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Purpose: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [18F]FDG PET (PET) in follicular lymphoma patients. Methods: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS). Results: Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97

The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70–0.91). Three-years PFS was 0.95 (95% CI 0.90–0.97) in eotPET negative and 0.22 (95% CI 0.11–0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

Background: Tumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, non-invasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging has been applied mainly on conventional magnetic resonance imaging (MRI), although virtually extendible to any imaging modality, including advanced MRI techniques such as perfusion and diffusion MRI as well as positron emission tomography (PET) imaging. Objectives: This study aims to evaluate an innovative PET and MRI approach for assessing hypoxia, perfusion, and tissue diffusion in HGGs and derive a combined map for clustering of intra-tumor heterogeneity. Materials and Methods: Seventeen patients harboring HGGs underwent a pre-operative acquisition of MR perfusion (PWI), Diffusion (dMRI) and 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET imaging to evaluate tumor vascularization, cellularity, and hypoxia, respectively. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and T1 post-contrast images, and voxel-wise clustering of each quantitative imaging map identified eight combined PET and physiologic MRI habitats. Habitats’ spatial distribution, quantitative features and histopathological characteristics were analyzed. Results: A highly reproducible distribution pattern of the clusters was observed among different cases, particularly with respect to morphological landmarks as the necrotic core, contrast-enhancing vital tumor, and peritumoral infiltration and edema, providing valuable supplementary information to conventional imaging. A preliminary analysis, performed on stereotactic bioptic samples where exact intracranial coordinates were available, identified a reliable correlation between the expected microenvironment of the different spatial habitats and the actual histopathological features. A trend toward a higher representation of

Deep learning (DL) strategies applied to magnetic resonance (MR) images in positron emission tomography (PET)/MR can provide synthetic attenuation correction (AC) maps, and consequently PET images, more accurate than segmentation or atlas-registration strategies. As first objective, we aim to investigate the best MR image to be used and the best point of the AC pipeline to insert the synthetic map in. Sixteen patients underwent a 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) and a PET/MR brain study in the same day. PET/CT images were reconstructed with attenuation maps obtained: (1) from CT (reference), (2) from MR with an atlas-based and a segmentation-based method and (3) with a 2D UNet trained on MR image/attenuation map pairs. As for MR, T1-weighted and Zero Time Echo (ZTE) images were considered; as for attenuation maps, CTs and 511 keV low-resolution attenuation maps were assessed. As second objective, we assessed the ability of DL strategies to provide proper AC maps in presence of cranial anatomy alterations due to surgery. Three 11C-methionine (METH) PET/MR studies were considered. PET images were reconstructed with attenuation maps obtained: (1) from diagnostic coregistered CT (reference), (2) from MR with an atlas-based and a segmentation-based method and (3) with 2D UNets trained on the sixteen FDG anatomically normal patients. Only UNets taking ZTE images in input were considered. FDG and METH PET images were quantitatively evaluated. As for anatomically normal FDG patients, UNet AC models generally provide an uptake estimate with lower bias than atlas-based or segmentation-based methods. The intersubject average bias on images corrected with UNet AC maps is always smaller than 1.5%, except for AC maps generated on too coarse grids. The intersubject bias variability is the lowest (always lower than 2%) for UNet AC maps coming from ZTE images, larger for other methods. UNet models working on MR ZTE images and generating synthetic CT or 511 k

PURPOSE To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PATIENTS AND METHODS Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter $ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). RESULTS Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter. 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P 5.62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P 5.24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P 5.53) in subgroup C (classic bulky). CONCLUSION cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.

