Prognostic Value of Whole-Body Total Lesion Glycolysis at Pretreatment FDG PET/CT in Non–Small Cell Lung Cancer

Published Online:https://doi.org/10.1148/radiol.12111148

Whole-body total lesion glycolysis provides a strong prognostic indicator in patients with non-small cell lung cancer and could be an important guide for making treatment decisions.

Purpose

To determine whether whole-body total lesion glycolysis (TLG), which combines volumetric and metabolic information from fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), can provide a better evaluation of the prognosis for non–small cell lung cancer (NSCLC).

Materials and Methods

The institutional review board approved this retrospective study, and the requirement to obtain informed consent was waived. The authors identified 105 consecutive patients with NSCLC who underwent staging FDG PET/CT before any therapy. These patients were free of brain metastasis and underwent standard treatment and subsequent clinical follow-up. Metabolic tumor volume (MTV), mean standardized uptake value (SUV), and maximum SUV of each tumor over the whole body were determined. Whole-body MTV and whole-body TLG are the summation of all the MTVs and summation of individual tumor volume multiplied by its mean SUV, respectively. Univariate and multivariate analyses were performed to assess the prognostic significance of whole-body TLG and other factors, including whole-body MTV, lung TLG, lung MTV, maximum SUV, sex, age, performance status, histologic subtype, T stage, N stage, clinical stage, and treatment method.

Results

The median follow-up time was 3.1 years. The estimated median progression-free survival (PFS) and overall survival (OS) for the cohort was 10.8 months and 2.8 years, respectively. The 1-year PFS was 0.0% for patients with high whole-body TLG (>655) and 50.0% for those with low whole-body TLG (≤655). The 1-year OS was 58.8% for patients with high whole-body TLG and 84.1% for those with low whole-body TLG. Univariate analysis showed that whole-body TLG, whole-body MTV, lung TLG, lung MTV, maximum SUV, performance status, T stage, N stage, clinical stage, and treatment type (surgery vs other) were significant prognostic factors for PFS (P < .01 for all). With use of the forward stepwise multivariate Cox proportional hazards model, whole-body TLG (hazard ratio = 2.92; 95% confidence interval: 1.62, 5.26; P < .01) and surgical treatment (hazard ratio = 4.24; 95% confidence interval: 2.54, 7.07; P < .01) remained significant in PFS.

Conclusion

Whole-body TLG is of prognostic value for NSCLC. It may be a promising tool for stratifying patients with NSCLC for risk-adapted therapies.

