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DOI: 10.1055/s-0039-1696997
Mortality, Morbidity, and Prognostic Factors in the Surgical Resection of Brain Metastases: A Contemporary Cohort Study
Publication History
24 October 2018
03 January 2019
Publication Date:
27 February 2020 (online)
Abstract
Objective Despite advances in systemic therapy and radiotherapy (RT), neurosurgical resection (NSR) remains a mainstay of the treatment of brain metastases (BMs). Although it is unequivocal in instances of diagnostic doubt, radioresistance, and risk of death due to neurologic causes, NSR may be controversial in other situations. Many aspects related to NSR have not yet been well established, and the primary prognostic indices were proposed only in the last decade. This study evaluates the survival and the morbidity, causes of death, prognostic factors, and the impact of RT in patients with BMs treated by NSR in the current era.
Methods A total of 200 patients with BMs who were treated by NSR were evaluated sequentially and followed prospectively. We used logistic regression and Cox regression models to identify independent factors associated with mortality at 4 weeks and at 1 year, respectively. Clinical features, morbidity, recurrence, and causes of death were also studied.
Results Lung cancer was the most prevalent cancer (36.5%); the median Karnofsky Performance Status (KPS) score was 60. Total resection was achieved in 89%, and adjuvant RT was applied in 63% of the cases. The rates of surgical mortality, morbidity, and mortality at 4 weeks were 1.5%, 17%, and 7.5%, respectively. Systemic infections were the leading cause of death in 62.5% of the cases. The median survival was 5 months, and 34.5% of patients lived > 1 year. The postoperative KPS (KPSpo) score remained unchanged or improved in 94.5% of the cases. In the multivariate analysis, a KPSpo score ≥ 80 and the application of adjuvant RT were associated with a lower risk of death at 12 weeks and at 1 year. Interestingly, the variables of primary tumor site, number of BMs, and presence of carcinomatous meningitis were not significant.
Conclusion Morbidity and mortality were high, a third of the patients lived > 1 year, and the KPS score improved or remained unchanged in most cases. Prognostic indices and health conditions were important predictive factors, but the KPSpo score and adjuvant RT were independent variables for survival at 12 weeks and at 1 year. Therefore, new studies are needed to assess the influence of new therapies and specific molecular profiles.
Keywords
surgery resection of brain metastases - prognostic factors - mortality - survival - morbidityEthical Approval
Informed consent was obtained from the participant included in the study. This study, and data collection and scientific use, were approved by the local Ethics Committee.
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References
- 1 Nieder C, Spanne O, Mehta MP, Grosu AL, Geinitz H. Presentation, patterns of care, and survival in patients with brain metastases: what has changed in the last 20 years?. Cancer 2011; 117 (11) 2505-2512
- 2 Sperduto CM, Watanabe Y, Mullan J. , et al. A validation study of a new prognostic index for patients with brain metastases: the Graded Prognostic Assessment. J Neurosurg 2008; 109 (Suppl): 87-89
- 3 Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 2004; 22 (14) 2865-2872
- 4 Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol 2005; 75 (01) 5-14
- 5 Shaffrey ME, Mut M, Asher AL. , et al. Brain metastases. Curr Probl Surg 2004; 41 (08) 665-741
- 6 Davey P. Brain metastases: treatment options to improve outcomes. CNS Drugs 2002; 16 (05) 325-338
- 7 Smedby KE, Brandt L, Bäcklund ML, Blomqvist P. Brain metastases admissions in Sweden between 1987 and 2006. Br J Cancer 2009; 101 (11) 1919-1924
- 8 Owonikoko TK, Arbiser J, Zelnak A. , et al. Current approaches to the treatment of metastatic brain tumours. Nat Rev Clin Oncol 2014; 11 (04) 203-222
- 9 Walker AE, Robins M, Weinfeld FD. Epidemiology of brain tumors: the national survey of intracranial neoplasms. Neurology 1985; 35 (02) 219-226
- 10 Welsh JW, Komaki R, Amini A. , et al. Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer. J Clin Oncol 2013; 31 (07) 895-902
- 11 Sperduto PW, Jiang W, Brown PD. , et al. Estimating survival in melanoma patients with brain metastases: an update of the graded prognostic assessment for melanoma using molecular markers (Melanoma-molGPA). Int J Radiat Oncol Biol Phys 2017; 99 (04) 812-816
