ArticleFrontiers in oncology2026
Late radiation necrosis following stereotactic radiosurgery after COVID-19 vaccination: a case report and hypothesis of immune-mediated inflammatory activation.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Radiation necrosis (RN) is a recognized complication of stereotactic radiosurgery (SRS) for brain metastases, typically occurring within 6-24 months after treatment. Late RN occurring several years after SRS remains uncommon and may present substantial diagnostic challenges, particularly in patients with prolonged systemic immune exposure and evolving imaging abnormalities. Case presentation: A 66-year-old female with metastatic non-small cell lung cancer (NSCLC) presented in 2018 with four brain metastases treated with single-fraction SRS to 20 Gy. She subsequently received carboplatin, pemetrexed, and prolonged pembrolizumab therapy with complete extracranial response. Serial surveillance MRIs demonstrated excellent intracranial response and long-term stability for several years. Approximately 46 months after SRS, new enhancing lesions with surrounding edema and hemorrhagic changes developed within previously treated regions. Over subsequent follow ups, imaging demonstrated fluctuating enhancement, progressive FLAIR abnormalities, and mixed interval changes despite predominantly decreased perfusion characteristics suggestive of treatment effect. Fluciclovine positron emission tomography (PET) demonstrated multiple radiotracer-avid lesions concerning recurrent metastatic disease. Due to persistent concern for progression, the dominant right temporal lesion underwent preoperative re-irradiation followed by surgical resection. Histopathology demonstrated RN without viable tumor. During the interval preceding radiographic progression, the patient had also received multiple COVID-19 vaccinations. Although causality cannot be established, systemic immune activation within chronically irradiated tissue may have contributed to inflammatory activation of subclinical radiation injury. Conclusion: This case highlights the potential for delayed RN several years after SRS and demonstrates the diagnostic limitations of advanced imaging modalities, including amino acid PET tracers, in distinguishing RN from recurrent metastases. Chronic immune priming, prior immunotherapy exposure, and systemic inflammatory activation may contribute to delayed manifestation of RN in susceptible irradiated CNS tissue.
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