Radiation-Induced Contrast Enhancement After Proton Therapy for Paediatric Brain Tumours: Association with Variable Relative Biological Effectiveness and Linear Energy Transfer.
9 affiliations
- 1Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
- 2Heidelberg Institute for Radiation Oncology (HIRO), 69120 Heidelberg, Germany.
- 3Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany.
- 4Cantonal Hospital Frauenfeld, Spital Thurgau Ag, Pfaffholzstrasse 4, 8500 Frauenfeld, Switzerland.
- 5National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany.
- 6Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
- 7Translational Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
- 8Centro Nazionale di Adroterapia Oncologica (CNAO), 27100 Pavia, Italy.
- 9German Cancer Consortium (DKTK), Partner Site, 69120 Heidelberg, Germany.
Abstract
Background/Objectives: Proton therapy is widely used in paediatric neuro-oncology because of its favourable dose distribution and reduced exposure to radiation of healthy tissue. Nevertheless, current knowledge regarding radiation-induced contrast enhancements (RICE) is largely derived from adult proton therapy cohorts, while evidence in paediatric patients remains limited and the underlying biological mechanisms are still incompletely understood. This study investigated the incidence of RICE in paediatric patients with low-grade glioma (LGG) and ependymoma and evaluated potential associations with linear energy transfer (LET) and variable relative biological effectiveness (RBE)-weighted dose distributions. Methods: In this retrospective single-centre study, paediatric patients with LGG or ependymoma were identified from a prospectively maintained institutional registry patients treated with proton therapy at the Heidelberg Ion-Beam Therapy Centre (HIT) between 2010 and 2024. Follow-up magnetic resonance imaging examinations were systematically reviewed for RICE. Lesions were contoured in RayStation and assessed dosimetrically using a fixed RBE of 1.1 and three variable RBE models. LET-weighted dose metrics and Dose(RBE) × LET products were compared between RICE regions and planning target volumes (PTVs). Overall survival and progression-free survival were estimated using Kaplan-Meier method. Results: Seventy-six patients met the inclusion criteria, including 33 patients with LGG and 43 with ependymoma. A total of 724 follow-up magnetic resonance imaging examinations were reviewed. RICE occurred in six patients (7.9%), exclusively in the ependymoma subgroup (14.0%). Higher prescribed radiation dose was significantly associated with RICE occurrence (p = 0.031). Across all variable RBE models, biologically weighted dose estimates and Dose(RBE) × LET products were consistently elevated within RICE regions compared with corresponding PTV regions, particularly at low- and intermediate-dose levels. Five-year overall survival rates were 91.7% for LGG and 86.6% for ependymoma, while corresponding progression-free survival rates were 84.4% and 69.3%, respectively. Conclusions: Variable RBE models identified biologically relevant dose heterogeneities within RICE regions that were not adequately captured by the conventional fixed RBE approach. These findings suggest that LET-associated biological dose escalation may contribute to radiation-related brain tissue changes after proton therapy and support further investigation and prospective validation of LET- and RBE-informed normal-tissue risk assessment in paediatric neuro-oncology.
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BibTeX
@article{brack2026radiationinduced,
title = {{Radiation-Induced Contrast Enhancement After Proton Therapy for Paediatric Brain Tumours: Association with Variable Relative Biological Effectiveness and Linear Energy Transfer.}},
author = {Julian Brack and Valon Gllareva and Bastian von Nettelbladt and Eva Meixner and Line Hoeltgen and Laila Koenig and Hanna Waldsperger and Katharina Kozyra and Habiba Sallem and Alexander Neuholz and Thomas Tessonnier and Andrea Mairani and Jürgen Debus and Klaus Herfarth and Semi B Harrabi},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18193243},
url = {https://europepmc.org/article/MED/42882938},
note = {CC BY},
}
RIS
TY - JOUR
TI - Radiation-Induced Contrast Enhancement After Proton Therapy for Paediatric Brain Tumours: Association with Variable Relative Biological Effectiveness and Linear Energy Transfer.
AU - Julian Brack
AU - Valon Gllareva
AU - Bastian von Nettelbladt
AU - Eva Meixner
AU - Line Hoeltgen
AU - Laila Koenig
AU - Hanna Waldsperger
AU - Katharina Kozyra
AU - Habiba Sallem
AU - Alexander Neuholz
AU - Thomas Tessonnier
AU - Andrea Mairani
AU - Jürgen Debus
AU - Klaus Herfarth
AU - Semi B Harrabi
PY - 2026
DA - 2026/10/08
JO - Cancers
DO - 10.3390/cancers18193243
UR - https://europepmc.org/article/MED/42882938
AB - Background/Objectives: Proton therapy is widely used in paediatric neuro-oncology because of its favourable dose distribution and reduced exposure to radiation of healthy tissue. Nevertheless, current knowledge regarding radiation-induced contrast enhancements (RICE) is largely derived from adult proton therapy cohorts, while evidence in paediatric patients remains limited and the underlying biological mechanisms are still incompletely understood. This study investigated the incidence of RICE in paediatric patients with low-grade glioma (LGG) and ependymoma and evaluated potential associations with linear energy transfer (LET) and variable relative biological effectiveness (RBE)-weighted dose distributions. Methods: In this retrospective single-centre study, paediatric patients with LGG or ependymoma were identified from a prospectively maintained institutional registry patients treated with proton therapy at the Heidelberg Ion-Beam Therapy Centre (HIT) between 2010 and 2024. Follow-up magnetic resonance imaging examinations were systematically reviewed for RICE. Lesions were contoured in RayStation and assessed dosimetrically using a fixed RBE of 1.1 and three variable RBE models. LET-weighted dose metrics and Dose(RBE) × LET products were compared between RICE regions and planning target volumes (PTVs). Overall survival and progression-free survival were estimated using Kaplan-Meier method. Results: Seventy-six patients met the inclusion criteria, including 33 patients with LGG and 43 with ependymoma. A total of 724 follow-up magnetic resonance imaging examinations were reviewed. RICE occurred in six patients (7.9%), exclusively in the ependymoma subgroup (14.0%). Higher prescribed radiation dose was significantly associated with RICE occurrence (p = 0.031). Across all variable RBE models, biologically weighted dose estimates and Dose(RBE) × LET products were consistently elevated within RICE regions compared with corresponding PTV regions, particularly at low- and intermediate-dose levels. Five-year overall survival rates were 91.7% for LGG and 86.6% for ependymoma, while corresponding progression-free survival rates were 84.4% and 69.3%, respectively. Conclusions: Variable RBE models identified biologically relevant dose heterogeneities within RICE regions that were not adequately captured by the conventional fixed RBE approach. These findings suggest that LET-associated biological dose escalation may contribute to radiation-related brain tissue changes after proton therapy and support further investigation and prospective validation of LET- and RBE-informed normal-tissue risk assessment in paediatric neuro-oncology.
SN - 2072-6694
ER -