Survival of Patients With Multiple Intracranial Metastases Treated With Stereotactic Radiosurgery

American Journal of Clinical Oncology: Cancer Clinical Trials - Tập 41 Số 5 - Trang 425-431 - 2018
Miriam A. Knoll1, Eric K. Oermann2, Andrew Yang3, Ima Paydar4, Jeremy Steinberger2, Brian T. Collins4, Sean P. Collins4, Matthew G. Ewend5, Douglas Kondziolka3
1Radiation Oncology
2Neurological Surgery, Mount Sinai Health System
3Department of Neurosurgery, New York University Langone Medical Center, New York City, NY
4Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC
5Department of Neurological Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC

Tóm tắt

Background: Defining prognostic factors is a crucial initial step for determining the management of patients with brain metastases. Randomized trials assessing radiosurgery have commonly limited inclusion criteria to 1 to 4 brain metastases, in part due to multiple retrospective studies reporting on the number of brain metastases as a prognostic indicator. The present study reports on the survival of patients with 1 to 4 versus ≥5 brain metastases treated with radiosurgery. Methods: We evaluated a retrospective multi-institutional database of 1523 brain metastases in 507 patients who were treated with radiosurgery (Gamma Knife or Cyberknife) between 2001 and 2014. A total of 243 patients were included in the analysis. Patients with 1 to 4 brain metastases were compared with patients with ≥5 brain metastases using a standard statistical analysis. Cox hazard regression was used to construct a multivariable model of overall survival (OS). To find covariates that best separate the data at each split, a machine learning technique Chi-squared Automated Interaction Detection tree was utilized. Results: On Pearson correlation, systemic disease status, number of intracranial metastases, and overall burden of disease (number of major involved organ systems) were found to be highly correlated (P<0.001). Patients with 1 to 4 metastases had a median OS of 10.8 months (95% confidence interval, 6.1-15.6 mo), compared with a median OS of 8.5 months (95% confidence interval, 4.4-12.6 mo) for patients with ≥5 metastases (P=0.143). The actuarial 6 month local failure rate was 5% for patients with 1 to 4 metastases versus 3.2% for patients with ≥5 metastases (P=0.404). There was a significant difference in systemic disease status between the 2 groups; 30% of patients had controlled systemic disease in the <5 lesions group, versus 8% controlled systemic disease in the ≥5 lesions group (P=0.005). Patients with 1 to 4 metastases did not have significantly improved OS in a multivariable model adjusting for systemic disease status, systemic extracranial metastases, and other key variables. The Chi-squared Automated Interaction Detection tree (machine learning technique) algorithm consistently identified performance status and systemic disease status as key to disease classification, but not intracranial metastases. Conclusions: Although the number of brain metastases has previously been accepted as an independent prognostic indicator, our multicenter analysis demonstrates that the number of intracranial metastases is highly correlated with overall disease burden and clinical status. Proper matching and controlling for these other determinants of survival demonstrates that the number of intracranial metastases alone is not an independent predictive factor, but rather a surrogate for other clinical factors.

Từ khóa


Tài liệu tham khảo

Lassman, 2003, Brain metastases, Neurol Clin, 21, 1, 10.1016/S0733-8619(02)00035-X

Barnholtz-Sloan, 2004, Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System, J Clin Oncol, 22, 2865, 10.1200/JCO.2004.12.149

Scoccianti, 2012, Treatment of brain metastases: review of phase III randomized controlled trials, Radiother Oncol, 102, 168, 10.1016/j.radonc.2011.08.041

Tsao, 2012, International practice survey on the management of brain metastases: Third International Consensus Workshop on Palliative Radiotherapy and Symptom Control, Clin Oncol (R Coll Radiol), 24, e81, 10.1016/j.clon.2012.03.008

Tsao, 2012, Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): an American Society for Radiation Oncology evidence-based guideline, Pract Radiat Oncol, 2, 210, 10.1016/j.prro.2011.12.004

Yamamoto, 2014, Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study, Lancet Oncol, 15, 387, 10.1016/S1470-2045(14)70061-0

Kondziolka, 2014, It is time to reevaluate the management of patients with brain metastases, Neurosurgery, 75, 1, 10.1227/NEU.0000000000000354

Chang, 2009, Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial, Lancet Oncol, 10, 1037, 10.1016/S1470-2045(09)70263-3

Andrews, 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, 10.1016/S0140-6736(04)16250-8

Kocher, 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, 10.1200/JCO.2010.30.1655

Patchell, 1998, Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial, JAMA, 280, 1485, 10.1001/jama.280.17.1485

Lin, 2007, Brain metastases: the HER2 paradigm, Clin Cancer Res, 13, 1648, 10.1158/1078-0432.CCR-06-2478

Amit, 2013, The impact of bevacizumab (avastin) on survival in metastatic solid tumors—a meta-analysis and systematic review, PLoS One, 8, e51780, 10.1371/journal.pone.0051780

Likhacheva, 2013, Predictors of survival in contemporary practice after initial radiosurgery for brain metastases, Int J Radiat Oncol Biol Phys, 85, 656, 10.1016/j.ijrobp.2012.05.047

Serizawa, 2010, 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, 163, 10.1007/s11060-010-0169-x

Oermann, 2013, The impact of radiosurgery fractionation and tumor radiobiology on the local control of brain metastases, J Neurosurg, 119, 1131, 10.3171/2013.8.JNS122177

Kass, 1980, An exploratory technique for investigating large quantities of categorical data, Appl Stat, 29, 119, 10.2307/2986296

Sawrie, 2008, Predictors of distant brain recurrence for patients with newly diagnosed brain metastases treated with stereotactic radiosurgery alone, Int J Radiat Oncol Biol Phys, 70, 181, 10.1016/j.ijrobp.2007.05.084

Chen, 2011, Risk factors of distant brain failure for patients with newly diagnosed brain metastases treated with stereotactic radiotherapy alone, Radiat Oncol, 6, 175, 10.1186/1748-717X-6-175

Chao, 2006, Five-year survivors of brain metastases: a single-institution report of 32 patients, Int J Radiat Oncol Biol Phys, 66, 801, 10.1016/j.ijrobp.2006.05.015

Caballero, 2012, Prognostic factors for survival in patients treated with stereotactic radiosurgery for recurrent brain metastases after prior whole brain radiotherapy, Int J Radiat Oncol Biol Phys, 83, 303, 10.1016/j.ijrobp.2011.06.1987

Sperduto, 2011, 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, 38, 419

Monje, 2003, Radiation injury and neurogenesis, Curr Opin Neurol, 16, 129, 10.1097/00019052-200304000-00002

Sun, 2011, Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis, J Clin Oncol, 29, 279, 10.1200/JCO.2010.29.6053

Niemiec, 2011, Characteristics of long-term survivors of brain metastases from lung cancer, Rep Pract Oncol Radiother, 16, 49, 10.1016/j.rpor.2011.01.002

Hodgson, 2013, A multi-institutional study of factors influencing the use of stereotactic radiosurgery for brain metastases, Int J Radiat Oncol Biol Phys, 85, 335, 10.1016/j.ijrobp.2012.05.002