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

Purpose: We evaluated the prognostic value of immunotherapy-induced organ inflammation observed on 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. FDG PET/CT exams were performed at baseline (PET) and repeated after 7-8 weeks (PET1) and 12-16 weeks (PET2) of treatment, using iPERCIST for tumor response evaluation. The occurrence of abnormal organ FDG uptake, deemed to be due to ICPI-related organ inflammation, was collected.

Results: Exploratory cohort (Nice, France): PET1 and PET2 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 FDG PET in around 20% of patients with NSCLC treated with ICPI is a novel and reproducible imaging biomarker of improved OS.