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Role of stereotactic radiosurgery in patients with more than four brain metastases

    Vikram Jairam

    * Author for correspondence

    Yale School of Medicine, Department of Therapeutic Radiology, New Haven, CT, USA. .

    ,
    Veronica LS Chiang

    Yale Cancer Center, New Haven, CT, USA

    Yale School of Medicine, Department of Neurosurgery, New Haven, CT, USA

    ,
    James B Yu

    Yale School of Medicine, Department of Therapeutic Radiology, New Haven, CT, USA

    Yale Cancer Center, New Haven, CT, USA

    Cancer Outcomes, Public Policy, & Effectiveness Research (COPPER) Center at Yale, New Haven, CT, USA

    &
    Jonathan PS Knisely

    Department of Radiation Medicine, North Shore-Long Island Jewish Health System & Hofstra-North Shore-LIJ School of Medicine, Manhasset, NY, USA

    Published Online:https://doi.org/10.2217/cns.13.4

    SUMMARY For patients presenting with brain metastases, two methods of radiation treatment currently exist: stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT). SRS is a minimally invasive to noninvasive technique that delivers a high dose of ionizing radiation to a precisely defined focal target volume, whereas WBRT involves multiple smaller doses of radiation delivered to the whole brain. Evidence exists from randomized controlled trials for SRS in the treatment of patients with one to four brain metastases. Patients with more than four brain metastases generally receive WBRT, which can effectively treat undetected metastases and protect against intracranial relapse. However, WBRT has been associated with an increased potential for toxic neurocognitive side effects, including memory loss and early dementia, and does not provide 100% protection against relapse. For this reason, physicians at many medical centers are opting to use SRS as first-line treatment for patients with more than four brain metastases, despite evidence showing an increased rate of intracranial relapse compared with WBRT. In light of the evolving use of SRS, this review will examine the available reports on institutional trials and outcomes for patients with more than four brain metastases treated with SRS alone as first-line therapy.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

