A Phase-1 Trial to Investigate the Use of Pulsed Low-dose Rate Radiotherapy in Diffuse Midline Gliomas.

Over the past decades, advances in radiation therapy technology have significantly reduced treatment-related toxicity. In patients with diffuse midline glioma (DMG), these improvements have enhanced the tolerability of radiotherapy but have not improved disease control. Pulsed low-dose-rate radiotherapy (pLDRT) may offer additional advantages by further reducing treatment-related toxicity, preserving tumor vascularization to facilitate the delivery and efficacy of subsequent chemotherapy, and exploiting the low-dose hyper-radiosensitivity phenomenon. To the best of our knowledge, no clinical studies have evaluated pLDRT in patients with DMG. Therefore, the primary objective of this phase I study is to evaluate the tolerability of pLDRT in this predominantly pediatric population and to determine a safe dose level for future clinical investigation.

Inclusion Criteria: * Radiological and/or histological diagnosis of diffuse midline glioma (DMG). * Ability to maintain the treatment position or undergo sedation, if required. * Written informed consent provided by the parent(s) or legal guardian(s), or by the patient if aged ≥18 years. Exclusion Criteria: * Refusal to undergo radiotherapy (i.e., lack of signed informed consent). * Concurrent chemotherapy. * Leptomeningeal dissemination of disease. * Ongoing pregnancy (for post-pubertal female patients). * Previous radiotherapy to the brainstem.