Background: The AHL2011 study demonstrated that a PET-driven strategy allows to deescalate treatment to 4 x ABVD in PET negative patients after 2 cycles of escalated BEACOPP (BEACOPPesc) without loss of tumor control in patients with advanced Hodgkin lymphoma (HL) compared to a non PET-monitored treatment delivering 6 x BEACOPPesc (Casasnovas RO et al, Lancet Oncol 2019). The interim PET results after 2 (PET2) and 4 (PET4) cycles of chemotherapy were found to influence patients PFS and OS independently of IPS. To further refine the patients outcome prediction we evaluate the prognostic value of baseline Total Metabolic Tumor Volume (TMTV) and tumor dissemination (SDmax) in Ann Arbor stage III-IV patients included in the AHL2011 trial.

Component-trees constitute an efficient data structure for hierarchical image modeling. In particular they are relevant for processing and analyzing images where the structures of interest correspond either to local maxima or local minima of intensity. This is indeed the case of functional data in medical imaging. This motivates the use of component-tree-based approaches for analyzing Positron Emission Tomography (PET) images in the context of oncology. In this article, we present a simple, yet efficient, methodological framework for PET image analysis based on component-trees. More precisely, we show that the second-order paradigm of shaping, that broadly consists of computing the component-tree of a component-tree, provides a relevant way of generalizing the threshold-based strategies classically used by medical practitioners for handling PET images. In addition, it also allows to embed relevant priors regarding the sought cancer lesions.

To determine whether [18F]FDG PET/CT-derived radiomic features alone or in combination with clinical, laboratory and biological parameters are predictive of 2-year progression-free survival (PFS) in patients with mantle cell lymphoma (MCL), and whether they enable outcome prognostication. Included in this retrospective study were 107 treatment-naive MCL patients scheduled to receive CD20 antibody-based immuno(chemo)therapy. Standardized uptake values (SUV), total lesion glycolysis, and 16 co-occurrence matrix radiomic features were extracted from metabolic tumour volumes on pretherapy [18F]FDG PET/CT scans. A multilayer perceptron neural network in combination with logistic regression analyses for feature selection was used for prediction of 2-year PFS. International prognostic indices for MCL (MIPI and MIPI-b) were calculated and combined with the radiomic data. Kaplan–Meier estimates with log-rank tests were used for PFS prognostication. SUVmean (OR 1.272, P = 0.013) and Entropy (heterogeneity of glucose metabolism; OR 1.131, P = 0.027) were significantly predictive of 2-year PFS: median areas under the curve were 0.72 based on the two radiomic features alone, and 0.82 with the addition of clinical/laboratory/biological data. Higher SUVmean in combination with higher Entropy (SUVmean >3.55 and entropy >3.5), reflecting high “metabolic risk”, was associated with a poorer prognosis (median PFS 20.3 vs. 39.4 months, HR 2.285, P = 0.005). The best PFS prognostication was achieved using the MIPI-bm (MIPI-b and metabolic risk combined): median PFS 43.2, 38.2 and 20.3 months in the low-risk, intermediate-risk and high-risk groups respectively (P = 0.005). In MCL, the [18F]FDG PET/CT-derived radiomic features SUVmean and Entropy may improve prediction of 2-year PFS and PFS prognostication. The best results may be achieved using a combination of metabolic, clinical, laboratory and biological parameters.

In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT's ability to expend energy has made it a potential target for novel therapies to ameliorate obesity and associated metabolic disorders in humans. Though this tissue has been well studied in small animals, BAT's thermogenic capacity in humans remains largely unknown due to the difficulties of measuring its volume, activity, and distribution. Identifying and quantifying active human BAT is commonly performed using 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography and computed tomography (PET/CT) scans following cold-exposure or pharmacological activation. Here we describe a detailed image-analysis approach to quantify total-body human BAT from 18F-FDG PET/CT scans using an open-source software. We demonstrate the drawing of user-specified regions of interest to identify metabolically active adipose tissue while avoiding common non-BAT tissues, to measure BAT volume and activity, and to further characterize its anatomical distribution. Although this rigorous approach is time-consuming, we believe it will ultimately provide a foundation to develop future automated BAT quantification algorithms.

PURPOSE:This study aims to predict hematological toxicity induced by Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18-fluorocholine (F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with Ra radionuclide therapy. PATIENTS AND METHODS:F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with Ra. Bone metastatic disease was quantified on the basis of the maximum standardized uptake value (SUV), total lesion activity (TLA=MBTV×SUVmean), or MBTV/height (MBTV/H) and TLA/H. F-FCH PET/CT bone tumor burden and activity were analyzed to identify which parameters could predict hematological toxicity [on hemoglobin (Hb), platelets (PLTs), and lymphocytes] while on Ra therapy. Pearson's correlation was used to identify the correlations between age, prostate-specific antigen, and F-FCH PET parameters. RESULTS:MBTV ranged from 75 to 1259 cm (median: 392 cm). TLA ranged from 342 to 7198 cm (median: 1853 cm). Patients benefited from two to six cycles of Ra (n=56 cycles in total). At the end of Ra therapy, five of the 15 (33%) patients presented grade 2/3 toxicity on Hb and lymphocytes, whereas three of the 15 (20%) patients presented grade 2/3 PLT toxicity.Age was correlated negatively with both MBTV (r=-0.612, P=0.015) and TLA (r=-0.596, P=0.018). TLA, TLA/H, and MBTV/H predicted hematological toxicity on Hb, whereas TLA/H and MBTV/H predicted toxicity on PLTs at the end of Ra cycles. Receiver operating characteristic curve analysis allowed to define the cutoffs for MBTV (915 cm) and TLA (4198 cm) predictive for PLT toxicity, with an accuracy of 0.92 and 0.99. CONCLUSION:Tumor bone burden calculation is feasible with F-FCH PET/CT with freely available open-source software. In this pilot study, baseline F-FCH PET/CT markers (TLA, MBTV) have shown abilities to predict Hb and PLT toxicity after Ra therapy and could be explored for patient selection and treatment optimization.

