Developing and validating a novel metabolic tumor volume risk stratification system for supplementing non-small cell lung cancer staging
- 211 Downloads
We hypothesized that whole-body metabolic tumor volume (MTVwb) could be used to supplement non-small cell lung cancer (NSCLC) staging due to its independent prognostic value. The goal of this study was to develop and validate a novel MTVwb risk stratification system to supplement NSCLC staging.
We performed an IRB-approved retrospective review of 935 patients with NSCLC and FDG-avid tumor divided into modeling and validation cohorts based on the type of PET/CT scanner used for imaging. In addition, sensitivity analysis was conducted by dividing the patient population into two randomized cohorts. Cox regression and Kaplan-Meier survival analyses were performed to determine the prognostic value of the MTVwb risk stratification system.
The cut-off values (10.0, 53.4 and 155.0 mL) between the MTVwb quartiles of the modeling cohort were applied to both the modeling and validation cohorts to determine each patient’s MTVwb risk stratum. The survival analyses showed that a lower MTVwb risk stratum was associated with better overall survival (all p < 0.01), independent of TNM stage together with other clinical prognostic factors, and the discriminatory power of the MTVwb risk stratification system, as measured by Gönen and Heller’s concordance index, was not significantly different from that of TNM stage in both cohorts. Also, the prognostic value of the MTVwb risk stratum was robust in the two randomized cohorts. The discordance rate between the MTVwb risk stratum and TNM stage or substage was 45.1% in the modeling cohort and 50.3% in the validation cohort.
This study developed and validated a novel MTVwb risk stratification system, which has prognostic value independent of the TNM stage and other clinical prognostic factors in NSCLC, suggesting that it could be used for further NSCLC pretreatment assessment and for refining treatment decisions in individual patients.
KeywordsNon-small cell lung cancer Whole-body metabolic tumor volume Risk stratification TNM staging 18F-FDG PET/CT Tumor burden
We acknowledge the contributions of Kristen Wroblewski, MS, Department of Public Health Sciences, The University of Chicago, Chicago, IL, USA, for her statistical guidance; and Mark K. Ferguson, MD, Thoracic Surgery Service, The University of Chicago, Chicago, IL, USA, for constructive comments. This work was supported in part by a grant (R21 CA181885) from the National Cancer Institute of the National Institutes of Health. We particularly thank our chest oncological team at the University of Chicago for taking care of our study patients. The authors have not used writing assistance.
Guarantors of the integrity of the entire study: Yonglin Pu, James X. Zhang and Bill C. Penney.
Study concepts/study design, data acquisition and data analysis/interpretation: all authors.
Manuscript drafting and revision for important intellectual content: all authors.
Approval of final version of submitted manuscript: all authors.
Agreement to appropriately resolve any questions related to the work: all authors.
Literature research: Yonglin Pu and James X. Zhang.
Clinical studies: Daniel Appelbaum, Haiyan Liu and Yonglin Pu.
Statistical analysis: Yonglin Pu, Jianfeng Meng, and James X. Zhang.
Manuscript editing: all authors.
This work was supported in part by a grant (R21 CA181885) from the National Cancer Institute of the National Institutes of Health.
Compliance with ethical standards
This study was approved by our Institutional Review Board of the University of Chicago, which waived the requirement for informed consent, and all procedures were carried out in accordance with relevant guidelines and regulations.
The requirement for informed consent was waived.
