Abstract

Purpose/ObjectiveIdentifying early predictors of treatment response is highly desirable for patients with high grade gliomas, as it might permit the selection of more intensive therapies for the appropriate patient population. The purpose of this study was to test our hypothesis that changes in regional tumor microvasculature, measured from T1-weighted MR and Gd-DPTA uptake signal intensity (SI) changes following radiotherapy may predict the outcome in patients with high grade gliomas.Materials/Methods14 patients with newly diagnosed high grade gliomas (4 patients with Gr 3 anaplastic astrocytomas/ 8 patients with glioblastoma multiforme) underwent MRI T1 weighted imaging pre-contrast and after intravenous bolus administration of a single dose of gadopentetate dimeglumine(Gd-DTPA), T2-weighted and fluid-attenuated inversion recovery imaging (FLAIR) as part of a clinical prospective study. MRI’s were performed 1–2 wks prior to radiotherapy, at Wks 1–2 and Wk 3–4 of treatment as well as during routine q3 month intervals following treatment. Median RT dose was 70 Gy (range: 60–70 Gy) with/without concurrent chemotherapy. Median follow-up was 7 months (range: 3–35 months). Using threshold values based on the normal brain, the contrast-enhancing tumor rim, and the non-enhancing tumor core were defined as regions of interest (ROI). Regional changes in T1-weighted signal intensity and Gd-DPTA uptake within the contrast enhancing rim and tumor core were calculated using a ratio of post to pre-contrast T1-weighted images. Pre-treatment MRI signal intensity was compared to those following radiotherapy at Wk 1–2 and Wk 3–4 as well as at 1, 3, and 6 months post RT. Clinical and MRI parameters including age, tumor grade, pre-treatment tumor volume, and recursive partitioning analysis (RPA) classification were then tested for prediction of overall survival.ResultsRegional T1-weighted signal intensity changes in both the enhancing rim and the tumor core were observed in all patients following 10 Gy and 30 Gy of radiotherapy at wks 1 and 3 respectively. Among clinical and MRI parameters, RPA classification (p = <0.001, R = .76) and decreased signal intensity in T1-weighted images within the non-enhancing tumor core following 30 Gy RT (p = <0.0036, R = .79) independently predicted for overall survival. Using multiple regression analysis, decreased MRI signal intensity at 30 Gy RT in addition to RPA classification was a better predictor of overall survival (p = <0.001, R = .83). Gd-DPTA uptake changes within the pre-treatment tumor volume and signal intensity changes in the tumor enhancing rim were not predictive of outcome.ConclusionsQuantitative measurements of T1 weighted MRI signal intensity changes in the non-enhancing tumor core (using ratios of pre-post values) may provide valuable information regarding response during treatment and improve our ability to predict post-treatment outcome. Further investigation is required regarding the use of regional changes in response to radiotherapy after 30 Gy for decision-making regarding dose intensification using IMRT. Purpose/ObjectiveIdentifying early predictors of treatment response is highly desirable for patients with high grade gliomas, as it might permit the selection of more intensive therapies for the appropriate patient population. The purpose of this study was to test our hypothesis that changes in regional tumor microvasculature, measured from T1-weighted MR and Gd-DPTA uptake signal intensity (SI) changes following radiotherapy may predict the outcome in patients with high grade gliomas. Identifying early predictors of treatment response is highly desirable for patients with high grade gliomas, as it might permit the selection of more intensive therapies for the appropriate patient population. The purpose of this study was to test our hypothesis that changes in regional tumor microvasculature, measured from T1-weighted MR and Gd-DPTA uptake signal intensity (SI) changes following radiotherapy may predict the outcome in patients with high grade gliomas. Materials/Methods14 patients with newly diagnosed high grade gliomas (4 patients with Gr 3 anaplastic astrocytomas/ 8 patients with glioblastoma multiforme) underwent MRI T1 weighted imaging pre-contrast and after intravenous bolus administration of a single dose of gadopentetate dimeglumine(Gd-DTPA), T2-weighted and fluid-attenuated inversion recovery imaging (FLAIR) as part of a clinical prospective study. MRI’s were performed 1–2 wks prior to radiotherapy, at Wks 1–2 and Wk 3–4 of treatment as well as during routine q3 month intervals following treatment. Median RT dose was 70 