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European Journal of Nuclear Medicine and Molecular Imaging

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01-08-2019 | NSCLC | Original Article

¹⁸F-FDG PET metabolic-to-morphological volume ratio predicts PD-L1 tumour expression and response to PD-1 blockade in non-small-cell lung cancer

Authors: Mario Jreige, Igor Letovanec, Kariman Chaba, Stephanie Renaud, Sylvie Rusakiewicz, Valerie Cristina, Solange Peters, Thorsten Krueger, Laurence de Leval, Lana E. Kandalaft, Marie Nicod-Lalonde, Pedro Romero, John O. Prior, George Coukos, Niklaus Schaefer

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2019

Abstract

Purpose

Anti-PD-1/PD-L1 blockade can restore tumour-specific T-cell immunity and is an emerging therapy in non-small-cell lung cancer (NSCLC). We investigated the correlation between ¹⁸F-FDG PET/CT-based markers and tumour tissue expression of PD-L1, necrosis and clinical outcome in patients receiving checkpoint inhibitor treatment.

Methods

PD-Li expression in biopsy or resection specimens from 49 patients with confirmed NSCLC was investigated by immunohistochemistry. Maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were obtained from ¹⁸F-FDG PET/CT images. The ratio of metabolic to morphological lesion volumes (MMVR) and its association with PD-L1 expression in each lesion were calculated. The associations between histologically reported necrosis and ¹⁸F-FDG PET imaging patterns and radiological outcome (evaluated by iRECIST) following anti-PD-1/PD-L1 therapy were also analysed. In 14 patients, the association between necrosis and MMVR and tumour immune contexture were analysed by multiple immunofluorescent (IF) staining for CD8, PD-1, granzyme B (GrzB) and NFATC2.

Results

In total, 25 adenocarcinomas and 24 squamous cell carcinomas were analysed. All tumours showed metabolic ¹⁸F-FDG PET uptake. MMVR was correlated inversely with PD-L1 expression in tumour cells. Furthermore, PD-L1 expression and low MMVR were significantly correlated with clinical benefit. Necrosis was correlated negatively with MMVR. Multiplex IF staining showed a greater frequency of activated CD8⁺ cells in necrotic tumours than in nonnecrotic tumours in both stromal and epithelial tumour compartments.

Conclusion

This study introduces MMVR as a new imaging biomarker and its ability to noninvasively capture increased PD-L1 tumour expression and predict clinical benefit from checkpoint blockade in NSCLC should be further evaluated.

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Title: 18F-FDG PET metabolic-to-morphological volume ratio predicts PD-L1 tumour expression and response to PD-1 blockade in non-small-cell lung cancer
Authors: Mario Jreige
Igor Letovanec
Kariman Chaba
Stephanie Renaud
Sylvie Rusakiewicz
Valerie Cristina
Solange Peters
Thorsten Krueger
Laurence de Leval
Lana E. Kandalaft
Marie Nicod-Lalonde
Pedro Romero
John O. Prior
George Coukos
Niklaus Schaefer
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
Lung Cancer
Lung Cancer
NSCLC
Lung Cancer
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-019-04348-x

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¹⁸F-FDG PET metabolic-to-morphological volume ratio predicts PD-L1 tumour expression and response to PD-1 blockade in non-small-cell lung cancer

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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