- 1.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. https://doi.org/10.1016/j.jtho.2015.09.009.CrossRefPubMedPubMedCentralGoogle Scholar
- 2.Liao S, Penney BC, Wroblewski K, Zhang H, Simon CA, Kampalath R, et al. Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2012;39:27–38. https://doi.org/10.1007/s00259-011-1934-6.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Dashevsky BZ, Zhang C, Yan L, Yuan C, Xiong L, Liu Y, et.al. Whole body metabolic tumor volume is a prognostic marker in patients with newly diagnosed stage 3B non-small cell lung cancer, confirmed with external validation. European Journal of Hybrid Imaging EJNMMI Multimodality Journal. 2017;1:8. https://doi.org/10.1186/s41824-017-0013-z
- 13.Abelson JA, Murphy JD, Trakul N, Bazan JG, Maxim PG, Graves EE, et al. Metabolic imaging metrics correlate with survival in early stage lung cancer treated with stereotactic ablative radiotherapy. Lung Cancer. 2012;78:219–24. https://doi.org/10.1016/j.lungcan.2012.08.016.CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Yoo SW, Kim J, Chong A, Kwon SY, Min JJ, Song HC, et al. Metabolic tumor volume measured by F-18 FDG PET/CT can further stratify the prognosis of patients with stage IV non-small cell lung cancer. Nucl Med Mol Imaging. 2012;46:286–93. https://doi.org/10.1007/s13139-012-0165-5.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Ancestry.com. U.S., Social Security Death Index, 1935-2014. Provo, UT: Ancestry.com Operations Inc; 2014. https://search.ancestry.com/search/db.aspx?dbid=3693
- 20.Zhang C, Liao C, Penney BC, Appelbaum DE, Simon CA, Pu Y. Relationship between overall survival of patients with non-small cell lung cancer and whole-body metabolic tumor burden seen on postsurgical fluorodeoxyglucose PET images. Radiology. 2015;275:862–9. https://doi.org/10.1148/radiol.14141398.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Werner-Wasik M, Nelson AD, Choi W, Arai Y, Faulhaber PF, Kang P, et al. What is the best way to contour lung tumors on PET scans? Multiobserver validation of a gradient-based method using a NSCLC digital PET phantom. Int J Radiat Oncol Biol Phys. 2012;82:1164–71. https://doi.org/10.1016/j.ijrobp.2010.12.055.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Ramnath N, Dilling TJ, Harris LJ, Kim AW, Michaud GC, Balekian AA, et al. Treatment of stage III non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e314S–40S. https://doi.org/10.1378/chest.12-2360.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Obara PL, Wroblewski K, Zhang CP, Hou P, Jiang Y, Chen P, et al. Quantification of metabolic tumor activity and burden in patients with NSCLC: is manual adjustment of semi-automatic gradient based measurements necessary? Nucl Med Commun. 2015;36:782–9. https://doi.org/10.1097/MNM.0000000000000317.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Lee P, Bazan JG, Lavori PW, Weerasuriya DK, Quon A, Le QT, et al. Metabolic tumor volume is an independent prognostic factor in patients treated definitively for nonsmall-cell lung cancer. Clin Lung Cancer. 2012;13:52–8. https://doi.org/10.1016/j.cllc.2011.05.001.CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Hyun SH, Choi JY, Kim K, Kim J, Shim YM, Um SW, et al. Volume-based parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography improve outcome prediction in early-stage non-small cell lung cancer after surgical resection. Ann Surg. 2013;257:364–70. https://doi.org/10.1097/SLA.0b013e318262a6ec.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Carvalho S, Leijenaar RTH, Velazquez ER, Oberije C, Parmar C, Van Elmpt W, et al. Prognostic value of metabolic metrics extracted from baseline positron emission tomography images in non-small cell lung cancer. Acta Oncol. 2013;52:1398–404. https://doi.org/10.3109/0284186X.2013.812795.CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Liu H, Chen P, Wroblewski K, Hou P, Zhang C, Jiang Y, et al. Consistency of metabolic tumor volume of non-small-cell lung cancer primary tumor measured using 18F-FDG PET/CT at two different tracer uptake times. Nucl Med Commun. 2016;37:50–6. https://doi.org/10.1097/MNM.0000000000000396.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Cancer Trends Progress Report. National Cancer Institute, NIH, DHHS, Bethesda, MD, February 2018. https://progressreport.cancer.gov