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
- 149 Downloads
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.
KeywordsFDG PET/CT PD-L1 Imaging NSCLC
Compliance with ethical standards
Conflicts of interest
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 was waived due to the retrospective nature of this study.
- 14.Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50. https://doi.org/10.1016/S0140-6736(15)01281-7.CrossRefGoogle Scholar
- 15.Pai-Scherf L, Blumenthal GM, Li H, Subramaniam S, Mishra-Kalyani PS, He K, et al. FDA approval summary: Pembrolizumab for treatment of metastatic non-small cell lung cancer: first-line therapy and beyond. Oncologist. 2017;22(11):1392–9. https://doi.org/10.1634/theoncologist.2017-0078.CrossRefGoogle Scholar
- 20.Steinbach JP, Wolburg H, Klumpp A, Probst H, Weller M. Hypoxia-induced cell death in human malignant glioma cells: energy deprivation promotes decoupling of mitochondrial cytochrome c release from caspase processing and necrotic cell death. Cell Death Differ. 2003;10:823–32. https://doi.org/10.1038/sj.cdd.4401252.CrossRefGoogle Scholar
- 21.Soussan M, Cyrta J, Pouliquen C, Chouahnia K, Orlhac F, Martinod E, et al. Fluorine 18 fluorodeoxyglucose PET/CT volume-based indices in locally advanced non-small cell lung cancer: prediction of residual viable tumor after induction chemotherapy. Radiology. 2014;272:875–84. https://doi.org/10.1148/radiol.1413219.CrossRefGoogle Scholar
- 29.Zhou ZJ, Zhan P, Song Y. PD-L1 over-expression and survival in patients with non-small cell lung cancer: a meta-analysis. Transl Lung Cancer Res. 2015;4:203–8. https://doi.org/10.3978/j.issn.2218-6751.2015.03.02.CrossRefGoogle Scholar
- 32.Tormanen U, Eerola AK, Rainio P, Vahakangas K, Soini Y, Sormunen R, et al. Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma. Cancer Res. 1995;55:5595–602.Google Scholar
- 40.Dworakowska D, Jassem E, Jassem J, Karmolinski A, Lapinski M, Tomaszewski D, et al. Prognostic value of the apoptotic index analysed jointly with selected cell cycle regulators and proliferation markers in non-small cell lung cancer. Lung Cancer. 2009;66:127–33. https://doi.org/10.1016/j.lungcan.2009.01.008.CrossRefGoogle Scholar