Baseline metabolic tumor volume as a strong predictive and prognostic biomarker in patients with non-small cell lung cancer treated with PD1 inhibitors: a prospective study

Abstract

BackgroundReliable predictive and prognostic markers are still lacking for patients treated with programmed death receptor 1 (PD1) inhibitors for non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic and predictive values of different baseline metabolic parameters, including metabolic tumor volume (MTV), from 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET/CT) scans in patients with NSCLC treated with PD1 inhibitors.MethodsMaximum and peak standardized uptake values, MTV and total lesion glycolysis (TLG), as well as clinical and biological parameters, were recorded in 75 prospectively included patients with NSCLC treated with PD1 inhibitors. Associations between these parameters and overall survival (OS) were evaluated as well as their accuracy to predict early treatment discontinuation (ETD).ResultsA high MTV and a high TLG were significantly associated with a lower OS (p<0.001). The median OS in patients with MTV above the median (36.5 cm3) was 10.5 months (95% CI: 6.2 to upper limit: unreached), while the median OS in patients with MTV below the median was not reached. Patients with no prior chemotherapy had a poorer OS than patients who had received prior systemic treatment (p=0.04). MTV and TLG could reliably predict ETD (area under the receiver operating characteristic curve=0.76, 95% CI: 0.65 to 0.87 and 0.72, 95% CI: 0.62 to 0.84, respectively).ConclusionMTV is a strong prognostic and predictive factor in patients with NSCLC treated with PD1 inhibitors and can be easily determined from routine 18F-FDG PET/CT scans. MTV, could help to personalize immunotherapy and be used to stratify patients in future clinical studies.

Tumor Burden and Immunotherapy: Impact on Immune Infiltration and Therapeutic Outcomes

“…This negative correlation of tumor size and ICB sensitivity is borne out in patients where total tumor volume is predictive of response to αPD-1 with local or metastatic melanoma ( 47 , 48 ). In patients with NSCLC, metabolic tumor volume was also a prognostic factor for sensitivity to PD-1 blockade in both retrospective and prospective studies ( 22 , 49 ). Furthermore, dual ICB, which targets both PD-1 and CTLA-4 at the same time, has shown greater efficacy than single ICB in patients with metastatic NSCLC and melanoma ( 40 , 43 ), and is more effective in melanoma patients with smaller baseline tumor diameters ( 50 ).…”

Metabolic Parameters as Biomarkers of Response to Immunotherapy and Prognosis in Non-Small Cell Lung Cancer (NSCLC): A Real World Experience

“…Several studies have compared PET/CT to CT imaging in monitoring ICI treatment, with results suggesting an additional prognostic value of metabolic response assessments [ 10 ]. The role of pre-ICI 18F-FDG PET/CT scanning has been investigated in some monocentric retrospective studies, with different findings [ 11 , 12 , 13 , 14 ].…”

“…Some authors have described maximum standardized uptake value (SUVmax) as a potential predictive marker of response to ICIs [ 11 , 15 ], whereas others have not found any correlation [ 12 ]. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) appear to be the most promising quantitative indexes in predicting the therapy response [ 12 , 13 , 15 ]. A prognostic value for both MTV and TLG has been found in different kinds of malignancies [ 14 , 16 , 17 , 18 ], as demonstrated in previous studies assessing their values at baseline PET [ 19 , 20 , 21 ].…”

Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis

“…Kim et al reported that inhibiting PD-1/PD-L1 increased the infiltration of CD8+ T cells resulting in the killing of the tumor cells ( Kim et al, 2018 ). PD-1 checkpoint inhibitors such as atezolizumab and nivolumab have been shown to significantly improve the clinical symptoms of patients and prolong survival time in non-small cell lung cancer ( Chardin et al, 2020 ), renal cell carcinoma ( Buchbinder et al, 2019 ), breast cancer ( Szekely et al, 2018 ), and melanoma ( Luke et al, 2017 ). However, Chiu’s study demonstrated that upregulation of PVRL1 inhibited the cytotoxic T cell response through the T-cell immunoglobulin and ITIM domain (TIGIT), thus mediating resistance to PD1 inhibitors in HCC ( Chiu et al, 2020 ).…”