Stereotactic Radiosurgery for Brain Metastases in Patients With a Heterozygous Germline Ataxia Telangiectasia Mutated Gene.

Germline mutations in the ataxia telangiectasia mutated () gene are associated with increased radiation sensitivity. Present literature lacks consensus on whether patients with heterozygous germline mutations may be at greater risk of radiation-associated toxicities when treated with radiation therapy (RT), and there is little data considering more modern and conformal RT techniques such as stereotactic radiosurgery (SRS). Our report presents two cases of patients with heterozygous germline mutations treated with SRS for brain metastases. One patient developed grade 3 radiation necrosis (RN) of an irradiated 16.3 cm resection cavity, but did not develop RN at other sites of punctate brain metastases treated with SRS. Similarly, the second report describes a patient who did not develop RN at any of the 31 irradiated sites of sub-centimeter (all ≤5 mm) brain metastases. The described cases demonstrate that some patients with germline variants can safely undergo SRS for smaller brain metastases; however, clinical caution should be considered for patients with larger targets or a history of prior radiation toxicity. Given these findings and the lingering uncertainty surrounding the degree of radiosensitivity across variants, future research is needed to determine whether more conservative dose-volume limits would potentially mitigate the risk of RN when treating larger brain metastases in this radiosensitive population.