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      Dynamic FDG-PET imaging for differentiating metastatic from non-metastatic lymph nodes of lung cancer

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          Abstract

          Objectives

          18F-fluorodeoxyglucose (FDG) PET/CT has been widely used in tumor diagnosis, staging, and response evaluation. To determine an optimal therapeutic strategy for lung cancer patients, accurate staging is essential. Semi-quantitative standardized uptake value (SUV) is known to be affected by multiple factors and may fail to differentiate between benign and malignant lesions. Lymph nodes (LNs) in the mediastinal and pulmonary hilar regions with high FDG uptake due to granulomatous lesions such as tuberculosis, which has a high prevalence in China, pose a diagnostic challenge. This study aims to evaluate the diagnostic value of the quantitative metabolic parameters derived from dynamic 18F-FDG PET/CT in differentiating metastatic and non-metastatic LNs in lung cancer.

          Methods

          One hundred and eight patients with pulmonary nodules were enrolled to perform 18F-FDG PET/CT dynamic + static imaging with informed consent. One hundred and thirty-five LNs in 29 lung cancer patients were confirmed by pathology. Static image analysis parameters including LN-SUVmax, LN-SUVmax/primary tumor SUVmax (LN-SUVmax/PT-SUVmax), mediastinal blood pool SUVmax (MBP-SUVmax), LN-SUVmax/MBP-SUVmax, and LN-SUVmax/short diameter. Quantitative parameters including K 1, k 2, k 3 and K i and of each LN were obtained by applying the irreversible two-tissue compartment model using in-house Matlab software. K i/K 1 was computed subsequently as a separate marker. We further divided the LNs into mediastinal LNs ( N=82) and pulmonary hilar LNs ( N=53). Wilcoxon rank-sum test or Independent-samples T-test and receiver-operating characteristic (ROC) analysis was performed on each parameter to compare the diagnostic efficacy in differentiating lymph node metastases from inflammatory uptake. P<0.05 were considered statistically significant.

          Results

          Among the 135 FDG-avid LNs confirmed by pathology, 49 LNs were non-metastatic, and 86 LNs were metastatic. LN-SUVmax, MBP-SUVmax, LN-SUVmax/MBP-SUVmax, and LN-SUVmax/short diameter couldn’t well differentiate metastatic from non-metastatic LNs ( P>0.05). However, LN-SUVmax/PT-SUVmax have good performance in the differential diagnosis of non-metastatic and metastatic LNs ( P=0.039). Dynamic metabolic parameters in addition to k 3, the parameters including K 1, k 2, K i, and K i/K 1, on the other hand, have good performance in the differential diagnosis of metastatic and non-metastatic LNs ( P=0.045, P=0.001, P=0.001, P=0.001, respectively). For ROC analysis, the metabolic parameters K i (AUC of 0.672 [0.579-0.765], sensitivity 0.395, specificity 0.918) and K i/K 1 (AUC of 0.673 [0.580-0.767], sensitivity 0.570, specificity 0.776) have good performance in the differential diagnosis of metastatic from non-metastatic LNs than SUVmax (AUC of 0.596 [0.498-0.696], sensitivity 0.826, specificity 0.388), included the mediastinal region and pulmonary hilar region.

          Conclusion

          Compared with SUVmax, quantitative parameters such as K 1, k 2, K i and K i/K 1 showed promising results for differentiation of metastatic and non-metastatic LNs with high uptake. The K i and K i/K 1 had a high differential diagnostic value both in the mediastinal region and pulmonary hilar region.

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          Most cited references51

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          Cancer statistics, 2022

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.
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            The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer.

            The IASLC Staging and Prognostic Factors Committee has collected a new database of 94,708 cases donated from 35 sources in 16 countries around the globe. This has now been analysed by our statistical partners at Cancer Research And Biostatistics and, in close collaboration with the members of the committee proposals have been developed for the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published late 2016. In this publication we describe the methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition.
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              NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2021.

              The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                10 November 2022
                2022
                : 12
                : 1005924
                Affiliations
                [1] 1 Department of Nuclear Medicine, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Shenzhen, China
                [2] 2 Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences , Shenzhen, China
                [3] 3 Shenzhen Middle School , Shenzhen, China
                Author notes

                Edited by: Rocco Trisolini, Agostino Gemelli University Polyclinic (IRCCS), Italy

                Reviewed by: Fiori Alite, Geisinger Commonwealth School of Medicine, United States; Franca Chierichetti, Azienda Provinciale per i Servizi Sanitari (APSS), Italy

                *Correspondence: Ying Liang, liangy_2000@ 123456sina.com ; Tao Sun, tao.sun@ 123456siat.ac.cn

                †These authors have contributed equally to this work

                This article was submitted to Cancer Imaging and Image-directed Interventions, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.1005924
                9686335
                36439506
                d3150995-9900-4431-863c-4fb2b0cf3d6f
                Copyright © 2022 Wumener, Zhang, Wang, Zhang, Zang, Huang, Liu, Huang, Huang, Wang, Liang and Sun

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 July 2022
                : 25 October 2022
                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 51, Pages: 11, Words: 4684
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                dynamic imaging,pet/ct, 18f-fdg,lung cancer,lymph node
                Oncology & Radiotherapy
                dynamic imaging, pet/ct, 18f-fdg, lung cancer, lymph node

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