Quality of life outcomes for brain metastasis patients treated with stereotactic radiosurgery: pre-procedural predictive factors from a prospective national registry

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Stereotactic radiosurgery (SRS) is increasingly used for the treatment of brain metastasis. To date, most studies have focused on survival, radiological response, or surrogate quality endpoints such as Karnofsky Performance Scale status or neurocognitive indices. The current study prospectively evaluated pre-procedural factors impacting quality of life in brain metastasis patients undergoing SRS.


Using a national, cloud-based platform, patients undergoing SRS for brain metastasis were accrued to the registry. Quality of life prior to SRS was assessed using the 5-level EQ-5D (EQ5D-L) validated tool; additionally, patient and treatment attributes were collected. Patient quality of life was assessed as part of routine follow-up after SRS. Factors predicting a difference in the aggregate EQ5D-L score or the subscores were evaluated. Pre-SRS covariates impacting changes in EQ5D-L were statistically evaluated. Statistical analyses were conducted using multivariate linear regression models.


EQ5D-L results were available for 116 patients. EQ5D-L improvement (average of 0.387) was noted in patients treated with earlier SRS (p = 0.000175). Worsening overall EQ5D-L (average of 0.052 per lesion) was associated with an increased number of brain metastases at the time of initial presentation (p = 0.0399). Male sex predicted a risk of worsening (average of 0.347) of the pain and discomfort subscore at last follow-up (p = 0.004205). Baseline subscores of pain/discomfort were not correlated with pain/discomfort subscores at follow-up (p = 0.604), whereas baseline subscores of anxiety/depression were strongly positively correlated with the anxiety/depression follow-up subscores (p = 0.0039).


After SRS, quality of life was likely to improve in patients treated early with SRS and worsen in those with a greater number of brain metastases. Sex differences appear to exist regarding pain and discomfort worsening after SRS. Those with high levels of anxiety and depression at SRS may benefit from medical treatment as this particular quality of life factor generally remains unchanged after SRS.

ABBREVIATIONS ASTRO = American Society for Radiation Oncology; BRCS = brain cancer subscale; EORTC = European Organisation for Research and Treatment of Cancer; EQ5D-L = 5-level EQ-5D; FACT-BR = Functional Assessment of Cancer Therapy–Brain; HRQOL = health-related QOL; KPS = Karnofsky Performance Scale; NPA = NeuroPoint Alliance; QOL = quality of life; SRS = stereotactic radiosurgery; WBRT = whole-brain radiotherapy.

Article Information

Correspondence Jason P. Sheehan: University of Virginia Health System, Charlottesville, VA. jps2f@virginia.edu.

INCLUDE WHEN CITING Published online December 21, 2018; DOI: 10.3171/2018.8.JNS181599.

Disclosures The registry effort was supported by grant funding to NPA from BrainLab, Elekta, AANS, and ASTRO. Individual sites received nominal grant funding from NPA. Drs. Sheehan and Kondziolka serve as representatives for NPA.

Dr. Grills reports having stock ownership in and serving on the Executive Board of Directors of Greater Michigan Gamma Knife and receiving funding for non–study-related research from Elekta through her institution.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Upper: Scatterplot of change in EQ5D-L score from time of initial assessment to the last follow-up time point for individual patients as recorded in the registry’s database. Data are plotted as a function of the time elapsed from each individual patient’s time of initial SRS. Lower: Differences in overall EQ5D-L score from the time of initial SRS to last follow-up for the overall cohort of 116 patients.

  • View in gallery

    Differences in EQ5D-L anxiety and depression subscores from the time of initial SRS to last follow-up for the overall cohort of 116 patients. Circles represent patients tested.

  • View in gallery

    Differences in EQ5D-L pain and discomfort subscores from the time of initial SRS to last follow-up for the overall cohort of 116 patients. Circles represent patients tested.



