sites. Therefore, in the setting of re-RT with PT, conclusive data on the efficacy and toxicity profile of hypofractionated schedules could not be provided yet. Re-RT remains a personalized approach in almost all settings of tumor recurrence.
Evidence supporting the use of hypofractionated PT re-RT remains limited but encouraging. Identifying predictors of toxicity and treatment response is essential to guide future research and to establish this approach as a viable option for selected patients.

PMID:
42831235
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.

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