Rationale and Objectives
Stage IV non–small-cell lung cancer (NSCLC) consists of a heterogeneous group of patients with different prognoses. We assessed the prognostic value of baseline whole body tumor burden as measured by metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake values (SUV max and SUV mean ) of all tumors in nonsurgical patients with Stage IV NSCLC.
Materials and Methods
Ninety-two consecutive patients with newly diagnosed Stage IV NSCLC who had a pretreatment F-18 fludeoxyglucose positron emission tomography/computed tomography scan were retrospectively reviewed. The MTV, TLG, SUV mean , and SUV max of whole-body (WB) tumors were measured with the MIMvista workstation with manual adjustment.
Results
There was a statistically significant association between overall survival (OS) and ln(MTV)/ln(TLG) at the level of WB tumor burden (MTV WB ) and of primary tumor (MTV T ). The hazard ratio (HR) for a 1-unit increase of ln(MTV WB ) and ln(MTV T ) before and after adjusting for age and gender was 1.48/1.48 (both P < .001) and 1.25/1.25 ( P = .006, .007), respectively. The HR for a 1-unit increase of ln(TLG WB ) and ln(TLG T ) before and after adjusting for age and gender was 1.37/1.37 (both P = .001) and 1.19/1.19 ( P = .001, .017), respectively. There was no statistically significant association between OS and ln(SUV max ) and ln(SUV mean ) at WB tumor burden, primary tumor, nodal metastasis, or distant metastasis ( P > .05). There was low interobserver variability between two radiologists with concordance correlation coefficients of 0.90 for ln(MTV WB ) and greater than 0.90 for SUV maxWB , SUV meanWB , and ln(TLG WB ).
Conclusion
Baseline WB metabolic tumor burden, as measured with MTV and TLG, is a prognostic measurement in patients within Stage IV NSCLC with low interobserver variability. This study also suggests pretreatment MTV and TLG measurements may be used to further stratify patients with Stage IV NSCLC and are better prognostic measures than SUV max and SUV mean measurements.
Lung cancer is the most common cause of cancer death in the world and the second most common cancer in both men and women, and number one cause of cancer-related deaths in the United States. In the United States in 2010, 157,300 people were projected to die from lung cancer, which is more than the number of deaths from colon and rectal, breast, and prostate cancer combined . Non–small-cell lung cancer (NSCLC) comprises 80%–85% of all lung cancer cases .
Stage IV non–small-cell lung cancer (NSCLC) consists of a heterogeneous group of patients who are often treated with different modalities . Based on the comprehensive analysis of 67,149 patients with Stage IV NSCLC as defined by the 6th edition of the Union International Contra la Cancrum (UICC)/American Joint Committee on Cancer (AJCC) staging system for NSCLC enrolled in the Surveillance, Epidemiology, and End Results (SEER) program, the patients with distant metastasis have worse prognosis . The patients with tumor nodules on both sides of the chest have worse prognosis than those with separate ipsilateral tumor nodules in different lobes. The nodal status is a strong determinant of survival.
