Extent of resection of glioblastoma revisited: personalized survival modeling facilitates more accurate survival prediction and supports a maximum-safe-resection approach to surgery.

PURPOSE Approximately 12,000 glioblastomas are diagnosed annually in the United States. The median survival rate for this disease is 12 months, but individual survival rates can vary with patient-specific factors, including extent of surgical resection (EOR). The goal of our investigation is to develop a reliable strategy for personalized survival prediction and for quantifying the relationship between survival, EOR, and adjuvant chemoradiotherapy. PATIENTS AND METHODS We used accelerated failure time (AFT) modeling using data from 721 newly diagnosed patients with glioblastoma (from 1993 to 2010) to model the factors affecting individualized survival after surgical resection, and we used the model to construct probabilistic, patient-specific tools for survival prediction. We validated this model with independent data from 109 patients from a second institution. RESULTS AFT modeling using age, Karnofsky performance score, EOR, and adjuvant chemoradiotherapy produced a continuous, nonlinear, multivariable survival model for glioblastoma. The median personalized predictive error was 4.37 months, representing a more than 20% improvement over current methods. Subsequent model-based calculations yield patient-specific predictions of the incremental effects of EOR and adjuvant therapy on survival. CONCLUSION Nonlinear, multivariable AFT modeling outperforms current methods for estimating individual survival after glioblastoma resection. The model produces personalized survival curves and quantifies the relationship between variables modulating patient-specific survival. This approach provides comprehensive, personalized, probabilistic, and clinically relevant information regarding the anticipated course of disease, the overall prognosis, and the patient-specific influence of EOR and adjuvant chemoradiotherapy. The continuous, nonlinear relationship identified between expected median survival and EOR argues against a surgical management strategy based on rigid EOR thresholds and instead provides the first explicit evidence supporting a maximum safe resection approach to glioblastoma surgery.

[1]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data: Kalbfleisch/The Statistical , 2002 .

[2]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[3]  C. Kruchko,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. , 2012, Neuro-oncology.

[4]  R. Mirimanoff,et al.  Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  J. Klein,et al.  Survival Analysis: Techniques for Censored and Truncated Data , 1997 .

[6]  Tarik Tihan,et al.  Volumetric extent of resection and residual contrast enhancement on initial surgery as predictors of outcome in adult patients with hemispheric anaplastic astrocytoma. , 2006, Journal of neurosurgery.

[7]  M. Berger,et al.  Extent of resection influences outcomes for patients with gliomas. , 2011, Revue neurologique.

[8]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[9]  Paul S Mischel,et al.  MR imaging correlates of survival in patients with high-grade gliomas. , 2005, AJNR. American journal of neuroradiology.

[10]  M. Berger,et al.  The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere. , 1999, Surgical neurology.

[11]  J. Barnholtz-Sloan,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. , 2012, Neuro-oncology.

[12]  M. Berger,et al.  GLIOMA EXTENT OF RESECTION AND ITS IMPACT ON PATIENT OUTCOME , 2008, Neurosurgery.

[13]  Nader Sanai,et al.  The Value of Glioma Extent of Resection in the Modern Neurosurgical Era , 2012, Front. Neur..

[14]  John D. Kalbfleisch,et al.  The Statistical Analysis of Failure Data , 1986, IEEE Transactions on Reliability.

[15]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[16]  Z L Gokaslan,et al.  A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. , 2001, Journal of neurosurgery.

[17]  Mitchel S Berger,et al.  An extent of resection threshold for newly diagnosed glioblastomas. , 2011, Journal of neurosurgery.