Adverse radiation effect versus tumor progression following stereotactic radiosurgery for brain metastases: Implications of radiologic uncertainty

Background Adverse radiation effect (ARE) following stereotactic radiosurgery (SRS) for brain metastases is challenging to distinguish from tumor progression. This study characterizes the clinical implications of radiologic uncertainty (RU). Methods Cases reviewed retrospectively at a single-institutional, multi-disciplinary SRS Tumor Board between 2015–2022 for RU following SRS were identified. Treatment history, diagnostic or therapeutic interventions performed upon RU resolution, and development of neurologic deficits surrounding intervention were obtained from the medical record. Differences in lesion volume and maximum diameter at RU onset versus resolution were compared with paired t-tests. Median time from RU onset to resolution was estimated using the Kaplan–Meier method. Univariate and multivariate associations between clinical characteristics and time to RU resolution were assessed with Cox proportional-hazards regression. Results Among 128 lesions with RU, 23.5% had undergone ≥ 2 courses of radiation. Median maximum diameter (20 vs. 16 mm, p < 0.001) and volume (2.7 vs. 1.5 cc, p < 0.001) were larger upon RU resolution versus onset. RU resolution took > 6 and > 12 months in 25% and 7% of cases, respectively. Higher total EQD2 prior to RU onset (HR = 0.45, p = 0.03) and use of MR perfusion (HR = 0.56, p = 0.001) correlated with shorter time to resolution; larger volume (HR = 1.05, p = 0.006) portended longer time to resolution. Most lesions (57%) were diagnosed as ARE. Most patients (58%) underwent an intervention upon RU resolution; of these, 38% developed a neurologic deficit surrounding intervention. Conclusions RU resolution took > 6 months in > 25% of cases. RU may lead to suboptimal outcomes and symptom burden. Improved characterization of post-SRS RU is needed.