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Purpose: To investigate the value of the metabolic tumor response assessed with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiologic markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in women with triple-negative breast cancer (TNBC).Experimental Design: Fifty consecutive women with TNBC and an indication for NAC were prospectively included. Different pretreatment clinical, biologic, and pathologic biomarkers, including SBR grade, the Ki-67 proliferation index, androgen receptor expression, EGF receptor (EGFR), and cytokeratin 5/6 staining, were assessed. Tumor glucose metabolism at baseline and its change after the first cycle of NAC (ΔSUVmax) were assessed using FDG-PET.Results: The pCR rate was 42%. High Ki-67 proliferation index (P = 0.016), negative EGFR status (P = 0.042), and high ΔSUVmax (P = 0.002) were significantly associated with pCR. In multivariate logistic regression, both negative EGFR status (OR, 6.4; P = 0.043) and high ΔSUVmax (OR, 7.1; P = 0.014) were independent predictors of pCR. Using a threshold at −50%, tumor ΔSUVmax predicted pCR with a negative, a positive predictive value, and an accuracy of 79%, 70%, and 75%, respectively. Combining a low ΔSUVmax and positive EGFR status could predict non-pCR with an accuracy of 92%.Conclusions: It is important to define the chemosensitivity of TNBC to NAC early. Combining EGFR status and the metabolic response assessed with FDG-PET can help the physician to early predict the probability of achieving pCR or not. Given these results, the interest of response-guided tailoring of the chemotherapy might be tested in multicenter trials. Clin Cancer Res; 21(24); 5460–8. ©2015 AACR.

Supplementary Figure 1: Graphical display of changes in primary tumor SUVmax between baseline and interim 18F-FDG PET exams.

Introduction: Whereas numerous studies on several cancers describe the link between social conditions and disease severity, little is known about the social and demographic characteristics of Hodgkin lymphoma (HL) patients. At diagnosis, 10–15% of the patients in the advanced stages have a well-known poor outcome owing to their chemoresistance, but the determinants of the more advanced stages remain elusive. The objective of the present study was to decipher the potential impact of social disparities on the disease features at diagnosis and analyze how the sociodemographic patient features could impact the HL outcome of patients with advanced-stage HL enrolled in the AHL2011 trial. Methods: This ancillary study was conducted on a cohort of patients from French centers that had recruited more than five patients in the phase III AHL2011 study (NCT0135874). Patients had to be alive at the time of the ancillary study and had to have given their consent to answer the questionnaire. Pre-treatment data (age, gender, stage, B symptoms, IPS), the treatment received, the responses to PET-CT, and the presence of serious adverse events (serious adverse events—SAEs) were all extracted from the AHL2011 trial database. Sociodemographic data—marital status, living area, level of education, socio-professional category, and professional situation—were extracted from the questionnaires. The population density at the point of diagnosis was determined based on ZIP Code, and the distance from the reference medical center was then calculated by the road network. Baseline PET acquisition was performed before any treatment. PET images at baseline were centrally reviewed. The total metabolic tumor volume (TMTV) at the baseline was calculated using a 41% SUVmax cutoff for each lesion. Progression-free survival was defined as the time from randomization to the first progression, relapse, or death from any cause or the last follow-up. The data cutoff for the analyses presented here was 31 October 2017. The progression-free survival was analyzed on an intention-to-treat basis. Results: Among the 823 patients enrolled in the AHL2011 study, the questionnaire was sent to 394 patients, of whom 232 (58.9%) responded. At the time of HL diagnosis, 61.9% (N = 143) of patients declared that they were not socially isolated, 38.1% (N = 88) that they were single, 163 (71.2%) had a professional activity, and 66 (28.8%) were inactive owing to unemployment, retirement, or sick leave. Of the patients, 31.1% (N = 71) lived in a rural region, compared to 68.9% (N = 157) that lived in an urban region. The residence ZIP Code at the time of HL diagnosis was available for 163 (70%). Sociodemographic characteristics did not influence the presence of usual prognostic factors (ECOG, B symptoms, bulky mass, IPS) except for professional activity, which was associated with more frequent low IPS (0–2) (79 (48.5%) active versus 20 (30.3%) inactive patients; p = 0.012). Likewise, no correlation was observed between TMTV and sociodemographic characteristics. However, the TMTV quartile distribution was different according to the living area, with the two upper quartiles being enriched with patients living in a rural area (p = 0.008). Moreover, a negative correlation between the average number of the living area’s inhabitants and TMTV (R Pearson = −0.29, p = 0.0004) was observed. Conclusion: This study focused on sociodemographic parameters in advanced-stage HL patients and shows that professional activity is associated with more favorable disease features (low IPS), while patients living in rural or low-populated areas are more likely to have an unfavorable HL presentation with a high tumor burden (high TMTV). These data suggest that some patient sociodemographic characteristics might impact either access to medical care or environmental exposure, leading to a higher frequency of unfavorable presentations. Further prospective sociodemographic studies are necessary to confirm these preliminary results.

Follicular lymphoma (FL) is the most common indolent lymphoma. Despite the clear benefit of CD20-based therapy, a subset of FL patients still progress to aggressive lymphoma. Thus, identifying early biomarkers that incorporate positron emission tomography metrics could be helpful to identify patients with a high risk of treatment failure with rituximab. We retrospectively included a total of 132 untreated FL patients separated into training and validation cohorts. Optimal threshold of baseline whole-body maximum standardized uptake (SUVmax) was first determined in the training cohort (n=48) to predict progression-free survival (PFS). The PET results were investigated along with the tumor and immune microenvironment, which were determined by immunochemistry and transcriptome studies involving gene set enrichment analyses and immune cell deconvolution, together with the tumor mutation profile. We report that baseline SUVmax>14.5 was associated with poorer PFS than baseline SUVmax≤14.5 (hazard ratio =0.28; P=0.00046). Neither immune T-cell infiltration nor immune checkpoint expression were associated with baseline PET metrics. By contrast, FL samples with Ki-67 staining ≥10% showed enrichment of cell cycle/DNA genes (P=0.013) and significantly higher SUVmax values (P=0.007). Despite similar oncogenic pathway alterations in both SUVmax groups of FL samples, four out of five cases harboring the infrequent FOXO1 transcription factor mutation were seen in FL patients with SUVmax>14.5. Thus, high baseline SUVmax reflects FL tumor proliferation and, together with Ki-67 proliferative index, can be used to identify patients at risk of early relapse with rituximab chemotherapy.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).

ALK-positive histiocytosis is a recently described entity with few reported cases in literature. Herein, we report an unusual case of ALK-positive histiocytosis showing an Erdheim-Chester disease (ECD)-like presentation, occurring in a 37-year-old woman with a 2-year history of chronic lymphocytic leukaemia (CLL). Our CLL patient relapsed 6 months after the end of fludarabine, cyclophosphamide and rituximab frontline therapy and complained of lower limb pains. A bone marrow biopsy was performed and showed concomitant CLL/small lymphocytic lymphoma and ALK-positive histiocytosis with an identical immunoglobulin heavy-chain gene rearrangement in both neoplasms, suggesting clonal relationship. After 4 years under ibrutinib therapy, our patient remains free of both diseases. This report extends the spectrum of composite hematolymphoid neoplasms and shows that ALK rearrangement should be considered in all histiocytosis subtypes. Moreover, both tumours eradication under ibrutinib suggests that BTK inhibitors may also be effective in histiocytic neoplasms.

