Predictive Value of Baseline FDG-PET/CT for the Durable Response to Immune Checkpoint Inhibition in NSCLC Patients Using the Morphological and Metabolic Features of Primary Tumors

Simple Summary Lung cancer is the leading cause of cancer-related death worldwide. Nonsmall cell lung cancer (NSCLC) accounts for 80-85% of all cases. Immune checkpoint inhibitors (ICIs) have revolutionized the field of oncology by improving survival in cancer patients. However, given their limited response rate and high immunotoxicity, an accurate selection of NSCLC patients eligible for ICIs appears to be of great importance. We aimed to investigate the predictive value of baseline 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) for a durable response to ICIs by linking the morphological and metabolic features of primary tumors in NSCLC patients. The baseline FDG-PET/CT could be used to predict the durable response to ICIs in NSCLC patients. Age, clinical stage IV, lymphangiosis features (on imaging), primary tumor (PT) volume (thus PT metabolic tumor volume MTV due to the demonstrated linear correlation), PT standardized uptake value maximum (SUVmax), and total lesion glycolysis (TLG) were very strong long-term outcome predictors. Our results highlight the importance of linking clinical data, as much as morphological features, to the metabolic parameters of primary tumors in a multivariate outcome-predicting model using baseline FDG-PET/CT. Objectives: We aimed to investigate the predictive value of baseline 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) for durable responses to immune checkpoint inhibitors (ICIs) by linking the morphological and metabolic features of primary tumors (PTs) in nonsmall cell lung cancer (NSCLC) patients. Methods: For the purpose of this single-center study, the imaging data of the patients with a first diagnosis of NSCLC and an available baseline FDG-PET/CT between 2020 and 2021 were retrospectively assessed. The baseline characteristics were collected based on clinical reports and interdisciplinary tumor board documentation. The metabolic (such as standardized uptake value SUV maximum and mean (SUVmax, SUV mean), metabolic tumor volume (MTV), total lesion glycolysis (TLG)) and morphological (such as volume, morphology, margin, and presence of lymphangiosis through imaging) features of all the PTs were retrospectively assessed using FDG-PET/CT. Overall survival (OS), progression-free survival (PFS), clinical benefit (CB) and mortality rate were used as endpoints to define the long-term response to therapy. A backward, stepwise logistic regression analysis was performed in order to define the best model for predicting lasting responses to treatment. Statistical significance was assumed at p < 0.05. Results: A total of 125 patients (median age +/- standard deviation (SD) 72.0 +/- 9.5 years) were enrolled: 64 men (51.2%) and 61 women (48.8%). Adenocarcinoma was by far the most common histological subtype of NSCLC (47.2%). At the initial diagnosis, the vast majority of all the included patients showed either locally advanced disease (34.4%) or metastatic disease (36.8%). Fifty patients were treated with ICIs either as a first-line (20%) or second-line (20%) therapy, while 75 patients did not receive ICIs. The median values +/- SD of PT SUVmax, mean, MTV, and TLG were respectively 10.1 +/- 6.0, 6.1 +/- 3.5, 13.5 +/- 30.7, and 71.4 +/- 247.7. The median volume of PT +/- SD was 13.7 +/- 30.7 cm(3). The PTs were most frequently solid (86.4%) with irregular margins (76.8%). Furthermore, in one out of five cases, the morphological evidence of lymphangiosis was seen through imaging (n = 25). The median follow-up +/- SD was 18.93 +/- 6.98 months. The median values +/- SD of OS and PFS were, respectively, 14.80 +/- 8.68 months and 14.03 +/- 9.02 months. Age, PT volume, SUVmax, TLG, the presence of lymphangiosis features through imaging, and clinical stage IV were very strong long-term outcome predictors of patients treated with ICIs, while no significant outcome predictors could be found for the cohort with no ICI treatment. The optimal cut-off values were determined for PT volume (26.94 cm(3)) and SUVmax (15.05). Finally, 58% of NSCLC patients treated with ICIs had a CB vs. 78.7% of patients in the cohort with no ICI treatment. However, almost all patients treated with ICIs and with disease progression over time died (mortality in the case of disease progression 95% vs. 62.5% in the cohort without ICIs). Conclusion: Baseline FDG-PET/CT could be used to predict a durable response to ICIs in NSCLC patients. Age, clinical stage IV, lymphangiosis features through imaging, PT volume (thus PT MTV due to a previously demonstrated linear correlation), PT SUVmax, and TLG were very strong long-term outcome predictors. Our results highlight the importance of linking clinical data, as much as morphological features, to the metabolic parameters of primary tumors in a multivariate outcome-predicting model using baseline FDG-PET/CT.

Automated summary

This study aimed to investigate the predictive value of baseline FDG-PET/CT for durable responses to ICIs in NSCLC patients by linking the morphological and metabolic features of primary tumors. The results showed that baseline FDG-PET/CT could be used to predict a durable response to ICIs in NSCLC patients, and age, clinical stage IV, lymphangiosis features, PT volume, PT SUVmax, and TLG were strong long-term outcome predictors.