Toward Patient-Specific, Biologically Optimized Radiation Therapy Plans for the Treatment of Glioblastoma

Abstract

PurposeTo demonstrate a method of generating patient-specific, biologically-guided radiotherapy dose plans and compare them to the standard-of-care protocol.Methods and MaterialsWe integrated a patient-specific biomathematical model of glioma proliferation, invasion and radiotherapy with a multiobjective evolutionary algorithm for intensity-modulated radiation therapy optimization to construct individualized, biologically-guided plans for 11 glioblastoma patients. Patient-individualized, spherically-symmetric simulations of the standard-of-care and optimized plans were compared in terms of several biological metrics.ResultsThe integrated model generated spatially non-uniform doses that, when compared to the standard-of-care protocol, resulted in a 67% to 93% decrease in equivalent uniform dose to normal tissue, while the therapeutic ratio, the ratio of tumor equivalent uniform dose to that of normal tissue, increased between 50% to 265%. Applying a novel metric of treatment response (Days Gained) to the patient-individualized simulation results predicted that the optimized plans would have a significant impact on delaying tumor progression, with increases from 21% to 105% for 9 of 11 patients.ConclusionsPatient-individualized simulations using the combination of a biomathematical model with an optimization algorithm for radiation therapy generated biologically-guided doses that decreased normal tissue EUD and increased therapeutic ratio with the potential to improve survival outcomes for treatment of glioblastoma.

Simulating the growth of hepatic metastases from carcinoma of the pancreas using LabVIEW

“…The next step with the simulator will be to use patient survival data and tumor growth velocity to calibrate the values of p and D, so that the model can be tested to predict survival. We know that the values of p and D vary widely among patients with glioblastomas [16]. We suspect similar variation in hepatic metastases, but this will be important to evaluate in detail.…”

A 3-dimensional DTI MRI-based model of GBM growth and response to radiation therapy

“…Despite the aggressiveness of GBM, radiation therapy has been shown to significantly improve survival in multiple trials (3,4). However, the standard approach to radiation therapy has remained relatively stable for several decades, using conformal radiation therapy with regimens such as 60 Gy over 30 doses of 2 Gy or 63 Gy over 35 doses of 1.8 Gy with 1-2 cm margins surrounding the visible tumor (5,6).…”

“…These treatment plans constitute standardized therapeutic regimens which do not account for the biological heterogeneity of GBM among different patients (6). Thus, investigators have recently started trying to optimize radiation therapy protocols using a concept termed 'the fundamental principle of personalized management' (7).…”

“…Thus, investigators have recently started trying to optimize radiation therapy protocols using a concept termed 'the fundamental principle of personalized management' (7). When applied to GBM, this concept seeks to individualize both prognostic estimates and treatment plans based on the biological parameters of each patient's tumor (6). It is suggested that this individualized approach may allow more tailored treatment based, for example, on differences in tumor invasiveness and proliferation, which would lead to different cell density profiles between patients (6,8).…”

“…Such models would not only have the potential to optimize therapy, but also to potentially predict individual patient response patterns to a proposed treatment regimen (6,9,10).…”