Quantitative assessment of the asphericity of pretherapeutic FDG uptake as an independent predictor of outcome in NSCLC

BackgroundThe aim of the present study was to evaluate the predictive value of a novel quantitative measure for the spatial heterogeneity of FDG uptake, the asphericity (ASP) in patients with non-small cell lung cancer (NSCLC).MethodsFDG-PET/CT had been performed in 60 patients (15 women, 45 men; median age, 65.5 years) with newly diagnosed NSCLC prior to therapy. The FDG-PET image of the primary tumor was segmented using the ROVER 3D segmentation tool based on thresholding at the volume-reproducing intensity threshold after subtraction of local background. ASP was defined as the relative deviation of the tumor’s shape from a sphere. Univariate and multivariate Cox regression as well as Kaplan-Meier (KM) analysis and log-rank test with respect to overall (OAS) and progression-free survival (PFS) were performed for clinical variables, SUVmax/mean, metabolically active tumor volume (MTV), total lesion glycolysis (TLG), ASP and “solidity”, another measure of shape irregularity.ResultsASP, solidity and “primary surgical treatment” were significant independent predictors of PFS in multivariate Cox regression with binarized parameters (HR, 3.66; p < 0.001, HR, 2.11; p = 0.05 and HR, 2.09; p = 0.05), ASP and “primary surgical treatment” of OAS (HR, 3.19; p = 0.02 and HR, 3.78; p = 0.01, respectively). None of the other semi-quantitative PET parameters showed significant predictive value with respect to OAS or PFS. Kaplan-Meier analysis revealed a probability of 2-year PFS of 52% in patients with low ASP compared to 12% in patients with high ASP (p < 0.001). Furthermore, it showed a higher OAS rate in the case of low versus high ASP (1-year-OAS, 91% vs. 67%: p = 0.02).ConclusionsThe novel parameter asphericity of pretherapeutic FDG uptake seems to provide better prognostic value for PFS and OAS in NCSLC compared to SUV, metabolic tumor volume, total lesion glycolysis and solidity.

[1]  Vicky Goh,et al.  Are Pretreatment 18F-FDG PET Tumor Textural Features in Non–Small Cell Lung Cancer Associated with Response and Survival After Chemoradiotherapy? , 2013, The Journal of Nuclear Medicine.

[2]  S. J. Henley,et al.  Lung Cancer Incidence Trends Among Men and Women — United States, 2005–2009 , 2014, MMWR. Morbidity and mortality weekly report.

[3]  M. Agarwal,et al.  Revisiting the prognostic value of preoperative 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in early-stage (I & II) non-small cell lung cancers (NSCLC) , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[4]  M. Hatt,et al.  Reproducibility of Tumor Uptake Heterogeneity Characterization Through Textural Feature Analysis in 18F-FDG PET , 2012, The Journal of Nuclear Medicine.

[5]  T. Nakajima,et al.  Biological significance of 18F-FDG uptake on PET in patients with non-small-cell lung cancer. , 2014, Lung cancer.

[6]  M. Soussan,et al.  Prognostic implications of volume-based measurements on FDG PET/CT in stage III non-small-cell lung cancer after induction chemotherapy , 2013, European Journal of Nuclear Medicine and Molecular Imaging.

[7]  U. Ficola,et al.  Prediction of 2 years-survival in patients with stage I and II non-small cell lung cancer utilizing 18F-FDG PET/CT SUV quantification , 2013, Radiology and oncology.

[8]  F Hofheinz,et al.  Automatic volume delineation in oncological PET , 2011, Nuklearmedizin.

[9]  S. Chevret,et al.  Blood vessel and lymphatic vessel invasion in resected nonsmall cell lung carcinoma: Correlation with TNM stage and disease free and overall survival , 1996, Cancer.

[10]  L. Gianolli,et al.  New positron emission tomography derived parameters as predictive factors for recurrence in resected stage I non-small cell lung cancer. , 2013, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[11]  W. Moore,et al.  Prognostic value of metabolic tumor volume and total lesion glycolysis from 18F-FDG PET/CT in patients undergoing stereotactic body radiation therapy for stage I non-small-cell lung cancer , 2013, Nuclear medicine communications.