    References

    • Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J. Neurooncol.75(1),5–14 (2005).
    • Posner JB. Management of brain metastases. Rev. Neurol.148(6–7),477–487 (1992).
    • Reveiz L, Rueda JR, Cardona AF. Chemotherapy for brain metastases from small-cell lung cancer. Cochrane Database Syst. Rev.13(6),CD007464 (2012).
    • Margolin K, Ernstoff MS, Hamid O et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, Phase 2 trial. Lancet Oncol.13(5),459–465 (2012).
    • Dea N, Borduas M, Kenny B, Fortin D, Mathieu D. Safety and efficacy of Gamma-knife surgery for brain metastases in eloquent locations. J. Neurosurg.113(Suppl.),79–83 (2010).
    • Elliott RE, Rush S, Morsi A et al. Neurological complications and symptom resolution following Gamma-knife surgery for brain metastases 2 cm or smaller in relation to eloquent cortices. J. Neurosurg.113(Suppl.),53–64 (2010).
    • Park HS, Yu JB, Knisely JPS, Chang VLS. Outcomes following Gamma-knife for metastases. Gamma-Knife Radiosurg.1,1–26 (2011).
    • Rauch PJ, Park HS, Knisely JP, Chiang VL, Vortmeyer AO. Delayed radiation-induced vasculitic leukoencephalopathy. Int. J. Radiat. Oncol. Biol. Phys.83(1),369–375 (2012).
    • DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology39(6),789–796 (1989).
    • 10  Tallet AV, Azria D, Barlesi F et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiat. Oncol.7,77 (2012).
    • 11  Raber J, Rola R, Lefevour A et al. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat. Res.162(1),39–47 (2004).
    • 12  Gondi V, Hermann BP, Mehta MP, Tome WA. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int. J. Radiat. Oncol. Biol. Phys.83(4),e487–493 (2012).
    • 13  Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int. J. Radiat. Oncol. Biol. Phys.45(2),427–434 (1999).
    • 14  Andrews DW, Scott CB, Sperduto PW et al. Whole-brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase III results of the RTOG 9508 randomised trial. Lancet363(9422),1665–1672 (2004).▪ Important study, despite its problems, because it provides class I evidence of the benefit of stereotactic radiosurgery (SRS) for patients with one to three brain metastases. A survival advantage was only seen for patients with a single metastasis, but analyses showed better lesion control and less steroid use for patients with two to three brain metastases.
    • 15  Aoyama H, Shirato H, Tago M et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA295(21),2483–2491 (2006).▪ Class I evidence is provided of equivalent survival and 1year neurocognitive outcomes for patients with one to four brain metastases with either whole-brain radiation therapy (WBRT) and SRS or SRS alone.
    • 16  Aoyama H, Tago M, Kato N et al. 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(5),1388–1395 (2007).▪ Class I evidence is provided of equivalent survival and 1year neurocognitive outcomes for patients with one to four brain metastases with either WBRT and SRS or SRS alone.
    • 17  Chang EL, Wefel JS, Hess KR et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol.10(11),1037–1044 (2009).▪▪ Neurocognitive outcomes were inferior after 4 months in patients who had WBRT as part of initial management after SRS for one to three brain metastases. Although only the Hopkins Verbal Learning Test-Revised was significantly different, none of the results from other neurocognitive testing instruments favored the group that received WBRT. There is little reason to assume that the neurocognitive harm from WBRT would be substantially different for individuals with more than three brain metastases.
    • 18  Kocher M, Soffietti R, Abacioglu U et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 2295226001 study. J. Clin. Oncol.29(2),134–141 (2011).
    • 19  Serizawa T, Iuchi T, Ono J et al. Gamma-knife treatment for multiple metastatic brain tumors compared with whole-brain radiation therapy. J. Neurosurg.93(Suppl. 3),32–36 (2000).
    • 20  Park SH, Hwang SK, Kang DH et al. Gamma-knife radiosurgery for multiple brain metastases from lung cancer. J. Clin. Neurosci.16(5),626–629 (2009).
    • 21  Hunter GK, Suh JH, Reuther AM et al. Treatment of five or more brain metastases with stereotactic radiosurgery. Int. J. Radiat. Oncol. Biol. Phys.83(5),1394–1398 (2012).
    • 22  Chang WS, Kim HY, Chang JW, Park YG, Chang JH. Analysis of radiosurgical results in patients with brain metastases according to the number of brain lesions: is stereotactic radiosurgery effective for multiple brain metastases? J. Neurosurg.113(Suppl.),73–78 (2010).
    • 23  Raldow AC, Chiang VL, Knisely JP, Yu JB. Survival and intracranial control of patients with 5 or more brain metastases treated with Gamma-knife stereotactic radiosurgery. Am. J. Clin. Oncol.14,14 (2012).
    • 24  Serizawa T, Hirai T, Nagano O et al. Gamma-knife surgery for 1–10 brain metastases without prophylactic whole-brain radiation therapy: analysis of cases meeting the Japanese prospective multi-institute study (JLGK0901) inclusion criteria. J. Neurooncol.98(2),163–167 (2010).
    • 25  Suzuki S, Omagari J, Nishio S, Nishiye E, Fukui M. Gamma-knife radiosurgery for simultaneous multiple metastatic brain tumors. J. Neurosurg.3(Suppl. 3),30–31 (2000).
    • 26  Kim CH, Im YS, Nam DH, Park K, Kim JH, Lee JI. Gamma-knife radiosurgery for ten or more brain metastases. J. Korean Neurosurg. Soc.44(6),358–363 (2008).
