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EJNMMI Research
Published in: EJNMMI Research 1/2020

01-12-2020 | NSCLC | Original research

PD-L1 expression correlation with metabolic parameters of FDG PET/CT and clinicopathological characteristics in non-small cell lung cancer

Authors: Xiaodong Wu, Yan Huang, Qingping Zhao, Lei Wang, Xiao Song, Yi Li, Lei Jiang

Published in: EJNMMI Research | Issue 1/2020

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Abstract

Background

Immunotherapy targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has shown promising results in non-small cell lung cancer (NSCLC) patients. Exploring PD-L1 expression could help to select NSCLC candidates for immunotherapy. Fluorine-18 fluorodeoxyglucose (FDG) PET/CT could provide phenotypic information on malignant tumors. Thus, this study investigated PD-L1 expression correlation with metabolic parameters of FDG PET/CT and clinicopathological characteristics in NSCLC.

Methods

FDG PET/CT metabolic parameters including maximum standard uptake (SUVmax), metabolic tumor volume and total lesion glycolysis of primary lesion (MTV-P, TLG-P), and combination of primary lesion and metastases (MTV-C, TLG-C) were compared with PD-L1-positive expression in patients with NSCLC. Moreover, clinicopathological characteristics, including age, gender, smoking history, serum tumor markers, tumor location, size, TNM stage, and genetic mutation were also reviewed.

Results

All 374 patients (215 men; 159 women; age 63 ± 9 years) included 283 adenocarcinomas (ACs) and 91 squamous cell carcinomas (SCCs). PD-L1 expression was positive in 27.8% (104/374) cases. SUVmax, TLG-P, and TLG-C of PD-L1 positivity were significantly higher than PD-L1 negativity. Moreover, PD-L1 expression was obviously correlated with man, smoking, and central NSCLC. If ACs and SCCs were separately analyzed, PD-L1 positivity in ACs and SCCs was 21.6% (61/283) and 47.5% (43/91), respectively, and only SUVmax was obviously associated with PD-L1 expression. Furthermore, multivariate analysis revealed that only SUVmax was an independent predictor of PD-L1 positive expression in overall NSCLC, AC, and SCC. Using a SUVmax cut-off value of 12.5, PD-L1 status of NSCLC was predicted by FDG PET/CT with sensitivity, specificity, and accuracy of 65.4%, 86.7%, and 80.7%, respectively.