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Materials and methods
Patient Recruitment
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Imaging Protocols
PET/CT imaging
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Measurement of tumor volume on PET/CT
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Statistical Analysis
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Results
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Table 1
The Distribution of the Gender and Age, and PET/CT Measurements with Corresponding Survival Probabilities in 92 Stage IV Nonsurgical Cases with Non–small-cell Lung Cancer
Mean ± SD Overall Survival Median (mo) 1-year (%) 2-year (%) Gender (n) Female (55) 9.09 41.82 21.82 Male (37) 9.68 37.84 13.51 Age 65.6 ± 10.81 <Median (65) 56.69 ± 6.47 10.13 41.30 15.22 ≥Median 74.51 ± 5.67 8.24 39.13 21.74 SUV max SUV maxWB 10.99 ± 6.03 <Median 70.1 ± 1.47 11.17 47.83 21.74 ≥Median 14.99 ± 6.23 8.9 32.61 15.22 SUV maxT 9.32 ± 436 <Median 6.03 ± 1.91 10.37 45.65 19.57 ≥Median 12.62 ± 3.54 8.89 34.48 17.39 SUV maxN 5.81 ± 5.64 <Median 2.29 ± 2.02 11.67 50.00 23.91 ≥Median 9.32 ± 5.92 7.36 30.43 13.04 SUV maxM 5.88 ± 5.94 <Median 2.03 ± 1.93 10.25 43.48 23.91 ≥Median 9.73 ± 6.11 8.06 36.96 13.04 SUV mean SUV meanWB 3.78 ± 1.48 <Median 2.88 ± 0.44 9.12 39.13 15.22 ≥Median 4.68 ± 1.59 10.13 41.30 21.74 SUV meanT 3.67 ± 1.19 <Median 2.75 ± 0.63 9.42 43.48 17.39 ≥Median 4.58 ± 0.87 9.26 36.96 19.57 SUV meanN 4.15 ± 6.39 <Median 2.48 ± 0.46 9.68 37.84 13.51 ≥Median 5.83 ± 8.76 8.12 41.82 21.82 SUV meanM 3.13 ± 1.51 <Median 2.21 ± 0.60 8.69 35.14 13.51 ≥Median 4.07 ± 1.58 10.12 43.64 21.82 MTV MTV WB 248.21 ± 251.95 <Median 72.02 ± 44.50 13.89 58.57 32.61 ≥Median 424.41 ± 250.83 6.51 21.74 4.35 MTV T 142.95 ± 197.29 <Median 22.56 ± 16.40 12.72 52.17 28.26 ≥Median 263.34 ± 220.93 6.8 28.26 8.7 MTV N 40.53 ± 63.92 <Median 3.85 ± 4.23 10.84 47.83 21.74 ≥Median 77.20 ± 74.13 7.36 32.61 15.22 MTV M 62.32 ± 123.92 <Median 3.49 ± 4.01 10.7 43.48 23.91 ≥Median 121.14 ± 154.79 8.06 36.96 13.04 TLG TLG WB 968.4 ± 1029.48 <Median 255.61 ± 174.89 13.62 56.52 32.61 ≥Median 1681.19 ± 1036.30 6.8 23.91 4.35 TLG T 573.29 ± 810.85 <Median 77.04 ± 59.54 13.35 54.35 30.43 ≥Median 1069.54 ± 906.95 6.8 26.09 6.52 TLG N 157.12 ± 291.79 <Median 11.21 ± 13.71 11.67 50.00 21.74 ≥Median 303.04 ± 358.41 7.07 30.43 15.22 TLG M 229.56 ± 501.57 <Median 8.59 ± 11.02 10.25 41.30 23.91 ≥Median 450.53 ± 639.37 9.12 39.13 13.04
CI, confidence interval; HR, hazard ratio; mo, months; MTV, metabolic tumor volume (mL); MTV WB , MTV of whole body tumor (a median of 154.35 mL); MTV T , MTV of primary tumor (a median of 56.57 mL); MTV N , MTV of nodal metastasis (a median of 13.16 mL); MTV M , MTV of distant metastasis (a median of 12.46 mL); OS, overall survival; SD, standard deviation; SUV max , maximum standardized uptake value; SUV maxWB , SUV max of whole body tumor (with a median of 9.28); SUV maxT , SUV max of primary tumor (a median of 8.67); SUV maxN , SUV max of nodal metastasis (a median of 5.47); SUV maxM , SUV max of distant metastasis (a median of 4.99); SUV mean , mean standardized uptake value; SUV meanWB , SUV mean of whole body tumor (a median of 3.43); SUV meanT , SUV mean of primary tumor (a median of 3.51); SUV mean , SUV mean of nodal metastasis (a median of 3.04); SUV meanM , SUV mean of distant metastasis (a median of 2.94); TLG, total lesion glycolysis (SUV*mL); TLG WB , TLG of whole body tumor (a median of 574.65 SUV∗mL); TLG T , TLG of primary tumor (a median of 214.13 SUV∗mL); TLG N , TLG of nodal metastasis (a median of 48.95 SUV∗mL); TLG M , TLG of distant metastasis (a median of 34.26 SUV∗mL).
