Monitoring Radiation Treatment Effects in Glioblastoma: FLAIR Volume as Significant Predictor of Survival

Abstract

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 Oncology 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 overall 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 = .048 on Pearson's correlation and P = .017 and P = .043 on univariable and multivariable Cox regression analyses, respectively) and progression-free survival (P = .002 on Pearson's correlation and P = < .001 and P = < .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.

Predicting the true extent of glioblastoma based on probabilistic tractography

“…Although both sequences have promising results, their routine application is limited. Using FLAIR to guide surgical resection and irradiation has not resulted in longer survival (Garrett et al, 2017;Altieri et al, 2019). MRS has a low resolution which makes it challenging to use for such precise image guided procedures (Deviers et al, 2014(Deviers et al, ).…”

Challenges in Glioblastoma Radiomics and the Path to Clinical Implementation

“…FLAIR imaging is also utilised in delineating GBM tumour volumes on MRI. Hyperintense T2-FLAIR volumes are used in the delineation of tumour radiotherapy volumes, especially in defining areas of peritumoural cancer infiltration in oedema [ 13 ]; however, this has limitations as the prognostic value of FLAIR signal has not been clearly shown in GBM tumour response assessment [ 13 ]. Radiomics could help provide a method to quantify the extent of tumour infiltration beyond the contrast enhancing boundaries [ 12 , 14 ], potentially enabling the adaptation of treatment plans tailored to the characteristics of each patient’s individual tumour [ 15 ].…”

Non-invasive tumor probability maps developed using autopsy tissue identify novel areas of tumor beyond the imaging-defined margin

“…Gadolinium contrast agents are used to highlight disruptions in the blood brain barrier due to tumor angiogenesis, which results in an enhanced signal in T1-weighted imaging that is used to define the primary tumor mass [8][9][10] . Hyperintensities on T2-weighted fluid attenuated inversion recovery (FLAIR) images correspond to a mixture of infiltrative tumor and edema, though differentiating between tumor and non-tumor remains a source of uncertainty in imaging interpretation [11][12][13][14] . Apparent diffusion coefficient (ADC) images derived from diffusion-weighted imaging have shown promise in highlighting areas of diffusion restricting hypercellularity associated with tumor, though recent studies validating this signature beyond the contrast-enhancing margin have disputed the strength of this relationship [14][15][16][17][18][19] .…”