- 12 Sperduto PW, Yang TJ, Beal K. , et al. Estimating survival in patients with lung cancer and brain metastases: an update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA). JAMA Oncol 2017; 3 (06) 827-831
- 13 Al-Shamy G, Sawaya R. Management of brain metastases: the indispensable role of surgery. J Neurooncol 2009; 92 (03) 275-282
- 14 de Lima Oliveira M, Picarelli H, Menezes MR, Amorim RL, Teixeira MJ, Bor-Seng-Shu E. Ultrasonography during surgery to approach cerebral metastases: effect on Karnofsky index scores and tumor volume. World Neurosurg 2017; 103: 557-565
- 15 Lin X, DeAngelis LM. Treatment of brain metastases. J Clin Oncol 2015; 33 (30) 3475-3484
- 16 Mehta AI, Brufsky AM, Sampson JH. Therapeutic approaches for HER2-positive brain metastases: circumventing the blood-brain barrier. Cancer Treat Rev 2013; 39 (03) 261-269
- 17 Reveiz L, Rueda JR, Cardona AF. Chemotherapy for brain metastases from small cell lung cancer. Cochrane Database Syst Rev 2012; (06) CD007464
- 18 Narita Y, Shibui S. Strategy of surgery and radiation therapy for brain metastases. Int J Clin Oncol 2009; 14 (04) 275-280
- 19 Thomas SS, Dunbar EM. Modern multidisciplinary management of brain metastases. Curr Oncol Rep 2010; 12 (01) 34-40
- 20 Tsao MN, Lloyd N, Wong RK. , et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev 2012; (04) CD003869
- 21 Brown PD, Asher AL, Ballman KV. , et al. NCCTG N0574 (Alliance): a phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases [abstract LBA4]. J Clin Oncol 2015; 33: 18_Suppl
- 22 Hart MG, Grant R, Walker M, Dickinson H. Surgical resection and whole brain radiation therapy versus whole brain radiation therapy alone for single brain metastases. Cochrane Database Syst Rev 2005; (01) CD003292
- 23 Patchell RA, Tibbs PA, Walsh JW. , et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990; 322 (08) 494-500
- 24 Hall WA, Djalilian HR, Nussbaum ES, Cho KH. Long-term survival with metastatic cancer to the brain. Med Oncol 2000; 17 (04) 279-286
- 25 Sawaya R, Hammoud M, Schoppa D. , et al. Neurosurgical outcomes in a modern series of 400 craniotomies for treatment of parenchymal tumors. Neurosurgery 1998; 42 (05) 1044-1055 ; discussion 1055–1056
- 26 Schödel P, Schebesch K-M, Brawanski A, Proescholdt MA. Surgical resection of brain metastases—impact on neurological outcome. Int J Mol Sci 2013; 14 (05) 8708-8718
- 27 Stark AM, Tscheslog H, Buhl R, Held-Feindt J, Mehdorn HM. Surgical treatment for brain metastases: prognostic factors and survival in 177 patients. Neurosurg Rev 2005; 28 (02) 115-119
- 28 Lagerwaard FJ, Levendag PC, Nowak PJ, Eijkenboom WM, Hanssens PE, Schmitz PI. Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys 1999; 43 (04) 795-803
- 29 Patel AJ, Suki D, Hatiboglu MA. , et al. Factors influencing the risk of local recurrence after resection of a single brain metastasis. J Neurosurg 2010; 113 (02) 181-189
- 30 Patel AJ, Suki D, Hatiboglu MA, Rao VY, Fox BD, Sawaya R. Impact of surgical methodology on the complication rate and functional outcome of patients with a single brain metastasis. J Neurosurg 2015; 122 (05) 1132-1143
- 31 Ahn JH, Lee SH, Kim S. , et al. Risk for leptomeningeal seeding after resection for brain metastases: implication of tumor location with mode of resection. J Neurosurg 2012; 116 (05) 984-993
- 32 Suki D, Abouassi H, Patel AJ, Sawaya R, Weinberg JS, Groves MD. Comparative risk of leptomeningeal disease after resection or stereotactic radiosurgery for solid tumor metastasis to the posterior fossa. J Neurosurg 2008; 108 (02) 248-257
- 33 Dummer R, Goldinger SM, Turtschi CP. , et al. Vemurafenib in patients with BRAF(V600) mutation-positive melanoma with symptomatic brain metastases: final results of an open-label pilot study. Eur J Cancer 2014; 50 (03) 611-621
- 34 Grommes C, Oxnard GR, Kris MG. , et al. “Pulsatile” high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol 2011; 13 (12) 1364-1369
- 35 Lin NU, Diéras V, Paul D. , et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res 2009; 15 (04) 1452-1459
- 36 Long GV, Trefzer U, Davies MA. , et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13 (11) 1087-1095
- 37 Margolin K, Ernstoff MS, Hamid O. , et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol 2012; 13 (05) 459-465
- 38 Shapiro DG, Samlowski WE. Management of melanoma brain metastases in the era of targeted therapy. J Skin Cancer 2011; 2011: 845863
- 39 Shimato S, Mitsudomi T, Kosaka T. , et al. EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of gefitinib. Neuro Oncol 2006; 8 (02) 137-144