The story begins in the 1970s, when the RTOG Brain Tumor Committee emerged in the wake of the seminal Brain Tumor Study Group trials to prospectively evaluate new strategies for CNS malignancies. Early protocols tackled the most basic questions: how much radiation should be delivered, to what volume, and in how many fractions. These studies established foundational paradigms, including the biphasic 60 Gy approach for glioblastoma, in which 46 Gy is delivered to a larger target volume followed by a 14 Gy boost, and demonstrated the feasibility of combining radiation with nitrosourea chemotherapy. Just as importantly, they revealed a sobering truth that would steer the field for decades: pushing radiation doses higher and intensifying schedules was technically achievable but did not translate into longer survival, and it frequently increased toxicity. Randomized phase I and II studies of hyperfractionated and accelerated regimens, fast neutrons, and hypoxic-cell and S-phase sensitizers collectively established the limits of radiotherapy intensification in malignant gliomas.

That negative finding proved generative rather than deflating. It spawned three hypotheses that still animate research today: that gliomas harbor innate radioresistance, later attributed in part to stem-like cells; that legacy imaging inadequately targets microscopic disease, catalyzing advanced imaging-based targeting; and that combinatorial approaches are needed to eradicate disease lurking outside the radiation field. It also redirected the group toward methodological refinement. Large accumulated datasets enabled the creation of prognostic tools such as the recursive partitioning analysis, or RPA, classification, which stratified patients by expected outcome and became a standard stratification variable. A series of highly efficient single-arm phase II trials harnessed historical data for comparison, minimizing the number of control patients required and predating the modern concept of synthetic control arms. Agents such as the hypoxic-cell toxin tirapazamine and anti-angiogenic thalidomide were screened in this disciplined framework; most failed to justify phase III testing, but the triage system itself became a durable cooperative-group asset.

The molecular era arrived through some of the group’s most consequential work. Long-term follow-up of RTOG 94-02, a trial first launched in the 1990s that added procarbazine, lomustine, and vincristine, known as PCV chemotherapy, to radiotherapy for anaplastic oligodendroglial tumors, demonstrated that patients whose tumors carried both the 1p/19q co-deletion and an IDH mutation, now classified as grade 3 oligodendroglioma, saw their survival roughly doubled by PCV. Patients with IDH-mutant but non-co-deleted tumors, now called grade 3 astrocytoma, benefited less dramatically, while those with IDH-wildtype disease, now termed molecular glioblastoma, gained nothing. This was among the earliest prospective validations of molecularly informed treatment benefit in neuro-oncology, and it directly influenced subsequent tumor classification systems and trial eligibility paradigms. The companion trial RTOG 9402, together with its European counterpart, cemented PCV plus radiotherapy as a categorical standard for these tumors, even as temozolomide was being adopted broadly across all glioma grades on thinner evidence, prompting definitive head-to-head testing through the CODEL trial.

Glioblastoma itself proved a harder nut to crack, and the trial record is a study in disciplined negative results. After the EORTC and NCI-Canada trial established temozolomide-based chemoradiation as the standard for glioblastoma, RTOG 9813 extended temozolomide to anaplastic astrocytoma, finding no overall survival advantage over nitrosourea but a more favorable toxicity profile, effectively making temozolomide the standard, with post-hoc analysis identifying IDH mutation as both a prognostic and predictive biomarker. RTOG 0525 then showed that dose-dense temozolomide improved neither survival nor progression-free survival and carried higher toxicity, measured with a battery of neurocognitive, symptom, and quality-of-life tests. RTOG 0825 tested the addition of the anti-angiogenic antibody bevacizumab to standard chemoradiation and found no survival benefit despite longer progression-free survival, along with worse patient-reported outcomes and cognitive decline over time. NRG-BN011 could not reproduce the survival benefit of combined temozolomide and lomustine seen in a smaller German trial. Each disappointment sharpened the field’s appreciation that functional endpoints, not just survival curves, must anchor brain tumor research.