© RSNA, 2012

References

  • 1 Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60(5):277–300.
  • 2 Richards MA, Stockton D, Babb P, Coleman MP. How many deaths have been avoided through improvements in cancer survival? BMJ 2000;320(7239):895–898.
  • 3 van Rens MT, de la Rivière AB, Elbers HR, van Den Bosch JM. Prognostic assessment of 2,361 patients who underwent pulmonary resection for non–small cell lung cancer, stage I, II, and IIIA. Chest 2000;117(2):374–379.
  • 4 Brundage MD, Davies D, Mackillop WJ. Prognostic factors in non–small cell lung cancer: a decade of progress. Chest 2002;122(3):1037–1057.
  • 5 Hicks RJ, Kalff V, MacManus MP, et al.. (18)F-FDG PET provides high-impact and powerful prognostic stratification in staging newly diagnosed non–small cell lung cancer. J Nucl Med 2001;42(11):1596–1604.
  • 6 Hicks RJ, Kalff V, MacManus MP, et al.. The utility of (18)F-FDG PET for suspected recurrent non–small cell lung cancer after potentially curative therapy: impact on management and prognostic stratification. J Nucl Med 2001;42(11):1605–1613.
  • 7 Hoekstra CJ, Stroobants SG, Hoekstra OS, et al.. The value of [18F]fluoro-2-deoxy-D-glucose positron emission tomography in the selection of patients with stage IIIA-N2 non–small cell lung cancer for combined modality treatment. Lung Cancer 2003;39(2):151–157.
  • 8 Higashi K, Ueda Y, Arisaka Y, et al.. 18F-FDG uptake as a biologic prognostic factor for recurrence in patients with surgically resected non–small cell lung cancer. J Nucl Med 2002;43(1):39–45.
  • 9 Vansteenkiste JF, Stroobants SG, Dupont PJ, et al.. Prognostic importance of the standardized uptake value on (18)F-fluoro-2-deoxy-glucose-positron emission tomography scan in non–small-cell lung cancer: an analysis of 125 cases. Leuven Lung Cancer Group. J Clin Oncol 1999;17(10):3201–3206.
  • 10 Downey RJ, Akhurst T, Gonen M, et al.. Preoperative F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value predicts survival after lung cancer resection. J Clin Oncol 2004;22(16):3255–3260.
  • 11 Cerfolio RJ, Bryant AS, Ohja B, Bartolucci AA. The maximum standardized uptake values on positron emission tomography of a non–small cell lung cancer predict stage, recurrence, and survival. J Thorac Cardiovasc Surg 2005;130(1):151–159.
  • 12 Sasaki R, Komaki R, Macapinlac H, et al.. [18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non–small cell lung cancer. J Clin Oncol 2005;23(6):1136–1143.
  • 13 Vesselle H, Freeman JD, Wiens L, et al.. Fluorodeoxyglucose uptake of primary non–small cell lung cancer at positron emission tomography: new contrary data on prognostic role. Clin Cancer Res 2007;13(11):3255–3263.
  • 14 Paesmans M, Berghmans T, Dusart M, et al.. Primary tumor standardized uptake value measured on fluorodeoxyglucose positron emission tomography is of prognostic value for survival in non–small cell lung cancer: update of a systematic review and meta-analysis by the European Lung Cancer Working Party for the International Association for the Study of Lung Cancer Staging Project. J Thorac Oncol 2010;5(5):612–619.
  • 15 Lee P, Weerasuriya DK, Lavori PW, et al.. Metabolic tumor burden predicts for disease progression and death in lung cancer. Int J Radiat Oncol Biol Phys 2007;69(2):328–333.
  • 16 Hyun SH, Choi JY, Shim YM, 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(1):115–122.
  • 17 La TH, Filion EJ, Turnbull BB, et al.. Metabolic tumor volume predicts for recurrence and death in head-and-neck cancer. Int J Radiat Oncol Biol Phys 2009;74(5):1335–1341.
  • 18 Lee HY, Hyun SH, Lee KS, et al.. Volume-based parameter of (18)F-FDG PET/CT in malignant pleural mesothelioma: prediction of therapeutic response and prognostic implications. Ann Surg Oncol 2010;17(10):2787–2794.
  • 19 Kim BS, Kim IJ, Kim S, et al.. The prognostic value of the metabolic tumor volume in FIGO stage IA to IIB cervical cancer for tumor recurrence: measured by F-18 FDG PET/CT. Nucl Med Mol Imaging 2011;45(1):36–42.
  • 20 Larson SM, 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 Positron Imaging 1999;2(3):159–171.
  • 21 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(3):278–286.
  • 22 Erdi YE, Macapinlac H, Rosenzweig KE, et al.. Use of PET to monitor the response of lung cancer to radiation treatment. Eur J Nucl Med 2000;27(7):861–866.
