Prognostic value of immunotherapy-induced organ inflammation assessed on 18FDG PET in patients with metastatic non-small cell lung cancer

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Abstract Purpose We evaluated the prognostic value of immunotherapy-induced organ inflammation observed on 18 FDG PET in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs). Methods Data from patients with IIIB/IV NSCLC included in two different prospective trials were analyzed. 18 FDG PET/CT exams were performed at baseline (PET Baseline ) and repeated after 7–8 weeks (PET Interim 1) and 12–16 weeks (PET Interim 2) of treatment, using iPERCIST for tumor response evaluation. The occurrence of abnormal organ 18 FDG uptake, deemed to be due to ICPI-related organ inflammation, was collected. Results Exploratory cohort (Nice, France): PET Interim 1 and PET Interim 2 revealed the occurrence of at least one ICPI-induced organ inflammation in 72.8% of patients, including midgut/hindgut inflammation (33.7%), gastritis (21.7%), thyroiditis (18.5%), pneumonitis (17.4%), and other organ inflammations (9.8%). iPERCIST tumor response was associated with improved progression-free survival ( p < 0.001). iPERCIST tumor response and immuno-induced gastritis assessed on PET were both associated with improved overall survival (OS) ( p < 0.001 and p = 0.032). Combining these two independent variables, we built a model predicting patients' 2-year OS with a sensitivity of 80.3% and a specificity of 69.2% (AUC = 72.7). Validation cohort (Genova, Italy): Immuno-induced gastritis (19.6% of patients) was associated with improved OS ( p = 0.04). The model built previously predicted 2-year OS with a sensitivity and specificity of 72.0% and 63.6% (AUC = 70.7) and 3-year OS with a sensitivity and specificity of 69.2% and 80.0% (AUC = 78.2). Conclusion Immuno-induced gastritis revealed by early interim 18 FDG PET in around 20% of patients with NSCLC treated with ICPI is a novel and reproducible imaging biomarker of improved OS.

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