To evaluate the prognostic role of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) measured by FDG–positron emission tomography (PET)/computed tomography (CT) in patients with primary lung adenocarcinoma undergoing surgical resection.
Methods:
All consecutive patients undergoing curative surgery for primary lung adenocarcinoma at the Thoracic Surgery Unit of the University Hospital of Parma between January 2009 and December 2014 were retrospectively analyzed. The cutoff point of each continuous PET parameter was determined through receiver operating characteristic curve and Youden index, using overall survival (OS) as the classification status. Univariate and multivariate Cox proportional hazards models were applied to evaluate the association between OS and potential prognostic variables, including SUVmax, MTV, and TLG.
Results:
A total of 193 patients were considered eligible for this study. The mean 5-year OS rate was 70.5 ± 3.5%. Acinar and lepidic patterns were more frequently associated with absent or low (<2.5) SUVmax values [18F]FDG uptake. At univariate analysis, male sex, advanced stage, micropapillary and solid pattern, lymphatic, blood vessels and pleural invasion, high SUVmax, MTV, and TLG were significantly associated with poorer OS. Multivariate analyses revealed that only sex, stage, and TLG were independent factors for OS, with male sex, stage 3+4, and high TLG value (p = 0.041) significantly associated with poorer OS.
Conclusions:
In this study, [18F]FDG PET/CT parameters SUVmax, MTV, and TLG were prognostic factors in patients with surgically resected lung adenocarcinoma, able to predict OS and helping to further stratify these patients into prognostic subsets. Elevated TLG was also an independent predictor for shorter OS.
GoldstrawPCrowleyJChanskyK, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol2007; 2: 706–714.
2.
GouldMKDoningtonJLynchWR, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest2013; 143(5 Suppl): e93–e120S.
3.
KawaguchiTTakadaMKuboA, et al. Performance status and smoking status are independent favorable prognostic factors for survival in non-small cell lung cancer: a comprehensive analysis of 26,957 patients with NSCLC. J Thorac Oncol2010; 5: 620–630.
4.
van RensMTde la RivièreABElbersHR, et al. Prognostic assessment of 2,361 patients who underwent pulmonary resection for nonsmall cell lung cancer, stage I, II, and IIIA. Chest2000; 117: 374–379.
5.
ZhuALeeDShimH. Metabolic positron emission tomography imaging in cancer detection and therapy response. Semin Oncol2011; 38: 55–69.
6.
NaFWangJLiC, et al. Primary tumor standardized uptake value measured on F18- Fluorodeoxyglucose positron emission tomography is of prediction value for survival and local control in non-small-cell lung cancer receiving radiotherapy: meta-analysis. J Thorac Oncol2014; 9: 834–842.
7.
SugawaraYZasadnyKRNeuhoffAW, et al. Reevaluation of the standardized uptake value for FDG: variations with body weight and methods for correction. Radiology1999; 213: 521–525.
8.
BoellaardR. Standards for PET image acquisition and quantitative data analysis. J Nucl Med2009; 50 Suppl1: 11S–20S.
9.
CazaentreTMorschhauserFVermandelM, et al. Pre-therapy 18FFDG PET quantitative parameters help in predicting the response to radioimmunotherapy in non-Hodgkin lymphoma. Eur J Nucl Med Mol Imaging2010; 37: 494–504.
10.
LeePWeerasuriyaDKLavoriPW, et al. Metabolic tumor burden predicts for disease progression and death in lung cancer. Int J Radiat Oncol Biol Phys2007; 69: 328–333.
11.
LarsonSMErdiYAkhurstT, 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 Imaging1999; 2: 159–171.
12.
RoedlJBColenRRHolalkereNS, 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 Oncol2008; 89: 278–286.
13.
LaTHFilionEJTurnbullBB, et al. Metabolic tumor volume predicts for recurrence and death in head and neck cancer. Int J Radiat Oncol Biol Phys2009; 74: 1335–1341.
14.
PankowskaVMalkowskiBWedrowskiM, et al. FDG PET/CT as a survival prognostic factor in patients with advanced renal cell carcinoma. Clin Exp Med2019; 19: 143–148.
