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Intratumoral uptake heterogeneity in 18 F-FDG PET has been associated with patient treatment outcomes in several cancer types. Textural feature analysis is a promising method for its quantification. An open issue associated with textural features for the quantification of intratumoral heterogeneity concerns its added contribution and dependence on the metabolically active tumor volume (MATV), which has already been shown to be a significant predictive and prognostic parameter. Our objective was to address this question using a larger cohort of patients covering different cancer types. Methods: A single database of 555 pretreatment 18 F-FDG PET images (breast, cervix, esophageal, head and neck, and lung cancer tumors) was assembled. Four robust and reproducible textural feature-derived parameters were considered. The issues associated with the calculation of textural features using co-occurrence matrices (such as the quantization and spatial directionality relationships) were also investigated. The relationship between these features and MATV, as well as among the features themselves, was investigated using Spearman rank coefficients for different volume ranges. The complementary prognostic value of MATV and textural features was assessed through multivariate Cox analysis in the esophageal and non-small cell lung cancer (NSCLC) cohorts. Results: A large range of MATVs was included in the population considered (3-415 cm 3 ; mean, 35; median,19; SD, 50). The correlation between MATV and textural features varied greatly depending on the MATVs, with reduced correlation for increasing volumes. These findings were reproducible across the different cancer types. The quantization and calculation methods both had an impact on the correlation. Volume and heterogeneity were independent prognostic factors (P 5 0.0053 and 0.0093, respectively) along with stage (P 5 0.002) in non-small cell lung cancer, but in the esophageal tumors, volume and heterogeneity had less complementary value because of smaller overall volumes. Conclusion: Our results suggest that heterogeneity quantification and volume may provide valuable complementary information for volumes above 10 cm 3 , although the complementary information increases substantially with larger volumes. Fordi agnosis and staging in oncology, 18 F-FDG PET/CT is a powerful tool (1). Its use in therapy assessment (2,3) is increasing. Within this context, more emphasis is being given to image-derived indices (4). On the one hand, features extracted from PET images, including metabolically active tumor volume (MATV), mean standardized uptake value (SUV), and total lesion glycolysis, have provided potentially higher prognostic value than standard maximum SUV in various cancer types (5). On the other hand, more recently the heterogeneity of 18 F-FDG uptake within tumors has been associated with treatment failure (4,6-8). Proposed approaches to assessing the heterogeneity of intratumoral activity distribution include visual evaluation (9), SUV coefficient of variation (10), area under...

The goal of this study was to compare visual assessment of intratumor 18 F-FDG PET uptake distribution with a textural-features (TF) automated quantification and to establish their respective prognostic value in non-small cell lung cancer (NSCLC). Methods: The study retrospectively included 102 consecutive patients. Only primary tumors were considered. Intratumor heterogeneity was visually scored (3-level scale [H visu ]) by 2 nuclear medicine physicians. Tumor volumes were automatically delineated, and heterogeneity was quantified with TF. Mean and maximum standardized uptake value were also included. Visual interobserver agreement and correlations with quantitative assessment were evaluated using the κ test and Spearman rank (ρ) coefficient, respectively. Association with overall survival and recurrencefree survival was investigated using the Kaplan-Meier method and Cox regression models. Results: Moderate correlations (0.4 , ρ , 0.6) between TF parameters and H visu were observed. Interobserver agreement for H visu was moderate (κ 5 0.64, discrepancies in 27% of the cases). High standardized uptake value, large metabolic volumes, and high heterogeneity according to TF were associated with poorer overall survival and recurrence-free survival and remained an independent prognostic factor of overall survival with respect to clinical variables. Conclusion: Quantification of 18 F-FDG uptake heterogeneity in NSCLC through TF was correlated with visual assessment by experts. However, TF also constitutes an objective heterogeneity quantification, with reduced interobserver variability, and independent prognostic value potentially useful for patient stratification and management. PET/ CT imaging with 18 F-FDG is today a well-established tool for diagnostic oncology applications (1). Its exploitation for tumor delineation in the planning of radiotherapy treatment (2) or monitoring of response to therapy (3,4) is increasing. For non-small cell lung cancer (NSCLC), 18 F-FDG PET/CT image quantification has been shown to provide prognostic information. PET image-derived features, including metabolically active tumor volume (MATV), mean standardized uptake value (SUV mean ), and total lesion glycolysis (TLG, defined as MATV · SUV mean ), have been shown to provide an accurate assessment of tumor burden with potentially higher prognostic value than standard maximum SUV (SUV max ), for both surgical and nonsurgical patients (5-9).Intratumor 18 F-FDG uptake heterogeneity has been associated with treatment failure (10), and its quantification has recently generated interest (11-14), including in lung cancer (15). Several methodologies have been proposed to assess intratumor heterogeneity, including visual evaluation (16), SUV coefficient of variation (SUV COV ) (17), area under the curve of the cumulative histogram (CH AUC ) (18), and textural-features (TF) analysis (17,19).TF analysis can generate many features quantifying heterogeneity within a delineated MATV. Recent studies have identified a few of these features that are ...

Intratumour heterogeneity quantified using textural features on both CT and PET images from routine staging (18)F-FDG PET/CT acquisitions can be used to create a nomogram with higher stratification power than staging alone.

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