Purpose: The aim of the present systematic review was to provide an overview on the different positron emission tomography (PET) hypoxia radiotracers in the clinical setting of lung cancer. Methods: We performed a comprehensive literature review on the role of PET hypoxia imaging in lung cancer using the electronic databases PubMed and Scopus to select English written language articles on humans from January 2007 to February 2017. The following keywords have been used: “hypoxia” or “hypoxic” and “PET” and “lung cancer”. Reviews, clinical reports, and editorial articles were excluded. Results: Originally, we considered 76 manuscripts, coming to a selection of 37 original articles. In particular, the selected original articles included the following PET radiotracer categories: nitroimidazole compounds, glucose analogue and bis(thiosemicarbazone) complexes. PET radiotracers, particularly nitroimidazole compounds, are the most suitable method to directly identify the presence of hypoxia in lung cancer. Conclusions: Based on the literature review, the definition of the role of clinical application of PET hypoxia radiotracers has been provided reporting that in vivo hypoxia imaging is needed for effective treatment selection, individual treatment planning, and treatment monitoring in oncology.

Diagnostic accuracy in FDG-PET imaging highly depends on the operating procedures. In this clinical study on dementia, we compared the diagnostic accuracy at a single-subject level of a) Clinical Scenarios, b) Standard FDG Images and c) Statistical Parametrical (SPM) Maps generated via a new optimized SPM procedure. We evaluated the added value of FDG-PET, either Standard FDG Images or SPM Maps, to Clinical Scenarios. In 88 patients with neurodegenerative diseases (Alzheimer's Disease-AD, Frontotemporal Lobar Degeneration-FTLD, Dementia with Lewy bodies-DLB and Mild Cognitive Impairment-MCI), 9 neuroimaging experts made a forced diagnostic decision on the basis of the evaluation of the three types of information. There was also the possibility of a decision of normality on the FDG-PET images. The clinical diagnosis confirmed at a long-term follow-up was used as the gold standard. SPM Maps showed higher sensitivity and specificity (96% and 84%), and better diagnostic positive (6.8) and negative (0.05) likelihood ratios compared to Clinical Scenarios and Standard FDG Images. SPM Maps increased diagnostic accuracy for differential diagnosis (AD vs. FTD; beta 1.414, p = 0.019). The AUC of the ROC curve was 0.67 for SPM Maps, 0.57 for Clinical Scenarios and 0.50 for Standard FDG Images. In the MCI group, SPM Maps showed the highest predictive prognostic value (mean LOC = 2.46), by identifying either normal brain metabolism (exclusionary role) or hypometabolic patterns typical of different neurodegenerative conditions

Purpose: The effects of regularizing priors on the maximum likelihood (ML) reconstruction of activity patterns in Positron Emission Tomography (PET) were assessed. Methods: Two edge-preserving priors (one originally proposed by Nuyts et al. and nowadays implemented and commercialized by General Electric Medical Systems as Q. Clear software, and a second one originally proposed by Rapisarda et al. and our group) were assessed and compared to a standard Ordered Subset (OS)-ML reconstruction, assumed as reference. The main difference between the two priors is that Nuyts prior (NY-p) penalizes relative voxel differences while Rapisarda prior (RP-p) absolute ones. Prior parameters were selected by imposing a reference noise texture inside uniform regions with activity comparable to that measured in 18 F-FluoroDeoxyGlucose (FDG) patient livers overall the field of view. Comparisons were then made: (a) on phantom data in terms of sphere recovery coefficients, ability to correctly reconstruct uniform irregularly shaped objects and heterogeneous patterns in patient backgrounds; (b) on patient data in terms of lesion detectability and image quality. Results: On phantoms, both priors succeeded in improving all the assessed features with respect to standard OS-ML reconstruction, mainly thanks to the better signal convergence and to the noise breakup control. On 10 mm spheres, an average recovery coefficient augment of 9% (NY-p) and 34% (RP-p) was obtained; homogeneity of uniform activity objects augmented of 4% (NY-p) and 11% (RP-p); accuracy in reconstructing heterogeneous lesions improved on average of 5% (NY-p) and 15% (RP-p). On patients, lesion detectability resulted improved (on 27 of 30 lesions), regardless of lesion anatomical districts and position in the scanner field of view. NY-p provides a spatial resolution and a noise texture more uniform in the field of view and an image quality similar to standard OS-ML. RP-p has instead a behavior more dependent on the local c

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