Tomography

Vol. 3 No. 3 - Sep 2017

Tomography is a scientific journal for publication of articles in imaging research

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Monitoring Radiation Treatment Effects in Glioblastoma: FLAIR Volume as Significant Predictor of Survival Matthew D. Garrett 1 , Ted K. Yanagihara 1 , Randy Yeh 2 , Guy M. McKhann 3,4 , Michael B. Sisti 3,4 , Jeffrey N. Bruce 3,4 , Sameer A. Sheth 3,4 , Adam M. Sonabend 3,4 , and Tony J. C. Wang 1,4 1 Departments of Radiation Oncology; 2 Radiology; and 3 Neurological Surgery, Columbia University Medical Center, New York, NY; and 4 Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY Corresponding Author: Tony J. C. Wang, MD Department of Radiation Oncology, Columbia University Medical Center, 622 West 168th Street, BNH B011, New York, NY 10032; E-mail: tjw2117@cumc.columbia.edu Key Words: glioblastoma, radiation, FLAIR, MRI, brain cancer Abbreviations: Fluid-attenuated inversion recovery (FLAIR), Glioblastoma (GBM), magnetic resonance imaging (MRI), chemoradiotherapy (CRT), radiation therapy (RT), overall survival (OS), progression-free survival (PFS), O 6 -methylguanine DNA methyltransferase (MGMT), Karnofsky performance status (KPS) Glioblastoma is the most common adult central nervous system malignancy and carries a poor prognosis. Disease progression and recurrence after chemoradiotherapy are assessed via serial magnetic resonance imaging sequences. T2-weighted fluid-attenuated inversion recovery (FLAIR) signal is presumed to represent edema containing microscopic cancer infiltration. Here we assessed the prognostic impact of computerized volumetry of FLAIR signal in the peri-treatment setting for glioblastoma. We analyzed pre- and posttreatment FLAIR sequences of 40 patients treated at the Columbia University Medical Center between 2011 and 2014, excluding those without high-quality FLAIR imaging within 2 weeks before treatment and 60 to 180 days afterward. We manually contoured regions of FLAIR hyperintensity as per Radiation Therapy On- cology Group guidelines and calculated the volumes of nonenhancing tumor burden. At the time of this study, all but 1 patient had died. Pre- and posttreatment FLAIR volumes were assessed for correlation to over- all and progression-free survival. Larger post-treatment FLAIR volumes from sequences taken between 60 and 180 days after conclusion of chemoradiotherapy were negatively correlated with overall survival (P 5 .048 on Pearson's correlation and P 5 .017 and P 5 .043 on univariable and multivariable Cox regression anal- yses, respectively) and progression-free survival (P 5 .002 on Pearson's correlation and P 5 , .001 and P 5 , .001 on univariable and multivariable Cox regression analyses). This study suggests that higher FLAIR volumes in the 2- to 6-month posttreatment window are associated with worsened survival. INTRODUCTION Glioblastoma (GBM) is the most common primary malignant neoplasm of the central nervous system with an annual inci- dence in the United States of 4 –5 per 100,000 (1). The standard of care includes a maximal safe surgical resection and adjuvant radiotherapy with concurrent and continued adjuvant temozo- lomide chemotherapy (2). Despite aggressive trimodality ther- apy, patients invariably recur with a median interval to disease progression of ;8 months and a 5-year overall survival (OS) rate of ,10% (3). After completing radiation therapy, patients are monitored closely, typically with serial magnetic resonance imaging (MRI) and routine clinical assessment (4). Disease progression is diag- nosed radiographically and/or in the context of clinical symp- toms or declining performance status. The MacDonald criteria, introduced in 1990, provided an objective methodology for tumor response assessment using changes in tumor area derived from maximal bidimensional measurements of enhancing re- gions on T1-weighted imaging with gadolinium. In addition, corticosteroid use and performance status were also considered in these criteria (5). In 2010, the Response Assessment in Neuro- Oncology Working Group (RANO) proposed new criteria for response assessment following chemoradiotherapy (CRT) to ad- dress the limitations of the MacDonald criteria, including the problems of pseudoprogression and nonenhancing tumor pro- gression (6). Therefore, the criteria for disease progression differ depending on the time interval from initial treatment, with 12 weeks as a discriminator to account for pseudoprogression. In addition, nonenhancing tumor shown by increased T2- weighted Fluid-Attenuated Inversion Recovery (FLAIR) signal was included in the evaluation for disease progression. In addition to post-treatment follow-up, FLAIR signal is an integral component of radiation therapy (RT) planning for GBM. Clinical target volumes in radiation treatment include T1 and RESEARCH ARTICLE ABSTRACT © 2017 The Authors. Published by Grapho Publications, LLC This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ISSN 2379-1381 http://dx.doi.org/10.18383/j.tom.2017.00009 TOMOGRAPHY.ORG | VOLUME 3 NUMBER 3 | SEPTEMBER 2017 131

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