Abstract
With escalating focus on cost containment, there is increasing scrutiny on the practice of multiple stereotactic radiosurgeries (SRSs) for patients with cerebral metastases distant to the initial tumor site. Our goal was to determine the survival patterns of patients with cerebral metastasis who underwent multiple SRSs. We retrospectively analyzed survival outcomes of 801 patients with 3683 cerebral metastases from primary breast, colorectal, lung, melanoma and renal histologies consecutively treated at the University of California, San Diego/San Diego Gamma Knife Center (UCSD/SDGKC), comparing the survival pattern of patients who underwent a single (n = 643) versus multiple SRS(s) (n = 158) for subsequent cerebral metastases. Findings were recapitulated in an independent cohort of 2472 patients, with 26,629 brain metastases treated with SRS at the Katsuta Hospital Mito GammaHouse (KHMGH). For the UCSD/SDGKC cohort, no significant difference in median survival was found for patients undergoing 1, 2, 3, or ≥4 SRS(s) (median survival of 167, 202, 129, and 127 days, respectively). Median intervals between treatments consistently ranged 140–178 days irrespective of the number of SRS(s) (interquartile range 60–300; p = 0.25). Patients who underwent >1 SRSs tend to be younger, with systemic disease control, harbor lower cumulative tumor volume but increased number of metastases, and have primary melanoma (p < 0.001, <0.001, <0.001, 0.02, and 0.009, respectively). Comparable results were found in the KHMGH cohort. Using an independent validation study design, we demonstrated comparable overall survival between judiciously selected patients who underwent a single or multiple SRS(s).
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Schouten LJ, Rutten J, Huveneers HA, Twijnstra A (2002) Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 94:2698–2705
Davis FG, Dolecek TA, McCarthy BJ, Villano JL (2012) Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data. Neuro Oncol 14:1171–1177. doi:10.1093/neuonc/nos152
Suh JH, Videtic GM, Aref AM, Germano I, Goldsmith BJ, Imperato JP, Marcus KJ, McDermott MW, McDonald MW, Patchell RA, Robins HI, Rogers CL, Wolfson AH, Wippold FJ 2nd, Gaspar LE (2010) ACR appropriateness criteria: single brain metastasis. Curr Probl Cancer 34:162–174. doi:10.1016/j.currproblcancer.2010.04.003
Lutterbach J, Cyron D, Henne K, Ostertag CB (2003) Radiosurgery followed by planned observation in patients with one to three brain metastases. Neurosurgery 52:1066–1073; discussion 1073–1064
Kondziolka D, Kano H, Harrison GL, Yang HC, Liew DN, Niranjan A, Brufsky AM, Flickinger JC, Lunsford LD (2011) Stereotactic radiosurgery as primary and salvage treatment for brain metastases from breast cancer. J Neurosurg 114:792–800. doi:10.3171/2010.8.JNS10461
Stelzer KJ (2013) Epidemiology and prognosis of brain metastases. Surg Neurol Int 4:S192–S202. doi:10.4103/2152-7806.111296
Regine WF, Huhn JL, Patchell RA, St Clair WH, Strottmann J, Meigooni A, Sanders M, Young AB (2002) Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implications. Int J Radiat Oncol Biol Phys 52:333–338
Marko NW, Weil RJ (2010) The role of observational investigations in comparative effectiveness research. Value Health 13:989–997
Ammirati M, Cobbs CS, Linskey ME, Paleologos NA, Ryken TC, Burri SH, Asher AL, Loeffler JS, Robinson PD, Andrews DW, Gaspar LE, Kondziolka D, McDermott M, Mehta MP, Mikkelsen T, Olson JJ, Patchell RA, Kalkanis SN (2010) The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 96:85–96. doi:10.1007/s11060-009-0055-6