Bates GEMostel JLHesdorffer M: Cancer-related anxiety. JAMA Oncol 3:10072017


Bottomley AFlechtner HEfficace FVanvoorden VCoens CTherasse P: Health related quality of life outcomes in cancer clinical trials. Eur J Cancer 41:169717092005


Bragstad SFlatebø MNatvig GKEide GESkeie GOBehbahani M: Predictors of quality of life and survival following Gamma Knife surgery for lung cancer brain metastases: a prospective study. J Neurosurg 129:71832018


Chang ELWefel JSHess KRAllen PKLang FFKornguth DG: Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:103710442009


Emery ATrifiletti DMRomano KDPatel NSmolkin MESheehan JP: More than just the number of brain metastases: evaluating the impact of brain metastasis location and relative volume on overall survival after stereotactic radiosurgery. World Neurosurg 99:1111172017


EuroQol Group: EuroQol—a new facility for the measurement of health-related quality of life. Health Policy 16:1992081990


Hara WTran PLi GSu ZPuataweepong PAdler JR Jr: Cyberknife for brain metastases of malignant melanoma and renal cell carcinoma. Neurosurgery 64 (2 Suppl):A26A322009


Liang KYZeger SL: Longitudinal data analysis using generalized linear models. Biometrika 73:13221986


Miller JAKotecha RBarnett GHSuh JHAngelov LMurphy ES: Quality of life following stereotactic radiosurgery for single and multiple brain metastases. Neurosurgery 81:1471552017


Nayak LLee EQWen PY: Epidemiology of brain metastases. Curr Oncol Rep 14:48542012


Pan HCSun MHChen CCChen CJLee CHSheehan J: Neuroimaging and quality-of-life outcomes in patients with brain metastasis and peritumoral edema who undergo Gamma Knife surgery. J Neurosurg 109 Suppl:90982008


Pashos CLFlowers CRKay NEWeiss MLamanna NFarber C: Association of health-related quality of life with gender in patients with B-cell chronic lymphocytic leukemia. Support Care Cancer 21:285328602013


Pickard ASJiang RLin HWRosenbloom SCella D: Using patient-reported outcomes to compare relative burden of cancer: EQ-5D and Functional Assessment of Cancer Therapy-General in eleven types of cancer. Clin Ther 38:7697772016


Pickard ASWilke CTLin HWLloyd A: Health utilities using the EQ-5D in studies of cancer. Pharmacoeconomics 25:3653842007


Sheehan JPKavanagh BDAsher AHarbaugh RE: Inception of a national multidisciplinary registry for stereotactic radiosurgery. J Neurosurg 124:1551622016


Skeie BSEide GEFlatebø MHeggdal JILarsen EBragstad S: Quality of life is maintained using Gamma Knife radiosurgery: a prospective study of a brain metastases patient cohort. J Neurosurg 126:7087252017


Soffietti R: Reply to M.C. Chamberlain and C. Gemici. J Clin Oncol 31:263626372013


Soffietti RKocher MAbacioglu UMVilla SFauchon FBaumert BG: A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol 31:65722013


Soon YYTham IWLim KHKoh WYLu JJ: Surgery or radiosurgery plus whole brain radiotherapy versus surgery or radiosurgery alone for brain metastases. Cochrane Database Syst Rev (3):CD0094542014


Trifiletti DMLee CCKano HCohen JJanopaul-Naylor JAlonso-Basanta M: Stereotactic radiosurgery for brainstem metastases: an international cooperative study to define response and toxicity. Int J Radiat Oncol Biol Phys 96:2802882016


Trifiletti DMSheehan JPGrover SDutta SWRusthoven CGKavanagh BD: National trends in radiotherapy for brain metastases at time of diagnosis of non-small cell lung cancer. J Clin Neurosci 45:48532017


Yamamoto MSerizawa TShuto TAkabane AHiguchi YKawagishi J: Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15:3873952014


Zindler JDBruynzeel AMEEekers DBPHurkmans CWSwinnen ALambin P: Whole brain radiotherapy versus stereotactic radiosurgery for 4–10 brain metastases: a phase III randomised multicentre trial. BMC Cancer 17:5002017




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