Prediction of new brain metastases after radiosurgery: validation and analysis of performance of a multi-institutional nomogram

Abstract

Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients’ DBF risk within the validation dataset (c-index = 0.631) and Heller’s explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p < 0.0001). We present a multi-institutionally validated prognostic model and nomogram to predict risk of DBF and guide risk-stratification of patients who are appropriate candidates for radiosurgery versus upfront WBRT.

<p>Whole-brain helical tomotherapy with integrated boost for brain metastases in patients with malignant melanoma – final results of the BRAIN-RT trial</p>

“…In the cohort of Ostheimer et al, the reported median OS times for patients with multiple BM from MM were around 2.5 months despite systemic and local treatment and as short as 1.5 months with best supportive care only 29. In a recent analysis by Frinton et al, OS was 4.8 months from the diagnosis of BM and 2.2 months in patients receiving WBRT only 30. Our own previously published data had shown a median OS of 3.5 months in patients treated with WBRT and a relatively improved outcome with a higher irradiation total dose 5.…”

Analysis of the drivers of cost of management when patients with brain metastases are treated with upfront radiosurgery

“…An analysis by Savitz et al suggested that the cost effectiveness of using upfront SRS could be improved by concentrating the population with patients who are more likely to benefit from upfront SRS, such as those who with longer life expectancy and those with longer latency to needing salvage treatment [16]. Several statistical models have been devised to help triage patients for upfront SRS vs WBRT based on the likelihood of DBF, though the efficacy and cost-effectiveness of their use remain to be validated in a prospective setting [17–19].…”

Outcomes of Metastatic Brain Lesions Treated with Radioactive Cs-131 Seeds after Surgery: Experience from One Institution

“…Cs-131 radioisotopes have been reported to have distinct radiotherapeutic advantages over I-125 isotopes including a faster half-life (9.69 days vs. 59.4 days), which may better suit an active postoperative environment and therefore be more effective [ 14 ]. Overall, the outcomes of this series are notable especially in comparison to SRS treatment, where 20–50% of brain metastases develop new or recurrent lesions within 6–12 months [ 25 - 28 ]. The median overall follow-up reported in this case series was 9.4 months, while the median time from the first craniotomy to diagnosed recurrence has been previously reported to be 6.7 months for patients with brain metastases [ 29 , 30 ].…”