Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Nuclear Medicine
Published in: Annals of Nuclear Medicine 3/2022

01-03-2022 | Lung Cancer | Original Article

Tumor glycolytic heterogeneity improves detection of regional nodal metastasis in patients with lung adenocarcinoma

Authors: Kun-Han Lue, Sung-Chao Chu, Ling-Yi Wang, Yen-Chang Chen, Ming-Hsun Li, Bee-Song Chang, Sheng-Chieh Chan, Yu-Hung Chen, Chih-Bin Lin, Shu-Hsin Liu

Published in: Annals of Nuclear Medicine | Issue 3/2022

Login to get access

Abstract

Objective

The diagnostic performance of 18F-FDG PET for detecting regional lymph node metastasis in resectable lung cancer is variable, and its sensitivity for adenocarcinoma is even lower. We aimed to evaluate the value of 18F-FDG PET-derived features in predicting pathological lymph node metastasis in patients with lung adenocarcinoma.

Methods

We retrospectively analyzed pretreatment 18F-FDG PET-derived features of 126 lung adenocarcinoma patients who underwent curative surgery. A logistic regression model was used to analyze the association between study variables and pathological regional lymph node status obtained from the curative surgery. Furthermore, Cox regression analysis was used to test the effect of the study variables on survival outcomes, including disease-free survival (DFS) and overall survival (OS).

Results

The primary tumor entropy (OR = 1.7, p = 0.014) and visual interpretation of regional nodes via 18F-FDG PET (OR = 2.5, p = 0.026) independently predicted pathological regional lymph node metastasis. The areas under the receiver-operating-characteristic curves were 0.631, 0.671, and 0.711 for visual interpretation, primary tumor entropy, and their combination, respectively. Based on visual interpretation, a primary tumor entropy ≥ 3.0 improved the positive predictive value of positive visual interpretation from 51.2% to 63.0%, whereas an entropy < 3.0 improved the negative predictive value of negative visual interpretation from 75.3% to 82.6%. In cases with positive visual interpretation and low entropy, or negative visual interpretation and high entropy, the nodal metastasis rates were approximately 30%. In the survival analyses, the primary tumor entropy was also independently associated with DFS (HR = 2.7, p = 0.001) and OS (HR = 4.8, p = 0.001).