Gy (range: 60–70 Gy) with/without concurrent chemotherapy. Median follow-up was 7 months (range: 3–35 months). Using threshold values based on the normal brain, the contrast-enhancing tumor rim, and the non-enhancing tumor core were defined as regions of interest (ROI). Regional changes in T1-weighted signal intensity and Gd-DPTA uptake within the contrast enhancing rim and tumor core were calculated using a ratio of post to pre-contrast T1-weighted images. Pre-treatment MRI signal intensity was compared to those following radiotherapy at Wk 1–2 and Wk 3–4 as well as at 1, 3, and 6 months post RT. Clinical and MRI parameters including age, tumor grade, pre-treatment tumor volume, and recursive partitioning analysis (RPA) classification were then tested for prediction of overall survival. 14 patients with newly diagnosed high grade gliomas (4 patients with Gr 3 anaplastic astrocytomas/ 8 patients with glioblastoma multiforme) underwent MRI T1 weighted imaging pre-contrast and after intravenous bolus administration of a single dose of gadopentetate dimeglumine(Gd-DTPA), T2-weighted and fluid-attenuated inversion recovery imaging (FLAIR) as part of a clinical prospective study. MRI’s were performed 1–2 wks prior to radiotherapy, at Wks 1–2 and Wk 3–4 of treatment as well as during routine q3 month intervals following treatment. Median RT dose was 70 Gy (range: 60–70 Gy) with/without concurrent chemotherapy. Median follow-up was 7 months (range: 3–35 months). Using threshold values based on the normal brain, the contrast-enhancing tumor rim, and the non-enhancing tumor core were defined as regions of interest (ROI). Regional changes in T1-weighted signal intensity and Gd-DPTA uptake within the contrast enhancing rim and tumor core were calculated using a ratio of post to pre-contrast T1-weighted images. Pre-treatment MRI signal intensity was compared to those following radiotherapy at Wk 1–2 and Wk 3–4 as well as at 1, 3, and 6 months post RT. Clinical and MRI parameters including age, tumor grade, pre-treatment tumor volume, and recursive partitioning analysis (RPA) classification were then tested for prediction of overall survival. ResultsRegional T1-weighted signal intensity changes in both the enhancing rim and the tumor core were observed in all patients following 10 Gy and 30 Gy of radiotherapy at wks 1 and 3 respectively. Among clinical and MRI parameters, RPA classification (p = <0.001, R = .76) and decreased signal intensity in T1-weighted images within the non-enhancing tumor core following 30 Gy RT (p = <0.0036, R = .79) independently predicted for overall survival. Using multiple regression analysis, decreased MRI signal intensity at 30 Gy RT in addition to RPA classification was a better predictor of overall survival (p = <0.001, R = .83). Gd-DPTA uptake changes within the pre-treatment tumor volume and signal intensity changes in the tumor enhancing rim were not predictive of outcome. Regional T1-weighted signal intensity changes in both the enhancing rim and the tumor core were observed in all patients following 10 Gy and 30 Gy of radiotherapy at wks 1 and 3 respectively. Among clinical and MRI parameters, RPA classification (p = <0.001, R = .76) and decreased signal intensity in T1-weighted images within the non-enhancing tumor core following 30 Gy RT (p = <0.0036, R = .79) independently predicted for overall survival. Using multiple regression analysis, decreased MRI signal intensity at 30 Gy RT in addition to RPA classification was a better predictor of overall survival (p = <0.001, R = .83). Gd-DPTA uptake changes within the pre-treatment tumor volume and signal intensity changes in the tumor enhancing rim were not predictive of outcome. ConclusionsQuantitative measurements of T1 weighted MRI signal intensity changes in the non-enhancing tumor core (using ratios of pre-post values) may provide valuable information regarding response during treatment and improve our ability to predict post-treatment outcome. Further investigation is required regarding the use of regional changes in response to radiotherapy after 30 Gy for decision-making regarding dose intensification using IMRT. Quantitative measurements of T1 weighted MRI signal intensity changes in the non-enhancing tumor core (using ratios of pre-post values) may provide valuable information regarding response during treatment and improve our ability to predict post-treatment outcome. Further investigation is required regarding the use of regional changes in response to radiotherapy after 30 Gy for decision-making regarding dose intensification using IMRT.

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