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Adaptive MRI-Guided Reirradiation for High-Risk Recurrent Grade 4 Gliomas: Early Clinical Outcomes and Volumetric Response.

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Title: Adaptive MRI-Guided Reirradiation for High-Risk Recurrent Grade 4 Gliomas: Early Clinical Outcomes and Volumetric Response.
Authors: Schmitt, Luiza Giuliani1 (AUTHOR), Dohopolski, Michael1,2 (AUTHOR), de Vis, Jill1 (AUTHOR), Mostardeiro, Thomaz Rodrigues2 (AUTHOR), Mitre, Lucas Pari1 (AUTHOR), Youssef, Michael3 (AUTHOR), Noch, Evan3 (AUTHOR), Maher, Elizabeth3 (AUTHOR), Sun, Matthew3 (AUTHOR), Patel, Toral4 (AUTHOR), Patel, Ankur4 (AUTHOR), Lee, MinJae5 (AUTHOR), Iakovenko, Viktor1 (AUTHOR), Chiu, Tsuicheng1 (AUTHOR), Su, Fan-Chi1 (AUTHOR), Pompos, Arnold1 (AUTHOR), Lin, Mu-Han1 (AUTHOR), Cai, Xin1 (AUTHOR), Timmerman, Robert1 (AUTHOR), Dan, Tu1 (AUTHOR) Tu.Dan@UTSouthwestern.edu
Source: International Journal of Radiation Oncology, Biology, Physics. May2026, Vol. 125 Issue 1, p44-55. 12p.
Subjects: Linear accelerators, Radiotherapy, Radiotherapy complications, Glioblastoma multiforme
Abstract: Recurrent WHO grade 4 gliomas have poor outcomes and limited salvage options. Reirradiation (re-RT) can provide local control in selected patients but is constrained by cumulative dose and toxicity. Personalized ultrafractionated stereotactic adaptive radiation therapy (PULSAR) delivers re-RT as high-dose "pulses" spaced weeks apart, creating opportunities for interim magnetic resonance imaging (MRI) assessment and adaptive replanning on an MRI-linear accelerator We retrospectively analyzed 45 patients with recurrent WHO grade 4 gliomas treated with MRI-guided PULSAR re-RT on a 1.5-T MRI-linear accelerator (5 planned pulses; typical prescription 25-35 Gy in 5 fractions with dose painting). A 0-5-mm expansion from either or both GTVs was used to generate the treated CTV without an additional PTV margin. On-treatment MRI (T1 postcontrast ± T2-FLAIR) was used for volumetric assessment and adaptive replanning when indicated. Endpoints included overall survival (OS), progression-free survival (PFS), local failure (LF), and grade ≥3 toxicity (cerebral edema or hematologic events). Univariable regression explored associations between clinical factors and outcomes. Median age was 54.2 years; 78% of tumors were IDH wild type, with frequent corpus callosum involvement (68.9%) and multifocal/multicentric disease (40.0%). Thirty-six patients (80%) underwent ≥1 adaptive replan, and 30 (66.7%) completed the planned course. Median follow-up was 16.7 months. Median OS and PFS from re-RT start were 6.9 and 5.1 months, respectively. The 12-month cumulative incidence of LF was 56.0% (68.0% in a sensitivity analysis accounting for cause-specific mortality). The 12-month cumulative incidence of grade ≥3 cerebral edema was 40.0%, and grade ≥3 hematologic toxicity was 38.0%. Concurrent bevacizumab was associated with a lower incidence of grade ≥3 cerebral edema (20% vs 60%; HR = 0.32; P =.04). ECOG performance status ≥2 and IDH wild type status were associated with worse OS and PFS. Volumetric response on T1 postcontrast or T2-FLAIR imaging was not significantly associated with OS or PFS. MRI-guided PULSAR re-RT with adaptive replanning was feasible in a high-risk recurrent WHO grade 4 glioma cohort. Interim MRI assessment supported real-time treatment decision-making, but the clinical benefit of this adaptive strategy relative to conventional re-RT remains unclear without a control arm. Prospective studies are needed to standardize imaging/adaptation workflows, optimize pulse spacing, refine margin strategies, and determine whether MRI-guided adaptive PULSAR improves clinically meaningful outcomes. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
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Abstract:Recurrent WHO grade 4 gliomas have poor outcomes and limited salvage options. Reirradiation (re-RT) can provide local control in selected patients but is constrained by cumulative dose and toxicity. Personalized ultrafractionated stereotactic adaptive radiation therapy (PULSAR) delivers re-RT as high-dose "pulses" spaced weeks apart, creating opportunities for interim magnetic resonance imaging (MRI) assessment and adaptive replanning on an MRI-linear accelerator We retrospectively analyzed 45 patients with recurrent WHO grade 4 gliomas treated with MRI-guided PULSAR re-RT on a 1.5-T MRI-linear accelerator (5 planned pulses; typical prescription 25-35 Gy in 5 fractions with dose painting). A 0-5-mm expansion from either or both GTVs was used to generate the treated CTV without an additional PTV margin. On-treatment MRI (T1 postcontrast ± T2-FLAIR) was used for volumetric assessment and adaptive replanning when indicated. Endpoints included overall survival (OS), progression-free survival (PFS), local failure (LF), and grade ≥3 toxicity (cerebral edema or hematologic events). Univariable regression explored associations between clinical factors and outcomes. Median age was 54.2 years; 78% of tumors were IDH wild type, with frequent corpus callosum involvement (68.9%) and multifocal/multicentric disease (40.0%). Thirty-six patients (80%) underwent ≥1 adaptive replan, and 30 (66.7%) completed the planned course. Median follow-up was 16.7 months. Median OS and PFS from re-RT start were 6.9 and 5.1 months, respectively. The 12-month cumulative incidence of LF was 56.0% (68.0% in a sensitivity analysis accounting for cause-specific mortality). The 12-month cumulative incidence of grade ≥3 cerebral edema was 40.0%, and grade ≥3 hematologic toxicity was 38.0%. Concurrent bevacizumab was associated with a lower incidence of grade ≥3 cerebral edema (20% vs 60%; HR = 0.32; P =.04). ECOG performance status ≥2 and IDH wild type status were associated with worse OS and PFS. Volumetric response on T1 postcontrast or T2-FLAIR imaging was not significantly associated with OS or PFS. MRI-guided PULSAR re-RT with adaptive replanning was feasible in a high-risk recurrent WHO grade 4 glioma cohort. Interim MRI assessment supported real-time treatment decision-making, but the clinical benefit of this adaptive strategy relative to conventional re-RT remains unclear without a control arm. Prospective studies are needed to standardize imaging/adaptation workflows, optimize pulse spacing, refine margin strategies, and determine whether MRI-guided adaptive PULSAR improves clinically meaningful outcomes. [ABSTRACT FROM AUTHOR]
ISSN:03603016
DOI:10.1016/j.ijrobp.2026.02.195