Table 2
The Association of Overall Survival (OS) with Age, Gender, and PET/CT Measurements in 92 Stage IV Nonsurgical Cases with Non–small-cell Lung Cancer
Univariate Analysis Multivariate Analysis ∗ HR (95% CI)P Value HR (95% CI)P Value Gender Male vs. female 1.24 (0.79–1.96) .349 Age (y) <65.6 vs. ≥65.6 0.996 (0.98–1.02) .712 SUV max ln(SUV maxWB ) 1.27 (082–1.99) .28 1.24 (0.80–1.95) .335 ln(SUV maxT ) 1.35 (0.92–1.99) .13 1.35 (0.91–1.98) .134 ln(SUV maxN ) 1.00 (0.63–1.61) .98 0.98 (0.61–1.57) .918 ln(SUV maxM ) 1.16 (0.77–1.73) .48 1.17 (0.77–1.77) .464 SUV mean ln(SUV meanWB ) 1.14 (0.57–2.25) .72 1.07 (0.53–2.15) .85 ln(SUV meanT ) 1.20 (0.70–2.06) .50 1.18 (0.69–2.01) .554 ln(SUV mean ) 1.34 (0.81–2.20) .26 1.26 (0.75–2.13) .385 ln(SUV meanM ) 1.00 (0.56–1.81) .99 0.99 (0.55–1.80) .99 MTV ln(MTV WB ) 1.48 (1.20–1.82) <.001 1.48 (1.19–1.84) <.001 ln(MTV T ) 1.25 (1.07–1.47) .006 1.25 (1.06–1.47) .007 ln(MTV N) 1.21 (0.99–1.47) .06 1.19 (0.97–1.46) .09 ln(MTV M ) 1.06 (0.90–1.25) .48 1.07 (0.90–1.27) .42 TLG ln(TLG WB ) 1.37 (1.13–1.65) .001 1.37 (1.13–1.66) .001 ln(TLG T ) 1.19 (1.04–1.37) .01 1.19 (1.03–1.36) .017 ln(TLG N ) 1.17 (0.98–1.39) .08 1.15 (0.96–1.38) .118 ln(TLG M ) 1.04 (0.91–1.20) .55 1.05 (0.91–1.22) .495
CI, confidence interval; HR, hazard ratio; ln, natural log transformation was performed before Cox regression analysis. See Table 1 for other abbreviations.
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Table 3
Association of Overall Survival (OS) with Gender, Age, and PET/CT Measurements in 79 Nonsurgical Patients in Stage IV with Non–small-cell Lung Cancer
Univariate Analysis Multivariate Analysis ∗ HR (95% CI)P Value HR (95% CI)P Value Gender Female Reference .476 Male 1.20 (0.73–1.98) Age 0.99 (0.97–1.01) .388 SUV max ln(SUV maxWB ) 1.14 (0.70–1.86) .600 1.11 (0.68–1.83) .668 ln(SUVmaxT) 1.28 (0.85–1.95) .241 1.28 (0.85–1.95) .240 ln(SUVmaxN) 0.98 (0.60–1.62) .949 0.96 (0.58–1.59) .877 ln(SUV max M) 1.00 (0.63–1.58) .983 0.96 (0.60–1.54) .862 SUV mean ln(SUV meanWB ) 1.00 (0.47–2.12) .992 0.97 (0.46–2.06) .939 ln(SUV meanT ) 1.13 (0.64–1.98) .673 1.11 (0.64–1.95) .707 ln(SUV meanN ) 1.18 (0.65–2.15) .584 1.12 (0.61–2.07) .717 ln(SUV meanM ) 0.83 (0.44–1.55) .552 0.80 (0.43–1.50) .489 MTV ln(MTV WB ) 1.41 (1.11–1.78) .005 1.39 (1.09–1.78) .009 ln(MTV T ) 1.20 (1.00–1.44) .045 1.19 (0.99–1.42) .063 ln(MTV N ) 1.16 (0.94–1.44) .167 1.15 (0.92–1.42) .211 ln(MTV M ) 1.00 (0.84–1.20) .987 0.98 (0.81–1.19) .842 TLG ln(TLG WB ) 1.30 (1.05–1.60) .014 1.28 (1.03–1.59) .023 ln(TLG T ) 1.15 (0.99–1.33) .078 1.14 (0.97–1.32) .104 ln(TLG N ) 1.12 (0.93–1.35) .228 1.11 (0.92–1.34) .289 ln(TLG M ) 0.99 (0.85–1.15) .898 0.97 (0.82–1.15) .729
Abbreviations as in Tables 1 and 2 .