AIM:Evaluate response and predict prognosis of patients with newly diagnosed metastatic breast cancer treated with first line systemic therapy using European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in solid Tumours (PERCIST). METHODS:From December 2006 to August 2013, 57 women with newly diagnosed metastatic breast cancer were retrospectively evaluated. FDG-PET/CT was performed within one month before treatment and repeated after at least 3 cycles of treatment. Metabolic response evaluation was evaluated by two readers according to both EORTC criteria and PERCIST, classifying the patients into 4 response groups: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). RESULTS:With EORTC criteria, 22 patients had CMR, 17 PMR, 6 SMD and 12 PMD. With PERCIST, 20 patients had CMR, 15 PMR, 10 SMD and 12 PMD. There was agreement between EORTC and PERCIST in 84% of the patients. By log-rank analysis, metabolic response evaluated with both EORTC criteria and PERCIST was able to predict overall survival (p = 0.028 and 0.002 respectively). CMR patient group had longer median OS than patients in the combined PMR+SMD+PMD group (60 vs 26 months both with EORTC and PERCIST; p = 0.009 and 0.006 respectively). By multivariate analysis, CMR either with EORTC or PERCIST remained an independent predictor of survival. CONCLUSION:Metabolic response evaluation with EORTC criteria and PERCIST gave similar prognostic stratification for metastatic breast cancer treated with a first line of systemic therapy.

Significance Brown adipose tissue (BAT) is currently being explored as a target for the treatment of obesity and diabetes after repeated demonstrations on positron emission tomography-computed tomography (PET/CT) imaging of its ability to metabolize glucose following acute cold exposure. Measurement of whole-body BAT volume, activity, and distribution is difficult because brown adipocytes are structurally commingled among white adipose tissue, muscle, and blood vessels. Thus, BAT’s potential contribution to metabolism remains unclear. To address this, we have identified several refinements to improve current PET/CT analyses and demonstrated their impact in healthy lean vs. obese individuals. Using the refined technique, we defined whole-body BAT distribution and estimated its metabolic capacity and found that it is substantially higher than usually reported.

7509 Background: The TMTV assessed on the baseline FDG-PET is a novel approach of tumor burden measurement. It has been reported to influence HL outcome in a retrospective series (Kanoun, EJNM 2014). We designed a study evaluating the TMTV prognosis value in patients (pts) prospectively enrolled in a phase III randomized trial testing a treatment strategy driven by PET, compared to a standard treatment not monitored by PET. Methods: Eligible pts had to be enrolled in the AHL2011 trial (NCT01358747) and to have a baseline PET (PET0) available for central review and TMTV calculation. Pts were 16-60 y, with a previously untreated advanced HL (Ann Arbor stage III, IV or high risk IIB) and were randomly assigned to a treatment strategy driven by PET after 2 escalated BEACOPP (BEA) cycles (PET2), delivering 4 cycles of ABVD for PET2- pts and 4 cycles of BEA for PET2+ pts or a standard treatment not monitored by PET and delivering 6 cycles of BEA. PET2 were centrally reviewed and interpreted according to Deauville criteria. TMTV was computed on PET0 by summing the metabolic volumes of the individual lesions using the 41% SUVmax thresholding method already described in lymphoma. Results: 392 pts with a median age of 30 y were included: 64% were male, 89% had stage III/IV, and 59% an IPS ≥ 3. Median TMTV was 200 ml (23 – 2149). Using a X-tile method a 350 ml cut off value was identified from a training set (n = 262) and confirmed in a validation set (n = 130) of pts obtained from the whole series. With a 16 months median follow up, 2y-PFS was 81% vs 93% in pts with high and low TMTV respectively in the whole population (p = 0.0015; HR = 3). PET2 positivity was also related to a lower 2y-PFS compared to PET2- pts (76% vs 92%; p < 0.0001). Then 3 groups could be identified: pts with either [high TMTV and PET2+ (n = 23; 6%)], or [high TMTV and PET2-, or low TMTV and PET2+ (n = 103; 27%)], or [low TMTV and PET2- (n = 261; 67%)] had a 61%, 88%, 94% 2y-PFS respectively (p < 0.0001). Conclusions: TMTV predicts the outcome of young advanced HL pts independently of the early metabolic response to treatment. The combination of TMTV and PET2 allows identifying 3 subsets of HL pts with significantly different outcome that may help clinician to better tailor therapy. Clinical trial information: NCT01358747.

