Management outcomes for biopsy-proven radiation necrosis in patients with brain metastases in the era of immune-checkpoint blockade.
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2025-10
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Abstract
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Immunotherapy and stereotactic radiosurgery (SRS) are frequently combined in the management of brain metastases from non-small cell lung cancer (NSCLC) and melanoma. However, concurrent SRS and dual immune-checkpoint inhibition (ICPI) elevate the risk for symptomatic radionecrosis. As optimal radionecrosis management in the setting of immunotherapy is unknown, we aimed to characterize our institutional approaches and outcomes in patients with biopsy-proven radionecrosis.Methods
Patients with NSCLC and melanoma brain metastases treated with SRS from 2014 to 2022 were identified from a prospective database. Only cases with biopsy-confirmed radionecrosis were included. The primary outcome was radiographic stabilization following treatment. Secondary outcomes included symptomatic resolution, overall survival, and cause of death.Results
Twenty-five patients [14 women (56%); median age, 58 years; 15 NSCLC (60%), 10 melanoma (40%); median follow-up: 66 months] with 30 cases of necrosis met inclusion criteria. 84% of patients received immunotherapy and twenty-one (84%) were symptomatic. Twenty-three cases (77%) received prophylactic steroids during SRS. Median time from SRS to biopsy-confirmed radionecrosis was 9.3 (95%CI: 6.8-17.9) months. Thirty-two interventions were performed: 21 laser interstitial thermal therapy, seven resection, and four medical management. Estimated 6-month radiographic stabilization was 80% (95%CI: 59-90%). Median time to stabilization with dual, single, and no ICPI was 2.7 (95%CI: 1.4-NR), 1.2 (95%CI: 0.8-NR), and 0 (95%CI: 0-NR) months, respectively. Three (14%) and two (29%) CTCAE grade ≥ 3 adverse events occurred following LITT and resection, respectively, with no grade 5 events.Conclusion
Existing radionecrosis management strategies appear effective in patients receiving immunotherapy, though prospective trials are needed for validation.Trial registration number
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Publication Info
Seidel, Jazlyn A, Laura Alder, April KS Salama, Carey K Anders, Jordan Komisarow, Peter E Fecci, Paul Sperduto, Trey Mullikin, et al. (2025). Management outcomes for biopsy-proven radiation necrosis in patients with brain metastases in the era of immune-checkpoint blockade. Journal of neuro-oncology, 175(1). pp. 199–208. 10.1007/s11060-025-05120-y Retrieved from https://hdl.handle.net/10161/33517.
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Scholars@Duke
April Kelly Scott Salama
Jordan Komisarow
Paul Wayne Sperduto
I am a board-certified radiation oncologist, have been active in clinical research and am now an adjunct professor of radiation oncology at Duke and senior editor of the 2022 textbook, Khan’s Treatment Planning in Radiation Oncology, 5thedition. My research focus involves the treatment and prognosis of patients with brain metastases.
Trey Carlton Mullikin
John P. Kirkpatrick
Malignant and benign tumors of the brain, spine and base of skull. Mathematical modelling of tumor metabolism, mass transfer and the response to ionizing radiation. Enhancing clinical outcome in stereotactic radiosurgery, fractionated stereotactic radiotherapy and stereotactic body radiotherapy.
Scott Richard Floyd
Diseases of the brain carry particular morbidity and mortality, given the fundamental function of the brain for human life and quality of life. Disease of the brain are also particularly difficult to study, given the complexity of the brain. Model systems that capture this complexity, but still allow for experiments to test therapies and mechanisms of disease are badly needed. We have developed an experimental model system that uses slices made from rat and mouse brains to create a test platform to research new treatments for brain diseases such as stroke, Alzheimer's disease, Huntington's disease and brain tumors. This model system reduces the number of experimental animals used, and streamlines experiments so that final testing in laboratory animals is more efficient. We use this brainslice system and limited numbers of experimental animals to test drugs and genetic pathways to treat stroke, Alzheimer's disease, Huntington's disease and brain tumors. As many brain tumors are treated with radiation therapy, we have a particular interest in the cellular response to DNA damage caused by radiation. DNA damage signaling and repair are fundamental processes necessary for cells to maintain genomic integrity. Problems with these processes can lead to cancer. As many cancer cells have altered DNA damage and repair pathways, we can apply DNA damage as cancer therapy. Our knowledge of how normal and neoplastic cells handle DNA damage is still incomplete. A deeper understanding can lead to improved cancer treatment, and to better protection from the harmful effects of DNA damaging agents like radiation. To this end, we plan experiments that test the effects of radiation on normal animal tissues and animal models of cancer, as well as molecular pathways in brain diseases such as Alzheimer’s, Huntington’s and stroke.
Zachary James Reitman
Dr. Reitman’s clinical interests include radiotherapy for primary and metastatic tumors of the brain and spine. He is also interested in basic and translational research studies to develop new treatment approaches for pediatric and adult brain tumors. He uses genomic analysis, radiation biology studies, and genetically engineered animal models of cancer to carry out this research
Eugene John Vaios
Eugene John Vaios, MD, MBA, is an NIH-funded Assistant Professor of Radiation Oncology at the Duke Cancer Institute. He was previously at Harvard University where he completed his undergraduate and graduate education, as well as his internship at Cambridge Health Alliance. Eugene's research focus is at the intersection of radiation therapy and immunotherapy for patients with primary and metastatic brain tumors. Active translational research includes the development of a liquid biopsy for non-invasive diagnosis, surveillance, and prediction of treatment response in patients with brain tumors. Other interests include leveraging artificial intelligence and big data to improve cancer outcomes. Outside Duke, Eugene holds leadership positions on the ASTRO Board Finance and Audit Committee and serves on the Lancet Commission on Neurorehabilitation.
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