ObjectMalignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas.MethodsIn 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness.ResultsWe demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532) from gross total resection over subtotal/biopsy, while those with nodular (less diffuse) tumors showed a significant benefit (P = 0.00142) with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors).ConclusionsThese results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection.
Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor. GBM growth dynamics vary widely across patients, making it difficult to accurately gauge their response to treatment. We developed a model-based metric of therapy response called Days Gained that accounts for this heterogeneity. Here we demonstrate in 63 newly diagnosed GBM patients that Days Gained scores from a simple GBM growth model computed at the time of the first post-radiation therapy MRI scan are prognostic for time to tumor recurrence and overall patient survival. After radiation treatment, Days Gained also distinguished patients with pseudoprogression from those with true progression. Since Days Gained scores can be easily computed with routinely available clinical imaging devices, it offers immediate potential to be used in ongoing prospective studies.
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