T2-FLAIR Mismatch Sign and Response to Radiotherapy in Diffuse Intrinsic Pontine Glioma

Abstract

<b><i>Purpose:</i></b> The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign was previously reported as a diagnostic indicator of diffuse astrocytoma, isocitrate dehydrogenase-mutant, and 1p/19q noncodeletion. Subsequently, it was reported that the same findings were observed in diffuse intrinsic pontine glioma (DIPG). We investigated the clinical significance of T2-FLAIR mismatch sign in DIPG. <b><i>Methods:</i></b> Twenty-one patients with DIPG (Male: Female = 12:9) were treated at our institute between 2004 and 2019. All patients were treated with local radiotherapy of 54 Gy/30 fractions. The positive T2-FLAIR mismatch sign was defined if it fulfilled the following criteria: (1) T2-FLAIR mismatch volume was >50% of T2 high volume at nonenhanced area, (2) the FLAIR low lesion is not associated with gadolinium enhancement (inside of enhancement or just outside of enhancement defined as edema), and (3) signal-intensity of FLAIR lowest lesion at tumor is lower than the normal cerebellar cortex. <b><i>Results:</i></b> In our patient series, T2-FLAIR mismatch sign was found in 5 out of 21 patients. Objective response rate of radiotherapy was 100% in patients positive for T2-FLAIR mismatch, while it was 25.0% in patients negative for T2-FLAIR mismatch, and this difference was statistically significant (<i>p</i> < 0.01, Fisher’s exact test). In patients under the age of 18-years, T2-FLAIR mismatch positive had a slightly better prognosis (<i>p</i> < 0.05, Wilcoxon test). <b><i>Conclusion:</i></b> T2-FLAIR mismatch sign in DIPG may be an indicator for better response to radiotherapy and a better prognostic factor.

IDH-mutant Astrocytoma Arising in the Brainstem with Symptom Improvement by Foramen Magnum Decompression: A Case Report

“…24) The patient described herein is being kept under observation, considering the slow rate of tumor progression and the fact that she is currently asymptomatic and willing to be observed. Yamasaki et al uncovered that the T2-FLAIR mismatch sign in DIPG may be an indicator for better response to radiotherapy, 25) but this sign was not observed in our case. Genomic profiling assays to identify CDKN2A/B were unable to be performed due to the lack of biopsy volume.…”

Prognostic Indicators and Treatment Strategies for Diffuse Midline Glioma: a Systematic Review

“…All patients received radiotherapy. Response rate of radiotherapy in patients positive for T2-FLAIR mismatch was 100%, while it was 25.0% in patients negative for T2-FLAIR mismatch [40].…”

Diffuse Midline Gliomas: Challenges and New Strategies in a Changing Clinical Landscape

“…Radiographically, these tumors share common features, such as an enlargement of the native cytoarchitecture (for DIPG, upwards of 50% of the pons), a wispy, non-capsular gadolinium enhancement, and a significant FLAIR signal that often extends beyond the contrast-enhancement pattern ( Figure 2 C,D) [ 24 , 25 ]. Importantly, dichotomizing FLAIR signal into tumor proper and reactive inflammation without obvious tumor cells has been a challenge and the matter of much research aimed at defining better biopsy targets [ 26 , 27 ]. Albeit the subject of much research, this matter is yet to be put to rest: novel imaging modalities are emerging in an effort to answer this question, but to date, biopsy can be the only definitive diagnostic.…”

“…This is challenging for DMGs, where treatment-related changes (following chemotherapy or radiation) often present as edema with T2 shortening on MRI or FLAIR imaging, similar to actual tumor growth. Some have advocated the use of T2/FLAIR mismatch (an imaging finding where a lesion is characterized by a strong T2 shortening but appears hypointense on FLAIR imaging) as a tool for response monitoring, but this needs further clinical validation [ 27 ]. Novel algorithms are still being developed to optimize clinical protocols; however, early clinical applications are starting to emerge with significant clinical promise [ 89 , 90 , 91 ].…”