[Predictive value of ¹⁸F-FDG PET-CT for the major pathologic response to neoadjuvant immunotherapy in non-small cell...

Objective: To explore the predictive value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) for the major pathologic response (MPR) in non-small cell lung cancer (NSCLC) patients receiving neoadjuvant immunotherapy. Methods: A total of 36 patients who received neoadjuvant immunotherapy monotherapy and 54 patients who received neoadjuvant immunotherapy combined with other treatments at the Cancer Hospital, Chinese Academy of Medical Sciences from April 2018 to February 2022 were enrolled in this study. Radiologists measured the standardized uptake value lean body mass (SUL), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor before and after neoadjuvant immunotherapy, and evaluated the treatment response in accordance with the PET Response Criteria in Solid Tumors (PERCIST). Pathologists assessed the pathologic response of the primary tumor. The expression level of programmed cell death-ligand 1 (PD-L1) was detected by immunohistochemistry, and the tumor mutational burden (TMB) level was detected by next-generation sequencing. Receiver operating characteristic (ROC) curves were used to evaluate the performance of PET-CT metabolic parameters (baseline, post-neoadjuvant immunotherapy, and percentage change), PERCIST, PD-L1 expression, and TMB in predicting MPR. Results: Among the 90 patients, 40 (44.4%) achieved MPR after neoadjuvant immunotherapy. Compared with the baseline, the SUL_max, SUL_peak, SUL_mean, MTV and TLG in the MPR group decreased after neoadjuvant immunotherapy (all P＜0.001), while no significant changes in SUL_max, SUL_peak, SUL_mean, MTV, and TLG were observed in the non-MPR group (all P＞0.05). ROC curve analysis showed that baseline PET-CT metabolic parameters had no predictive value for MPR in NSCLC after neoadjuvant immunotherapy, with the AUCs ranging from 0.504 to 0.619 (all P＞0.05). The AUCs of post-neoadjuvant PET-CT metabolic parameters for predicting MPR ranged from 0.757 to 0.927 (all P＜0.001). The AUCs of the percentage changes in PET-CT metabolic parameters before and after neoadjuvant immunotherapy for predicting MPR ranged from 0.848 to 0.976 (all P＜0.001). Among these metabolic parameters, the ΔSUL_max% exhibited the highest predictive performance, with an AUC of 0.976 (P＜0.001). When the optimal cutoff value of ΔSUL_max% was set at -33%, the sensitivity, specificity, and accuracy were 0.960, 0.975, and 0.967, respectively. The AUC of PERCIST for predicting MPR in NSCLC after neoadjuvant immunotherapy was 0.931 (95% CI: 0.881-0.981). The AUCs of PD-L1 expression and TMB for predicting MPR in NSCLC after neoadjuvant immunotherapy were 0.686 (95% CI: 0.562-0.810) and 0.693 (95% CI: 0.566-0.820), respectively. The AUCs of PET-CT metabolic parameters (post-neoadjuvant immunotherapy, percentage changes and PERCIST) for predicting MPR were superior than those of PD-L1 expression (all P＜0.05) and TMB (all P＜0.05). Conclusions: PET-CT metabolic parameters post neoadjuvant immunotherapy and the percentage changes of metabolic parameters before and after neoadjuvant immunotherapy along with PERCIST can predict MPR in NSCLC receiving neoadjuvant immunotherapy. Among these parameters, the ΔSUL_max% exhibited the highest predictive performance.