Simple Summary We focus on the role and current applications of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in the management of lymphoma patients through improved staging or treatment response assessment or through early PET-driven therapeutic strategies, leading the way to a novel area of personalized medicine, optimizing disease control and toxicity. We discuss the potential future directions of innovative metabolic metrics that are being developed, notably to assess response to new immunotherapy regimens and to provide an improved prognostic factor for predicting patients’ survival. Finally, we present new radiopharmaceuticals developed following the identification of pathways or specific receptors in lymphomas, providing great opportunities for molecular imaging in treatment evaluation and management. Abstract 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) is an essential part of the management of patients with lymphoma at staging and response evaluation. Efforts to standardize PET acquisition and reporting, including the 5-point Deauville scale, have enabled PET to become a surrogate for treatment success or failure in common lymphoma subtypes. This review summarizes the key clinical-trial evidence that supports PET-directed personalized approaches in lymphoma but also points out the potential place of innovative PET/CT metrics or new radiopharmaceuticals in the future.

International audience; Chimeric antigen receptor (CAR) T-cells are a novel immunotherapy available for patients with refractory/relapsed non-Hodgkin lymphoma. In this indication, clinical trials have demonstrated that CAR T-cells achieve high rates of response, complete response, and long-term response (up to 80%, 60%, and 40%, respectively). Nonetheless, the majority of patients ultimately relapsed. This review provides an overview about the current and future role of medical imaging in guiding the management of non-Hodgkin lymphoma patients treated with CAR T-cells. It discusses the value of predictive and prognostic biomarkers to better stratify the risk of relapse, and provide a patient-tailored therapeutic strategy. At baseline, high tumor volume (assessed on CT-scan or on [18F]-FDG PET/CT) is a prognostic factor associated with treatment failure. Response assessment has not been studied extensively yet. Available data suggests that current response assessment developed on CT-scan or on [18F]-FDG PET/CT for cytotoxic systemic therapies remains relevant to estimate lymphoma response to CAR T-cell therapy. Nonetheless, atypical patterns of response and progression have been observed and should be further analyzed. The potential advantages as well as limitations of artificial intelligence and radiomics as tools providing high throughput quantitative imaging features is described.

International audience; Purpose Lymphoma lesion detection and segmentation on whole-body FDG-PET/CT are a challenging task because of the diversity of involved nodes, organs or physiological uptakes. We sought to investigate the performances of a three-dimensional (3D) convolutional neural network (CNN) to automatically segment total metabolic tumour volume (TMTV) in large datasets of patients with diffuse large B cell lymphoma (DLBCL). Methods The dataset contained pre-therapy FDG-PET/CT from 733 DLBCL patients of 2 prospective LYmphoma Study Association (LYSA) trials. The first cohort (n = 639) was used for training using a 5-fold cross validation scheme. The second cohort (n = 94) was used for external validation of TMTV predictions. Ground truth masks were manually obtained after a 41% SUVmax adaptive thresholding of lymphoma lesions. A 3D U-net architecture with 2 input channels for PET and CT was trained on patches randomly sampled within PET/CTs with a summed cross entropy and Dice similarity coefficient (DSC) loss. Segmentation performance was assessed by the DSC and Jaccard coefficients. Finally, TMTV predictions were validated on the second independent cohort. Results Mean DSC and Jaccard coefficients (± standard deviation) in the validations set were 0.73 ± 0.20 and 0.68 ± 0.21, respectively. An underestimation of mean TMTV by − 12 mL (2.8%) ± 263 was found in the validation sets of the first cohort (P = 0.27). In the second cohort, an underestimation of mean TMTV by − 116 mL (20.8%) ± 425 was statistically significant (P = 0.01). Conclusion Our CNN is a promising tool for automatic detection and segmentation of lymphoma lesions, despite slight underestimation of TMTV. The fully automatic and open-source features of this CNN will allow to increase both dissemination in routine practice and reproducibility of TMTV assessment in lymphoma patients.

We propose a semi-automatic segmentation pipeline designed for longitudinal studies considering structures with large anatomical variability, where expert interactions are required for relevant segmentations. Our pipeline builds on the regularized Fast Marching (rFM) segmentation approach by Risser et al (2018). It consists in transporting baseline multi-label FM seeds on follow-up images, selecting the relevant ones and finally performing the rFM approach. It showed increased, robust and faster results compared to clinical manual segmentation. Our method was evaluated on 3D synthetic images and patients’ whole-body MRI. It allowed a robust and flexible handling of organs longitudinal deformations while considerably reducing manual interventions.

Since 2017, medical students at the University of Bergen were taught PET/CT "hands-on" by viewing PET/CT cases in native format on diagnostic workstations in the hospital. Due to the COVID-19 pandemic, students were barred access. This prompted us to launch and evaluate a new freeware PET/CT viewing system hosted in the university network. We asked our students to install the multiplatform Fiji viewer with Beth Israel PET/CT plugin (http://petctviewer.org) on their personal computers and connect to a central image database in the university network based on the public domain orthanc server (https://orthanc-server.com). At the end of course, we conducted an anonymous student survey. The new system was online within eight days, including regulatory approval. All 76 students (100 %) in the fifth year completed their course work, reading five anonymized PET/CT cases as planned. 41 (53 %) students answered the survey. Fiji was challenging to install with a mean score of 1.8 on a 5-point Likert scale (5 = easy, 1 = difficult). Fiji was more difficult to use (score 3.0) than the previously used diagnostic workstations in the hospital (score 4.1; p 0.001, paired t-test). Despite the technical challenge, 47 % of students reported having learnt much (scores 4 and 5); only 11 % were negative (scores 1 and 2). 51 % found the PET/CT tasks engaging (scores 4 and 5) while 20 % and 5 % returned scores 2 and 1, respectively. Despite the initial technical challenge, "hands-on" learning of PET/CT based on the freeware Fiji/orthanc PET/CT-viewer was associated with a high degree of student satisfaction. We plan to continue running the system to give students permanent access to PET/CT cases in native format regardless of time or location.ZIEL: Seit 2017 wurden Medizinstudenten an der Universität Bergen in der Praxis in PET/CT unterrichtet, indem sie PET/CT-Fälle im nativen Format an diagnostischen Arbeitsplätzen im Krankenhaus betrachteten. Aufgrund der COVID-19-Pandemie wurde den Studenten dieser Zugang verwehrt. Dies veranlasste uns zur Einführung und Evaluierung eines neuen kostenlosen PET/CT-Bildbetrachtungssystems, das vom Universitätsnetz zur Verfügung gestellt wird. Wir baten unsere Studierenden, den Multiplattform-Fiji-Viewer mit dem Beth-Israel-PET/CT-Plugin (http://petctviewer.org) auf ihren PCs zu installieren und Verbindung zur zentralen Bilddatenbank im Universitätsnetz herzustellen, die auf dem frei zugänglichen Orthanc-Server (https://orthanc-server.com) basiert. Am Ende des Kurses führten wir eine anonyme Studentenbefragung durch. Das neue System war innerhalb von 8 Tagen online, einschließlich der behördlichen Genehmigung. Alle 76 Studenten (100 %) im fünften Ausbildungsjahr schlossen ihren Kurs ab und bearbeiteten wie geplant 5 anonymisierte PET/CT-Fälle. 41 (53 %) Studenten beantworteten die Umfrage. Fiji wies bei der Installation Probleme auf mit einer durchschnittlichen Bewertung von 1,8 auf einer 5er-Likert-Skala (5 = einfach, 1 = schwierig). Fiji war schwieriger zu bedienen (Bewertung 3,0) als die zuvor im Krankenhaus verwendeten diagnostischen Arbeitsplätze (Bewertung 4,1; p 0,001; gepaarter t-Test). Trotz der technischen Herausforderung gaben 47 % der Studierenden an, viel gelernt zu haben (Bewertung 4 und 5); nur 11 % gaben negative Bewertungen ab (Bewertung 1 und 2). 51 % fanden die PET/CT-Aufgaben ansprechend (Bewertung 4 und 5), während 20 % die Bewertung 2 und 5 % die Bewertung 1 abgaben. Trotz der anfänglichen technischen Herausforderung war das „praktische“ Erlernen von PET/CT auf der Basis der Freeware Fiji/Orthanc-PET/CT-Viewer mit einem hohen Grad an Zufriedenheit der Studierenden verbunden. Wir planen, das System weiter zu betreiben, um den Studenten unabhängig von Zeit und Ort einen permanenten Zugang zu PET/CT-Fällen im nativen Format zu ermöglichen.