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![Figure 2, Kaplan-Meier curves of overall survival after baseline positron emission tomography (PET)/computed tomography grouped according to PET measurements in 92 nonsurgical patients with stage IV non–small-cell lung cancer show the association of the natural logarithm of whole-body metabolic tumor volume [ln(MTV WB )] with cumulative survival. The dashed lines indicate the group with values less than the median and the solid lines are the group with values greater than or equal to the median of the PET measurements.](https://storage.googleapis.com/dl.dentistrykey.com/clinical/PrognosticValueoftheQuantitativeMetabolicVolumetricMeasurementon18FFDGPETCTinStageIVNonsurgicalSmallcellLungCancer/1_1s20S1076633211004430.jpg)
![Figure 3, Kaplan-Meier curves of overall survival after baseline positron emission tomography (PET)/computed tomography grouped according to PET measurements in 92 nonsurgical patients with stage IV non–small-cell lung cancer show the association of the natural logarithm of whole-body total lesion glycolysis [ln(TLG WB )] and cumulative survival. The dashed lines indicate the group with values less than the median and the solid lines are the group with values greater than or equal to the median of the PET measurements.](https://storage.googleapis.com/dl.dentistrykey.com/clinical/PrognosticValueoftheQuantitativeMetabolicVolumetricMeasurementon18FFDGPETCTinStageIVNonsurgicalSmallcellLungCancer/2_1s20S1076633211004430.jpg)
![Figure 4, Kaplan-Meier curves of overall survival after baseline positron emission tomography (PET)/computed tomography grouped according to PET measurements in 92 nonsurgical patients with stage IV non–small-cell lung cancer show the association of the natural logarithm of whole-body maximum standardized uptake value [ln(SUV maxWB )] and cumulative survival. The dashed lines indicate the group with values less than the median and the solid lines are the group with values greater than or equal to the median of the PET measurements.](https://storage.googleapis.com/dl.dentistrykey.com/clinical/PrognosticValueoftheQuantitativeMetabolicVolumetricMeasurementon18FFDGPETCTinStageIVNonsurgicalSmallcellLungCancer/3_1s20S1076633211004430.jpg)
![Figure 5, Kaplan-Meier curves of overall survival after baseline positron emission tomography (PET)/computed tomography grouped according to PET measurements in 92 nonsurgical patients with stage IV non–small-cell lung cancer show the association of the natural logarithm of whole-body mean standardized uptake value [ln(SUV meanWB )] and cumulative survival. The dashed lines indicate the group with values less than the median and the solid lines are the group with values greater than or equal to the median of the PET measurements.](https://storage.googleapis.com/dl.dentistrykey.com/clinical/PrognosticValueoftheQuantitativeMetabolicVolumetricMeasurementon18FFDGPETCTinStageIVNonsurgicalSmallcellLungCancer/4_1s20S1076633211004430.jpg)
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Discussion
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Conclusion
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References
1. Parkin D.M., Bray F.I., Devesa S.S.: Cancer burden in the year 2000: the global picture. Eur J Cancer 2001; 37: pp. S4-S66.
2. Jemal A., Siegel R., Xu J., et. al.: Cancer statistics, 2010. CA Cancer J Clinicians 2010; 60: pp. 277-300.
3. Traynor A.M., Schiller J.H.: Systemic treatment of advanced non-small cell lung cancer. Drugs of Today 2004; 40: pp. 697-710.
4. UyBico S.J., Wu C.C., Suh R.D., et. al.: Lung cancer staging essentials: the new TNM staging system and potential imaging pitfalls. Radiographics 2010; 30: pp. 1163-1181.
5. American Joint Committee on Cancer: AJCC Cancer Staging Manual.6th ed.2002.SpringerNew York, NY
6. William W.N., Lin H.Y., Lee J.J., et. al.: Revisiting stage IIIB and IV non-small cell lung cancer: analysis of the surveillance, epidemiology, and end results data. Chest 2009; 136: pp. 701-709.
7. Lee P., Weerasuriya D.K., Lavori P.W., et. al.: Metabolic tumor burden predicts for disease progression and death in lung cancer. Int J Radiat Oncol Biol Phys 2007; 69: pp. 328-333.
8. La T.H., Filion E.J., Turnbull B.B., et. al.: Metabolic tumor volume predicts for recurrence and death in head-and-neck cancer. Int J Radiat Oncol Biol Phys Physics 2009; 74: pp. 1335-1341.