Conclusions

Our preliminary results show that the primary tumor entropy may improve 18F-FDG PET visual interpretation in predicting pathological nodal metastasis in lung adenocarcinoma, and may also show a survival prognostic value. This versatile biomarker may facilitate tailored therapeutic strategies for patients with resectable lung adenocarcinoma.
Appendix
Available only for authorised users
Literature
1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.
2.
3.
Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, et al. 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. J Thorac Oncol. 2016;11:39–51.PubMed
4.
Asamura H, Chansky K, Crowley J, Goldstraw P, Rusch VW, Vansteenkiste JF, et al. The international association for the study of lung cancer lung cancer staging project: proposals for the revision of the N descriptors in the forthcoming 8th edition of the TNM classification for lung cancer. J Thorac Oncol. 2015;10:1675–84.PubMed
5.
Zhang Y, Hu X, Liu D, Wang R, Sun X, Peng Z, et al. Effectiveness of neoadjuvant chemotherapy on the survival outcomes of patients with resectable non-small-cell lung cancer: a meta-analysis of randomized controlled trials. Surg Oncol. 2021;38:101590.PubMed
6.
Birim O, Kappetein AP, Stijnen T, Bogers AJ. Meta-analysis of positron emission tomographic and computed tomographic imaging in detecting mediastinal lymph node metastases in nonsmall cell lung cancer. Ann Thorac Surg. 2005;79:375–82.PubMed
7.
Gomez-Caro A, Boada M, Cabanas M, Sanchez M, Arguis P, Lomena F, et al. False-negative rate after positron emission tomography/computer tomography scan for mediastinal staging in cI stage non-small-cell lung cancer. Eur J Cardiothorac Surg. 2012;42:93–100 (discussion 100).PubMed
8.
Bille A, Pelosi E, Skanjeti A, Arena V, Errico L, Borasio P, et al. Preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer: accuracy of integrated positron emission tomography and computed tomography. Eur J Cardiothorac Surg. 2009;36:440–5.PubMed
9.
Bille A, Okiror L, Skanjeti A, Errico L, Arena V, Penna D, et al. Evaluation of integrated positron emission tomography and computed tomography accuracy in detecting lymph node metastasis in patients with adenocarcinoma vs squamous cell carcinoma. Eur J Cardiothorac Surg. 2013;43:574–9.PubMed
10.
Schmidt-Hansen M, Baldwin DR, Hasler E, Zamora J, Abraira V, Roque IFM. PET-CT for assessing mediastinal lymph node involvement in patients with suspected resectable non-small cell lung cancer. Cochrane Database Syst Rev. 2014;2014:CD009519.PubMedCentral
11.
Serra Fortuny M, Gallego M, Berna L, Monton C, Vigil L, Masdeu MJ, et al. FDG-PET parameters predicting mediastinal malignancy in lung cancer. BMC Pulm Med. 2016;16:177.PubMedPubMedCentral
12.
Ouyang ML, Tang K, Xu MM, Lin J, Li TC, Zheng XW. Prediction of occult lymph node metastasis using tumor-to-blood standardized uptake ratio and metabolic parameters in clinical N0 lung adenocarcinoma. Clin Nucl Med. 2018;43:715–20.PubMed
13.
Ouyang ML, Xia HW, Xu MM, Lin J, Wang LL, Zheng XW, et al. Prediction of occult lymph node metastasis using SUV, volumetric parameters and intratumoral heterogeneity of the primary tumor in T1–2N0M0 lung cancer patients staged by PET/CT. Ann Nucl Med. 2019;33:671–80.PubMed
14.
Han S, Woo S, Suh CH, Kim YJ, Oh JS, Lee JJ. A systematic review of the prognostic value of texture analysis in 18F-FDG PET in lung cancer. Ann Nucl Med. 2018;32:602–10.PubMed
15.
Park S, Ha S, Lee SH, Paeng JC, Keam B, Kim TM, et al. Intratumoral heterogeneity characterized by pretreatment PET in non-small cell lung cancer patients predicts progression-free survival on EGFR tyrosine kinase inhibitor. PLoS ONE. 2018;13:e0189766.PubMedPubMedCentral
16.
Chen YH, Wang TF, Chu SC, Lin CB, Wang LY, Lue KH, et al. Incorporating radiomic feature of pretreatment 18F-FDG PET improves survival stratification in patients with EGFR-mutated lung adenocarcinoma. PLoS ONE. 2020;15:e0244502.PubMedPubMedCentral
17.
Caswell DR, Swanton C. The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome. BMC Med. 2017;15:133.PubMedPubMedCentral
18.
Detterbeck FC, Chansky K, Groome P, Bolejack V, Crowley J, Shemanski L, et al. The IASLC lung cancer staging project: methodology and validation used in the development of proposals for revision of the stage classification of NSCLC in the forthcoming (eighth) edition of the TNM classification of lung cancer. J Thorac Oncol. 2016;11:1433–46.PubMed
19.
Kim YK, Lee KS, Kim BT, Choi JY, Kim H, Kwon OJ, et al. Mediastinal nodal staging of nonsmall cell lung cancer using integrated 18F-FDG PET/CT in a tuberculosis-endemic country: diagnostic efficacy in 674 patients. Cancer. 2007;109:1068–77.PubMed
20.
Kim BT, Lee KS, Shim SS, Choi JY, Kwon OJ, Kim H, et al. Stage T1 non-small cell lung cancer: preoperative mediastinal nodal staging with integrated FDG PET/CT–a prospective study. Radiology. 2006;241:501–9.PubMed
21.
Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.PubMed
22.
Chen YH, Chu SC, Wang LY, Wang TF, Lue KH, Lin CB, et al. Prognostic value of combing primary tumor and nodal glycolytic-volumetric parameters of 18F-FDG PET in patients with non-small cell lung cancer and regional lymph node metastasis. Diagnostics (Basel). 2021;11:1065.
23.
Traverso A, Wee L, Dekker A, Gillies R. Repeatability and reproducibility of radiomic features: a systematic review. Int J Radiat Oncol Biol Phys. 2018;102:1143–58.PubMedPubMedCentral
24.
Desseroit MC, Tixier F, Weber WA, Siegel BA, Cheze Le Rest C, Visvikis D, et al. Reliability of PET/CT shape and heterogeneity features in functional and morphologic components of non-small cell lung cancer tumors: a repeatability analysis in a prospective multicenter cohort. J Nucl Med. 2017;58:406–11.PubMedPubMedCentral