In this work, we present a new strategy for the multimodal registration of atypical structures with boundaries that are difficult to define in medical imaging (e.g. lymph nodes). Instead of using a standard Mutual Information (MI) similarity metric, we propose to use the combination of MI with the Modality Independent Neighbourhood Descriptors (MIND) that can help enhancing the organs of interest from their adjacent structures. Our key contribution is then to learn the MIND parameters which optimally represent specific registered structures. As we register atypical organs, Neural-Network approaches requiring large databases of annotated training data cannot be used. We rather strongly constrain our learning problem using the MIND formalism, so that the optimal representation of images depends on a limited amount of parameters. In our results, pure MI-based registration is compared with MI-MIND registration on 3D synthetic images and CT/MR images, leading to improved structure overlaps by using MI-MIND. To our knowledge, this is the first time that MIND-MI is evaluated and appears as relevant for multi-modal registration.

International audience; 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.

Introduction: Older classical Hodgkin lymphoma (cHL) patients are characterized by a significant reduced survival as compared to younger patients. In relapsed and refractory HL, prospective and retrospective studies showed that bendamustine monotherapy provided interesting efficacy with 30% of complete response with an acceptable toxicity profile. We developed the PVAB (Prednisone, Vinblastine, Doxorubicin, Bendamustine) regimen in first line therapy to improve prognosis of older HL with advanced stage. Methods: In this prospective phase II, we recruited newly diagnosed classical HL patients age of 61 years or older with an advanced stage (Ann Arbor stage III, IV, IIB with risk factors). Inclusion criteria were: ECOG performance status 0-2; adequate cardio-pulmonary function with LVEF ≥ 50%; adequate renal function with creatinine clearance ≥ 40 mL/min; HIV negative; For patients aged 70 years old and more, a Mini Nutritional Assessment (MNA) ≥ 17. Treatment consisted of 6 cycles of prednisone (40mg/m 2 D1-5), vinblastine (6mg/m 2, D1), doxorubicin (40mg/m 2, D1) and bendamustine (120mg/m 2, D1) every 21 days. The primary endpoint was the complete metabolic response (CMR) rate according to local review after 6 cycles of study treatment or at premature treatment discontinuation according to Lugano Classification. We presented the final analysis of the study with a median follow-up of 42 months (range, 0.5-63.8), with prognostic analyses for progression free survival (PFS) measured from the date of inclusion to the date of progression, relapse or death from any cause. Prognostic factors included baseline clinical and biological characteristics, geriatric assessments and 18F-FDG PET/CT metabolic parameters especially baseline total metabolic tumor volume (TMTV). Optimal thresholds for some parameters were calculated using X-Tile approach. Results: Between July 2015 and July 2018, 89 patients were included in 34 LYSA centers. The median age was 68 years (range, 61-88) with 35 patients ≥70 years old (39%). The main histological subtype was nodular sclerosis cHL (n=56, 63%) with 26 EBV associated cases (LMP1 staining). Ann Arbor stages were as follows: II (n=3, 3%), III (n=30, 34%), IV (n=56, 63%). B symptoms were present in 57% of patients; 70 patients (80%) had IPS≥3. The median of CIRS-G score was 3 (range, 0-12). Seventy-eight patients (88%) completed the 6 cycles of PVAB. Update results for toxicity showed that 28 patients (32%) presented at least one serious adverse event (SAE) in particular infections (n=13, 15%), blood (n=11, 12%) and cardiac disorders (n=4, 4.5%). The CMR rate according to local review corresponding to the primary endpoint of the study was 77.5% (95%CI, 67-86) with 69 patients in CMR. After central review of 79 available PET/CT images, the CMR rate was 78.5%. Thirty-one patients relapsed or progressed (35%). The 4-year PFS rate was 50% (95%CI, 39-61). For the 69 patients achieving CMR, the 4-year disease free survival (DFS) rate was 62.8% (95%CI, 49-74). Twenty-four patients (27%) died: 11 cHL (46%), 4 treatment toxicity (17%), 6 second cancers (25%), 3 other causes after treatment (infection, cardiac insufficiency, pulmonary embolism, 12%). The 4-year overall survival rate was 69% (95%CI, 57-79). In univariate analysis, altered ECOG PS, Ann Arbor stage IV, bulky disease (>7cm), B-symptoms, extra-nodal involvement (>1), bone or medullar involvement, liver involvement, albumin (≤30g/l), hemoglobin level (88mg/l), TMTV (>450ml) and number of medications non-related to HL (>5) were associated with PFS. In multivariate analysis, liver involvement (HR: 3.79; 95%CI,1.71-8.43; P=0.001), lymphopenia (HR: 3.04; 95%CI,1.54-6.01; P=0.001), CRP (HR: 3.37; 95%CI, 1.69-6.69; P=0.0005) and co-medications (HR: 2.85; 95%CI,1.44-5.66; P=0.003) were independently associated with PFS. Conclusions: PVAB regimen provided high CMR (77.5%) with acceptable toxicity for advanced stage cHL patient over 60 years. The 4-year PFS and OS rates were 50% and 69% respectively, these survival endpoints were influenced by not related-lymphoma events. Prognostic analyses showed that specific involved site (liver), biological parameters (lymphocyte count and CRP) and patient's comorbidity (co-medications) influenced independently PFS. Disclosures Ghesquieres: Celgene: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Roche: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Gilead Sciences: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Mundipharma Research Limited: Consultancy, Honoraria; Takeda: Other: Travel, accommodation, expenses. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Jaccard: Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Abbvie: Honoraria. Laribi: Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; Takeda: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding. Morschhauser: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Genmab: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Janssen: Honoraria; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Brice: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria; MSD: Honoraria. OffLabel Disclosure: Bendamustine is off-label drug use in Hodgkin lymphoma

