Objective: Stereotactic radiosurgery (SRS) is a well-established treatment for brain arteriovenous malformations (bAVMs). However, data on radiation-induced neoplasms (RINs) following SRS in patients with bAVMs remain limited. In this study, authors aimed to evaluate the incidence of newly developed intracranial RINs following SRS for bAVMs.
Methods: The authors retrospectively analyzed anonymized data for patients who underwent SRS for bAVMs between 1990 and 2019 at 18 Gamma Knife centers in Japan. Patients with fewer than 3 years of radiological follow-up, prior radiotherapy, or genetic tumor predisposition were excluded. Newly developed tumors were classified as in field (within the 2-Gy isodose line) or out of field. Annual incidence rates were calculated based on total patient-years of follow-up.
Results: During a median radiological follow-up of 100 months, new intracranial tumors developed in 12 (0.27%) of the 4376 patients included in the study. In-field malignant tumors occurred in 5 patients (0.11%), with a median latency of 13.3 years. Out-of-field tumors were observed in 7 patients (0.16%), including malignant (n = 3) and benign (n = 4) neoplasms, with a median latency of 17.4 years. The cumulative incidence of in-field tumors at 10, 15, and 20 years was 0.08%, 0.16%, and 0.16%, respectively. The corresponding incidence of out-of-field tumors was 0.11%, 0.11%, and 0.58%, respectively. In terms of tumor histology, the cumulative incidence of new intracranial brain tumors at 10, 15, and 20 years was 0.15%, 0.24%, and 0.40% for malignant tumors and 0.03%, 0.03%, and 0.34% for nonmalignant tumors, respectively. Across 43,950.3 patient-years of radiological follow-up, the overall annual incidence was 0.027%, increasing from 0.005% within 5 years to 0.046% after 5 years. The annual incidence of in-field tumors was 0.011% (0% within and 0.021% after 5 years) and 0.016% for out-of-field tumors (0.005% within and 0.025% after 5 years). Malignant tumors had an annual incidence of 0.018% (0.005% within and 0.030% after 5 years), whereas benign tumors occurred only out of field with an annual incidence of 0.009% (0% within and 0.017% after 5 years).
Conclusions: The incidence of radiation-induced malignancies after SRS for bAVMs is extremely low but potentially fatal. Although the current risk is acceptable compared to the mortality associated with microsurgical resection, the possibility of late-onset malignancies, especially in younger patients, warrants caution. As more patients are treated and follow-up periods become extended, this risk may increase. Therefore, long-term surveillance is essential for accurately assessing and managing the potential for RINs over time.
Keywords: Gamma Knife; annual incidence; brain arteriovenous malformation; oncology; radiation-induced neoplasm; stereotactic radiosurgery; vascular disorders.