Conclusions

PD-L1 expression of NSCLC was related to SUVmax, TLG, man, smoking, and central location. However, only SUVmax was an independent predictor of PD-L1 positivity, which could help to explore the existence of immune checkpoints.
Literature
1.
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.PubMedCrossRef
2.
3.
Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10:1243–60.CrossRefPubMed
4.
Travis WD, Brambilla E, Burke AP, et al. Introduction to the 2015 World Health Organization classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol. 2015;10:1240–2.PubMedCrossRef
5.
Chai T, Zhang P, Lin Y, et al. Postoperative adjuvant therapy for resectable early non-small cell lung cancer: A protocol for a systematic review and meta-analysis. Medicine (Baltimore). 2019;98:e16468.CrossRef
6.
Nagasaka M, Gadgeel SM. Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer. Expert Rev Anticancer Ther. 2018;18:63–70.PubMedCrossRef
7.
Garon EB, Hellmann MD, Rizvi NA, et al. Five-Year overall survival for patients with advanced nonsmall-cell lung cancer treated with pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J Clin Oncol. 2019:Jco1900934.
8.
9.
Brody R, Zhang Y, Ballas M, et al. PD-L1 expression in advanced NSCLC: insights into risk stratification and treatment selection from a systematic literature review. Lung Cancer. 2017;112:200–15.PubMedCrossRef
10.
Sgambato A, Casaluce F, Sacco PC, et al. Anti PD-1 and PDL-1 immunotherapy in the treatment of advanced non- small cell lung cancer (NSCLC): a review on toxicity profile and its management. Curr Drug Saf. 2016;11:62–8.PubMedCrossRef
11.
Rolfo C, Caglevic C, Santarpia M, et al. Immunotherapy in NSCLC: a promising and revolutionary weapon. Adv Exp Med Biol. 2017;995:97–125.PubMedCrossRef
12.
Jiang M, Sun D, Guo Y, et al. Assessing PD-L1 expression level by radiomic features from PET/CT in nonsmall cell lung cancer patients: an initial result. Acad Radiol. 2019;27:171–9.PubMedCrossRef
13.
Jadvar H, Alavi A, Gambhir SS. 18F-FDG uptake in lung, breast, and colon cancers: molecular biology correlates and disease characterization. J Nucl Med. 2009;50:1820–7.PubMedCrossRef
14.
Zhou X, Chen R, Xie W, et al. Relationship between 18F-FDG accumulation and lactate dehydrogenase a expression in lung adenocarcinomas. J Nucl Med. 2014;55:1766–71.PubMedCrossRef
15.
Arslan E, Cermik TF, Trabulus FDC, et al. Role of 18F-FDG PET/CT in evaluating molecular subtypes and clinicopathological features of primary breast cancer. Nucl Med Commun. 2018;39:680–90.PubMedCrossRef
16.
Lv Z, Fan J, Xu J, et al. Value of (18)F-FDG PET/CT for predicting EGFR mutations and positive ALK expression in patients with non-small cell lung cancer: a retrospective analysis of 849 Chinese patients. Eur J Nucl Med Mol Imaging. 2018;45:735–50.PubMedCrossRef
17.
Park HL, Yoo IR, Boo SH, et al. Does FDG PET/CT have a role in determining adjuvant chemotherapy in surgical margin-negative stage IA non-small cell lung cancer patients? J Cancer Res Clin Oncol. 2019;145:1021–6.PubMedCrossRef
18.
Takada K, Toyokawa G, Tagawa T, et al. Association between PD-L1 expression and metabolic activity on (18)F-FDG PET/CT in patients with small-sized lung cancer. Anticancer Res. 2017;37:7073–82.PubMed
19.
Zhang M, Wang D, Sun Q, et al. Prognostic significance of PD-L1 expression and (18)F-FDG PET/CT in surgical pulmonary squamous cell carcinoma. Oncotarget. 2017;8:51630–40.PubMedPubMedCentralCrossRef
20.
Takada K, Toyokawa G, Okamoto T, et al. Metabolic characteristics of programmed cell death-ligand 1-expressing lung cancer on (18) F-fluorodeoxyglucose positron emission tomography/computed tomography. Cancer Med. 2017;6:2552–61.PubMedPubMedCentralCrossRef
21.
Kaira K, Shimizu K, Kitahara S, et al. 2-Deoxy-2-[fluorine-18] fluoro-d-glucose uptake on positron emission tomography is associated with programmed death ligand-1 expression in patients with pulmonary adenocarcinoma. Eur J Cancer. 2018;101:181–90.PubMedCrossRef
22.