Ancestry.com (1935–2011) United States Social Security Death Index, 2012
Pan H, Cervino LI, Pawlicki T, Jiang SB, Alksne J, Detorie N, Russell M, Carter BS, Murphy KT, Mundt AJ, Chen C, Lawson JD (2012) Frameless, real-time, surface imaging-guided radiosurgery: clinical outcomes for brain metastases. Neurosurgery 71:844–851. doi:10.1227/NEU.0b013e3182647ad5
Nabors LB, Portnow J, Ammirati M, Brem H, Brown P, Butowski N, Chamberlain MC, DeAngelis LM, Fenstermaker RA, Friedman A, Gilbert MR, Hattangadi-Gluth J, Hesser D, Holdhoff M, Junck L, Lawson R, Loeffler JS, Moots PL, Mrugala MM, Newton HB, Raizer JJ, Recht L, Shonka N, Shrieve DC, Sills AK Jr, Swinnen LJ, Tran D, Tran N, Vrionis FD, Wen PY, McMillian NR, Ho M (2014) Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines. J Natl Compr Cancer Netw 12:1517–1523
Lau SK, Zakeri K, Zhao X, Carmona R, Knipprath E, Simpson DR, Nath SK, Kim GY, Sanghvi P, Hattangadi-Gluth JA, Chen CC, Murphy KT (2015) Single-isocenter frameless volumetric modulated arc radiosurgery for multiple intracranial metastases. Neurosurgery 77:233–240; discussion 240. doi:10.1227/NEU.0000000000000763
Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr (2004) 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. Lancet 363:1665–1672. doi:10.1016/S0140-6736(04)16250-8
Yamamoto M, Kawabe T, Higuchi Y, Sato Y, Nariai T, Watanabe S, Barfod BE, Kasuya H (2014) Validity of prognostic grading indices for brain metastasis patients undergoing repeat radiosurgery. World Neurosurg 82:1242–1249. doi:10.1016/j.wneu.2014.08.008
Kaplan E, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481
Cox D (1972) Regression models and life tables. J R Stat Soc Ser B 34(2):187–220. Retrieved from http://www.jstor.org/stable/2985181
Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751
Gonda DD, Kim TE, Goetsch SJ, Kawabe T, Watanabe S, Alksne JF, Hattangadi JA, Nitta M, Ott K, Hodgens DW, Carter BS, Yamamoto M, Chen CC (2014) Prognostic factors for stereotactic radiosurgery-treated patients with cerebral metastasis: implications on randomised control trial design and inter-institutional collaboration. Eur J Cancer 50:1148–1158. doi:10.1016/j.ejca.2014.01.001
Ishihara K, Saida T, Otsuka F, Yamazaki N, Prognosis, Statistical Investigation Committee of the Japanese Skin Cancer S (2008) Statistical profiles of malignant melanoma and other skin cancers in Japan: 2007 update. Int J Clin Oncol 13:33–41. doi:10.1007/s10147-007-0751-1
American Academy of Actuaries (2008) Health insurance coverage and reimbursement decisions: implications for increased comparative effectiveness research. American Academy of Actuaries, Washington
Lal LS, Byfield SD, Chang EL, Franzini L, Miller LA, Arbuckle R, Reasonda L, Feng C, Adamus A, Swint JM (2012) Cost-effectiveness analysis of a randomized study comparing radiosurgery with radiosurgery and whole brain radiation therapy in patients with 1 to 3 brain metastases. Am J Clin Oncol 35:45–50. doi:10.1097/COC.0b013e3182005a8f
Hall MD, McGee JL, McGee MC, Hall KA, Neils DM, Klopfenstein JD, Elwood PW (2014) Cost-effectiveness of stereotactic radiosurgery with and without whole-brain radiotherapy for the treatment of newly diagnosed brain metastases. J Neurosurg 121(Suppl):84–90. doi:10.3171/2014.7.GKS14972
Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeki N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K (2014) Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15:387–395. doi:10.1016/S1470-2045(14)70061-0