Not every modern effort has come up short. RTOG/NRG 1205, reported in 2023, provided the first high-level evidence supporting re-irradiation in recurrent glioblastoma, showing that adding radiation to bevacizumab significantly improved progression-free survival compared with bevacizumab alone in a disease where median survival after recurrence hovers at six to nine months. On the technology frontier, NRG-BN001, a signal-seeking randomized phase II study, met its overall survival endpoint for dose-escalated proton therapy to 75 Gy, and a definitive phase III trial is now in development. NRG-BN005 has completed accrual comparing proton with photon therapy in IDH-mutant lower-grade gliomas with cognitive preservation as its primary focus, and a newly launched study, NRG-CC017, is testing temporally modulated pulsed reduced dose-rate radiotherapy for neurofunctional preservation in glioblastoma. Biomarker-selected trials, including RTOG 0627 of dasatinib in target-selected recurrent glioblastoma, RTOG Foundation Study 3508 of the EGFR-targeted antibody-drug conjugate depatuxizumab mafodotin, and NRG-BN007 of dual checkpoint inhibition in MGMT-unmethylated tumors, illustrate the steady shift toward biology-guided designs.

In brain metastases, the group’s trials arguably transformed practice most visibly. Early studies fixed whole brain radiotherapy schedules of 30 Gy in 10 fractions and 37.5 Gy in 15 fractions as standards, but subsequent attempts at dose escalation, altered fractionation, and radiosensitization yielded no survival gains. RTOG 9508 then inaugurated the stereotactic radiosurgery era, and subsequent randomized work established radiosurgery alone as a standard that preserves neurocognitive function without compromising survival for many patients with limited metastases. Ongoing studies now push the paradigm further, including a trial of radiosurgery for up to 15 brain metastases, a comparison of radiosurgery against hippocampal-avoidance whole brain radiotherapy in small cell lung cancer, and NRG-BN013’s formal test of single versus fractionated radiosurgery for larger lesions. On the spine, RTOG 0631 found no clinical benefit for single-fraction stereotactic body radiotherapy over conventional radiotherapy for localized metastases, a reminder that precision techniques must earn their place.

Perhaps the most patient-centered triumph is the neuroprotection portfolio. RTOG 0614 demonstrated that the NMDA receptor antagonist memantine could delay cognitive decline after whole brain radiotherapy, the first prospective evidence of pharmacologic neuroprotection in this setting. Building on the insight that the hippocampal neural stem-cell niche repopulates the cells subserving memory, the group developed hippocampal-avoidance techniques and validated them in NRG-CC001, a randomized phase III trial showing a significant reduction in cognitive failure when hippocampal-avoidance whole brain radiotherapy was combined with memantine. Crucially, the achievement was as much infrastructural as scientific: standardized contouring atlases, credentialing processes, real-time centralized plan review, and widespread educational programs trained large numbers of radiation oncologists in consistent hippocampal-sparing, enabling rapid adoption into routine practice. The strategy is now extending to prophylactic cranial irradiation in small cell lung cancer through NRG-CC003, and to leptomeningeal disease, where a recent randomized phase II trial showed that proton craniospinal irradiation significantly improved progression-free and overall survival, with the definitive NRG-BN014 trial underway.

The review also documents quieter but meaningful advances in meningioma and primary CNS lymphoma. RTOG 0539 pioneered risk-stratified, prospective radiotherapy for meningioma, demonstrating excellent progression-free survival in intermediate-risk patients treated after surgery, and its infrastructure of centralized imaging review and protocol-driven delivery has spun off a portfolio of trials incorporating molecular imaging with DOTATATE-PET and even a radioligand therapeutic, lutetium-177 DOTATATE, for recurrent high-risk disease. In primary CNS lymphoma, RTOG 1114 showed that reduced-dose whole brain radiotherapy added to R-MPV-A chemoimmunotherapy significantly improved progression-free survival, exemplifying response-adapted radiotherapy that balances disease control against neurotoxicity. The authors distill the lessons into a roadmap: enrich patient selection with molecular profiling, choose realistic endpoints, plan accrual conservatively, recognize barriers in de-escalation trials, insist on central pathology and real-time radiotherapy quality review, and keep trials patient-centric. Taken together, fifty years of cooperative group science trace a clear arc, from empiric dose-finding to precision, biology-informed, and cognitively protective care, and they suggest that the collaborative trial network remains the indispensable engine for the next generation of brain tumor breakthroughs.

