Neurocognitive evaluation of brain metastases patients treated with post-resection stereotactic radiosurgery: a prospective single arm clinical trial
Post-operative radiation therapy for brain metastases (BM) has become standard treatment. Concerns regarding the deleterious cognitive effects of Whole Brain Radiation Therapy spurred a trend to use focal therapies such as stereotactic radiosurgery (SRS). The purpose of this study was to prospectively evaluate the neuropsychological effects following post-resection SRS treatment since limited data exist in this context.
We conducted a prospective single arm cohort study of patients with 1–2 BM, who underwent resection of a single BM between May 2015 to December 2016. Patients were evaluated for cognitive functions (NeuroTrax computerized neuropsychological battery; Modiin, Israel) and quality of life (QOL; QLQ-30, QLQ-BN20) before and 3 months following post-resection SRS.
Twelve out of 14 patients completed pre- and post-SRS neurocognitive assessments. Overall, we did not detect significant neurocognitive or QOL changes 3 months following SRS. In a subgroup analysis among patients younger than 60 years, median global cognitive score increased from a pre-treatment score of 88 (72–102) to 95 (79–108), 3 months following SRS treatment, p = 0.042; Wilcoxon paired non-parametric test. Immediate verbal memory and executive functions scores increased from 86 (72–98) to 98 (92–112) and 86 (60–101) to 100 (80–126), respectively, p = 0.043. No significant cognitive changes were discovered among patients at the age of 60 or older.
Post-resection radiosurgery has a safe neuro-cognitive profile and is associated with preservation of nearly all quality of life parameters. Patients younger than 60 years benefit most and may even regain some cognitive functions within a few months after treatment.
KeywordsBrain metastases Stereotactic radiosurgery Cognition Quality of life
Compliance with ethical standards
Conflict of interest
the authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG II, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316:401–409. https://doi.org/10.1001/jama.2016.9839 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann RD, Carrie C, Ben Hassel M, Kouri M, Valeinis E, van den Berge D, Collette S, Collette L, Mueller RP (2011) Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952–26001 study. J Clin Oncol 29:134–141. https://doi.org/10.1200/jco.2010.30.1655 CrossRefPubMedGoogle Scholar
- 7.Brennan C, Yang TJ, Hilden P, Zhang Z, Chan K, Yamada Y, Chan TA, Lymberis SC, Narayana A, Tabar V, Gutin PH, Ballangrud A, Lis E, Beal K (2014) A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys 88:130–136. https://doi.org/10.1016/j.ijrobp.2013.09.051 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G (2006) Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295:2483–2491. https://doi.org/10.1001/jama.295.21.2483 CrossRefPubMedGoogle Scholar
- 9.Pessina F, Navarria P, Cozzi L, Ascolese AM, Maggi G, Riva M, Masci G, D’Agostino G, Finocchiaro G, Santoro A, Bello L, Scorsetti M (2016) Outcome evaluation of oligometastatic patients treated with surgical resection followed by hypofractionated stereotactic radiosurgery (HSRS) on the tumor bed, for single, large brain metastases. PLoS ONE 11:e0157869. https://doi.org/10.1371/journal.pone.0157869 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Chao ST, De Salles A, Hayashi M, Levivier M, Ma L, Martinez R, Paddick I, Regis J, Ryu S, Slotman BJ, Sahgal A (2017) Stereotactic radiosurgery in the management of limited (1–4) brain metasteses: Systematic review and international stereotactic radiosurgery society practice guideline. Neurosurgery. https://doi.org/10.1093/neuros/nyx522 CrossRefPubMedGoogle Scholar
- 11.Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:1037–1044. https://doi.org/10.1016/s1470-2045(09)70263-3 CrossRefPubMedGoogle Scholar
- 12.Strauss I, Corn BW, Krishna V, Shahar T, Matceyevsky D, Gez E, Shtraus N, Ram Z, Kanner AA (2015) Patterns of failure after stereotactic radiosurgery of the resection cavity following surgical removal of brain metastases. World Neurosurg 84:1825–1831. https://doi.org/10.1016/j.wneu.2015.07.073 CrossRefPubMedGoogle Scholar