15.
JaceneHAYounTDiPiroPJ, et al. Metabolic characterization of inflammatory breast cancer with baseline FDG-PET/CT: relationship with pathologic response after neoadjuvant chemotherapy, receptor status, and tumor grade. Clin Breast Cancer2019; 19: 146–155.
16.
BerghmansTDusartMPaesmansM, et al; European Lung Cancer Working Party for the IASLC Lung Cancer Staging Project. Primary tumor standardized uptake value (SUVmax) measured on fluorodeoxyglucose positron emission tomography (FDG-PET) is of prognostic value for survival in non-small cell lung cancer (NSCLC): a systematic review and meta-analysis (MA) by the European Lung Cancer Working Party for the IASLC Lung Cancer Staging Project. J Thorac Oncol2008; 3: 6–12.
17.
ChungHHKwonHWKangKW, et al. Prognostic value of preoperative metabolic tumor volume and total lesion glycolysis in patients with epithelial ovarian cancer. Ann Surg Oncol2012; 19: 1966–1972.
18.
DibbleEHLara AlvarezACTruongMT, et al. F-18 FDG metabolic tumor volume and total glycolytic activity of oral cavity and oropharyngeal squamous cell cancer: adding value to clinical staging. J Nucl Med2012; 53: 709–715.
19.
ChanDLBernardESchembriG, et al. High metabolic tumour volume on FDG PET predicts poor survival from neuroendocrine neoplasms. Neuroendocrinology Epub 2019Nov12.
20.
HyunSHAhnHKKimH, et al. Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer. Eur J Nucl Med Mol Imaging2014; 41: 50–58.
21.
LiaoSPenneyBCWroblewskiK, 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 Imaging2012; 39: 27–38.
22.
LinYLinWYKaoCH, et al. Prognostic value of preoperative metabolic tumor volumes on PET-CT in predicting disease-free survival of patients with stage I non-small cell lung cancer. Anticancer Res2012; 32: 5087–5091.
23.
BoellaardRDelgado-BoltonROyenWJ, et al; European Association of Nuclear Medicine (EANM). FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging2015; 42: 328–354.
Technical Committee. FDG-PET/CT as an Imaging Biomarker Measuring Response to Cancer Therapy, Quantitative Imaging Biomarkers Alliance, Version 1.13, Technically Confirmed Version. Oak Brook, IL: QIBA; 2016.
26.
Werner-WasikMNelsonADChoiW, 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 Phys2012; 82: 1164–1171.
27.
SilvestriGAGonzalezAVJantzMA, et al. Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest2013; 143(5 Suppl): e211S–e250S.
28.
HerderGJvan TinterenHGoldingRP, et al. Clinical prediction model to characterize pulmonary nodules: validation and added value of 18F-fluorodeoxyglucose positron emission tomography. Chest2005; 128: 2490–2496.
29.
NairVSKrupitskayaYGouldMK. Positron emission tomography 18F-fluorodeoxyglucose uptake and prognosis in patients with surgically treated, stage I non-small cell lung cancer: a systematic review. J Thorac Oncol2009; 4: 1473–1479.
30.
van BaardwijkADoomsCvan SuylenRJ, 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 Cancer2007; 43: 1392–1398.
31.
AgarwalMBrahmandayGBajajSK, et al. Revisiting the prognostic value of preoperative (18)F-fluoro-2-deoxyglucose ([18]F-FDG) positron emission tomography (PET) in early-stage (I & II) non-small cell lung cancers (NSCLC). Eur J Nucl Med Mol Imaging2010; 37: 691–698.
32.
LodgeMA. Repeatability of SUV in oncologic 18F-FDG PET. J Nucl Med2017; 58: 523–532.
33.
AdamsMCTurkingtonTGWilsonJM, et al. A systematic review of the factors affecting accuracy of SUV measurements. Am J Roentgenol2010; 195: 310–320.
34.
BradleyJDLeumwananonthachaiNPurdyJA, 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 Phys2002; 52: 49–57.