Subject of Research: Evolution of cooperative group clinical trials for central nervous system tumors by RTOG and NRG Oncology

Article Title: The evolution of RTOG and NRG Oncology CNS tumors clinical trials

Article References: Sehrawat, K., Polley, M.-Y. C., Vogelbaum, M. A., Gilbert, M., Chakravarti, A., Cahill, D. P., Lassman, A. B., Raleigh, D. R., Sulman, E. P., Machtay, M., Le, Q. T., Curran, W., Gondi, V., & Mehta, M. P. (2026). The evolution of RTOG and NRG Oncology CNS tumors clinical trials. Journal of Neuro-Oncology, 179(2), Article 83. https://doi.org/10.1007/s11060-026-05788-w

Image Credits: AI Generated

DOI: 10.1007/s11060-026-05788-w

Keywords: RTOG, NRG Oncology, CNS tumors, glioblastoma, brain metastases, stereotactic radiosurgery, hippocampal-avoidance radiotherapy, temozolomide, PCV chemotherapy, primary CNS lymphoma, meningioma, clinical trials

One of the most significant changes is the appointment of Dr. Vinai Gondi as the Chair of the NRG Brain Tumor Committee, effective March 1, 2026. Dr. Gondi, a renowned radiation oncologist and clinician-scientist, specializes in brain tumors, including primary and metastatic lesions. His innovative work on hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) has revolutionized neuro-oncological treatments by minimizing cognitive decline, a common side effect of conventional brain radiation. This technique, tested in landmark clinical trials such as RTOG 0933 and NRG-CC001, exemplifies how precise targeting in radiation oncology can preserve neurological function without compromising tumor control.

Dr. Gondi’s role as Service Line Director of Radiation Oncology at Northwestern Medicine’s Proton Center showcases his expertise in proton therapy, an advanced modality that uses charged particles to deliver radiation with high precision, sparing healthy tissue and reducing toxicity. His leadership in NCI-sponsored phase II and III trials has advanced understanding of both survival benefits and neurocognitive outcomes in brain tumor patients, underscoring the critical balance between therapeutic effectiveness and quality of life. His contributions have also influenced national guidelines through major professional societies including ASTRO, ASCO, and SNO, making him a cornerstone figure in neuro-oncology.

Assuming the Chair position of the NRG Ancillary Projects Committee is Dr. Bridget Koontz, effective November 1, 2025. Dr. Koontz is a distinguished radiation oncologist whose research focuses on genitourinary malignancies, particularly prostate cancer. Her investigations into radiation-induced erectile dysfunction have provided vital insights into minimizing treatment-related toxicity while preserving sexual function, an area of growing importance given the long survivorship of prostate cancer patients. Moreover, she has been at the forefront of research into novel radiopharmaceuticals and the therapeutic challenge of oligometastatic prostate cancer, influencing national clinical trial designs and protocols.

Dr. Koontz’s leadership experience encompasses roles as Medical Director at AdventHealth Cancer Institute and former Chief Medical Officer at GenesisCare USA, highlighting her operational and clinical expertise in radiation oncology services. As Principal Investigator of the ongoing NRG-GU011 “NRG PROMETHEAN” trial, she steers efforts to optimize radiotherapy in patients with limited metastatic disease. Her role embodies the integration of clinical leadership with cutting-edge research aimed at refining personalized cancer therapy.

