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. 2025 Aug 13.
doi: 10.1007/s11060-025-05152-4. Online ahead of print.

Comparing intraoperative radiotherapy (IORT) and hypofractionated stereotactic radiotherapy (HSRT) after brain metastasis surgery: impact on oncological outcome and radionecrosis

Maria Neu  1   2   3   4 , Ehab Shiban  5 , Philipp Krauss  2   3   4   6 , Björn Sommer  2   3   4   6 , Zoha Roushan  7 , Susanne Gutser  7 , Christoph J Maurer  8 , Tilman Janzen  7 , Georg Stüben  1   2   3   4 , Klaus-Henning Kahl  9   10   11   12   13
Affiliations

Comparing intraoperative radiotherapy (IORT) and hypofractionated stereotactic radiotherapy (HSRT) after brain metastasis surgery: impact on oncological outcome and radionecrosis

Maria Neu et al. J Neurooncol. .

Abstract

Purpose: Due to significantly lower neurocognitive toxicity, whole-brain irradiation (WBI) has largely been replaced by focal irradiation of the resection cavity following brain metastasis surgery. However, the optimal treatment modality and fractionation scheme remain controversial. This study conducts a comparative analysis of hypofractionated stereotactic radiotherapy (HSRT) and intraoperative radiotherapy (IORT), focusing on clinical outcomes and toxicity profiles.

Methods: A retrospective cohort study was conducted, analyzing 129 patients (HSRT: 72, IORT: 57) with 137 treated cavities (HSRT: 75, IORT: 62) at the University Hospital of Augsburg (UKA) between 2013 and 2021. Baseline characteristics, oncological outcomes, incidence of radionecrosis (RN), and time to further treatment were compared.

Results: Radionecrosis occurred significantly less frequently in the IORT group compared to HSRT, with 1-year RN rates of 3.7% (95% CI: 0.5-23.5%) and 21.8% (95% CI: 11.7-39.2%), respectively (p = 0.00025). At two years, the RN rate remained substantially lower after IORT (8.5% vs. 53.2%). Notably, in patients without prior cerebral irradiation, no symptomatic RN (sRN) occurred following IORT, whereas the 2-year sRN rate in the HSRT group reached 35.5% (p = 0.0036). Oncological outcomes, including overall survival (OS), local control (LC), intracranial disease control, leptomeningeal dissemination (LMD), and WBI avoidance, were comparable between the two groups. However, distant brain control (DBC) at one year was higher in the HSRT group. While HSRT was initiated after a median delay of 29 days (range: 14-71), IORT was delivered intraoperatively, enabling immediate continuation of systemic therapy.

Conclusion: In this retrospective single-center analysis, IORT demonstrated comparable oncological efficacy to HSRT while significantly reducing the risk of RN. Given its intraoperative delivery and the ability to promptly resume systemic therapy, and the precise application directly at the resection cavity, IORT may represent a practical and effective alternative in selected patients.

Keywords: Brain metastases; Cavity radiotherapy; Focal radiotherapy; Hypofractionated stereotactic radiotherapy; IORT; Local control; Radionecrosis; Surgery.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and approved by Ethics Committee of Ludwig-Maximilians-Universität München (protocol code 23–0845; 2023-11-17).” Consent for publication: Informed consent was obtained from all subjects involved in the study. Competing interests: K.H.K. has received speaker honoraria and travel grants from ELEKTA AB, Varian Medical Systems, Carl Zeiss Meditec AG, AstraZeneca, Bristol Myers Squibb, MSD, Merck, Sanofi-Aventis and IcoTec.; P.K. has received speaker honoraria and travel grants from Carl Zeiss Meditec AG, Boston Scientific Corporation and Abbott Laboratories. All other authors state that they have no conflicts of interest.

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