S366
Clinical - CNS
ESTRO 2026
Johnson 4 , Samir A. Dagher 5 , Shaan M. Raza 6 , Franco Demonte 6 , Debra N. Yeboa 7 , Todd A. Swanson 7 , Mary Frances McAleer 7 , Susan L. McGovern 7 , Helen A. Shih 1 1 Radiation Oncology, Massachusetts General Hospital, Boston, USA. 2 Medicine, Massachusetts General Hospital, Boston, USA. 3 Neurosurgery, Massachusetts General Hospital, Boston, USA. 4 Radiology, Yale University, New Haven, USA. 5 Neuroradiology, MD Anderson Cancer Center, Houston, USA. 6 Neurosurgery, MD Anderson Cancer Center, Houston, USA. 7 Radiation Oncology, MD Anderson Cancer Center, Houston, USA Purpose/Objective: Radiation therapy is a central treatment modality for grade 2 and 3 meningiomas. Despite its use, long-term local control and survival rates are poor. A few studies suggest a benefit from dose escalation, but safety concerns remain, given the risk of treatment-related toxicity. Proton therapy potentially allows for conformal dose escalation with an acceptable toxicity risk. This trial evaluates the safety and efficacy of dose escalation with intensity-modulated proton therapy (IMPT) for grade 2 and 3 meningiomas. Material/Methods: This prospective single-arm phase 1 trial enrolled patients with grade 2 meningioma with subtotal resection, biopsy, or recurrence, as well as patients with grade 3 meningioma after gross total resection. Patients underwent dose-escalated IMPT to 66 Gy (relative biological effectiveness, RBE) for grade 2 gross disease and 63 Gy(RBE) for grade 3 tumor beds. The primary endpoint was acute dose-limiting toxicity (DLT), i.e., any new acute grade ≥ 3 toxicity or ≥ 2 grade levels above baseline. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and late toxicity. The Common Terminology Criteria for Adverse Events, version 4.0, were used to grade toxicity. This trial was registered on ClinicalTrials.gov (trial identifier: NCT02693990). Results: Twenty-one patients with 16 grade 2 and five grade 3 meningiomas were enrolled and treated between 2016 and 2023. The median clinical and radiographic follow-up periods were 3.4 and 3.2 years, respectively. No DLT was observed. New late grade 3 toxicity occurred in four patients (19.0%). Two grade 3 fatigue, one grade 3 seizures, and one grade 3 hearing impairment were observed. No high-grade radiation necrosis was observed. Three local treatment failures were observed in two grade 2 and one grade 3 tumors. Two deaths occurred in two patients with grade 2 meningiomas. In both cases, there was no radiographic evidence of local disease progression prior to death. The 1-, 2-, and 3-year PFS rates were 100%, 94.1%, and 86.9%, respectively. The corresponding OS rates were 100%, 94.1%, and 94.1%,
respectively. Conclusion:
There is limited prospective evidence on the use of dose escalation for high-risk meningiomas. This first trial investigating dose-escalated IMPT for grade 2 and 3 meningiomas demonstrated a favorable early safety profile and clinical outcomes. Phase 2 and 3 studies are warranted to confirm the superiority of dose escalation for high-grade meningiomas. Keywords: Meningioma, Dose escalation, Proton therapy
Digital Poster Highlight 1820 CTRI/2025/03/082053: Targeting
Chemoradiotherapy Resistance in High Grade Gliomas Using Mycophenolate Mofetil-Interim Feasibility Results Kalyani A Nair 1 , Akanksha Solanki 1 , Sarbesh Tiwari 2 , Bharti Devnani 1 , Maya Gopalakrishnan 3 , Poonam Abhay Elhence 4 , Deepak Kumar Jha 5 , Puneet Pareek 1 1 Radiation Oncology, All India Institute Of Medical Sciences, Jodhpur, India. 2 Diagnostic and Interventional Radiology, All India Institute Of Medical Sciences, Jodhpur, India. 3 Internal Medicine, All India Institute Of Medical Sciences, Jodhpur, India. 4 Pathology and Lab Medicine, All India Institute Of Medical Sciences, Jodhpur, India. 5 Neurosurgery, All India Institute Of Medical Sciences, Jodhpur, India Purpose/Objective: High-grade gliomas are aggressive tumours, treated by surgical resection followed by chemoradiotherapy. While adjuvant treatment has improved survival, intrinsic resistance makes the improvement limited and recurrence is the rule. Targeting resistance pathways, such as the de-novo purine synthesis pathway among others could thus improve prognosis. Mycophenolate mofetil (MMF), a de-novo purine synthesis inhibitor, has demonstrated radiosensitising and chemosensitising potential in recent studies, with doses upto 1500mg BD being safely tolerated alongside standard chemoradiation in the western population. However, Asians may have lower tolerance to MMF due to genetic variations. This study evaluates the feasibility and safety of adding MMF to standard chemoradiotherapy in Indian patients with high-grade gliomas. Material/Methods: This prospective, single arm, interventional study is being conducted in the Department of Radiation Oncology AIIMS Jodhpur, India to assess the tolerability of escalating doses of MMF with concurrent chemoradiotherapy. Eligible patients ( ≥ 18 years) with newly diagnosed or recurrent grade 3–4 gliomas received MMF in one of three dose levels: 500 mg,
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