  • 23 Veit-Haibach P, Schaefer NG, Steinert HC, Soyka JD, Seifert B, Stahel RA. Combined FDG-PET/CT in response evaluation of malignant pleural mesothelioma. Lung Cancer 2010;67(3):311–317.
  • 24 Guillem JG, Moore HG, Akhurst T, et al.. Sequential preoperative fluorodeoxyglucose-positron emission tomography assessment of response to preoperative chemoradiation: a means for determining longterm outcomes of rectal cancer. J Am Coll Surg 2004;199(1):1–7.
  • 25 Melton GB, Lavely WC, Jacene HA, et al.. Efficacy of preoperative combined 18-fluorodeoxyglucose positron emission tomography and computed tomography for assessing primary rectal cancer response to neoadjuvant therapy. J Gastrointest Surg 2007;11(8):961–969; discussion 969.
  • 26 Benz MR, Allen-Auerbach MS, Eilber FC, et al.. Combined assessment of metabolic and volumetric changes for assessment of tumor response in patients with soft-tissue sarcomas. J Nucl Med 2008;49(10):1579–1584.
  • 27 Flamen P, Vanderlinden B, Delatte P, et al.. Multimodality imaging can predict the metabolic response of unresectable colorectal liver metastases to radioembolization therapy with Yttrium-90 labeled resin microspheres. Phys Med Biol 2008;53(22):6591–6603.
  • 28 Costelloe CM, Macapinlac HA, Madewell JE, et al.. 18F-FDG PET/CT as an indicator of progression-free and overall survival in osteosarcoma. J Nucl Med 2009;50(3):340–347.
  • 29 Xie P, Yue JB, Zhao HX, et al.. Prognostic value of 18F-FDG PET-CT metabolic index for nasopharyngeal carcinoma. J Cancer Res Clin Oncol 2010;136(6):883–889.
  • 30 Greene FL, Page DL, Fleming ID, et al.. AJCC cancer staging manual. 6th ed. New York, NY: Springer-Verlag, 2002.
  • 31 Duhaylongsod FG, Lowe VJ, Patz EF, Vaughn AL, Coleman RE, Wolfe WG. Lung tumor growth correlates with glucose metabolism measured by fluoride-18 fluorodeoxyglucose positron emission tomography. Ann Thorac Surg 1995;60(5):1348–1352.
  • 32 Higashi K, Ueda Y, Yagishita M, et al.. FDG PET measurement of the proliferative potential of non–small cell lung cancer. J Nucl Med 2000;41(1):85–92.
  • 33 Vesselle H, Schmidt RA, Pugsley JM, et al.. Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res 2000;6(10):3837–3844.
  • 34 Younes M, Brown RW, Stephenson M, Gondo M, Cagle PT. Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival. Cancer 1997;80(6):1046–1051.
  • 35 Sugawara Y, Quint LE, Iannettoni MD, et al.. Does the FDG uptake of primary non–small cell lung cancer predict prognosis? A work in progress. Clin Positron Imaging 1999;2(2):111–118.
  • 36 Bradley JD, Ieumwananonthachai N, Purdy JA, 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(1):49–57.
  • 37 Jefferson MF, Pendleton N, Faragher EB, Dixon GR, Myskow MW, Horan MA. “Tumour volume” as a predictor of survival after resection of non–small cell lung cancer (NSCLC). Br J Cancer 1996;74(3):456–459.
  • 38 Biehl KJ, Kong FM, Dehdashti F, et al.. 18F-FDG PET definition of gross tumor volume for radiotherapy of non–small cell lung cancer: is a single standardized uptake value threshold approach appropriate? J Nucl Med 2006;47(11):1808–1812.
  • 39 Kostakoglu L, Hardoff R, Mirtcheva R, Goldsmith SJ. PET-CT fusion imaging in differentiating physiologic from pathologic FDG uptake. RadioGraphics 2004;24(5):1411–1431.
  • 40 Wu K, Ung YC, Hornby J, et al.. PET CT thresholds for radiotherapy target definition in non–small cell lung cancer: how close are we to the pathologic findings? Int J Radiat Oncol Biol Phys 2010;77(3):699–706.
  • 41 Yaremko B, Riauka T, Robinson D, Murray B, McEwan A, Roa W. Threshold modification for tumour imaging in non–small cell lung cancer using positron emission tomography. Nucl Med Commun 2005;26(5):433–440.
  • 42 Thorwarth D, Schaefer A. Functional target volume delineation for radiation therapy on the basis of positron emission tomography and the correlation with histopathology. Q J Nucl Med Mol Imaging 2010;54(5):490–499.
  • 43 Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 1992;33(11):1972–1980.
  • 44 Ludwig V, Komori T, Kolb D, Martin WH, Sandler MP, Delbeke D. Cerebral lesions incidentally detected on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography images of patients evaluated for body malignancies. Mol Imaging Biol 2002;4(5):359–362.

Article History

Received June 4, 2011; revision requested July 21; revision received January 15,2012; accepted February 8,; final version accepted February 27.
Published online: Aug 2012
Published in print: Aug 2012