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PD-L1-R: A MR based surrogate for PD-L1 expression in Glioblastoma multiforme.

Francesco Sforazzini, Patrick Salome, Andreas Kudak, Matthias Ulrich, Laila Koenig, Rolf Warta, Nina Bougatf, Juergen Debus, Christel Herold-Mende, Maximilian Knoll, Amir Abdollahi

JOURNAL OF CLINICAL ONCOLOGY(2021)

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Abstract
2041 Background: Efficacy of PD-L1 immune checkpoint inhibitor therapy in Glioblastoma multiforme (GBM) is limited and the prognostic value of PD-L1 in GBM is an active field of research. We therefore sought to identify a MR based surrogate for PD-L1 expression in GBM. Methods: T1 post contrast images (T1ce) acquired immediately before surgery of 121 subjects with primary GBM (RTK I, II and mesenchymal subtype, as determined from Illumina Human Methylation array data) were analyzed. Following standard pre-processing (bias filed correction, brain extraction), 1150 radiomics features were calculated from gross tumor volumes (GTV). The cohort was then divided into training/validation (70%/30%). Cross-validation and model-selection were applied to identify features associated with PD-L1-M expression (estimated from methylation data and highly correlated with PD-L1 RNA-sequencing based measure, as recently reported). Features were used to identify two groups of tumors differing in PD-L1-M expression (PD-L1-R high and low), for which a logistic regression model was trained. Overall survival was assessed between PD-L1-R high/low. Results: PD-L1-R high and low groups showed significant differences in PD-L1-M values (training: p=0.002, validation: p=0.04, full cohort: p<0.001). The same model was used to split tumors into 2 groups, using features from non-T1ce sequences. All of the tested MR modalities showed at least a trend in PD-L1-M values in the two groups (T2w: p=0.037, T1w: p=0.089, FLAIR: p=0.091). Further investigations on the whole cohort (121 subjects) showed that PD-L1-R low group was enriched for RTK II sub-type (48%), while PD-L1-R high for mesenchymal sub-type (48%). Refer to Table 1 for more information. In addition, evaluation of survival data showed a difference in overall survival (likelihood ratio test p value 0.048, OR 0.52, 95% CI [0.27; 0.98]), with the PD-L1-R high group having a better prognosis. Conclusions: We presented a radiomics model PD-L1-R which allowed to identify GBM with low and high PD-L1-M expression from T1 post contrast agent images. Future work should validate these findings in independent cohorts.[Table: see text]
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glioblastoma multiforme
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