Marcus L, Marshall D, Hirshman B, McCutcheon B, Gonda D, Koiso T, Hattangadi-Gluth J, Carter B, Yamamoto M, Chen C (2015) Cumulative intracranial tumor volume (CITV) enhances the prognostic value of the lung-specific graded prognostic assessment (GPA) model. Neurosurgery. doi:10.1227/NEU.0000000000001123
McDuff SG, Taich ZJ, Lawson JD, Sanghvi P, Wong ET, Barker FG 2nd, Hochberg FH, Loeffler JS, Warnke PC, Murphy KT, Mundt AJ, Carter BS, McDonald CR, Chen CC (2013) Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases. J Neurol Neurosurg Psychiatry 84:1384–1391. doi:10.1136/jnnp-2013-305166
Gonda DD, Kim TE, Warnke PC, Kasper EM, Carter BS, Chen CC (2012) Ventriculoperitoneal shunting versus endoscopic third ventriculostomy in the treatment of patients with hydrocephalus related to metastasis. Surg Neurol Int 3:97. doi:10.4103/2152-7806.100185
Chen CC, Kasper E, Warnke P (2011) Palliative stereotactic-endoscopic third ventriculostomy for the treatment of obstructive hydrocephalus from cerebral metastasis. Surg Neurol Int 2:76. doi:10.4103/2152-7806.82083
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. doi:10.1016/S1470-2045(09)70263-3
Wang CC, Floyd SR, Chang CH, Warnke PC, Chio CC, Kasper EM, Mahadevan A, Wong ET, Chen CC (2012) Cyberknife hypofractionated stereotactic radiosurgery (HSRS) of resection cavity after excision of large cerebral metastasis: efficacy and safety of an 800 cGy × 3 daily fractions regimen. J Neurooncol 106:601–610. doi:10.1007/s11060-011-0697-z
Press RH, Prabhu RS, Nickleach DC, Liu Y, Shu HK, Kandula S, Patel KR, Curran WJ, Crocker I (2015) Novel risk stratification score for predicting early distant brain failure and salvage whole-brain radiotherapy after stereotactic radiosurgery for brain metastases. Cancer 121:3836–3843. doi:10.1002/cncr.29590
Ayala-Peacock DN, Peiffer AM, Lucas JT, Isom S, Kuremsky JG, Urbanic JJ, Bourland JD, Laxton AW, Tatter SB, Shaw EG, Chan MD (2014) A nomogram for predicting distant brain failure in patients treated with gamma knife stereotactic radiosurgery without whole brain radiotherapy. Neuro Oncol 16:1283–1288. doi:10.1093/neuonc/nou018
Karlsson B, Hanssens P, Wolff R, Soderman M, Lindquist C, Beute G (2009) Thirty years’ experience with Gamma Knife surgery for metastases to the brain. J Neurosurg 111:449–457. doi:10.3171/2008.10.JNS08214
Chen JC, Petrovich Z, Giannotta SL, Yu C, Apuzzo ML (2000) Radiosurgical salvage therapy for patients presenting with recurrence of metastatic disease to the brain. Neurosurgery 46:860–866; discussion 866–867
Madajewicz S, Karakousis C, West CR, Caracandas J, Avellanosa AM (1984) Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience. Cancer 53:2550–2552. doi:10.1002/1097-0142(19840601)53:11<2550:AID-CNCR2820531129>3.0.CO;2-B
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This study was funded in part by the National Institutes of Health (TL1TR00098 to D.C.M.; KL2TR00099 to J.H.G.; and, UL1TR000100 to J.H.G.).
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For this type of study formal consent is not required. The study protocol was approved by the Institutional Review Board.
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Masaaki Yamamoto and Clark C. Chen are equal contributions as senior authors.
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Marshall, D.C., Marcus, L.P., Kim, T.E. et al. Management patterns of patients with cerebral metastases who underwent multiple stereotactic radiosurgeries. J Neurooncol 128, 119–128 (2016). https://doi.org/10.1007/s11060-016-2084-2
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DOI: https://doi.org/10.1007/s11060-016-2084-2