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Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma.

ABSTRACT: We describe the imaging findings encountered in GBM patients receiving immune checkpoint blockade and assess the potential of quantitative MRI biomarkers to differentiate patients who derive therapeutic benefit from those who do not.A retrospective analysis was performed on longitudinal MRIs obtained on recurrent GBM patients enrolled on clinical trials. Among 10 patients with analyzable data, bidirectional diameters were measured on contrast enhanced T1 (pGd-T1WI) and volumes of interest (VOI) representing measurable abnormality suggestive of tumor were selected on pGdT1WI (pGdT1 VOI), FLAIR-T2WI (FLAIR VOI), and ADC maps. Intermediate ADC (IADC) VOI represented voxels within the FLAIR VOI having ADC in the range of highly cellular tumor (0.7-1.1 × 10-3 mm2/s) (IADC VOI). Therapeutic benefit was determined by tissue pathology and survival on trial. IADC VOI, pGdT1 VOI, FLAIR VOI, and RANO assessment results were correlated with patient benefit.Five patients were deemed to have received therapeutic benefit and the other five patients did not. The average time on trial for the benefit group was 194 days, as compared to 81 days for the no benefit group. IADC VOI correlated well with the presence or absence of clinical benefit in 10 patients. Furthermore, pGd VOI, FLAIR VOI, and RANO assessment correlated less well with response.MRI reveals an initial increase in volumes of abnormal tissue with contrast enhancement, edema, and intermediate ADC suggesting hypercellularity within the first 0-6 months of immunotherapy. Subsequent stabilization and improvement in IADC VOI appear to better predict ultimate therapeutic benefit from these agents than conventional imaging.

SUBMITTER: Qin L

PROVIDER: S-EPMC6097616 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma.

Qin Lei L Li Xiang X Stroiney Amanda A Qu Jinrong J Helgager Jeffrey J Reardon David A DA Young Geoffrey S GS

Neuroradiology 20170109 2

<h4>Introduction</h4>We describe the imaging findings encountered in GBM patients receiving immune checkpoint blockade and assess the potential of quantitative MRI biomarkers to differentiate patients who derive therapeutic benefit from those who do not.<h4>Methods</h4>A retrospective analysis was performed on longitudinal MRIs obtained on recurrent GBM patients enrolled on clinical trials. Among 10 patients with analyzable data, bidirectional diameters were measured on contrast enhanced T1 (pGd ...[more]

PMID: 28070598

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Project description:BackgroundCheckpoint inhibition has demonstrated clinical efficacy in a variety of solid tumors. Reports of programmed death ligand 1 (PD-L1) expression in glioblastoma are highly variable (ranging from 6% to 88%) and its role as a prognostic marker has yielded conflicting results.ObjectiveTo validate the prevalence and prognostic role of PD-L1 expression in a large cohort of diffuse gliomas according to the 2016 revised WHO classification.MethodsUsing tissue microarrays, we compared 5 PD-L1 monoclonal antibodies (n = 56) and validated expression (n = 183) using quantitative immunohistochemistry (IHC) and RNA in situ hybridization (RISH). Expression data from The Cancer Genome Atlas (TCGA) and published studies were compared with clinical outcome. Multiplexed immunophenotyping was used to identify PD-L1+ cell populations in post-treatment glioblastoma.ResultsUsing a 5% cut-off, PD-L1 expression was significantly associated with a poor prognosis in both histologically defined (n = 125, log-rank P < .001) and recurrent isocitrate dehydrogenase (IDH)-wildtype glioblastoma (n = 60, log-rank P = .015). PD-L1 remained a significant negative prognosticator in Cox regression analysis (hazard ratio: 1.96, P = .021). Analysis of TCGA data confirmed decreased overall survival in recurrent non-glioma CpG island methylator phenotype (G-CIMP) glioblastoma (n = 12, log-rank P = .023), but not in glioblastoma as a group (n = 444, log-rank P = .135). PD-L1 RISH showed a significant correlation with IHC (P < .0001). PD-L1 was observed in the proliferating perivascular stem cell and immune niche of post-treatment glioblastoma.ConclusionA 5% PD-L1 expression cut-off identified a subset of glioblastoma that is associated with a worse clinical outcome. This association remained significant within the newly defined IDH-wildtype classification. These findings could have implications for patient stratification in future clinical trials of PD-1/PD-L1 blockade.

Dataset Information

Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma.

Publications

Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma.

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