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. Patients and methods: 634 patients enrolled in the AHL2011 trial with stage Ann Arbor III or IV were included in the study. According to the AHL2011 trial, patients were randomized in a standard arm (6 x BEACOPPesc) or a PET-driven arm (2 x BEACOPPesc and 4 x ABVD in negative PET2 patients or 4 x BEACOPPesc in positive PET2 patients). For each patient, a semi automatic tumor segmentation was retrospectively performed in baseline PET to calculate TMTV using the 41% of SUVmax threshold and compute the maximum distance between the delineated lesions normalized by body surface area (SDmax). Optimal thresholds for TMTV and SDmax were calculated using X-Tile and ROC curve approaches in a randomly assigned training (n=317) and validation sets (n=317). The per protocol PET2 and PET4 responses were analyzed using the modified Deauville criteria (positive if residual uptake >140% background liver). Multivariate analysis included treatment arm, TMTV, SDmax, international prognosis score (IPS), PET2, and PET4 as covariates. The median follow-up was 5.6y. Results : Median TMTV and SDmax were 215 ml and 0.221 m-1 in the whole population and similar in both randomized arms and in the training and validation sets. Optimal cutoffs were 220ml for TMTV (312 patients [49%] had High TMTV) and 0.330 m-1 for SDmax (149 patients [24%] had High SDmax) and similar in the training and validation sets. 5-year PFS for patients with TMTV>220ml was 84.1% vs 90.2% in low TMTV patients (p=0.02) in the whole population (in the training set: 83% vs 89%, p=0.088 ; in the validation set : 86% vs 92% p=0.11). 5-year PFS was significantly lower in patients with SDmax>0.333 m-1 (78.8% vs 89.7%; HR=2.15 [95%CI: 1.38-3.35], p=0.0005) in the whole population (in the training set: 77% vs 89%; p=0.0037); in the validation set: 81% vs 91; p=0.046). The combination of TMTV and SDmax allows to identify two subgroups of patients, those having both low TMTV and low SDmax (n= 281; 44%) and those having high TMTV and/or SDmax (5-year PFS: 92% vs 83.4%; HR=2.24 [95%CI: 1.39-3.62], p=0.0007) (figure 1). In multivariate analysis, high TMTV (p=0.034), high SDmax (p=0.0002), PET2 (p=0.02) and PET4 (p Conclusion: Tumor burden (TMTV) and dissemination (SDmax) assessed on baseline 18FDG PET allow to predict, independently of early reponse to treatment, the outcome of patients with advanced HL. These two parameters overcome the prognosis value of IPS and could be included into new prognostic scores to tailor personalized therapy in advanced Hodgkin Lymphoma. Figure 1 : PFS according to TMTV and SDmax in stage III-IV HL patients enrolled in the AHL2011 study Figure 1 Figure 1. Disclosures Brice: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria; MSD: Honoraria. Ghesquieres: Janssen: Honoraria; Mundipharma: Consultancy, Honoraria; Roche: Consultancy; Celgene: Consultancy, Honoraria; Gilead Science: Consultancy, Honoraria. Stamatoullas-Bastard: Takeda: Consultancy. André: AbbVie: Other: Travel/accomodation/expenses; Roche: Other: Travel/accomodation/expenses, Research Funding; Johnson & Johnson: Research Funding; Incyte: Consultancy; Gilead: Consultancy, Other: Travel/Accommodations/Expenses; Karyopharm: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: Travel/Accommodations/Expenses; Celgene: Other: Travel/accomodation/expenses; Takeda: Consultancy, Research Funding. Rossi: ROCHE: Honoraria, Research Funding; Takeda: Honoraria; JANSSEN: Honoraria; ABBVIE: Honoraria. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria.

Purpose To compare the diagnostic performance of 18 F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT), multiparametric prostate magnetic resonance imaging (mpMRI), and a combination of both techniques for the detection of local recurrence of prostate cancer initially treated by radiation therapy. Methods and Materials This was a retrospective, single-institution study of 32 patients with suspected prostate cancer recurrence who underwent both FCH-PET/CT and 3T mpMRI within 3 months of one another for the detection of recurrence. All included patients had to be cleared for metastatic recurrence. The reference procedure was systematic 3-dimensional (3D)-transperineal prostate biopsy for the final assessment of local recurrence. Both imaging modalities were analyzed by 2 experienced readers blinded to clinical data. The analysis was made per-patient and per-segment using a 4-segment model. Results The median prostate-specific antigen value at the time of imaging was 2.92 ng/mL. The mean prostate-specific antigen doubling time was 14 months. Of the 32 patients, 31 had a positive 3D-transperineal mapping biopsy for a local relapse. On a patient-based analysis, the detection rate was 71% (22 of 31) for mpMRI and 74% (23 of 31) for FCH-PET/CT. On a segment-based analysis, the sensitivity and specificity were, respectively, 32% and 87% for mpMRI, 34% and 87% for FCH-PET/CT, and 43% and 83% for the combined analysis of both techniques. Accuracy was 64%, 65%, and 66%, respectively. The interobserver agreement was κ = 0.92 for FCH-PET/CT and κ = 0.74 for mpMRI. Conclusions Both mpMRI and FCH-PET/CT show limited sensitivity but good specificity for the detection of local cancer recurrence after radiation therapy, when compared with 3D-transperineal mapping biopsy. Prostate biopsy still seems to be mandatory to diagnose local relapse and select patients who could benefit from local salvage therapy.