[12]  I. Apostolova,et al.  Asphericity of pretherapeutic tumour FDG uptake provides independent prognostic value in head-and-neck cancer , 2014, European Radiology.

[13]  D. Heron,et al.  Pretreatment SUVmax predicts progression-free survival in early-stage non-small cell lung cancer treated with stereotactic body radiation therapy , 2014, Radiation Oncology.

[14]  B. Manaster Spatial Heterogeneity in Sarcoma 18F-FDG Uptake as a Predictor of Patient Outcome , 2010 .

[15]  N. Demirci,et al.  High FDG uptake predicts poorer survival in locally advanced nonsmall cell lung cancer patients undergoing curative radiotherapy, independently of tumor size , 2014, Journal of Cancer Research and Clinical Oncology.

[16]  D. Boffa,et al.  Treating locally advanced disease: an analysis of very large, hilar lymph node positive non-small cell lung cancer using the National Cancer Data Base. , 2014, The Annals of thoracic surgery.

[17]  Laura H. Tang,et al.  Effect of Tumor Heterogeneity on the Assessment of Ki67 Labeling Index in Well-differentiated Neuroendocrine Tumors Metastatic to the Liver: Implications for Prognostic Stratification , 2011, The American journal of surgical pathology.

[18]  Seok Chung,et al.  Intratumoral phenotypic heterogeneity as an encourager of cancer invasion. , 2014, Integrative biology : quantitative biosciences from nano to macro.

[19]  P. Mordant,et al.  A review of 250 ten-year survivors after pneumonectomy for non-small-cell lung cancer. , 2014, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[20]  J. Crowley,et al.  The IASLC Lung Cancer Staging Project: Validation of the Proposals for Revision of the T, N, and M Descriptors and Consequent Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours , 2007, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[21]  Florent Tixier,et al.  Visual Versus Quantitative Assessment of Intratumor 18F-FDG PET Uptake Heterogeneity: Prognostic Value in Non–Small Cell Lung Cancer , 2014, The Journal of Nuclear Medicine.

[22]  Issam El-Naqa,et al.  Exploring feature-based approaches in PET images for predicting cancer treatment outcomes , 2009, Pattern Recognit..

[23]  R. Subramaniam,et al.  PET-based primary tumor volumetric parameters and survival of patients with non-small cell lung carcinoma. , 2013, AJR. American journal of roentgenology.

[24]  G. V. von Schulthess,et al.  Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. , 2003, The New England journal of medicine.

[25]  David P. Dobkin,et al.  The quickhull algorithm for convex hulls , 1996, TOMS.

[26]  Jeffrey D Bradley,et al.  Prediction of survival by [18F]fluorodeoxyglucose positron emission tomography in patients with locally advanced non-small-cell lung cancer undergoing definitive chemoradiation therapy: results of the ACRIN 6668/RTOG 0235 trial. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  M. Hatt,et al.  Intratumor Heterogeneity Characterized by Textural Features on Baseline 18F-FDG PET Images Predicts Response to Concomitant Radiochemotherapy in Esophageal Cancer , 2011, The Journal of Nuclear Medicine.

[28]  C Huang,et al.  Feasibility study of FDG PET/CT-derived primary tumour glycolysis as a prognostic indicator of survival in patients with non-small-cell lung cancer. , 2014, Clinical radiology.

[29]  J. Pantarotto,et al.  Pretreatment [18F]-fluoro-2-deoxy-glucose positron emission tomography maximum standardized uptake value as predictor of distant metastasis in early-stage non-small cell lung cancer treated with definitive radiation therapy: rethinking the role of positron emission tomography in personalizing treatm , 2014, International journal of radiation oncology, biology, physics.

[30]  Joon Young Choi,et al.  Volume-based assessment by 18F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer , 2013, European Journal of Nuclear Medicine and Molecular Imaging.

[31]  F. O’Sullivan,et al.  Spatial Heterogeneity in Sarcoma 18F-FDG Uptake as a Predictor of Patient Outcome , 2008, Journal of Nuclear Medicine.