Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer
- 2k Downloads
The objective of this study was to assess the prognostic value of metabolic tumor burden on 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography (PET)/CT measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG), independent of Union Internationale Contra la Cancrum (UICC)/American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) stage, in comparison with that of standardized uptake value (SUV) in nonsurgical patients with non-small cell lung cancer (NSCLC).
This study retrospectively reviewed 169 consecutive nonsurgical patients (78 men, 91 women, median age of 68 years) with newly diagnosed NSCLC who had pretreatment 18F-FDG PET/CT scans. The 18F-FDG PET/CT scans were performed in accordance with National Cancer Institute guidelines. The MTV of whole-body tumor (MTVWB), of primary tumor (MTVT), of nodal metastases (MTVN), and of distant metastases (MTVM); the TLG of whole-body tumor (TLGWB), of primary tumor (TLGT), of nodal metastases (TLGN), and of distant metastases (TLGM); the SUVmax of whole-body tumor (SUVmaxWB), of primary tumor (SUVmaxT), of nodal metastases (SUVmaxN), and of distant metastases (SUVmaxM) as well as the SUVmean of whole-body tumor (SUVmeanWB), of primary tumor (SUVmeanT), of nodal metastases (SUVmeanN), and of distant metastases (SUVmeanM) were measured with the PETedge tool on a MIMvista workstation with manual adjustment. The median follow-up among survivors was 35 months from the PET/CT (range 2–82 months). Statistical methods included Kaplan-Meier curves, Cox regression, and C-statistics.
There were a total of 139 deaths during follow-up. Median overall survival (OS) was 10.9 months [95% confidence interval (CI) 9.0–13.2 months]. The MTV was statistically associated with OS. The hazard ratios (HR) for 1 unit increase of ln(MTVWB), √(MTVT), √(MTVN), and √(MTVM) before/after adjusting for stage were: 1.47/1.43 (p < 0.001/<0.001), 1.06/1.05 (p < 0.001/<0.001), 1.11/1.10 (p < 0.001/<0.001), and 1.04/1.03 (p = 0.007/0.043), respectively. TLG had statistically significant associations with OS with the HRs for 1 unit increase in ln(TLGWB), √(TLGT), √(TLGN), and √(TLGM) before/after adjusting for stage being 1.36/1.33 (p < 0.001/<0.001), 1.02/1.02 (p = 0.001/0.002), 1.05/1.04 (p < 0.001/<0.001), and 1.02/1.02 (p = 0.003/0.024), respectively. The ln(SUVmaxWB) and √(SUVmaxN) were statistically associated with OS with the corresponding HRs for a 1 unit increase before/after adjusting for stage being 1.46/1.43 (p = 0.013/0.024) and 1.22/1.16 (p = 0.002/0.040). The √(SUVmeanN) was statistically associated with OS before and after adjusting for stage with HRs for a 1 unit increase of 1.32 (p < 0.001) and 1.24 (p = 0.015), respectively. The √(SUVmeanM) and √(SUVmaxM) were statistically associated with OS before adjusting for stage with HRs for a 1 unit increase of 1.26 (p = 0.017) and 1.18 (p = 0.007), respectively, but not after adjusting for stage (p = 0.127 and 0.056). There was no statistically significant association between OS and √(SUVmaxT), ln(SUVmeanWB), or √(SUVmeanT). There was low interobserver variability among three radiologists with intraclass correlation coefficients (ICC) greater than 0.94 for SUVmaxWB, ln(MTVWB), and ln(TLGWB). Interobserver variability was higher for SUVmeanWB with an ICC of 0.806.
Baseline metabolic tumor burdens at the level of whole-body tumor, primary tumor, nodal metastasis, and distant metastasis as measured with MTV and TLG on FDG PET are prognostic measures independent of clinical stage with low inter-observer variability and may be used to further stratify nonsurgical patients with NSCLC. This study also suggests MTV and TLG are better prognostic measures than SUVmax and SUVmean. These results will need to be validated in larger cohorts in a prospective study.
Keywords18F-FDG Non-small cell lung cancer Tumor burden Metabolic tumor volume Total lesion glycolysis
Conflicts of interest
- 5.American Joint Committee on Cancer. AJCC cancer staging manual. 6th ed. New York: Springer; 2002.Google Scholar
- 12.Larson SM, Erdi Y, Akhurst T, Mazumdar M, Macapinlac HA, Finn RD, et al. Tumor treatment response based on visual and quantitative changes in global tumor glycolysis using PET-FDG imaging. The visual response score and the change in total lesion glycolysis. Clin Positron Imaging 1999;2:159–71.PubMedCrossRefGoogle Scholar
- 14.Roedl JB, Colen RR, Holalkere NS, Fischman AJ, Choi NC, Blake MA. Adenocarcinomas of the esophagus: response to chemoradiotherapy is associated with decrease of metabolic tumor volume as measured on PET-CT. Comparison to histopathologic and clinical response evaluation. Radiother Oncol 2008;89:278–86.PubMedCrossRefGoogle Scholar
- 15.Lee P, Bazan JG, Lavori PW, Weerasuriya DK, Quon A, Le QT, Wakelee HA, Graves EE, Loo BW Jr. Metabolic tumor volume is an independent prognostic factor in patients treated definitively for non-small-cell lung cancer. Clin Lung Cancer 2011 Jun 22. [Epub ahead of print].Google Scholar
- 19.Chung MK, Jeong H-S, Park SG, Jang JY, Son Y-I, Choi JY, et al. Metabolic tumor volume of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography predicts short-term outcome to radiotherapy with or without chemotherapy in pharyngeal cancer. Clin Cancer Res 2009;15:5861–8.PubMedCrossRefGoogle Scholar
- 22.Bradley JD, Ieumwananonthachai N, Purdy JA, Wasserman TH, Lockett MA, Graham MV, et al. Gross tumor volume, critical prognostic factor in patients treated with three-dimensional conformal radiation therapy for non-small-cell lung carcinoma. Int J Radiat Oncol Biol Phys 2002;52:49–57.PubMedCrossRefGoogle Scholar
- 25.Werner-Wasik M, Nelson AD, Choi W, Arai Y, Faulhaber PF, Kang P, Almeida FD, Xiao Y, Ohri N, Brockway KD, Piper JW, Nelson AS. 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. 2011 Apr 28. [Epub ahead of print].Google Scholar
- 26.Cox DR. Regression models and life-tables (with discussion). J R Stat Soc Series B Stat Methodol 1972;34:187–220.Google Scholar
- 33.van Baardwijk A, Dooms C, van Suylen RJ, Verbeken E, Hochstenbag M, Dehing-Oberije C, et al. The maximum uptake of (18)F-deoxyglucose on positron emission tomography scan correlates with survival, hypoxia inducible factor-1alpha and GLUT-1 in non-small cell lung cancer. Eur J Cancer 2007;43:1392–8.PubMedCrossRefGoogle Scholar