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

  • 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 SchaeferEmail author
Original Article
Part of the following topical collections:
  1. Oncology – Chest



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.


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.


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.


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.




Compliance with ethical standards

Conflicts of interest


Ethical approval

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.

Informed consent

Informed consent was waived due to the retrospective nature of this study.

Supplementary material

259_2019_4348_MOESM1_ESM.pptx (600 kb)
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)
259_2019_4348_MOESM2_ESM.pptx (2.7 mb)
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)
259_2019_4348_MOESM3_ESM.pptx (2.6 mb)
(PPTX 2640 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Mario Jreige
    • 1
  • Igor Letovanec
    • 2
  • Kariman Chaba
    • 3
  • Stephanie Renaud
    • 3
  • Sylvie Rusakiewicz
    • 3
  • Valerie Cristina
    • 4
  • Solange Peters
    • 5
  • Thorsten Krueger
    • 6
  • Laurence de Leval
    • 2
  • Lana E. Kandalaft
    • 3
  • Marie Nicod-Lalonde
    • 1
  • Pedro Romero
    • 4
  • John O. Prior
    • 1
  • George Coukos
    • 3
    • 4
  • Niklaus Schaefer
    • 1
    Email author
  1. 1.Department of Nuclear Medicine and Molecular ImagingLausanne University HospitalLausanneSwitzerland
  2. 2.Institute of PathologyLausanne University HospitalLausanneSwitzerland
  3. 3.Center of Experimental Therapies (CTE), Department of OncologyLausanne University Hospital and University of LausanneLausanneSwitzerland
  4. 4.Translational Tumor Immunology Group, Department of OncologyLausanne University HospitalEpalingesSwitzerland
  5. 5.Department of OncologyLausanne University HospitalLausanneSwitzerland
  6. 6.Department of Thoracic SurgeryLausanne University HospitalLausanneSwitzerland

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