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Patlak-Ki derived from ultra-high sensitivity dynamic total body [18F]FDG PET/CT correlates with the response to induction immuno-chemotherapy in locally advanced non-small cell lung cancer patients

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Abstract

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 [18F]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 [18F]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 (SUVmax), 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 [18F]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.

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Data availability

The datasets are available from the corresponding authors on reasonable request.

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Funding

This study was supported by the National Natural Science Foundation of China (Grant Number 82073328).

Author information

Author notes

  1. DaQuan Wang, Bo Qiu, QianWen Liu, LiangPing Xia and SongRan Liu are authors contributed equally to the study.

Authors and Affiliations

  1. Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China

    DaQuan Wang, Bo Qiu, ShiYang Zheng, NaiBin Chen, FangJie Liu, Rui Zhou, JinYu Guo & Hui Liu

  2. Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China

    QianWen Liu

  3. Department of VIP, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China

    LiangPing Xia

  4. Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China

    SongRan Liu & Jia Fu

  5. United Imaging Healthcare, Shanghai, China

    ChaoJie Zheng & Hui Liu

  6. Department of Nuclear Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China

    YiWen Mo, Xu Zhang, YingYing Hu & Wei Fan

  7. SuZhou TongDiao Company, Suzhou, China

    Yin Zhou

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  1. DaQuan Wang
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  2. Bo Qiu
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Contributions

HL, WF, DQW and BQ contributed to the study conception and design. All authors contributed to the patient recruitment, data collection and interpretation. HL, DQW, CJZ and SRL contributed to the data analysis, manuscript draft, review and editing. All the other authors were involved in patient recruitment and data curation. All authors contributed to the development of the article and approved the final version.

Corresponding authors

Correspondence to Wei Fan or Hui Liu.

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Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the institutional Ethics Committee(20201126/A2020-011).

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Written informed consent was obtained from all individual participants included in the study.

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The authors have no potential conflicts of interest to disclose.

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Wang, D., Qiu, B., Liu, Q. et al. Patlak-Ki derived from ultra-high sensitivity dynamic total body [18F]FDG PET/CT correlates with the response to induction immuno-chemotherapy in locally advanced non-small cell lung cancer patients. Eur J Nucl Med Mol Imaging 50, 3400–3413 (2023). https://doi.org/10.1007/s00259-023-06298-x

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