S358
Clinical - CNS
ESTRO 2026
1 Department of Radiation Oncology, University Medical Center Mannheim, Mannheim, Germany. 2 DKFZ Hector Cancer, German Cancer Research Center, Heidelberg, Germany. 3 Department of Neurosurgery, Medical Center Stuttgart, Stuttgart, Germany. 4 Department of Radiation Oncology, Medical Center Stuttgart, Stuttgart, Germany. 5 Department of Radiation Oncology, Technical University of Munich (TUM), München, Germany. 6 Department of Neurosurgery, Technical University of Munich (TUM), München, Germany. 7 Department of Neurooncology, University Hospital Bonn, Bonn, Germany. 8 Department of Neurosurgery, University Hospital Bonn, Bonn, Germany. 9 Department of Radiation Oncology, University Medical Center Augsburg, Augsburg, Germany. 10 Department of Neurosurgery, University Medical Center Augsburg, Augsburg, Germany. 11 Department of Radiation Oncology, Northwell Health, New York, USA. 12 Department of Neurosurgery, Northwell Health, New York, USA. 13 Department of Radiation Oncology, Institut Català d'Oncologia, Barcelona, Spain. 14 Department of Neurosurgery, Institut Català d'Oncologia, Barcelona, Spain. 15 Department of Neurosurgery, University Medical Center Mannheim, Mannheim, Germany. 16 Department of Radiation Oncology, Reina Sofía University Hospital, Córdoba, Spain. 17 Department of Neurosurgery, Reina Sofía University Hospital, Córdoba, Spain. 18 Department of Neurosurgery, West Virginia University, Morgantown, USA. 19 University Medical Center, University Hospital Freiburg, Freiburg, Germany. 20 Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany. 21 Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany. 22 Department of Radiological Sciences, University of California Los Angeles, Los Angeles, USA. 23 Department of Radiation Oncology, McGill University, Montreal, Canada. 24 Department of Neurology and Neurosurgery, McGill University, Montreal, Canada Purpose/Objective: Glioblastoma is the most aggressive primary brain tumour in adults with dismal prognosis. Despite resection, chemoradiotherapy, and maintenance chemotherapy, most tumours recur locally. However, the therapeutic value of local radiation dose escalation remains controversial. Intraoperative radiotherapy (IORT) enables the immediate delivery of a high radiation dose to the resection cavity, with a steep dose gradient, offering the potential to eradicate residual microscopic disease while sparing adjacent normal brain. Material/Methods: INTRAGO II was an international, randomised, open- label, phase 3 trial (NCT02685605) enrolling patients aged 18–80 years with supratentorial glioblastoma
(WHO grade IV), KPS ≥ 60%, and tumours amenable to total resection. Patients were randomly assigned intraoperatively (1:1) to receive additional IORT or surgery alone, stratified by age, KPS, and estimated residual tumour. IORT was delivered using a kilovoltage source and spherical applicators selected to fit the resection cavity. A dose of 30 Gy was prescribed to the applicator surface. Postoperative treatment in both groups consisted of external-beam radiotherapy to 60 Gy with concurrent temozolomide (75 mg/m ² ), followed by six adjuvant cycles (150–200 mg/m ² , 5/28). The primary endpoint was median progression-free survival (PFS) confirmed by blinded central review. Secondary endpoints included overall survival (OS), site of recurrence, toxicity, and quality of life. Results: Between December 2016 and June 2024, 314 patients were randomized across 18 international centres. The full analysis set comprised 298 patients (IORT, n=161; control, n=137). The median follow-up was 17.2 months (IQR 10.5–27.1). Baseline patient and tumour characteristics were balanced, including age, Karnofsky performance score, and MGMT promoter hypermethylation. Median PFS was 11.0 months (95% CI 9.2–12.6) in the IORT group versus 11.4 months (9.7–13.9) in the control group (hazard ratio 1.1, 95% CI 0.85–1.44; p=0.47). Median OS was 17.7 months (15.5– 21.1) with IORT and 18.7 months (17.2–21.1) with standard therapy (HR 1.2, 95% CI 0.91–1.54; p=0.20). Local recurrence was the predominant pattern of failure in both arms. Grade 3-4 radiation necrosis was diagnosed in 11 patients (6.8%) of the IORT vs. 3 patients (2.2%) of the control group. The incidence of other grade 3–4 adverse events was 1.4 versus 1.2 events per patient, respectively. Conclusion: Dose escalation with IORT in addition to standard of care did not improve survival outcomes in glioblastoma. Given the spatially precise dose delivery without temporal delay, these findings indicate that further intensification of local radiation dose is unlikely to improve outcomes in resectable glioblastoma. Keywords: glioblastoma, IORT, phase 3 trial
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Dose-escalated Proton Beam Therapy in base of skull chordoma and chondrosarcomas: a single institute's analysis of dosimetry and outcomes Mithushanaa Nesarajah, Namrata Das, Karthica Indramohan, Murtaza Kermali, Andrew Gosling, Naomi Fersht, Michael Kosmin
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