Wu X, Huang Y, Li Y, et al. (18)F-FDG PET/CT imaging in pulmonary sarcomatoid carcinoma and correlation with clinical and genetic findings. Ann Nucl Med. 2019;33:647–56.PubMedCrossRef
23.
Cheng G, Huang H. Prognostic value of (18)F-Fluorodeoxyglucose PET/computed tomography in non-small-cell lung cancer. PET Clin. 2018;13:59–72.PubMedCrossRef
24.
Anwar H, Vogl TJ, Abougabal MA, et al. The value of different (18)F-FDG PET/CT baseline parameters in risk stratification of stage I surgical NSCLC patients. Ann Nucl Med. 2018;32:687–94.PubMedCrossRef
25.
Chen R, Zhou X, Liu J, et al. Relationship between the expression of PD-1/PD-L1 and (18)F-FDG uptake in bladder cancer. Eur J Nucl Med Mol Imaging. 2019;46:848–54.PubMedCrossRef
26.
27.
Lin G, Fan X, Zhu W, et al. Prognostic significance of PD-L1 expression and tumor infiltrating lymphocyte in surgically resectable non-small cell lung cancer. Oncotarget. 2017;8:83986–94.PubMedPubMedCentralCrossRef
28.
Gandhi L, Garassino MC. Pembrolizumab plus chemotherapy in lung cancer. N Engl J Med. 2018;379:e18.PubMedCrossRef
29.
Miyazawa T, Marushima H, Saji H, et al. PD-L1 expression in non-small-cell lung cancer including various adenocarcinoma subtypes. Ann Thorac Cardiovasc Surg. 2019;25:1–9.PubMedCrossRef
30.
Yang CY, Lin MW, Chang YL, et al. Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes. Eur J Cancer. 2014;50:1361–9.PubMedCrossRef
31.
32.
Jreige M, Letovanec I, Chaba K, et al. (18)F-FDG PET metabolic-to-morphological volume ratio predicts PD-L1 tumour expression and response to PD-1 blockade in non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2019;46(9):1859–68.PubMedCrossRef
33.
34.
Pan ZK, Ye F, Wu X, et al. Clinicopathological and prognostic significance of programmed cell death ligand1 (PD-L1) expression in patients with non-small cell lung cancer: a meta-analysis. J Thorac Dis. 2015;7:462–70.PubMedPubMedCentral
35.
Toyokawa G, Takada K, Okamoto T, et al. Relevance between programmed death ligand 1 and radiologic invasiveness in pathologic stage i lung adenocarcinoma. Ann Thorac Surg. 2017;103:1750–7.PubMedCrossRef
36.
Takada K, Toyokawa G, Tagawa T, et al. PD-L1 expression according to the EGFR status in primary lung adenocarcinoma. Lung Cancer. 2018;116:1–6.PubMedCrossRef
37.
Azuma K, Ota K, Kawahara A, et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann Oncol. 2014;25:1935–40.PubMedCrossRef
38.
D'Incecco A, Andreozzi M, Ludovini V, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015;112:95–102.PubMedCrossRef
39.
Hirai A, Yoneda K, Shimajiri S, et al. Prognostic impact of programmed death-ligand 1 expression in correlation with human leukocyte antigen class I expression status in stage I adenocarcinoma of the lung. J Thorac Cardiovasc Surg. 2018;155:382–92.PubMedCrossRef
40.
Kim S, Koh J, Kwon D, et al. Comparative analysis of PD-L1 expression between primary and metastatic pulmonary adenocarcinomas. Eur J Cancer. 2017;75:141–9.PubMedCrossRef
41.
Mu CY, Huang JA, Chen Y, et al. High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol. 2011;28:682–8.PubMedCrossRef
42.
Zhou C, Che G, Zheng X, et al. Expression and clinical significance of PD-L1 and c-Myc in non-small cell lung cancer. J Cancer Res Clin Oncol. 2019;145:2663–74.PubMedCrossRef
43.
Sumitomo R, Hirai T, Fujita M, et al. PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer. Lung Cancer. 2019;136:136–44.PubMedCrossRef
44.
Dosani M, Yang R, McLay M, et al. Metabolic tumour volume is prognostic in patients with non-small-cell lung cancer treated with stereotactic ablative radiotherapy. Curr Oncol. 2019;26:e57–63.PubMedPubMedCentralCrossRef
45.
Metadata
Title
PD-L1 expression correlation with metabolic parameters of FDG PET/CT and clinicopathological characteristics in non-small cell lung cancer
Authors
Xiaodong Wu
Yan Huang
Qingping Zhao
Lei Wang
Xiao Song
Yi Li
Lei Jiang
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Keywords
NSCLC
NSCLC
Published in
EJNMMI Research / Issue 1/2020
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-020-00639-9

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