KEY POINTS
- A 66-year-old woman with metastatic non-small cell lung cancer received single-fraction stereotactic radiosurgery of 20 Gy to four brain metastases in 2018, followed by pembrolizumab-based systemic therapy.
- New enhancing lesions with edema and hemorrhagic changes appeared approximately 46 months after stereotactic radiosurgery, during the period in which she received a primary COVID-19 vaccination series and subsequent boosters.
- Serial perfusion magnetic resonance imaging repeatedly favored radiation necrosis, whereas fluciclovine positron emission tomography demonstrated avid uptake with a maximum standardized uptake value of 6.1, raising concern for recurrent disease.
- The dominant lesion received preoperative re-irradiation of 24 Gy in three fractions, followed by surgical resection in 2025. Histopathology showed radiation necrosis with no viable tumor.
- The authors hypothesize that vaccination-related systemic immune activation may have contributed to inflammatory activation of chronically irradiated brain tissue, but causality cannot be established from a single case.
CLINICAL TAKEAWAY
This case raises the hypothesis that systemic immune activation after COVID-19 vaccination could contribute to delayed inflammatory activation of previously irradiated brain tissue. The association is temporal and biologically plausible but unproven; the stronger clinical message is that very late radiation necrosis can mimic recurrence even on amino-acid positron emission tomography and may require histopathologic confirmation.