GATE (Geant4 Application for Emission Tomography) is a Monte Carlo simulation platform developed by the OpenGATE collaboration since 2001 and first publicly released in 2004. Dedicated to the modelling of planar scintigraphy, single photon emission computed tomography (SPECT) and positron emission tomography (PET) acquisitions, this platform is widely used to assist PET and SPECT research. A recent extension of this platform, released by the OpenGATE collaboration as GATE V6, now also enables modelling of x-ray computed tomography and radiation therapy experiments. This paper presents an overview of the main additions and improvements implemented in GATE since the publication of the initial GATE paper (Jan et al 2004 Phys. Med. Biol. 49 4543-61). This includes new models available in GATE to simulate optical and hadronic processes, novelties in modelling tracer, organ or detector motion, new options for speeding up GATE simulations, examples illustrating the use of GATE V6 in radiotherapy applications and CT simulations, and preliminary results regarding the validation of GATE V6 for radiation therapy applications. Upon completion of extensive validation studies, GATE is expected to become a valuable tool for simulations involving both radiotherapy and imaging.

¹⁸F-FDG PET is often used in clinical routine for diagnosis, staging, and response to therapy assessment or prediction. The standardized uptake value (SUV) in the primary or regional area is the most common quantitative measurement derived from PET images used for those purposes. The aim of this study was to propose and evaluate new parameters obtained by textural analysis of baseline PET scans for the prediction of therapy response in esophageal cancer. Methods: Forty-one patients with newly diagnosed esophageal cancer treated with combined radiochemotherapy were included in this study. All patients underwent pretreatment whole-body ¹⁸F-FDG PET. Patients were treated with radiotherapy and alkylatinlike agents (5-fluorouracil-cisplatin or 5-fluorouracil-carboplatin). Patients were classified as nonresponders (progressive or stable disease), partial responders, or complete responders according to the Response Evaluation Criteria in Solid Tumors. Different image-derived indices obtained from the pretreatment PET tumor images were considered. These included usual indices such as maximum SUV, peak SUV, and mean SUV and a total of 38 features (such as entropy, size, and magnitude of local and global heterogeneous and homogeneous tumor regions) extracted from the 5 different textures considered. The capacity of each parameter to classify patients with respect to response to therapy was assessed using the Kruskal–Wallis test (P < 0.05). Specificity and sensitivity (including 95% confidence intervals) for each of the studied parameters were derived using receiver-operating-characteristic curves. Results: Relationships between pairs of voxels, characterizing local tumor metabolic nonuniformities, were able to significantly differentiate all 3 patient groups (P < 0.0006). Regional measures of tumor characteristics, such as size of nonuniform metabolic regions and corresponding intensity nonuniformities within these regions, were also significant factors for prediction of response to therapy (P = 0.0002). Receiver-operating-characteristic curve analysis showed that tumor textural analysis can provide nonresponder, partial-responder, and complete-responder patient identification with higher sensitivity (76%–92%) than any SUV measurement. Conclusion: Textural features of tumor metabolic distribution extracted from baseline ¹⁸F-FDG PET images allow for the best stratification of esophageal carcinoma patients in the context of therapy-response prediction.

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. 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. 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 = 0.0053 and 0.0093, respectively) along with stage (P = 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. 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.

¹⁸F-FDG PET measurement of standardized uptake value (SUV) is increasingly used for monitoring therapy response and predicting outcome. Alternative parameters computed through textural analysis were recently proposed to quantify the heterogeneity of tracer uptake by tumors as a significant predictor of response. The primary objective of this study was to evaluate the reproducibility of these heterogeneity measurements. Methods: Double baseline ¹⁸F-FDG PET scans were acquired within 4 d of each other for 16 patients before any treatment was considered. A Bland–Altman analysis was performed on 8 parameters based on histogram measurements and 17 parameters based on textural heterogeneity features after discretization with values between 8 and 128. Results: The reproducibility of maximum and mean SUV was similar to that in previously reported studies, with a mean percentage difference of 4.7% ± 19.5% and 5.5% ± 21.2%, respectively. By comparison, better reproducibility was measured for some textural features describing local heterogeneity of tracer uptake, such as entropy and homogeneity, with a mean percentage difference of −2% ± 5.4% and 1.8% ± 11.5%, respectively. Several regional heterogeneity parameters such as variability in the intensity and size of regions of homogeneous activity distribution had reproducibility similar to that of SUV measurements, with 95% confidence intervals of −22.5% to 3.1% and −1.1% to 23.5%, respectively. These parameters were largely insensitive to the discretization range. Conclusion: Several parameters derived from textural analysis describing heterogeneity of tracer uptake by tumors on local and regional scales had reproducibility similar to or better than that of simple SUV measurements. These reproducibility results suggest that these ¹⁸F-FDG PET–derived parameters, which have already been shown to have predictive and prognostic value in certain cancer models, may be used to monitor therapy response and predict patient outcome.