Développer un logiciel gratuit, open source, multiplateforme et collaboratif pour automatiser le recueil des données d’imagerie en recherche clinique. Présentation globale : initialement développé par le Beth Israël Deaconess Medical Center (Boston), une collaboration depuis 2014 vise à proposer à la communauté scientifique un logiciel disponible à tous qui pourra s’enrichir des différentes problématiques de recherche pour créer un outil polyvalent venant simplifier et accélérer les étapes de recueil de données d’imagerie. Le logiciel est développé sous FIJI (distribution d’ImageJ), distribué sous licence GPL. Il est également utilisable sur n’importe quel système d’exploitation (Mac Os X, Windows ou GNU/Linux). La validation du logiciel a été réalisée en comparaison avec les stations commerciales (sur fantôme et données cliniques ; Kanoun et al. Plos One 2015). Fonctionnalités : - lecture et organisation des séries DICOM. - Affichage TEP/CT : affichage des deux modalités, fusion d’images, gestion de différentes Look-up-table pré-installées, reconstruction MPR et MIP, annotation d’image, captures secondaires. - Quantification : SUV (max, moyen, peak, écart-type), SUL, MTV (seuillage fixe ou relatif), TLG. Définitions de ROIs irrégulières ou géométriques. - Export des données quantitatives par fichiers CSV, ROI par ROI, dont la lecture peut être automatisée. Sauvegarde des ROIs. - Possibilité de création d’outils adaptés à chaque étude, de travail collaboratif et synchronisé multi-opérateur (collection des données dans une base de données centralisée). - Autres : recalage d’IRM, prétraitement possible des images dans FIJI/ImageJ (filtrage). Beth Israel Plugin for FIJI permet un recueil de données simplifié et organisé pouvant résoudre les problèmes de coût et de disponibilité de solutions logicielles. Basé sur un projet collaboratif, le logiciel pourra s’enrichir des différentes problématiques de recherche et créer un outil polyvalent qui viendra potentialiser les opportunités d’applications scientifiques.

AIM:To investigate the respective influence of software tool and total metabolic tumor volume (TMTV0) calculation method on prognostic stratification of baseline 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET) in newly diagnosed Hodgkin lymphoma (HL).METHODS:59 patients with newly diagnosed HL were retrospectively included. [18F]FDG-PET was performed before any treatment. Four sets of TMTV0 were calculated with Beth Israel (BI) software: based on an absolute threshold selecting voxel with standardized uptake value (SUV) >2.5 (TMTV02.5), applying a per-lesion threshold of 41% of the SUV max (TMTV041) and using a per-patient adapted threshold based on SUV max of the liver (>125% and >140% of SUV max of the liver background; TMTV0125 and TMTV0140). TMTV041 was also determined with commercial software for comparison of software tools. ROC curves were used to determine the optimal threshold for each TMTV0 to predict treatment failure.RESULTS:Median follow-up was 39 months. There was an excellent correlation between TMTV041 determined with BI and with the commercial software (r = 0.96, p<0.0001). The median TMTV0 value for TMTV041, TMTV02.5, TMTV0125 and TMTV0140 were respectively 160 (used as reference), 210 ([28;154] p = 0.005), 183 ([-4;114] p = 0.06) and 143 ml ([-58;64] p = 0.9). The respective optimal TMTV0 threshold and area under curve (AUC) for prediction of progression free survival (PFS) were respectively: 313 ml and 0.70, 432 ml and 0.68, 450 ml and 0.68, 330 ml and 0.68. There was no significant difference between ROC curves. High TMTV0 value was predictive of poor PFS in all methodologies: 4-years PFS was 83% vs 42% (p = 0.006) for TMTV02.5, 83% vs 41% (p = 0.003) for TMTV041, 85% vs 40% (p<0.001) for TMTV0125 and 83% vs 42% (p = 0.004) for TMTV0140.CONCLUSION:In newly diagnosed HL, baseline metabolic tumor volume values were significantly influenced by the choice of the method used for determination of volume. However, no significant differences were found in term of prognosis.

Aim Physiologic activity of 18F-fluorodeoxyglucose (FDG) in the intestinal tract occurs frequently in patients undergoing PET/computed tomography (CT) imaging, appearing most often in the colon. The purpose of this study is to determine the localization of the FDG within the colon. We hypothesize that intestinal FDG activity is intraluminal. Methods In a prospective Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, patients with physiologic colonic FDG activity on PET/CT scans were enrolled to undergo repeat imaging 2 h after stimulation of colonic motility with a high-fat meal. Results We identified 13 patients who had focal FDG activity in their colon during a routine clinical PET/CT scan. After administration of a high-fat meal, 10 patients (77%) demonstrated antegrade movement of FDG along the colon, consistent with luminal clearance. Conclusion Our results suggest that normal physiologic FDG activity within the large intestine, seen on PET/CT scans, is intraluminal.

As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by (18)F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.