Dr. Priya Rastogi is set to take the helm as Chair of the NRG Breast Cancer Committee starting March 1, 2026. A professor at the University of Pittsburgh and chief executive of the NSABP Foundation, Dr. Rastogi brings over two decades of experience in medical oncology with a focus on early-stage breast cancer treatment. Her leadership in Phase II and III trials has been instrumental in the adoption of therapies such as trastuzumab for HER2-positive breast cancer and abemaciclib for hormone receptor-positive disease, therapies that have significantly improved survival outcomes.

Her extensive involvement with international research organizations and steering committees reflects her influence on shaping clinical trial design and guidelines. Dr. Rastogi’s dual role as a clinician and researcher allows her to bridge the gap between laboratory research and bedside applications. Her presence on the NRG Board of Directors and auxiliary committees further exemplifies her commitment to fostering translational research that prioritizes patient-centered outcomes.

The appointment of Lisa Lenrow, MBA, as Vice Chair of the NRG Patient Advocate Committee marks an important infusion of patient-centered leadership into the organization. With over 25 years of expertise in biopharmaceutical marketing and patient engagement strategies, Ms. Lenrow’s unique perspective as both a strategic consultant and a caregiver to a brain tumor patient provides her with unparalleled insight into patient advocacy. Her involvement with organizations such as the National Brain Tumor Society and institutional review boards ensures that patient voices are integral to clinical research design and implementation.

Ms. Lenrow’s work extends beyond traditional marketing into health policy, grant review, and public advocacy, demonstrating the importance of interdisciplinary approaches in oncology research. Her contributions help balance scientific pursuits with the lived realities of patients and caregivers, an essential element in enhancing clinical trial accessibility and relevance.

These leadership transitions reflect NRG Oncology’s strategic emphasis on integrating cutting-edge scientific research with patient-centered care delivery. The incoming chairs bring expertise in radiation oncology, medical oncology, translational research, and advocacy, positioning the organization to tackle complex problems in cancer therapy—from neurocognitive preservation in brain tumors to minimizing toxicity in genitourinary cancers, and improving survival in breast cancer.

The outgoing leaders—Dr. Minesh Mehta (Brain Tumor), Dr. Eleftherios ‘Terry’ Mamounas (Breast Cancer), and Dr. Steven Waggoner (Ancillary Projects)—have left a lasting legacy in shaping the committees’ robust research frameworks. Their dedication fostered pivotal clinical trials and collaborative networks that continue to underpin NRG Oncology’s mission.

NRG Oncology remains at the forefront of oncology research as a multi-institutional network conducting translational and clinical studies that directly impact standards of care. Founded in 2012 through the consolidation of the NSABP, RTOG, and GOG programs, NRG brings together a multidisciplinary team spanning medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians across more than 1,300 sites worldwide. This comprehensive network facilitates the development of gender-specific and locality-driven cancer interventions, enhancing the precision and effectiveness of treatments.

The evolving leadership will harness this extensive infrastructure, pushing forward investigations with practical clinical endpoints such as survival, toxicity reduction, and quality of life improvements. Their work exemplifies the translation of scientific discovery into tangible benefits for cancer patients and exemplifies the promise of collaborative, multi-center clinical trials under the aegis of the National Cancer Institute’s National Clinical Trials Network.

As these leaders assume their new roles, NRG Oncology’s trajectory towards groundbreaking cancer research and patient-centric innovation is assured. These developments signal exciting advancements for oncology professionals, researchers, and patients globally, fueling hope for more effective, less toxic treatment paradigms in the years to come.

Subject of Research: Leadership changes in oncology research committees; advancements in brain tumor, genitourinary, and breast cancer clinical trials; patient advocacy in cancer research.

Article Title: Transforming Cancer Care: NRG Oncology’s New Leadership Poised to Advance Clinical Research and Patient Outcomes

News Publication Date: Not specified within the provided content.

Web References:
https://www.nrgoncology.org/Current-Openings

Keywords: Cancer research, Clinical research, Brain tumor, Neuro-oncology, Radiation oncology, Prostate cancer, Breast cancer, Clinical trials, Patient advocacy, National Cancer Institute, Neurocognitive outcomes, Radiopharmaceuticals