In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e13041-e13041
Abstract:
e13041 Background: Glioblastoma (GBM) is the most common and lethal of all brain tumors (median overall survival (OS)14.6 months), yet the incidence is low posing difficulty in creating statistically powered clinical trials, delaying advances in treatment. A patient-specific mathematical model for disease progression coupled with clinical imaging data may provide a tool for quantifying each individual tumor’s response relative to its inherent growth kinetics rather than a universal approach, and, potentially, predicting treatment efficacy. Methods: An exploratory analysis with a patient-specific mathematical model of GBM was used to evaluate therapeutic effect of a novel treatment for newly diagnosed GBM compared to standard care treatment. A cohort of 3 patients from a novel-chemoprotective stem cell gene therapy treatment study (CSCGT) received RT only, followed by dose-intense BCNU and infusion of autologous gene-modified hematopoietic stem cells. Patients then received TMZ combined with O 6 -benzylguanine (O 6 BG). Tumor volumes were calculated using T1 weighted gadolinium -enhanced and T2-weighted pretreatment MRI images to estimate patient-specific net rates of proliferation and invasion for predicting untreated tumor growth. Control patients were selected based on matching model-based rates of net proliferation and invasion and standard prognostic variables (age, performance, extent of resection). Deflection of tumor growth, days gained (DG), was determined by finding the time point on the untreated growth curve that corresponded to the post-treatment tumor size and calculating the amount of time treatment gained for the patient. DG per mg of TMZ dosed is used to compare treatment effects of TMZ with differing dose regimens. Results: CSCGT patients experienced higher DG per mg of TMZ dosed compared to their matched controls treated with standard care regimens. Conclusions: Patient-specific mathematical modeling can be used to evaluate treatment gains in small clinical trial design. The addition of O 6 BG to TMZ in the post RT milieu can provide greater treatment gains per mg of TMZ dose than TMZ alone. Clinical trial information: NCT 00669669.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.e13041
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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