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

Abstract

Immune-checkpoint inhibitors (ICIs) have been proven to have great efficacy in non-small cell lung cancer (NSCLC) as single agents or in combination therapy, being capable to induce deep and durable remission. However, severe adverse events may occur and about 40% of patients do not benefit from the treatment. Predictive factors of response to ICIs are needed in order to customize treatment. The aim of this study is to evaluate the correlation between quantitative positron emission tomography (PET) parameters defined before starting ICI therapy and responses to treatment and patient outcome. We retrospectively analyzed 92 NSCLC patients treated with nivolumab, pembrolizumab or atezolizumab. Basal PET/computed tomography (CT) scan parameters (whole-body metabolic tumor volume—wMTV, total lesion glycolysis—wTLG, higher standardized uptake volume maximum and mean—SUVmax and SUVmean) were calculated for each patient and correlated with outcomes. Patients who achieved disease control (complete response + partial response + stable disease) had significantly lower MTV median values than patients who had not (progressive disease) (77 vs. 160.2, p = 0.039). Furthermore, patients with MTV and TLG values lower than the median values had improved OS compared to patients with higher MTV and TLG (p = 0.03 and 0.05, respectively). No relation was found between the other parameters and outcome. In conclusion, baseline metabolic tumor burden, measured with MTV, might be an independent predictor of treatment response to ICI and a prognostic biomarker in NSCLC patients.

The Role of the Immune Metabolic Prognostic Index in Patients with Non-Small Cell Lung Cancer (NSCLC) in Radiological Progression during Treatment with Nivolumab

“…In a previous study by our group comparing the first response assessment to Nivolumab using CT and FDG PETbased criteria in the same cohort of patients, FDG imaging maintained a prognostic value even in patients classified as PD based on CT [28]. This prognostic value was also observed when tumor burden parameters (i.e., MTV and TLG) were applied [22,29,30]. Similarly, in previous studies on the use of PET-based response in melanoma patients receiving ICIs, it was demonstrated that as much as half of patients showing residual disease on CT have negative FDG-PET scans [31][32][33][34].…”

Immune Checkpoint Inhibitors in Advanced NSCLC: [18F]FDG PET/CT as a Troubleshooter in Treatment Response

“…However, volume-based PET parameters were extracted. In this context, a bicentric Italian study performed an analysis in a bigger cohort of 92 patients, demonstrating that those with PD had higher MTV median values compared to those with controlled disease [ 17 ]. Similarly, Polverani and colleagues observed a significant association of MTV and TLG of the primary lesions with PD, since lower MTV and TLG values were associated with non-PD status [ 18 ].…”

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images

“…More recently, new semiquantitative parameters, namely metabolic tumor volume (MTV) and total lesion glycolysis (TLG) rate, have been studied to evaluate the predictive and prognostic value of the metabolic tumor burden at baseline [18F]FDG PET/CT. Many of these studies have shown that new PET metabolic parameters are better in predicting prognosis in early and advanced NSCLC and SCLC patients than conventional PET parameters (SUVmax or SUVmean) [ 178 , 179 ].…”