Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: Safety profile for RTOG 0933

Background and purposeRTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5 mm margin).Materials/methodsPatients with ⩽10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p < 0.05 for statistical significance.Results1133 metastases were identified in 371 patients. Metastases within 5 mm of the hippocampus were observed in 8.6% of patients (95% CI 5.7–11.5%) and 3.0% of brain metastases. None of the metastases lay within the hippocampus. A 1-cm3 increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006–1.034, p = 0.003) for the presence of perihippocampal metastasis.ConclusionWith an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933.