The evolution of RTOG and NRG Oncology CNS tumors clinical trials.

Abstract

Radiation Therapy Oncology Group (RTOG) and NRG Oncology have played a key role in shaping evidence-based management of central nervous system (CNS) tumors. These have defined standards for radiotherapy delivery, integrated systemic therapies for multimodal approaches, and advanced trial methodology across a range of CNS malignancies through large, multi-institutional studies. This is a comprehensive narrative review of trials involving adult CNS tumors, focused on gliomas, metastases, meningioma, and primary CNS lymphoma (PCNSL). Trials were identified through protocol archives, published literature, and curated trial inventories, and were analyzed with respect to treatment strategies, trial evolution, and impact on practice. Early trials established foundational radiotherapy paradigms, including dose, volume, and fractionation standards. Subsequent studies demonstrated limitations of dose escalation and led to development of prognostic tools such as recursive partitioning analysis (RPA). In gliomas, these trials defined the role of chemoradiation, setting new standards of care (SOC), and clarified the limited benefit of treatment intensification, while recent studies explored molecularly selected therapies. In BM, randomized trials transformed management through stereotactic radiosurgery (SRS)-based approaches and hippocampal-avoidance whole brain radiotherapy (HA-WBRT), with incorporation of neurocognitive function (NCF) and quality-of-life (QOL) endpoints. Trials in meningioma provided some of the first prospective data supporting role of radiotherapy, and PCNSL trials established the superiority of chemoradiotherapy, and response-adapted deployment of WBRT. RTOG and NRG Oncology trials have driven iterative, evidence-based advances in transitioning to precision. These efforts continue to inform contemporary guidelines and provide a framework for future trials integrating molecular stratification, advanced imaging, and novel therapeutic strategies.