Reirradiation With Proton Therapy Using Hypofractionated Schedules: A Systematic Review of the Literature
In brief
Proton reirradiation evidence covers 478 patients, but outcomes vary widely
A review of 12 studies covering 478 adults found two-year survival ranged from 8.4% to 87.5% across tumor sites, while severe side effects remained a concern. Most reports were small, retrospective, single-center studies, leaving efficacy and safety uncertain; treatment remains individualized for selected patients.
- Journal
- International journal of particle therapy (Q1)
- Published
- 14 September 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Daniela Alterio, Vanessa Eleonora Pierini, Stefania Volpe, Maria Giulia Vincini, Mattia Zaffaroni, Annamaria Ferrari, et al.
- PMID
- 42831235
- DOI
- 10.1016/j.ijpt.2026.101963
Why clinicians should know about it
- Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (paper of the day, 7 October 2026): Reirradiation with hypofractionated proton therapy systematic review
Abstract
AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.