9. Larson S.M., Erdi Y., Akhurst T., 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 Pos Imaging 1999; 2: pp. 159-171.
10. Berkowitz A., Basua S., Srinivasa S., et. al.: Determination of whole-body metabolic burden as a quantitative measure of disease activity in lymphoma: a novel approach with fluorodeoxyglucose-PET. Nuc Med Commun 2008; 29: pp. 521-526.
11. Roedl J.B., Colen R.R., Holalkere N.S., et. al.: 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: pp. 278-286.
12. Zhu D., Ma T., Niu Z., et. al.: Prognostic significance of metabolic parameters measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with small cell lung cancer. Lung Cancer 2011; 73: pp. 332-337.
13. Seol Y.M., Kwon B.R., Song M.K., et. al.: Measurement of tumor volume by PET to evaluate prognosis in patients with head and neck cancer treated by chemoradiation therapy. Acta Oncol 2010; 49: pp. 201-208.
14. Xie P., Yue J.B., Zhao H.X., et. al.: Prognostic value of 18-F FDG PET-CT metabolic index for nasopharyngeal carcinoma. J Cancer Res Clin Oncol 2010; 136: pp. 883-889.
15. Man K.C., Jeong H.-S., Sang G.P., 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: pp. 5861-5868.
16. Hyun S.H., Choi J.Y., Shim Y.M., et. al.: Prognostic value of metabolic tumor volume measured by 18F-fluorodeoxyglucose positron emission tomography in patients with esophageal carcinoma. Ann Surg Oncol 2010; 17: pp. 115-122.
17. Wang W., Larson S.M., Fazzari M., et. al.: Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab 2000; 85: pp. 1107-1113.
18. Bradley J.D., Ieumwananonthachai N., Purdy J.A., 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: pp. 49-57.
19. Socinski M.A., Morris D.E., Masters G.A., et. al.: Chemotherapeutic management of stage IV non-small cell lung cancer. Chest 2003; 123: pp. 226S-243S.
20. Doi K.: Computer-aided diagnosis in medical imaging: historical review, current status and future potential. Comp Med Imaging Graphics 2007; 31: pp. 198-211.
21. Shankar L.K., Hoffman J.M., Bacharach S., et. al.: Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. J Nucl Med 2006; 47: pp. 1059-1066.
22. Werner-Wasik M., Nelson A.D., Choi W., 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 2011 Apr 28; [Epub ahead of print]
23. Cox D.R.: Regression models and life-tables (with discussion). J Royal Stat Soc Series B 1972; 34: pp. 187-220.
24. Kaplan E.L., Meier P.: Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: pp. 457-481.
25. Mountain C.F.: Revisions in the International System for Staging Lung Cancer. Chest 1997; 111: pp. 1710-1717.
26. Adebonojo S.A., Bowser A.N., Moritz D.M., et. al.: Impact of revised stage classification of lung cancer on survival: a military experience. Chest 1999; 115: pp. 1507-1513.
27. van Rens M.T., de la Riviere A.B., Elbers H.R., et. al.: Prognostic assessment of 2,361 patients who underwent pulmonary resection for non–small cell lung cancer, stage I, II, and IIIA. Chest 2000; 117: pp. 374-379.
28. Borst G.R., Belderbos J.S., Boellaard R., et. al.: Standardised FDG uptake: a prognostic factor for inoperable non-small cell lung cancer. Eur J Cancer 2005; 41: pp. 1533-1541.
29. Davies A., Tan C., Paschalides C., et. al.: FDG-PET maximum standardised uptake value is associated with variation in survival: Analysis of 498 lung cancer patients. Lung Cancer 2007; 55: pp. 75-78.
30. van Baardwijk A., Dooms C., van Suylen R.J., 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: pp. 1392-1398.
31. Lee K.H., Lee S.H., Kim D.W., et. al.: High fluorodeoxyglucose uptake on positron emission tomography in patients with advanced non-small cell lung cancer on platinum-based combination chemotherapy. Clin Cancer Res 2006; 12: pp. 4232-4236.
32. Wahl R.L., Jacene H., Kasamon Y., et. al.: From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med 2009; 50: pp. 122S-150S.