Overall survival and response to radiation and targeted therapies among patients with renal cell carcinoma brain metastases

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OBJECTIVE

The object of this retrospective study was to investigate the impact of targeted therapies on overall survival (OS), distant intracranial failure, local failure, and radiation necrosis among patients treated with radiation therapy for renal cell carcinoma (RCC) metastases to the brain.

METHODS

All patients diagnosed with RCC brain metastasis (BM) between 1998 and 2015 at a single institution were included in this study. The primary outcome was OS, and secondary outcomes included local failure, distant intracranial failure, and radiation necrosis. The timing of targeted therapies was recorded. Multivariate Cox proportional-hazards regression was used to model OS, while multivariate competing-risks regression was used to model local failure, distant intracranial failure, and radiation necrosis, with death as a competing risk.

RESULTS

Three hundred seventy-six patients presented with 912 RCC BMs. Median OS was 9.7 months. Consistent with the previously validated diagnosis-specific graded prognostic assessment (DS-GPA) for RCC BM, Karnofsky Performance Status (KPS) and number of BMs were the only factors prognostic for OS. One hundred forty-seven patients (39%) received vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Median OS was significantly greater among patients receiving TKIs (16.8 vs 7.3 months, p < 0.001). Following multivariate analysis, KPS, number of metastases, and TKI use remained significantly associated with OS.

The crude incidence of local failure was 14.9%, with a 12-month cumulative incidence of 13.4%. TKIs did not significantly decrease the 12-month cumulative incidence of local failure (11.4% vs 14.5%, p = 0.11). Following multivariate analysis, age, number of BMs, and lesion size remained associated with local failure. The 12-month cumulative incidence of radiation necrosis was 8.0%. Use of TKIs within 30 days of SRS was associated with a significantly increased 12-month cumulative incidence of radiation necrosis (10.9% vs 6.4%, p = 0.04).

CONCLUSIONS

Use of targeted therapies in patients with RCC BM treated with intracranial SRS was associated with improved OS. However, the use of TKIs within 30 days of SRS increases the rate of radiation necrosis without improving local control or reducing distant intracranial failure. Prospective studies are warranted to determine the optimal timing to reduce the rate of necrosis without detracting from survival.

ABBREVIATIONS BM = brain metastasis; DS-GPA = diagnosis-specific graded prognostic assessment; KPS = Karnofsky Performance Status; mTOR = mammalian target of rapamycin; OS = overall survival; RCC = renal cell carcinoma; SRS = stereotactic radiosurgery; TKI = tyrosine kinase inhibitor; VEGFR = vascular endothelial growth factor receptor; WBRT = whole-brain radiation therapy.

Article Information

Correspondence Samuel T. Chao: Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. chaos@ccf.org.

INCLUDE WHEN CITING Published online January 18, 2019; DOI: 10.3171/2018.8.JNS182100.

Disclosures Dr. Ahluwalia has direct stock ownership in Mimivax; has been a consultant for Monteris Medical, BMS, Astrazeneca, VBI Vacines, Abbvie, Varian, and Flatiron; and has received support from Novartis, Abbvie, Incyte, Astrazeneca, Novocure, Bayer, Merck, and Pharmacyclics for non–study-related clinical or research effort. Dr. Rini has received support from Pfizer for non–study-related clinical or research effort. Dr. Chao has received honorarium from Varian Medical System.

© AANS, except where prohibited by US copyright law.

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    Overall survival among patients with RCC BMs treated with and without VEGFR TKIs (A), treated with and without mTOR inhibitors (B), and stratified by the DS-GPA group (C).

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    Cumulative incidence of local failure among patients undergoing SRS and treated with and without VEGFR TKIs (A), stratified by maximum lesion diameter (B). Cumulative incidence of radiation necrosis among patients undergoing SRS and treated with and without VEGFR TKIs (C), stratified by maximum lesion diameter (D).

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