Developing and validating a novel metabolic tumor volume risk stratification system for supplementing non-small cell lung cancer staging
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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.
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