Background : AETHERA randomized controlled study (Moskowitz, Lancet 2015) showed that the administration of Brentuximab Vedotin (BV) maintenance after autologous stem cell transplantation (ASCT) improved progression free survival (PFS) in BV-naive refractory/relapsed (R/R) Hodgkin lymphoma (HL) patients. However, since BV approval for R/R HL in 2012, many patients are receiving salvage BV before ASCT, alone or combined with chemotherapy. In the AMAHRELIS retrospective nationwide French study, we investigated the real-life outcome of patients with R/R HL mostly treated with BV-based salvage therapies and who received post-ASCT BV maintenance. Objectives : As primary 0objective, we assessed 2 years-PFS of patients treated with post-ASCT BV maintenance from 2012 to 2017 in France. As secondary objectives, we correlated variables (such as use of salvage BV before ASCT, centrally reviewed TEP-assessed response) with survival, and evaluated reported tolerance of BV using the CTCAE v4.0 criteria. Methods : We conducted this observational retrospective study in 58 national centers. Inclusion criteria were R/R HL patients who received at least two infusions of BV after ASCT, at the exclusion of patients in progression after transplant. Among 1134 patients who underwent ASCT for R/R HL between 2012 and 2017 in France based on the French society of bone marrow transplantation database, 835 (74%) patients were screened and data were available for 794 (70%) patients. FDG-PET scan at relapse and before transplantation were recorded and centrally reviewed (still ongoing). FDG-PET scan were reported using the Deauville score (DS), and complete remission was defined by a DS < 4. Post-transplant status was evaluated based on CT-scan or on FDG-PET scan results. This study was approved by the SFGMTC and the LYSA. Results : Fifteen percent (115/794) of patients met eligibility criteria, and were enrolled in this study. Among them, 95% met inclusion criteria for BV maintenance according to the AETHERA study as primary refractory disease (43%), early relapse (27%) or extranodal disease (49%). The mean number of BV injections after ASCT was 11 (3-18). Patients characteristics were : mean age was 34 y (range between 16-70y), 54% were male, and 57% of patients were stage III or IV at relapse. Notably, 70% of patients received BV as salvage therapy and 81% achieved a complete remission before ASCT. The median follow-up period was 35 months. The 2 years survival for the whole cohort was 75,3% for PFS (95% CI : 68,4-84,3) and 96,4% for overall survival (95% CI : 94,2-100) (Figure 1). The use of BV as part of salvage therapy before transplant had no impact on PFS. We observed a trend to an increased occurrence of neuropathy in patients receiving BV before transplant without impact on early treatment discontinuation. We tested several variables for correlation with survival using a univariate Cox model including high risk patients defined as primary refractory disease or early relapse and disseminated disease, extranodal relapse, use of BV before transplant, number of salvage lines, remission status before and after transplant (complete response versus partial response or stable disease), time between ASCT and BV onset and number of BV cycles after transplant. Among these variables, high risk status, less than 10 post transplant BV cycles and absence of post transplant complete remission significantly correlated with a reduced survival probability, and remained significant after analysis using a multivariate Cox model (Table 1). Conclusion : From the real-life AMAHRELIS study, we confirmed the very good outcome of R/R HL patients in the era of post-transplant BV maintenance, with a 2y-PFS of 75% similar to the results of the AETHERA landmark study (2y-PFS of 63%). The results of current strategies with pre- and post-transplant BV outperformed historical series based on high dose therapies, including those of tandem transplant for high risk patients. Future studies incorporating BV strategies with immune checkpoint inhibitors might improve outcome in R/R HL patients. Disclosures Meignan: ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Sibon:takeda france: Consultancy. Stamatoulas Bastard:Pfizer: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Celgene: Honoraria; Takeda: Consultancy. Fornecker:Takeda: Consultancy; Roche: Consultancy. Casasnovas:Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses, Research Funding; Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Cartron:Gilead: Honoraria; Jansen: Honoraria; Abbvie: Honoraria; Celgene: Consultancy, Honoraria; Sanofi: Honoraria; F. Hoffmann-La Roche: Consultancy, Honoraria. Ghesquieres:Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; CELGENE: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen: Honoraria. Brice:Takeda: Consultancy; Roche: Consultancy. Hermine:AB Science: Consultancy, Current equity holder in publicly-traded company, Honoraria, Patents & Royalties, Research Funding; Celgene BMS: Consultancy, Research Funding; Roche: Consultancy; Novartis: Research Funding; Alexion: Research Funding. Rubio:Medac: Consultancy; Gilead: Honoraria; MSD: Honoraria; Novartis: Honoraria; Neovii: Research Funding. Deau Fischer:Takeda: Consultancy; Roche: Consultancy.

IF 5.303; International audience; Anti-PD-1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti-PD-1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti-PD-1 therapy, assessed by PET-CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pre-treated before anti-PD-1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti-PD1 therapy were progressive disease (PD) (n=24) and partial response (PR) (n=6). For the 24 PD patients, median anti-PD-1 related PFS was 7.5 months (95%CI, 5.7-11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti-PD-1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow-up of 12.1 months (7-14.7), the median PFS following the initiation of CT was 11 months (95%CI, 6.3; not reached) and the median of overall survival was not reached. These observations in highly pre-treated HL patients suggest that anti-PD-1 therapy might re-sensitize tumor cells to CT. This article is protected by copyright. All rights reserved.

International audience

International audience; In this paper, we propose a computationally efficient regularization strategy for the Fast Marching (FM) segmentation of multiple organs. Segmentation is based on interactive seeds placements, where the seeds define either organs of interest or the background. Regularization efficiently compensates for the sensitivity of the FM to narrow bridges between different organs with similar intensities. It also leads to segmentations that are far less sensitive to seeds location than by using the standard FM cost. The driving motivation of our work is the quantitative analysis of Chronic Lymphocytic Leukemia (CLL), which is the most common B-cell malignancy and mostly affects elderly people. This requires the segmentation of more than ten organs in whole-body Magnetic Resonance images. The disease path and progression being highly heterogeneous with important inter-patient variability, the segmentation is highly based on clinician experience, which is difficult to automatically reproduce. In this context, the proposed segmentation algorithm compares very favourably to the tools usually available for clinicians.

Introduction High risk stage IIB Hodgkin lymphoma (HL) with mediastinum-to-thorax ratio of ≥0.33 or extranodal localization are defined as a poor prognosis subset according to German Hodgkin study group (Sieber et al., Ann. of Oncol. 2000). These patients were treated consecutively in our group as limited stage in the EORTC/LYSA/FIL H10 study (André et al, JCO 2017) or advanced stage in the AHL2011 LYSA trial (Casasnovas et al., Lancet Oncol 2019). However, the relative efficacy of each of these strategies to control disease is unknown in this uncommon subset of patients. In the present retrospective study, we compared the outcome of patients with high risk stage IIB included in the H10 and AHL2011 studies, and analyzed prognostic factors. Methods We included patients with Ann-Arbor disease stage IIB with mediastinum-to-thorax (M/T) ratio of ≥0.33 or extranodal localization enrolled in the H10 or AHL2011 trials, aged between 16 and 60 years for AHL2011 and 18-60 years for H10 with newly diagnosed Hodgkin lymphoma excluding nodular lymphocyte predominant subtype, who had baseline PET and PET2 images available in the LYSA database. In H10 trial, after 2 cycles of ABVD patients received in the standard arm 2 additional cycles of ABVD plus INRT 30 Gy, in the experimental arm 2 to 4 additional cycles of ABVD;- in PET2 negative patients 4 additional cycles of ABVD (or after the trial amendment 2 additional cycles of ABVD plus INRT 30 Gy); - in PET2 positive patients 2 cycles of escalated BEACOPP plus INRT 30Gy. PET2 were reported according to IHP criteria. In AHL2011 study, after 2 upfront escalated BEACOPP patients received either 4 additional escalated BEACOPP in the standard arm and PET2 positive patients of the PET-driven arm, or 4 cycles of ABVD in PET2 negative patients of the PET-driven arm. PET2 were reported using Deauville score (DS 1-2-3 vs 4-5), DS4 being defined positive if SUVmax of the residual lesion >140% of SUVmax of the liver background. Baseline clinical and biological characteristics of patients enrolled in both studies were compared. Total metabolic tumor volume (TMTV) at baseline was calculated with the Beth Israel Fiji software based on a 41% SUVmax cutoff of each lesion. In this study, all PET2 response was reanalysed using Deauville score And PET positivity was defined according to the criteria used in the AHL2011 trial. Results 148 patients were eligible for the study, including 83 and 65 patients enrolled in the AHL2011 and H10 trials respectively. The median age was 27 years (16; 59), 51.4% of patients were treated according to the experimental arm of each trial, the median size of the bulky mass was 84 mm (20-197), the index prognostic score (IPS) was 3 or higher in 29.1% of cases (38.6% in AHL2011 and 16.9% in H10 patients), the median TMTV value was 155.5 ml (8.3-782.9). Most patients had M/T ratio of ≥0.33 (98.6%) and 10.9% had an extra-nodal involvement. 62.2 % of patients had a treatment strategy including escalated BEACOPP and 31.8% received radiotherapy. PET2 was positive in 16.9% (n=14) of AHL2011 cohort and 9.2% (n=6) in H10 cohort patients. With a median follow-up of 4.2 and 4.4 years in AHL2011 and H10 trials respectively, 16 patients (10.8%) relapsed including 7 (10.7%) patients in H10 and 9 (10.8%) in AHL2011, and five deaths occurred with three due to lymphoma progression . Eleven relapses (68.8% for all, 8 for AHL2011 and 3 for H10) were localized in mediastinum. In univariate analysis, PET2 response, baseline TMTV (155 ml cut off) and IPS (0-2 vs 3-7) significantly influenced PFS with hazard ratios of 6.26 (2.29-17.07), 3.37 (1.093-10.371), 2.89 (0.94-8.86) respectively. The strategy of treatment, either H10 or AHL2011, did not influence PFS. In multivariate analysis stratified on the study (figure 1), only the TMTV as continuous variable (HR: 1.003; 1.000-1.005) and PET2 response (HR: 5.38; 1.99-14.56) were prognostic factors. Among the thirteen patients with high TMTV and PET2 positivity, 7 relapsed (4 for AHL2011 and 3 for H10). Conclusions This is the first study comparing two strategies of treatment in high risk stage IIB lymphoma patients included in two large randomized clinical trials. PFS of these patients was 88.0% (95%CI = [81.2%; 92.4%]) at 4 years and similar regardless the study treatment. Baseline TMTV and PET2 response were the main factors influencing the outcome of high risk stage IIB lymphoma patients. Figure Disclosures André: Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers-Squibb: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel grants, Research Funding; Amgen: Other: Travel grants, Research Funding; Johnson & Johnson: Research Funding; Takeda Millenium: Research Funding; Chugai: Research Funding; Celgene: Other: Travel grants, Research Funding. Brice:Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria. Stamatoullas:Takeda: Consultancy; Celgene: Honoraria. Federico:Seattle Genetics: Research Funding; Allos: Research Funding; Spectrum: Consultancy, Honoraria; Medimmune: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Teva: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria. Casasnovas:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Merck Sharp and Dohme: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees.