35.
YangBJiHGeY, et al. Correlation study of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in pathological subtypes of invasive lung adenocarcinoma and prognosis. Front Oncol 2019; 9: 908.
36.
ChenHHChiuNTSuWC, et al. Prognostic value of whole-body total lesion glycolysis at pretreatment FDG PET/CT in non small cell lung cancer. Radiology2012; 264: 559–566.
37.
LeePBazanJGLavoriPW, et al. Metabolic tumor volume is an independent prognostic factor in patients treated definitively for non small cell lung-cancer. Clin Lung Cancer2012; 13: 52–58.
38.
Werner-WasikMNelsonADChoiW, 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 Phys2012; 82: 1164–1171.
39.
LiuHChenPWroblewskiK, 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 Commun2016; 37: 50–56.
40.
DowneyRJAkhurstTGonenM, et al. Preoperative F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value predicts survival after lung cancer resection. J Clin Oncol2004; 22: 3255–3260.
41.
ZhuDMaTNiuZ, et al. Prognostic significance of metabolic parameters measured by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with small cell lung cancer. Lung Cancer2011; 73: 332–337.
42.
XiePYueJBZhaoHX, et al. Prognostic value of 18F-FDG PET-CT metabolic index for nasopharyngeal carcinoma. J Cancer Res Clin Oncol2010; 136: 883–889.
43.
HyunSHChoiJYShimYM, et al. Prognostic value of metabolic tumor volume measured by 18F-fluorodeoxyglucose positron emission tomography in patients with esophageal carcinoma. Ann Surg Oncol2010; 17: 115–122.
44.
WangWLarsonSMFazzariM, et al. Prognostic value of 18F-fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab2000; 85: 1107–1113.
45.
LeeHYHyunSHLeeKS, et al. Volume-based parameter of 18F-FDG PET/CT in malignant pleural mesothelioma: prediction of therapeutic response and prognostic implications. Ann Surg Oncol2010; 17: 2787–2794.
46.
ArslanNTuncelMKuzhanO, et al. Evaluation of outcome prediction and disease extension by quantitative 2-deoxy-2-[18F] fluoro-D-glucose with positron emission tomography in patients with small cell lung cancer. Ann Nucl Med2011; 25: 406–413.
47.
YanHWangRZhaoF, et al. Measurement of tumor volume by PET to evaluate prognosis in patients with advanced non-small cell lung cancer treated by non-surgical therapy. Acta Radiol2011; 52: 646–650.
48.
LiaoSPenneyBCWroblewskiK, 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 Imaging2012; 39: 27–38.
49.
LiaoSPenneyBCZhangH, et al. Prognostic value of the quantitative metabolic volumetric measurement on 18F-FDG PET/CT in stage IV non-surgical small cell lung cancer. Acad Radiol2012; 19: 69–77.
50.
LeePWeerasuriyaDKLavoriPW, et al. Metabolic tumor burden predicts for disease progression and death in lung cancer. Int J Radiat Oncol Biol Phys2007; 69: 328–333.
51.
LeePBazanJGLavoriPW, et al. Metabolic tumor volume is an independent prognostic factor in patients treated definitively for non-small-cell lung cancer. Clin Lung Cancer2012; 13: 52–58.
52.
ZhangHWroblewskiKLiaoS, et al. Prognostic value of metabolic tumor burden from 18F-FDG PET in surgical patients with non-small cell lung cancer. Acad Radiol2013; 20: 32–40.
53.
HyunSHChoiJKKimK, 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 Surg2013; 257: 364–370.
54.
VanhoveKMesottenLHeylenM, et al. Prognostic value of total lesion glycolysis and metabolic active tumor volume in non-small cell lung cancer. Cancer Treat Res Commun2018; 15: 7–12.
55.
MoonSHHyunSHChoiJY. Prognostic significance of volume based PET parameters in cancer patients. Korean J Radiol2013; 14: 1–12.
56.
O’BrienRM. A caution regarding rules of thumb for variance inflation factors. Qual Quantity2007; 41: 673–690.
