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Objective: The study aims to investigate the role of dynamic [ 18 F]FDG PET/CT imaging by high-sensitivity PET/CT scanner for assessing patients with locally advanced non-small cell lung cancer (LA-NSCLC) who undergo induction immuno-chemotherapy, followed by concurrent hypo-fractionated chemoradiotherapy (hypo-CCRT) and consolidative immunotherapy., Methods: Patients with unresectable LA-NSCLC are prospectively recruited. Dynamic [ 18 F]FDG PET/CT scans are conducted at four timepoints: before treatment (Baseline), after induction immuno-chemotherapy (Post-IC), during hypo-CCRT (Mid-hypo-CCRT) and after hypo-CCRT (Post-hypo-CCRT). The primary lung tumors (PTs) are manually delineated, and the metabolic features, including the Patlak-Ki (Ki), maximum SUV (SUV max ), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been evaluated. The expressions of CD3, CD8, CD68, CD163, CD34 and Ki67 in primary lung tumors at baseline are assayed by immunohistochemistry. The levels of blood lymphocytes at four timepoints are analyzed with flow cytometry., Results: Fifteen LA-NSCLC patients are enrolled between December 2020 and December 2022. Baseline Ki of primary tumor yields the highest AUC values of 0.722 and 0.796 for predicting disease progression and patient death, respectively. Patients are classified into the High FDG Ki group (n = 8, Ki > 2.779 ml/min/100 g) and the Low FDG Ki group (n = 7, Ki ≤ 2.779 ml/min/100 g). The High FDG Ki group presents better progression-free survival (P = 0.01) and overall survival (P = 0.025). The High FDG Ki group exhibits more significant reductions in Ki after hypo-CCRT compared to the Low FDG Ki group. Patients with a reduction in Ki > 73.1% exhibit better progression-free survival than those with a reduction ≤ 73.1% in Ki (median: not reached vs. 7.33 months, P = 0.12). The levels of CD3 + T cells (P = 0.003), CD8 + T cells (P = 0.002), CD68 + macrophages (P = 0.071) and CD163 + macrophages (P = 0.012) in primary tumor tissues are higher in the High FDG Ki group. The High FDG Ki group has higher CD3 + CD8 + lymphocytes in blood at baseline (P = 0.108), post-IC (P = 0.023) and post-hypo-CCRT (P = 0.041) than the Low FDG Ki group., Conclusions: The metabolic features in the High FDG Ki group significantly decrease during the treatment, particularly after induction immuno-chemotherapy. The Ki value of primary tumor shows significant relationship with the treatment response and survival in LA-NSCLC patients by the combined immuno-chemoradiotherapy regimen., Trial Registration: ClinicalTrials.gov. NCT04654234. Registered 4 December 2020., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aimed to investigate the predictive value of metabolic features in response to induction immuno-chemotherapy in patients with locally advanced non-small cell cancer (LA-NSCLC), using ultra-high sensitivity dynamic total body [ 18 F]FDG PET/CT., Methods: The study analyzed LA-NSCLC patients who received two cycles of induction immuno-chemotherapy and underwent a 60-min dynamic total body [ 18 F]FDG PET/CT scan before treatment. The primary tumors (PTs) were manually delineated, and their metabolic features, including the Patlak-Ki, Patlak-Intercept, maximum SUV (SUV max ), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were evaluated. The overall response rate (ORR) to induction immuno-chemotherapy was evaluated according to RECIST 1.1 criteria. The Patlak-Ki of PTs was calculated from the 20-60 min frames using the Patlak graphical analysis. The best feature was selected using Laplacian feature importance scores, and an unsupervised K-Means method was applied to cluster patients. ROC curve was used to examine the effect of selected metabolic feature in predicting tumor response to treatment. The targeted next generation sequencing on 1021 genes was conducted. The expressions of CD68, CD86, CD163, CD206, CD33, CD34, Ki67 and VEGFA were assayed through immunohistochemistry. The