International audience; Previous studies have suggested that early changes in blood flow (BF) in response to neoadjuvant chemotherapy and evaluated with 150-water are a surrogate biomarker of outcome in women with breast cancer. This study investigates, in the triple-negative breast cancer subtype, the prognostic relevance of tumor BF changes (Delta BF) in response to chemotherapy, assessed using a short dynamic F-18-FDG PET acquisition. Methods: Forty-six consecutive women with triple-negative breast cancer and an indication for neoadjuvant chemotherapy were prospectively included. Women benefited from a baseline F-18-FDG PET examination with a 2-min chest-centered dynamic acquisition, started at the time of F-18-FDG injection. Breast tumor perfusion was calculated from this short dynamic image using a first-pass model. This dynamic PET acquisition was repeated after the first cycle of chemotherapy to measure early Delta BF. Delayed static PET acquisitions were also performed (90 min after F-18-FDG injection) to measure changes in tumor glucose metabolism (Delta SUVmax). The association between tumor BF, clinicopathologic characteristics, and patients' overall survival (OS) was evaluated. Results: Median baseline tumor BF was 21 mL/min/100 g (range, 6-46 mL/min/100 g) and did not significantly differ according to tumor size, Scarf-Bloom-Richardson grade, or Ki-67 expression. Median tumor Delta BF was-30%, with highly scattered values (range, -93% to +118%). A weak correlation was observed between Delta BF and Delta SUVmax (r = +0.40, P = 0.01). The median follow-up was 30 mo (range, 6-73 mo). Eight women developed recurrent disease, 7 of whom died. Low OS was associated with menopausal history (P = 0.03), persistent or increased tumor vascularization on the interim PET (6.13F cutoff =-30%; P = 0.03), non-breast-conserving surgery (P = 0.04), and the absence of a pathologic complete response (pCR) (P = 0.01). Delta BF and pCR provided incremental prognostic stratification: 3-y OS was 100% in pCR women, 87% in no-pCR women but achieving an early tumor BF response, and only 48% in no-pCR/no-BF-response women (Delta BF cutoff = -30%, P < 0.001). Conclusion: This study suggests the clinical usefulness of an early user- and patient-friendly 2-min dynamic acquisition to monitor breast tumor Delta BF to neoadjuvant chemotherapy using F-18-FDG PET/CT. Monitoring tumor perfusion and angiogenesis response to treatment seems to be a promising target for PET tracers.

International audience; Most peripheral T-cell lymphoma (PTCL) patients have a poor outcome and the identification of prognostic factors at diagnosis is needed.; The prognostic impact of total metabolic tumor volume (TMTV0), measured on baseline [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography, was evaluated in a retrospective study including 108 PTCL patients (27 PTCL not otherwise specified, 43 angioimmunoblastic T-cell lymphomas and 38 anaplastic large-cell lymphomas). All received anthracycline-based chemotherapy. TMTV0 was computed with the 41% maximum standardized uptake value threshold method and an optimal cut-off point for binary outcomes was determined and compared with others prognostic factors.; With a median follow-up of 23 months, 2-year progression-free survival (PFS) was 49% and 2-year overall survival (OS) was 67%. High TMTV0 was significantly associated with a worse prognosis. At 2 years, PFS was 26% in patients with a high TMTV0 (>230 cm(3), n = 53) versus 71% for those with a low TMTV0, [P < 0.0001, hazard ratio (HR) = 4], whereas OS was 50% versus 80%, respectively, (P = 0.0005, HR = 3.1). In multivariate analysis, TMTV0 was the only significant independent parameter for both PFS and OS. TMTV0, combined with PIT, discriminated even better than TMTV0 alone, patients with an adverse outcome (TMTV0 >230 cm(3) and PIT >1, n = 33,) from those with good prognosis (TMTV0 ≤230 cm(3) and PIT ≤1, n = 40): 19% versus 73% 2-year PFS (P < 0.0001) and 43% versus 81% 2-year OS, respectively (P = 0.0002). Thirty-one patients (other TMTV0-PIT combinations) had an intermediate outcome, 50% 2-year PFS and 68% 2-year OS.; TMTV0 appears as an independent predictor of PTCL outcome. Combined with PIT, it could identify different risk categories at diagnosis and warrants further validation as a prognostic marker.

International audience; Functional imaging using 18-fluorodeoxyglycose ([18F]FDG) positron emission tomography combined with computed tomography (PET/CT) has become a major imaging modality in Hodgkin lymphoma. This imaging modality allows for a significant improvement in staging, increased sensitivity, which involves differentiating residual tumors from fibrosis during assessment, and highly impacts treatment decisions into new PET-driven strategies. This review presents the main scientific data concerning the current applications of [18F]FDG-PET/CT in Hodgkin lymphoma at baseline, interim, and the end of treatment evaluation along with the main PET-driven trials for therapeutic decisions. The emergence of total metabolic tumor volume as a new functional prognostic factor will also be discussed.

