Impact of systemic targeted agents on the clinical outcomes of patients with brain metastases

Abstract

BackgroundTo determine the clinical benefits of systemic targeted agents across multiple histologies after stereotactic radiosurgery (SRS) for brain metastases.MethodsBetween 2000 and 2013, 737 patients underwent upfront SRS for brain metastases. Patients were stratified by whether or not they received targeted agents with SRS. 167 (23%) received targeted agents compared to 570 (77%) that received other available treatment options. Time to event data were summarized using Kaplan-Meier plots, and the log rank test was used to determine statistical differences between groups.ResultsPatients who received SRS with targeted agents vs those that did not had improved overall survival (65% vs. 30% at 12 months, p < 0.0001), improved freedom from local failure (94% vs 90% at 12 months, p = 0.06), improved distant failure-free survival (32% vs. 18% at 12 months, p = 0.0001) and improved freedom from whole brain radiation (88% vs. 77% at 12 months, p = 0.03). Improvement in freedom from local failure was driven by improvements seen in breast cancer (100% vs 92% at 12 months, p < 0.01), and renal cell cancer (100% vs 88%, p = 0.04). Multivariate analysis revealed that use of targeted agents improved all cause mortality (HR = 0.6, p < 0.0001).ConclusionsTargeted agent use with SRS appears to improve survival and intracranial outcomes.

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

“…Variations in provider treatment discretion and follow-up across institutions has likely contributed to the discrepancy between rates of events in the derivation and validation datasets. Moreover, molecular subtyping of the recorded primary malignancies was not available for most histologies in this analysis, but is suspected to contribute to the rate of DBF [26]. A preliminary analysis was performed for the available data suggesting trends in higher rates of DBF for triple negative breast cancer as compared to non-triple negative breast cancers in the pooled training and validation datasets.…”

Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastases

“…An additional caveat to and a 1-year OS of 65% versus 30% (p<0.0001). 31 In terms post-RT lesion size, reports with combined therapy have been conflicting. Qian et al 8 recently reported results regarding 313 melanoma BMs in 53 patients treated concurrently (defined as RT and IT delivery within 4 weeks of each other).8 IT was as follows: 54 patients (72%) received anti-CTLA-4 and 21 patients (28%) received anti-PD-1.…”

“…To this end, a recent report by Johnson et al 31 demonstrated the impact of systemic agents on the clinical outcomes of patients with BM. Although this review included patients with many primary tumor types, and a variety of agents (BRAF inhibitors, ipilimumab in patients with melanoma primaries), the authors did show that patients receiving IT with SRS compared to SRS alone had a median survival of 18 versus 7 months Figure 4.…”

The Influence of Biomarker Mutations and Systemic Treatment on Cerebral Metastases from NSCLC Treated with Radiosurgery

“…However in the current study, the use of target agents resulted in survival advantage in NSCLC patients with brain metastases. Some series have suggested that subgroups of brain metastases benefit from upfront or post-SRS systemic therapy by improving overall survival, and local control following SRS13,16,17,24). Because of the specificity of target agents and the various cascades of tumorigenesis across tumor types, the target agents are generally specific to tumor subtype and/or histological subtype.…”