25.
Oliver JA, Budzevich M, Zhang GG, Dilling TJ, Latifi K, Moros EG. Variability of image features computed from conventional and respiratory-gated PET/CT images of lung cancer. Transl Oncol. 2015;8:524–34.PubMedPubMedCentral
26.
Xu H, Lv W, Zhang H, Ma J, Zhao P, Lu L. Evaluation and optimization of radiomics features stability to respiratory motion in 18F-FDG 3D PET imaging. Med Phys. 2021;48:5165–78.PubMed
27.
van Griethuysen JJM, Fedorov A, Parmar C, Hosny A, Aucoin N, Narayan V, et al. Computational radiomics system to decode the radiographic phenotype. Cancer Res. 2017;77:e104–7.PubMedPubMedCentral
28.
Zwanenburg A, Vallieres M, Abdalah MA, Aerts HJ, Andrearczyk V, Apte A, et al. The image biomarker standardization initiative: standardized quantitative radiomics for high-throughput image-based phenotyping. Radiology. 2020;295:328–38.CrossRef
29.
Polley MC, Dignam JJ. Statistical considerations in the evaluation of continuous biomarkers. J Nucl Med. 2021;62:605–11.PubMedPubMedCentral
30.
Zwanenburg A. Radiomics in nuclear medicine: robustness, reproducibility, standardization, and how to avoid data analysis traps and replication crisis. Eur J Nucl Med Mol Imaging. 2019;46:2638–55.PubMed
31.
Okour M, Jacobson PA, Israni A, Brundage RC. Comparative evaluation of median versus Youden index dichotomization methods: exposure-response analysis of mycophenolic acid and acyl-glucuronide metabolite. Eur J Drug Metab Pharmacokinet. 2019;44:629–38.PubMedPubMedCentral
32.
Aragaki M, Kato T, Fujiwara-Kuroda A, Hida Y, Kaga K, Wakasa S. Preoperative identification of clinicopathological prognostic factors for relapse-free survival in clinical N1 non-small cell lung cancer: a retrospective single center-based study. J Cardiothorac Surg. 2020;15:229.PubMedPubMedCentral
33.
Turajlic S, Swanton C. Metastasis as an evolutionary process. Science. 2016;352:169–75.PubMed
34.
Caswell DR, Chuang CH, Yang D, Chiou SH, Cheemalavagu S, Kim-Kiselak C, et al. Obligate progression precedes lung adenocarcinoma dissemination. Cancer Discov. 2014;4:781–9.PubMedPubMedCentral
35.
Moon SH, Kim J, Joung JG, Cha H, Park WY, Ahn JS, et al. Correlations between metabolic texture features, genetic heterogeneity, and mutation burden in patients with lung cancer. Eur J Nucl Med Mol Imaging. 2019;46:446–54.PubMed
36.
Kim G, Kim J, Cha H, Park WY, Ahn JS, Ahn MJ, et al. Metabolic radiogenomics in lung cancer: associations between FDG PET image features and oncogenic signaling pathway alterations. Sci Rep. 2020;10:13231.PubMedPubMedCentral
37.
Sellitto A, Pecoraro G, Giurato G, Nassa G, Rizzo F, Saggese P, et al. Regulation of metabolic reprogramming by long non-coding RNAs in cancer. Cancers (Basel). 2021;13:3485.
38.
39.
Chiu LC, Lin SM, Lo YL, Kuo SC, Yang CT, Hsu PC. Immunotherapy and vaccination in surgically resectable non-small cell lung cancer (NSCLC). Vaccines (Basel). 2021;9:689.PubMedCentral
40.
Shukla N, Hanna N. Neoadjuvant and adjuvant immunotherapy in early-stage non-small cell lung cancer. Lung Cancer (Auckl). 2021;12:51–60.
41.
Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Wei YC, et al. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1–N2) EGFR-mutant NSCLC: final overall survival analysis of CTONG1104 phase III trial. J Clin Oncol. 2021;39:713–22.PubMed
42.
Provencio M, Nadal E, Insa A, Garcia-Campelo MR, Casal-Rubio J, Domine M, et al. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020;21:1413–22.PubMed
43.
van Velden FH, Kramer GM, Frings V, Nissen IA, Mulder ER, de Langen AJ, et al. Repeatability of radiomic features in non-small-cell lung cancer [(18)F]FDG-PET/CT studies: impact of reconstruction and delineation. Mol Imaging Biol. 2016;18:788–95.PubMedPubMedCentral
44.
Konert T, Everitt S, La Fontaine MD, van de Kamer JB, MacManus MP, Vogel WV, et al. Robust, independent and relevant prognostic 18F-fluorodeoxyglucose positron emission tomography radiomics features in non-small cell lung cancer: are there any? PLoS ONE. 2020;15:e0228793.PubMedPubMedCentral
45.
Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med. 2007;48:932–45.PubMed
Metadata
Title
Tumor glycolytic heterogeneity improves detection of regional nodal metastasis in patients with lung adenocarcinoma
Authors
Kun-Han Lue
Sung-Chao Chu
Ling-Yi Wang
Yen-Chang Chen
Ming-Hsun Li
Bee-Song Chang
Sheng-Chieh Chan
Yu-Hung Chen
Chih-Bin Lin
Shu-Hsin Liu
Publication date
01-03-2022
Publisher
Springer Singapore
Published in
Annals of Nuclear Medicine / Issue 3/2022
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-021-01698-1

Other articles of this Issue 3/2022

Annals of Nuclear Medicine 3/2022 Go to the issue

Original Article

Detection efficacy of PET/CT with 18F-FSU-880 in patients with suspected recurrent prostate cancer: a prospective single-center study

Original Article

A design of forceps-type coincidence radiation detector for intraoperative LN diagnosis: clinical impact estimated from LNs data of 20 esophageal cancer patients

Original Article

I-124 PET/CT image-based dosimetry in patients with differentiated thyroid cancer treated with I-131: correlation of patient-specific lesional dosimetry to treatment response

Original Article

Dual time point imaging of staging PSMA PET/CT quantification; spread and radiomic analyses

Short Communication

Development of a novel Indium-111 radiolabeled mogamulizumab targeting CCR4 for imaging adult T-cell leukemia/lymphoma in vivo

Original Article

Serial change in perfusion–metabolism mismatch after coronary artery bypass grafting