Introduction: Hodgkin lymphoma (HL) pts who relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV) therapy have a poor outcome. For these relapsed and refractory (R/R) HL pts, anti-PD-1 therapy gives a high rate of objective responses. However, the rate of complete response (CR) remains modest and in the updated results of anti-PD-1 therapy clinical trials, about 50% of pts are still without progressive disease after one year of treatment. As anti-PD-1 therapy modifies the anticancer immune response, we hypothesize that anti-PD-1 therapy may increase sensitivity to chemotherapy (CT) given after anti-PD-1 therapy (sequential strategy) or in combination with anti-PD-1 therapy after an unsatisfactory response to immunotherapy (concomitant strategy). We retrospectively analyzed these two clinical situations in 30 R/R HL pts from LYSA centers treated with anti-PD-1 therapy. Methods: We included R/R HL pts from 14 LYSA centers who received anti-PD-1 therapy in the context of clinical trials (N=4) or an authorization for temporary use (ATU) from the French medical drug agency (N=26). Before the anti-PD-1 therapy, pts had received a median of six (range, 2-14) lines of therapy, 69% had HDT+ASCT, 14% had allograft and 93% had been treated with BV. We considered two groups of pts: i. 19 pts (63%) in whom the anti-PD-1 therapy was stopped at the introduction of CT (Group 1); ii. 11 pts (37%) with an unsatisfactory response to anti-PD-1 therapy in whom a combination of CT with immunotherapy was initiated to optimize the response (Group 2). The quality of the response after the introduction of CT was evaluated retrospectively by each treating physicians according to Cheson 2007 or 2014 criteria. We also determined whether new CT treatments after and in combination with anti-PD-1 therapy led to unexpected toxicities and whether new treatment schedules made pts eligible for allograft. Results: At the start of anti-PD-1, the median age of pts was 37 years old (range, 20-75), 24% had Ann Arbor III/IV stages, 34% had B symptoms and 21% had a performance status (PS) of 2-3. Patients received a median of 10 infusions (range, 2-52) of anti-PD-1 therapy with nivolumab (N=26, 87%) or pembrolizumab (N=4, 13%). The best responses achieved during anti-PD-1 therapy were a complete response (CR) for 5 patients, a partial response (PR) for 17 pts, stable disease (SD) for 2 pts and progression for 6 pts. In group 1, 17 pts were in progression, one pt in PR, and another pt in SD at the end of anti-PD-1 therapy alone. In group 1, after anti-PD-1 therapy, the pts were treated with vinblastine (N=3), gemcitabine (N=2) or bendamustine alone (N=3) or in combination with BV (N=4), GVD (N=1), ICE (N=1), DHAP (N=1), escalated BEACOPP (N=1), vinorelbine (N=1), vepeside (N=1) and caelyx (N=1). In group 2, before the combination, the response status was progression for 7 pts and PR for 4 pts. In group 2, to optimize the response to anti-PD-1, pts received vinblastine (N=7), gemcitabine (N=2) and BV (N=2). In the 28 evaluable pts, 11/18 (61%) in group 1 and 9/10 (90%) in group 2 showed an improved response after chemotherapy alone or combination with anti-PD-1 therapy respectively. In group 1, there were 6 CR (32%), 5 PR (26%), 1 SD (5%) and 6 PD (32%) (Figure 1B). In group 2, there were 5 CR (45%), 5 PR (45%) and 1 SD (10%) (Figure 1A). Of note, among the ten pts treated with vinblastine, 4 were in CR, 3 in RP, 1 in SD and 2 in progression. No unexpected toxicity was observed during the CT. Four pts had an allograft after the sequential CT (N=3) and concomitant CT strategy (N=1). Three pts were in CR 274, 279 and 480 days after the allograft and the fourth has not yet been evaluated. Allografts are now scheduled for 6 pts. With a median follow-up of 9.1 months (95%CI, 6.1-14) following the initiation of chemotherapy (alone or combined) the median PFS and OS were 8.4 and 14.6 months, respectively. Conclusions: Our retrospective study showed that pts with an unsatisfactory response or PD with anti-PD-1 therapy had a new objective response with CT alone (61%) or CT in combination with anti-PD-1 therapy (90%). This response could make some pts eligible for allograft. Prospective clinical trials are needed to confirm the synergistic effect of CT with anti-PD-1 therapy and to determine which CT provides the best results in combination with these checkpoint inhibitors. Figure 1 Figure 1. Disclosures Ysebaert: Janssen: Consultancy, Research Funding, Speakers Bureau. Ghesquières: Celgene and Mundipharma: Consultancy, Honoraria; Roche: Research Funding.

Purpose: To investigate the value of the metabolic tumor response assessed with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiologic markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in women with triple-negative breast cancer (TNBC). Experimental Design: Fifty consecutive women with TNBC and an indication for NAC were prospectively included. Different pretreatment clinical, biologic, and pathologic biomarkers, including SBR grade, the Ki-67 proliferation index, androgen receptor expression, EGF receptor (EGFR), and cytokeratin 5/6 staining, were assessed. Tumor glucose metabolism at baseline and its change after the first cycle of NAC (ΔSUVmax) were assessed using FDG-PET. Results: The pCR rate was 42%. High Ki-67 proliferation index (P = 0.016), negative EGFR status (P = 0.042), and high ΔSUVmax (P = 0.002) were significantly associated with pCR. In multivariate logistic regression, both negative EGFR status (OR, 6.4; P = 0.043) and high ΔSUVmax (OR, 7.1; P = 0.014) were independent predictors of pCR. Using a threshold at −50%, tumor ΔSUVmax predicted pCR with a negative, a positive predictive value, and an accuracy of 79%, 70%, and 75%, respectively. Combining a low ΔSUVmax and positive EGFR status could predict non-pCR with an accuracy of 92%. Conclusions: It is important to define the chemosensitivity of TNBC to NAC early. Combining EGFR status and the metabolic response assessed with FDG-PET can help the physician to early predict the probability of achieving pCR or not. Given these results, the interest of response-guided tailoring of the chemotherapy might be tested in multicenter trials. Clin Cancer Res; 21(24); 5460–8. ©2015 AACR.

We highlight the dual role of I-MIBG scintigraphy in inverted-Takotsubo pattern cardiomyopathy, the diagnosis of which is sometimes challenging: Firstly, I-MIBG scintigraphy can show myocardial sympathetic dysfunction (low I-MIBG uptake) in the hypokinetic basal segments, sparing the left ventricle apex. It is helpful in the imaging diagnosis of inverted-Takotsubo pattern cardiomyopathy and confirms that acute dysfunction of myocardial sympathetic nerve endings occurs with this cardiomyopathy. Secondly, I-MIBG scintigraphy is an accurate imaging examination to detect and localize pheochromocytoma; it can help in the search for an endogenous cause of this adrenergic stress-related cardiomyopathy.

This review considers the potential utility of positron emission tomography (PET) tracers in the setting of response monitoring in breast cancer, with a special emphasis on glucose metabolic changes assessed with 18F-fluorodeoxyglucose (FDG). In the neoadjuvant setting of breast cancer, the metabolic response can predict the final complete pathologic response after the first cycles of chemotherapy. Because tumor metabolic behavior highly depends on cancer subtype, studies are ongoing to define the optimal metabolic criteria of tumor response in each subtype. The recent multicentric randomized AVATAXHER trial has suggested, in the human epidermal growth factor 2-positive subtype, a clinical benefit of early tailoring the neoadjuvant treatment in women with poor metabolic response after the first course of treatment. In the bone-dominant metastatic setting, there is increasing clinical evidence that FDG-PET/computed tomography (CT) is the most accurate imaging modality for assessment of the tumor response to treatment when both metabolic information and morphologic information are considered. Nevertheless, there is a need to define standardized metabolic criteria of response, including the heterogeneity of response among metastases, and to evaluate the costs and health outcome of FDG-PET/CT compared with conventional imaging. New non-FDG radiotracers highlighting specific molecular hallmarks of breast cancer cells have recently emerged in preclinical and clinical studies. These biomarkers can take into account the heterogeneity of tumor biology in metastatic lesions. They may provide valuable clinical information for physicians to select and monitor the effectiveness of novel therapeutics targeting the same molecular pathways of breast tumor.

