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Discriminant analysis of ¹?F-fluorothymidine kinetic parameters to predict survival in patients with recurrent high-grade glioma.

ABSTRACT: The primary objective of this study was to investigate whether changes in 3'-deoxy-3'-[¹?F]fluorothymidine (¹?F-FLT) kinetic parameters, taken early after the start of therapy, could predict overall survival (OS) and progression-free survival (PFS) in patients with recurrent malignant glioma undergoing treatment with bevacizumab and irinotecan.High-grade recurrent brain tumors were investigated in 18 patients (8 male and 10 female), ages 26 to 76 years. Each had 3 dynamic positron emission tomography (PET) studies as follows: at baseline and after 2 and 6 weeks from the start of treatment, ¹?F-FLT (2.0 MBq/kg) was injected intravenously, and dynamic PET images were acquired for 1 hour. Factor analysis generated factor images from which blood and tumor uptake curves were derived. A three-compartment, two-tissue model was applied to estimate tumor ¹?F-FLT kinetic rate constants using a metabolite- and partial volume-corrected input function. Different combinations of predictor variables were exhaustively searched in a discriminant function to accurately classify patients into their known OS and PFS groups. A leave-one-out cross-validation technique was used to assess the generalizability of the model predictions.In this study population, changes in single parameters such as standardized uptake value or influx rate constant did not accurately classify patients into their respective OS groups (<1 and ? 1 year; hit ratios ? 78%). However, changes in a set of ¹?F-FLT kinetic parameters could perfectly separate these two groups of patients (hit ratio = 100%) and were also able to correctly classify patients into their respective PFS groups (<100 and ? 100 days; hit ratio = 88%).Discriminant analysis using changes in ¹?F-FLT kinetic parameters early during treatment seems to be a powerful method for evaluating the efficacy of therapeutic regimens.

SUBMITTER: Wardak M

PROVIDER: S-EPMC3833447 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Discriminant analysis of ¹⁸F-fluorothymidine kinetic parameters to predict survival in patients with recurrent high-grade glioma.

Wardak Mirwais M Schiepers Christiaan C Dahlbom Magnus M Cloughesy Timothy T Chen Wei W Satyamurthy Nagichettiar N Czernin Johannes J Phelps Michael E ME Huang Sung-Cheng SC

Clinical cancer research : an official journal of the American Association for Cancer Research 20110825 20

<h4>Purpose</h4>The primary objective of this study was to investigate whether changes in 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT) kinetic parameters, taken early after the start of therapy, could predict overall survival (OS) and progression-free survival (PFS) in patients with recurrent malignant glioma undergoing treatment with bevacizumab and irinotecan.<h4>Experimental design</h4>High-grade recurrent brain tumors were investigated in 18 patients (8 male and 10 female), ages 26 to 76 years ...[more]

PMID: 21868765

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Project description:Background:Patients with recurrent glioma after prior radiotherapy have a poor prognosis. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of this study was to analyze toxicity, local control and overall survival after reirradiation of recurrent high-grade glioma with carbon ion radiotherapy. Methods:Between 10/2015 and 12/2018, 30 patients (median age: 59 years) with recurrent high-grade glioma were reirradiated with carbon ion beams and retrospectively analyzed. Diagnosis of recurrent glioma was based on magnetic resonance imaging. Thirteen patients had repeated resection prior to reirradiation and 24 patients underwent additional chemotherapy. The median initial radiation dose was 60 Gy and the median time interval between the initial and repeated radiotherapy was 10 months. The reirradiation dose was 45 Gy (relative biological effectiveness) applied in 15 fractions. All patients received regular follow-up imaging after reirradiation. Kaplan-Meier estimation, log rank test and Cox regression analysis were used for statistical assessment. Results:Applying common toxicity criteria, there were no grade 5 or 4 adverse events, while 8 patients showed grade 3 adverse events. The median follow-up after reirradiation was 11 months and the median overall survival after diagnosis of recurrent high-grade glioma was 13 months. The 6-, 12- and 24-month overall survival rates after diagnosis of recurrent high-grade glioma were 76%, 50% and 19%, respectively. Upon multivariate Cox regression analysis, a Ki67 score of the initial tumor histology of less than 20% was prognostic. Repeated resection or chemotherapy for the recurrent disease did not result in significantly prolonged survival. Conclusion:Carbon ion reirradiation in recurrent high-grade glioma is safe and feasible. No radiation-associated grade 4 toxicities were documented and treatment was tolerated well.

Dataset Information

Discriminant analysis of ¹?F-fluorothymidine kinetic parameters to predict survival in patients with recurrent high-grade glioma.

Publications

Discriminant analysis of ¹⁸F-fluorothymidine kinetic parameters to predict survival in patients with recurrent high-grade glioma.

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