Refinement of response assessment in neuro-oncology (RANO) using non-enhancing lesion type and contrast enhancement evolution pattern in IDH wild-type glioblastomas

Hye Hyeon Moon,Ji Eun Park,Jeong Hoon Kim,Ho Sung Kim,Young-Hoon Kim

doi:10.1186/s12885-021-08414-2

Hye Hyeon Moon, Ji Eun Park + Show 3 more

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https://doi.org/10.1186/s12885-021-08414-2

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Abstract

BackgroundUpdated response assessment in neuro-oncology (RANO) does not consider peritumoral non-enhancing lesion (NEL) and baseline (residual) contrast enhancement (CE) volume. The objective of this study is to explore helpful imaging characteristics to refine RANO for assessing early treatment response (pseudoprogression and time-to-progression [TTP]) in patients with IDH wild-type glioblastoma.MethodsThis retrospective study enrolled 86 patients with IDH wild-type glioblastoma who underwent consecutive MRI examinations before and after concurrent chemoradiotherapy (CCRT). NEL was classified as edema- or tumor-dominant type on pre-CCRT MRI. CE evolution was categorized into 4 patterns based on post-operative residual CE (measurable vs. non-measurable) and CE volume change (same criteria with RANO) during CCRT. Multivariable logistic regression, including clinical parameters, NEL type, and CE evolution pattern, was used to analyze pseudoprogression rate. TTP and OS according to NEL type and CE evolution pattern was analyzed by the Kaplan–Meier method.ResultsPseudoprogression rate was significantly lower (chi-square test, P = .047) and TTP was significantly shorter (hazard ratio [HR] = 2.03, P = .005) for tumor-dominant type than edema-dominant type of NEL. NEL type was the only predictive marker of pseudoprogression on multivariate analysis (odds ratio = 0.26, P = .046). Among CE evolution patterns, TTP and OS was shortest in patients with residual CE compared with those exhibiting new CE (HR = 4.33, P < 0.001 and HR = 3.71, P = .009, respectively). In edema-dominant NEL type, both TTP and OS was stratified by CE evolution pattern (log-rank, P = .001), whereas it was not in tumor-dominant NEL.ConclusionsNEL type improves prediction of pseudoprogression and, together with CE evolution pattern, further stratifies TTP and OS in patients with IDH wild-type glioblastoma and may become a helpful biomarker for refining RANO.

Highlights

Updated response assessment in neuro-oncology (RANO) does not consider peritumoral nonenhancing lesion (NEL) and baseline contrast enhancement (CE) volume
The present study evaluated whether categorizing NEL type and CE evolution pattern during concurrent chemoradiotherapy (CCRT) can better predict time to progression (TTP) and pseudoprogression in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma
Patients were included if they (i) had been histologically diagnosed with IDH wild-type glioblastoma according to the World Health Organization (WHO) criteria; (ii) underwent adjuvant CCRT that included six cycles of temozolomide (TMZ) treatment after surgical resection or biopsy; (iii) had been evaluated by magnetic resonance imaging (MRI), including contrast-enhanced T1-weighted imaging (CE-T1WI) and fluid-attenuated inversion recovery (FLAIR) imaging, within 2 weeks after surgery or biopsy and before CCRT, and again 4 weeks after completing CCRT; (iv) had a newly developed or persistent CE on post-CCRT MRI; and (vi) were sequentially followed-up by contrast-enhanced MRI at 2–3 month intervals for at least 12 months to confirm the final diagnosis of pseudoprogression and progression

Summary

Introduction

Updated response assessment in neuro-oncology (RANO) does not consider peritumoral nonenhancing lesion (NEL) and baseline (residual) contrast enhancement (CE) volume. The objective of this study is to explore helpful imaging characteristics to refine RANO for assessing early treatment response (pseudoprogression and time-to-progression [TTP]) in patients with IDH wild-type glioblastoma. Peritumoral non-enhancing lesions (NELs), which appear as hyperintense lesions on T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging [5], usually consist of mixtures of edema and tumor [6]. NELs can affect patient prognosis [7,8,9], as they represent the portion of tumors extending beyond the contrast-enhanced margins. Tumordominant NELs have several characteristic imaging features, including relatively mild FLAIR hyperintensity, gray matter involvement, eccentric extension not accounted for by anatomic constraints, focal parenchymal expansion, and mass effect [14,15,16]

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