independent samples t test and the Mann-Whitney U test were applied in the intergroup comparison. Statistical significance was considered at P < 0.05., Results: Thirty-seven LA-NSCLC patients were analyzed between September 2020 and November 2021. All patients received two cycles of induction chemotherapy combined with Nivolumab/ Camrelizumab. The Laplacian scores showed that the Patlak-Ki of PTs had the highest importance for patient clustering, and the unsupervised K-Means derived decision boundary of Patlak-Ki was 2.779 ml/min/100 g. Patients were categorized into two groups based on their Patlak-Ki values: high FDG Patlak-Ki (H-FDG-Ki, Patlak-Ki > 2.779 ml/min/100 g) group (n = 23) and low FDG Patlak-Ki (L-FDG-Ki, Patlak-Ki ≤ 2.779 ml/min/100 g) group (n = 14). The ORR to induction immuno-chemotherapy was 67.6% (25/37) in the whole cohort, with 87% (20/23) in H-FDG-Ki group and 35.7% (5/14) in L-FDG-Ki group (P = 0.001). The sensitivity and specificity of Patlak-Ki in predicting the treatment response were 80% and 75%, respectively [AUC = 0.775 (95%CI 0.605-0.945)]. The expression of CD3 + /CD8 + T cells and CD86 + /CD163 + /CD206 + macrophages were higher in the H-FDG-Ki group, while Ki67, CD33 + myeloid cells, CD34 + micro-vessel density (MVD) and tumor mutation burden (TMB) were comparable between the two groups., Conclusions: The total body [ 18 F]FDG PET/CT scanner performed a dynamic acquisition of the entire body and clustered LA-NSCLC patients into H-FDG-Ki and L-FDG-Ki groups based on the Patlak-Ki. Patients with H-FDG-Ki demonstrated better response to induction immuno-chemotherapy and higher levels of immune cell infiltration in the PTs compared to those with L-FDG-Ki. Further studies with a larger patient cohort are required to validate these findings., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aimed to quantitatively assess [ 18 F]FDG uptake in primary tumor (PT) and metastatic lymph node (mLN) in newly diagnosed non-small cell lung cancer (NSCLC) using the total-body [ 18 F]FDG PET/CT and to characterize the dynamic metabolic heterogeneity of NSCLC., Methods: The 60-min dynamic total-body [ 18 F]FDG PET/CT was performed before treatment. The PTs and mLNs were manually delineated. An unsupervised K-means classification method was used to cluster patients based on the imaging features of PTs. The metabolic features, including Patlak-Ki, Patlak-Intercept, SUV mean , metabolic tumor volume (MTV), total lesion glycolysis (TLG), and textural features, were extracted from PTs and mLNs. The targeted next-generation sequencing of tumor-associated genes was performed. The expression of Ki67, CD3, CD8, CD34, CD68, and CD163 in PTs was determined by immunohistochemistry., Results: A total of 30 patients with stage IIIA-IV NSCLC were enrolled. Patients were divided into fast dynamic FDG metabolic group (F-DFM) and slow dynamic FDG metabolic group (S-DFM) by the unsupervised K-means classification of PTs. The F-DFM group showed significantly higher Patlak-Ki (P < 0.001) and SUV mean (P < 0.001) of PTs compared with the S-DFM group, while no significant difference was observed in Patlak-Ki and SUV mean of mLNs between the two groups. The texture analysis indicated that PTs in the S-DFM group were more heterogeneous in FDG uptake than those in the F-DFM group. Higher T cells (CD3 + /CD8 + ) and macrophages (CD68 + /CD163 + ) infiltration in the PTs were observed in the F-DFM group. No significant difference was observed in tumor mutational burden between the two groups., Conclusion: The dynamic total-body [ 18 F]FDG PET/CT stratified NSCLC patients into the F-DFM and S-DFM groups, based on Patlak-Ki and SUV mean of PTs. PTs in the F-DFM group seemed to be more homogenous in terms of [ 18 F]FDG uptake than those in the S-DFM group. The higher infiltrations of T cells and macrophages were observed in the F-DFM group, which suggested a potential benefit from immunotherapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)