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. 2025 Jan 9;20(1):4.
doi: 10.1186/s13014-024-02579-3.

High incidence of radiation-induced brain necrosis in the periventricular deep white matter: stereotactic radiotherapy for brain metastases using volumetric modulated arc therapy

Takayuki Ohguri  1 , Hirohide Itamura  2 , Subaru Tani  2 , Eiji Shiba  2 , Junkoh Yamamoto  3
Affiliations

High incidence of radiation-induced brain necrosis in the periventricular deep white matter: stereotactic radiotherapy for brain metastases using volumetric modulated arc therapy

Takayuki Ohguri et al. Radiat Oncol. .

Abstract

Purpose: In this retrospective study, we aimed to evaluate the efficacy and incidence of radiation-induced brain necrosis (RBN) after volumetric modulated arc therapy-based stereotactic irradiation (VMAT-STI) for brain metastases.

Methods: In the 220 brain metastatic lesions included between January 2020 and June 2022, there were 1-9 concurrently treated lesions (median 1). A biologically effective dose (BED)10 of 80 Gy and a reduced BED10 of 50 Gy were prescribed to the gross tumor volume (GTV) and planning target volume (PTV) (PTV = GTV + 3 mm) margins, respectively. The number of fractions was adjusted from 3 to 15 to accommodate different GTV sizes; for larger tumor volumes, this was increased while maintaining the BED10 values comparable to those for GTV and PTV margins.

Results: Of the total patients, 16 (7%) exhibited locally progressive lesions; local tumor recurrence was observed in 2 (1%) patients, while RBN was noted in 14 (6%) patients. RBN was significantly more prevalent in the deep white matter around the lateral ventricles (DWM-LV) than in other sites, occurring in 9/22 (41%) lesions of metastases in the DWM-LV. The 2-year actuarial incidence risk of developing RBN was significantly higher in the DWM-LV (69%) than at other sites (5%).

Conclusion: The recurrence rate of brain metastases was low, and the incidence of RBN was lower in tumor sites other than the DWM-LV. However, the frequency of RBN was significantly higher in the DWM-LV region. Additional VMAT-STI-prescribed dose protocols are necessary to reduce RBN incidence in DWM-LVs.

Keywords: Radiation-induced brain necrosis; Stereotactic radiotherapy; Volumetric modulated arc therapy.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Our study was reviewed and approved by the Ethics Committee of University of Occupational and Environmental health. Consent for publication: Not applicable. Human Ethics declaration: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
VMAT-STI protocol for brain metastases. a) Schematic diagram. b) Example of STI plan-ning with VMAT. Biologically Effective Dose (BED10) of 80 Gy (as red line of 43 Gy in 5 fractions in this case) is matched to the GTV marginal dose (as green line). BED10 of 50 Gy (as cyan line of 31 Gy in 5 fractions in this case) is matched to the PTV (GTV + 3 mm as yellow line). Tumor center dose is increased to at least 125% of the GTV marginal dose (as dark red line of 54 Gy in 5 fractions in this case)
Fig. 2
Fig. 2
Actuarial incidence risk of developing RBN. a) The incidence rate of developing RBN between DWM-LV and other sites. b) The incidence rate of developing RBN based on the dose fractionation
Fig. 3
Fig. 3
Patient (no. 2 in Table 2) of radiation brain necrosis (RBN) in deep white matter around the lateral ventricle. a) Dose distribution diagram of stereotactic irradiation with VMAT. b) GTV mar-ginal dose is matched to 36 Gy in 3 fractions (red line) and GTV + 3 mm PTV marginal dose to 27 Gy (light blue line). Tumor center is increased to 45 Gy (dark red line). b) Dose volume histogram shows the coverage of the GTV dose, the dose reduction in the GTV + 3 mm region and the increase in the tumor center dose. Gadolinium-enhanced T1-weighted axial MR images show deep white matter brain metastasis around the lateral ventricle c) before stereotactic irradiation with VMAT, d) complete response 12 months after the stereotactic irradiation and e) re-growth 18 months after the stereotactic irradiation. f) In 11 C-methionine-PET, 20 months after the stereotactic irradiation, the re-growth lesion is lower lesion-to-brain ratio of 1.37, which is diagnostic of radiation brain necrosis. g) Gadolinium-enhanced T1-weighted axial MR images shows increased radiation brain necrosis 24 months after the stereotactic irradiation
Fig. 4
Fig. 4
The local control rate of the brain metastatses treated with VMAT-STI. a) The local control rate of all the 220 brain metastases. The 3-year local control rate in all the 220 brain me-tastases was 82%. b) The local control rate of brain metastases based on the dose fractionation. c) Differences in local control rates of brain metastases between DWM-LV and other sites of brain metastasis location. d) The overall survival rate and DPFS rates
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