    • 27  Grandhi R, Kondziolka D, Panczykowski D et al. Stereotactic radiosurgery using the Leksell Gamma-knife Perfexion unit in the management of patients with 10 or more brain metastases. J. Neurosurg.25,25 (2012).
    • 28  Yamamoto M, Ide M, Nishio S, Urakawa Y. Gamma-knife radiosurgery for numerous brain metastases: is this a safe treatment? Int. J. Radiat. Oncol. Biol. Phys.53(5),1279–1283 (2002).
    • 29  Yang CC, Ting J, Wu X, Markoe A. Dose volume histogram analysis of the Gamma-knife radiosurgery treating twenty-five metastatic intracranial tumors. Stereotact. Funct. Neurosurg.70(Suppl. 1),41–49 (1998).
    • 30  Yamamoto M, Barfod BE, Urakawa Y. Gamma-knife radiosurgery for brain metastases of non-lung cancer origin: focusing on multiple brain lesions. Prog. Neurol. Surg.22,154–169 (2009).
    • 31  Yamamoto M, Kawabe T, Barfod BE. How many metastases can be treated with radiosurgery? Prog. Neurol. Surg.25,261–272 (2012).
    • 32  Nam TK, Lee JI, Jung YJ et al. Gamma-knife surgery for brain metastases in patients harboring four or more lesions: survival and prognostic factors. J. Neurosurg.102(Suppl.),147–150 (2005).
    • 33  Bhatnagar AK, Flickinger JC, Kondziolka D, Lunsford LD. Stereotactic radiosurgery for four or more intracranial metastases. Int. J. Radiat. Oncol. Biol. Phys.64(3),898–903 (2006).
    • 34  Gaspar L, Scott C, Rotman M et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int. J. Radiat. Oncol. Biol. Phys.37(4),745–751 (1997).
    • 35  Karlsson B, Hanssens P, Wolff R, Soderman M, Lindquist C, Beute G. Thirty years’ experience with Gamma-knife surgery for metastases to the brain. J. Neurosurg.111(3),449–457 (2009).
    • 36  Serizawa T, Yamamoto M, Nagano O et al. Gamma-knife surgery for metastatic brain tumors. J. Neurosurg.109(Suppl.),118–121 (2008).
    • 37  Yamamoto M, Sato Y, Serizawa T et al. Subclassification of recursive partitioning analysis class II patients with brain metastases treated radiosurgically. Int. J. Radiat. Oncol. Biol. Phys.83(5),1399–1405 (2012).▪▪ Provides tools to help better predict the survival prognosis of RTOG recursive partitioning analysis class II brain metastasis patients who are primarily managed with SRS.
    • 38  Serizawa T, Yamamoto M, Sato Y et al. Gamma-knife surgery as sole treatment for multiple brain metastases: 2-center retrospective review of 1508 cases meeting the inclusion criteria of the JLGK0901 multi-institutional prospective study. J. Neurosurg.113(Suppl.),48–52 (2010).
    • 39  Sperduto PW, Kased N, Roberge D et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J. Clin. Oncol.30(4),419–425 (2012).▪▪ Provides a means to help prognosticate survival outcomes for patients with brain metastases of various histologies and has been used to stratify patients in ongoing and upcoming clinical trials.
    • 40  Sperduto PW, Kased N, Roberge D et al. Effect of tumor subtype on survival and the graded prognostic assessment for patients with breast cancer and brain metastases. Int. J. Radiat. Oncol. Biol. Phys.82(5),2111–2117 (2012).▪▪ Provides a means to help prognosticate survival outcomes for patients with brain metastases of various histologies and has been used to stratify patients in ongoing and upcoming clinical trials.
    • 41  Knisely JP, Yamamoto M, Gross CP, Castrucci WA, Jokura H, Chiang VL. Radiosurgery alone for 5 or more brain metastases: expert opinion survey. J. Neurosurg.113(Suppl.),84–89 (2010).
    • 42  Mehta MP, Tsao MN, Whelan TJ et al. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases. Int. J. Radiat. Oncol. Biol. Phys.63(1),37–46 (2005).
    • 43  Tsao MN, Lloyd NS, Wong RK. Clinical practice guideline on the optimal radiotherapeutic management of brain metastases. BMC Cancer5,34 (2005).
    • 101  Radiation Therapy Oncology Group. RTOG 0614 results at ASTRO 2012: memantine shown to have cognition benefit. www.rtog.org/News/tabid/72/articleType/ArticleView/articleId/48/RTOG-0614-Resuts-at-ASTRO-2012-Memantine-Shown-to-Have-Cognition-Benefit.aspx▪ First study to provide class I evidence that an intervention given during WBRT can improve the neurocognitive performance of patients treated with WBRT
    • 102  Radiation Therapy Oncology Group. A Phase II trial of hippocampal avoidance during whole brain radiotherapy for brain metastases – RTOG CCOP study. www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0933
    • 103  North Central Cancer Treatment Group. Stereotactic radiation therapy with or without whole-brain radiation therapy in treating patients with brain metastases. http://clinicaltrials.gov/ct2/show/NCT00377156
    • 104  World Science. Higuchi Y, Serizawa T, Yamamoto M et al. Prospective multi-institute study of gamma-knife radiosurgery alone treatment for patients with 1–10 brain metastases (JLGK0901): Interim Monitoring Report. www.world-sci.com/read.aspx?id=307
    • 105  National Comprehensive Cancer Network. NCCN guidelines for CNS cancer. www.nccn.org/professionals/physician_gls/f_guidelines.asp#cns
    • 106  Cancer Care. Tsao MN, Laetsch NS, Wong RKS, Laperriere N. Supportive Care Guidelines Group and Neuro-Oncology Disease Site Group of Cancer Care Ontario’s Program in evidence-based care. Management of brain metastases: role of radiotherapy alone or in combination with other treatment modalities. Program in evidence-based care practice guideline. www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=34399
    • 107  North American Gamma-knife Consortium. NAGKC newsletter fall 2012. www.nagkc.com/news/newsletter/2012-05-spring.pdf