Hot-to-Global Volume Ratio (HGVR): A novel tool to predict PD-L1 tumoral expression and outcome in NSCLC patients treated with checkpoint inhibitors using standard FDG PET/CT

• Published in: The Journal of nuclear medicine (1978) Vol. 59; p. 124
• Main Authors: Jreige, Mario, Letovanec, Igor, Peters, Solange, Cristina, Valerie, Coukos, Georges, Prior, John, Schaefer, Niklaus
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01-05-2018
• Subjects: Biopsy; Cancer therapies; Computed tomography; Correlation analysis; Fluorine isotopes; Glycolysis; Immune checkpoint; Immunity; Immunoglobulin G; Immunohistochemistry; Inhibitors; Lesions; Lung cancer; Lymphocytes T; Medical imaging; Monoclonal antibodies; Non-small cell lung carcinoma; Patients; PD-1 protein; PD-L1 protein; Positron emission; Positron emission tomography; Squamous cell carcinoma; Statistical analysis; Surgery; Surgical instruments; T cell receptors; Therapy; Tomography; Tumors
• ISSN: 0161-5505; 1535-5667

Purpose: Humanized anti-PD-L1 or anti-PD-1 IgG1 monoclonal antibody can restore tumor-specific T-cell immunity by inhibiting the binding of PD-L1 to PD-1. It is considered as an emerging, novel therapy in non-small cell lung cancer (NSCLC). Herein, we investigate the correlation of known and new metabolic markers on 18F-FDG PET/CT with tumoral tissue expression of PD-L1 and its correlation to radiological outcome using iRECIST in patients under checkpoint inhibitor treatment. Materials and Methods: All patients with a confirmed NSCLC who were investigated by immunohistochemistry (IHC) for PD-L1 (Roche-Ventana Clone SP263) on biopsy sample or on resection specimen and who had an FDG-PET prior to surgery or biopsy, were retrospectively included in the study. From January 2016 to March 2017, 49 patients were investigated. Sampled surgical and biopsy tumor specimens were analyzed by immunohistochemistry (IHC) for PD-L1 tumor expression. 18F-FDG-PET images were analyzed for SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) with a threshold of 42% of the maximum SUV signal intensity for the biopsied or resected tumor lesion. Metabolic information on 18F-FDG PET/CT was correlated using Spearman rank correlation with the positivity of expression of PD-L1 in corresponding tissue. Finally, the ratio of morphologic and metabolic lesion volumes (HGVR) was calculated and correlated to PD-L1 expression of the respective lesion and all obtained imaging variables of FDG - PET were correlated to radiological outcomes on follow-up after targeted anti-PD-1/PD-L1 therapy by iRECIST criteria using Spearman’s rank correlation. Results: 25/49 adenocarcinomas (ADC) and 24/49 squamous cell carcinomas (SCC) were analyzed. All tumors showed metabolic FDG-PET uptake with mean SUVmax 13.3 g/ml (range: 3.3-28.1), SUVmean 7.4 g/ml (range: 1.9-16.3), MTV 50.3 cm3 (range: 1.2-456) and TLG 284 g·cm3/mL (range: 5.0-2,233). We found a statistically significant correlation analysis only for the proposed HGVR (R = 0.618, p < 0.005) - but not MTV (R = -0.042, p = 0.773), TLG (R = 0.139, p = 0.34), morphologic tumoral volume (R = 0.21, p = 0.15), SUVmax (R = 0.171, p = 0.24) and SUVmean (R = 0.119, p = 0.42) - and PD-L1 tumor expression. 19/49 patients underwent anti-PD-1 or anti-PD-L1 therapy, follow up imaging was available for 17/19 patients. Only PD-L1 expression and HGVR were significantly correlated to radiological outcome using iRECIST criteria (p = 0.017 and p = 0.042, respectively). Conclusion: This study introduces HGVR, evaluating FDG avid versus non - FDG avid necrotic tumor lesions, as new imaging marker. It is significantly correlating with tumoral PD - L1 expression and radiological outcome by iRECIST in NSCLC patients under checkpoint inhibitor treatment.