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Simple Summary  The advent of immune-checkpoint inhibitors (ICIs) has significantly changed the management of patients with non-small cell lung cancer (NSCLC). Although the assessment of PD-L1 expression remains the gold standard for the selection of cases for immunotherapy, previous experiments have investigated whether metabolic parameters from positron emission tomography (PET) scans could have a similar predictive role. In our retrospective study, we assessed if baseline fluorodeoxyglucose PET (FDG PET) can represent a further tool for selecting patients who are eligible for ICI therapy. Among the parameters tested, a surrogate of the entire tumor burden (metabolic tumor volume, MTV) demonstrated better performance in selecting patients with adequate disease control, as well as those with better overall and progression-free survival. These promising findings from a real-world experiment stress once again the pivotal role of PET scanning in the management of patients with NSCLC, requiring further validation on larger and prospective cohorts before its implementation in the stratification of patients for immunotherapy.    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.

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