- 13.Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, Greenspoon J, Parney IF, Laack NNI, Ashman JB, Bahary JP, Hadjipanayis CG, Urbanic JJ, Barker FG II, Farace E, Khuntia D, Giannini C, Buckner JC, Galanis E, Roberge D (2017) Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 18:1049–1060. https://doi.org/10.1016/s1470-2045(17)30441-2 CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Minniti G, Soltys SG, Halasz LM, Breneman JC, Chan M, Laack NN, Kirkpatrick JP (2018) Stereotactic radiosurgery for resected brain metastases: new evidence supports a practice shift, but questions remain. Int J Radiat Oncol Biol Phys 100:535–538. https://doi.org/10.1016/j.ijrobp.2017.08.024 CrossRefPubMedGoogle Scholar
- 15.Lamba N, Muskens IS, DiRisio AC, Meijer L, Briceno V, Edrees H, Aslam B, Minhas S, Verhoeff JJC, Kleynen CE, Smith TR, Mekary RA, Broekman ML (2017) Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection: a systematic review and meta-analysis. Radiat Oncol 12:106. https://doi.org/10.1186/s13014-017-0840-x CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S, Shioura H, Inomata T, Kunieda E, Hayakawa K, Nakagawa K, Kobashi G, Shirato H (2007) Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys 68:1388–1395. https://doi.org/10.1016/j.ijrobp.2007.03.048 CrossRefPubMedGoogle Scholar
- 18.Hausdorff JM, Doniger GM, Springer S, Yogev G, Simon ES, Giladi N (2006) A common cognitive profile in elderly fallers and in patients with Parkinson’s disease: the prominence of impaired executive function and attention. Exp Aging Res 32:411–429. https://doi.org/10.1080/03610730600875817 CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Leung A, Lien K, Zeng L, Nguyen J, Caissie A, Culleton S, Holden L, Chow E (2011) The EORTC QLQ-BN20 for assessment of quality of life in patients receiving treatment or prophylaxis for brain metastases: a literature review. Expert Rev Pharmacoecon Outcomes Res 11:693–700. https://doi.org/10.1586/erp.11.66 CrossRefPubMedGoogle Scholar
- 23.Caissie A, Nguyen J, Chen E, Zhang L, Sahgal A, Clemons M, Kerba M, Arnalot PF, Danjoux C, Tsao M, Barnes E, Holden L, Danielson B, Chow E (2012) Quality of life in patients with brain metastases using the EORTC QLQ-BN20 + 2 and QLQ-C15-PAL. Int J Radiat Oncol Biol Phys 83:1238–1245. https://doi.org/10.1016/j.ijrobp.2011.09.025 CrossRefPubMedGoogle Scholar
- 25.Foreman PM, Jackson BE, Singh KP, Romeo AK, Guthrie BL, Fisher WS, Riley KO, Markert JM, Willey CD, Bredel M, Fiveash JB (2017) Postoperative radiosurgery for the treatment of metastatic brain tumor: evaluation of local failure and leptomeningeal disease. J Clin Neurosci. https://doi.org/10.1016/j.jocn.2017.12.009 PubMedCrossRefGoogle Scholar
- 26.Caine C, Deshmukh S, Gondi V, Mehta M, Tome W, Corn BW, Kanner A, Rowley H, Kundapur V, DeNittis A, Greenspoon JN, Konski AA, Bauman GS, Raben A, Shi W, Wendland M, Kachnic L (2016) CogState computerized memory tests in patients with brain metastases: secondary endpoint results of NRG oncology RTOG 0933. J Neurooncol 126:327–336. https://doi.org/10.1007/s11060-015-1971-2 CrossRefPubMedGoogle Scholar
- 27.Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, Rowley H, Kundapur V, DeNittis A, Greenspoon JN, Konski AA, Bauman GS, Shah S, Shi W, Wendland M, Kachnic L, Mehta MP (2014) Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol 32:3810–3816. https://doi.org/10.1200/jco.2014.57.2909 CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Martins R, Joanette Y, Monchi O (2015) The implications of age-related neurofunctional compensatory mechanisms in executive function and language processing including the new temporal hypothesis for compensation. Front Hum Neurosci 9:221. https://doi.org/10.3389/fnhum.2015.00221 CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Chen L, Shen C, Redmond KJ, Page BR, Kummerlowe M, McNutt T, Bettegowda C, Rigamonti D, Lim M, Kleinberg L (2017) Use of stereotactic radiosurgery in elderly and very elderly patients with brain metastases to limit toxicity associated with whole brain radiation therapy. Int J Radiat Oncol Biol Phys 98:939–947. https://doi.org/10.1016/j.ijrobp.2017.02.031 CrossRefPubMedGoogle Scholar
- 30.Zeng KL, Raman S, Sahgal A, Soliman H, Tsao M, Wendzicki C, Chow E, Lo SS (2017) Patient preference for stereotactic radiosurgery plus or minus whole brain radiotherapy for the treatment of brain metastases. Ann Palliat Med 6:S155–Ss160. https://doi.org/10.21037/apm.2017.06.11 CrossRefPubMedGoogle Scholar