Total Metabolic Tumor Volume on 18F-FDG PET/CT Is a Useful Prognostic Biomarker for Patients with Extensive Small-Cell Lung Cancer Undergoing First-Line Chemo-Immunotherapy

SIMPLE SUMMARY: Chemotherapy with immune checkpoint inhibitors is the new standard of care for first-line systemic therapy in extensive small-cell lung cancer. The identification of biomarkers for patients that are likely or not likely to respond to such therapy is critical. We aimed at determining whether imaging could help to predict outcomes among these patients. We showed that the total metabolic tumor burden, extracted from pre-treatment 18-FDG PET/CT imaging, may be a useful biomarker associated with survival. Finally, we think that this result should be taken into account in clinical trials, and that it might need further validation through large, independent, and prospective cohorts. ABSTRACT: Background: We aimed to evaluate the prognostic value of imaging biomarkers on 18F-FDG PET/CT in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing first-line chemo-immunotherapy. Methods: In this multicenter and retrospective study, we considered two cohorts, depending on the type of first-line therapy: chemo-immunotherapy (CIT) versus chemotherapy alone (CT). All patients underwent baseline 18-FDG PET/CT before therapy between June 2016 and September 2021. We evaluated clinical, biological, and PET parameters, and used cutoffs from previously published studies or predictiveness curves to assess the association with progression-free survival (PFS) or overall survival (OS) with Cox prediction models. Results: Sixty-eight patients were included (CIT: CT) (36: 32 patients). The median PFS was 5.9:6.5 months, while the median OS was 12.1:9.8 months. dNLR (the derived neutrophils/(leucocytes-neutrophils) ratio) was an independent predictor of short PFS and OS in the two cohorts (p < 0.05). High total metabolic tumor volume (TMTV(high) if > 241 cm(3)) correlated with outcomes, but only in the CIT cohort (PFS for TMTV(high) in multivariable analysis: HR 2.5; 95%CI 1.1–5.9). Conclusion: Baseline 18F-FDG PET/CT using TMTV could help to predict worse outcomes for ES-SCLC patients undergoing first-line CIT. This suggests that baseline TMTV may be used to identify patients that are unlikely to benefit from CIT.