Baseline total metabolic tumour volume on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography-computed tomography as a promising biomarker in patients with advanced non–small cell lung cancer treated with first-line pembrolizumab

• Published in: European journal of cancer (1990) Vol. 150; pp. 99 - 107
• Main Authors: Dall’Olio, Filippo G., Calabrò, Diletta, Conci, Nicole, Argalia, Giulia, Marchese, Paola Valeria, Fabbri, Francesca, Fragomeno, Benedetta, Ricci, Dalia, Fanti, Stefano, Ambrosini, Valentina, Ardizzoni, Andrea
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2021; Elsevier Science Ltd
• Subjects: [18F]FDG PET/CT; Advanced cancer; Apoptosis; Biomarker; Biomarkers; Chemotherapy; Computed tomography; Confidence intervals; Emission analysis; Epidermal growth factor; Epidermal growth factor receptors; Fluorine isotopes; Glucose; Growth factors; Immune checkpoint inhibitors; Immunotherapy; Inhibitors; Kinases; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Lesions; Leukocytes (neutrophilic); Lung cancer; Lymphocytes; Metabolism; Metastases; Monoclonal antibodies; MTV; Non-small cell lung carcinoma; NSCLC; Parameters; PD-L1; PD-L1 protein; Pembrolizumab; Positron emission; Positron emission tomography; Predictive; Prognostic; Protein-tyrosine kinase; Small cell lung carcinoma; Targeted cancer therapy; Tomography; Total metabolic tumour volume; Tumors; Tyrosine; Advanced cancer; Biomarker; NSCLC; Lung cancer; Total metabolic tumour volume; Predictive; PD-L1; [18F]FDG PET/CT; Immune checkpoint inhibitors; Prognostic; MTV
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2021.03.020

Immune checkpoint inhibitors (ICIs) have become the standard of care in the management of advanced non–small cell lung cancer (NSCLC). Nevertheless, only a small proportion of patients benefit from ICIs. The aim of the present study is to assess whether 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography-computed tomography ([18F]FDG-PET/CT)–derived parameters may be used as biomarkers in patients with advanced NSCLC receiving first-line pembrolizumab. This is a monocentric retrospective cohort study including patients with advanced NSCLC (stage IV) and Programmed death-ligand 1 (PD-L1) expression ≥50% treated with pembrolizumab. A control group of patients treated with epidermal growth factor receptor (EGFR) inhibitors for EGFR-mutated NSCLC was also enrolled. Only patients with a positive [18F]18F-FDG PET/CT result within 60 days from treatment initiation were included.Total metabolic tumour volume (tMTV) was calculated for each lesion using a dedicated software (PET VCAR; GE Healthcare), which semiautomatically delineates the tumour's contours with a maximum standardised uptake value (SUVmax) threshold of 42% within the lesion. tMTV was obtained summing each lesion's MTV. Potential prognostic parameters for overall survival (OS) were analysed (tMTV, SUVmax, bone/liver metastasis, neutrophil:lymphocyte ratio ≥4, Eastern Cooperative Oncology Group performance status ≥2, lactate dehydrogenase above the upper limit of normal). Overall, 34 patients treated with first line-pembrolizumab and 40 patients treated with EGFR tyrosine kinase inhibitors were included. In the pembrolizumab group, the median follow-up was 20.3, while the median OS was 4.7 months (95% confidence interval [CI] = 0.3–9.1) for patients with tMTV ≥75 cm3 vs not reached (NR) for patients with tMTV <75 cm3 (95% CI = NR–NR; hazard ratio [HR] = 5.37; 95% CI = 1.72–16.77; p = 0.004). No difference was found in the control group (HR = 1.43; 95% CI = 0.61–3.34; p = 0.411). Our data suggest that tMTV ≥75cm3 can be used as a prognostic biomarker of poor outcomes in patients with PD-L1–high advanced NSCLC treated with first-line pembrolizumab. This information could be useful for the selection of patients who may require the addition of chemotherapy to pembrolizumab. •Patients with high total metabolic tumour value (tMTV) have limited benefit from immune checkpoint inhibitors alone including first-line pembrolizumab.•There is no correlation with outcomes in epidermal growth factor receptor–mutated patients treated with tyrosine kinase inhibitors.•A score comprising Eastern Cooperative Oncology Group performance status and neutrophil:lymphocyte ratio could be promising.•Further research should focus on cut-off or nomogram establishment.•Patients with high tMTV could benefit from combination therapy.