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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

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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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Authors and Affiliations

  1. Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland

    Mario Jreige, Marie Nicod-Lalonde, John O. Prior & Niklaus Schaefer

  2. Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland

    Igor Letovanec & Laurence de Leval

  3. Center of Experimental Therapies (CTE), Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

    Kariman Chaba, Stephanie Renaud, Sylvie Rusakiewicz, Lana E. Kandalaft & George Coukos

  4. Translational Tumor Immunology Group, Department of Oncology, Lausanne University Hospital, Epalinges, Switzerland

    Valerie Cristina, Pedro Romero & George Coukos

  5. Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland

    Solange Peters

  6. Department of Thoracic Surgery, Lausanne University Hospital, Lausanne, Switzerland

    Thorsten Krueger

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  1. Mario Jreige
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Correspondence to Niklaus Schaefer.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Supplementary Fig. 1

Multispectral Immunofluorescence images at x10 magnification in a patient with tumour-associated necrosis (a) and a patient with no tumour-associated necrosis (b). (PPTX 600 kb)

Supplementary Fig. 2

High-resolution multispectral images at x20 magnification in a patient with tumour-associated necrosis (a) and a patient with no tumour-associated necrosis (b). pink cytokeratin (CK), red CD8, green PD1, cyan granzyme B (GrzB), yellow NFATC2. (PPTX 2746 kb)

(PPTX 2640 kb)

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Jreige, M., Letovanec, I., Chaba, K. et al. 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. Eur J Nucl Med Mol Imaging 46, 1859–1868 (2019). https://doi.org/10.1007/s00259-019-04348-x

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