Objectif Evaluation prospective de l’utilite de la TEP/TDM au 18-F-fluorocholine (TEP FCH) lors de la prise en charge des patients avec cancer prostatique metastatique osseux hormono-resistant par 223Ra(223RaCl2) ainsi que de la reponse therapeutique en correlation avec les marqueurs biologiques : taux des PSA et phosphatases alcalines (PA). Materiel et methodes Trente et un patients ont ete adresses pour traitement au 223Ra. Trente patients d’âge median 75 ans ont beneficie d’un total de 138 cycles de 223Ra depuis aout 2014 jusqu’a janvier 2017. Quatorze patients ont beneficie d’une evaluation initiale de l’etendue des metastases osseuses par une evaluation radiologique et scintigraphie osseuse (groupe 1). Dix-sept patients ont beneficie en plus d’une evaluation par TEP-FCH avant et 13 patients apres 3 cycles de 223Ra (groupe 2). PSA et PA ont ete mesures avant et 4 semaines apres chaque cycle de 223Ra. Les valeurs des PSA et PA chez 13 patients avec deuxieme examen TEP-FCH ont ete evaluees et correlees avec la TEP-FCH. Resultats La TEP FCH initiale a exclu un patient avec atteintes osteo-medullaire diffuse et ganglionnaire (ggl > 3 cm). Dans le groupe 1, 7/14 (50 %) des patients ont eu une baisse de PSA, dont 1 de plus de 50 % et 8/14 patients (56 %) ont eu une baisse des PA, dont deux de plus de 50 %. Dans le groupe 2, 6/16 (38 %) des patients presentaient une baisse des PSA dont 2 de plus de 50 % et 5/16 (31 %) des patients avaient une baisse de la PA. La distribution des baisses des marqueurs etait non-significativement differente entre les deux groupes ( p = 0,43 pour PSA et p = 0,33 pour PA). L’analyse visuelle comparative des deux TEP (initiale et apres 3 cycles) montre une correlation significative entre le statut de repondeur en fixation osseuse a la FCH (stabilite ou reponse partielle en nombre de lesions osseuses fixantes) et la baisse des PSA ( p = 0,03), mais pas avec la baisse des PA ( p = 0,09). La TEP-FCH apres le 3e cycle a permis l’interruption du traitement par 223Ra en raison d’une progression osseuse et ganglionnaire chez 6/13 (46 %) patients, avec implications medico-economiques et changement rapide de prise en charge des patients. Conclusion La TEP-FCH est un examen utile pour l’evaluation initiale de l’etendue de la maladie metastatique (osseuse, viscerale et ganglionnaire). La progression du taux des PSA est correlee a une progression en TEP-FCH. D’autres marqueurs en TEP-FCH (variation de charge volumique osseuse fixante, variations des SUV) sont en cours d’analyse.

Major improvements in the field of radiotherapy planning such as stereotactic radiation therapy, have recently been performed, aiming to the development of personalized therapeutic strategies in patients with biochemical failure of prostate cancer. However, this needs an early and accurate location of sites of recurrence. Development of multimodality magnetic resonance imaging (MRI) and positron emission tomography (PET) permits to consider this objective. Thus, it is worthwhile to apprehend the respective performance of these imaging techniques in order to rationalize their use. We propose a review of the recent literature organized by technique and by location, regarding the performance of multimodality MRI and PET for restaging of patients with biochemical failure of prostate cancer initially treated with curative intent.

Although progression free survival and overall survival of patients with Hodgkin lymphoma (HL) has improved with modern treatment in the past 10 years, 10 % of patients will fail to conventional therapy and die of their lymphoma. The search of new prognostic factors for identifying these high risk patients at diagnosis of HL remains challenging in daily practice. The evaluation of the tumor microenvironnement was shown to help identifying a subset of patients treated with ABVD having a high risk of treatment failure (Tan KL et al, Blood 2012). PET positivity after 2 cycles of chemotherapy allows also identifying a subset of patients with poor outcome (Gallamini, JCO 2007) and PET-guided strategy were developed to improve the management of HL patients in order to either intensify treatment for high risk patients or deescalate treatment for sparing the others from toxicities. The aim of this study was therefore to evaluate the impact of baseline tumor microenvironnement in a large cohort of HL patients prospectively treated with upfront escalated BEACOPP in a randomized phase III clinical trial evaluating a PET-driven strategy (AHL 2011, NCT01358747) and to compare its prognostic value with other clinicopathological markers. Material and Methods Tumoral material was collected from May 2011 to May 2014 from HL patients prospectively enrolled in the AHL 2011 study. The AHL 2011 trial was designed to evaluate in 16-60 years old HL patients with Ann Arbor stage III, IV or high risk IIB, a de-escalade PET-driven strategy after 2 cycles of BEACOPPesc randomly compared to a standard treatment not driven by PET and delivering 6 cycles of BEACOPPesc. PET were centrally reviewed and interpreted according to Deauville criteria. As recently reported (Casasnovas, ASH 2015 Abs 577), the 2y-PFS was similar in the PET-driven (88%) and the standard arm (91%; p =0.79). The tumor microenvironnement was analyzed on formalin fixed paraffin embedded lymph node biopsy obtained for the diagnosis before treatment by morphological evaluation on standard staining (% polynuclear eosinophils, % lymphocytes, % plasmocytes, % histiocytes), and immunohistochemistry (IHC) scoring (score 0-1-2-3) for CD20, CD3, CD68-TAMs (tumor-associated macrophages) and CD163 and were centrally reviewed. Percentage of tumoral cells and EBV status were also analysed. In this analysis, the prognosis value of tissue markers expressions were compared to those of clinical and biological patient's characteristics, and PET results after 2 cycles of escalated BEACOPP. Results Six hundred fifty eight patients with available IHC data out of 823 enrolled in AHL2011 study were included in the analysis. With a median follow-up of 16.1 months, 2-year PFS was 89.4% (95% CI [86.2% ; 91.9%]) and 2-year OS 98.7% (95% CI [96.4% ; 99.5%]). In univariate analysis male gender, at least one extra-nodal involvement, B symptoms, Hemoglobin Among baseline patients characteristics, male gender, hemoglobin In conclusion, CD68 expression was confirmed to be an important prognostic marker in this large prospective cohort of patients treated with upfront escalated BEACOPP in a modern PET-guided strategy. Baseline high CD68 expression is associated to a higher risk of PET2 positivity and the combination of this microenvironment marker and PET2 results allowed identifying a population of patients with high risk of treatment failure. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Brice: Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Bristol Myers-Squibb: Honoraria; Seattle Genetics: Research Funding; Gilead: Honoraria; Roche: Honoraria. Casasnovas:BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; ROCHE: Consultancy, Honoraria, Research Funding.

International audience; PURPOSE: The presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study. METHODS: From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease. RESULTS: Median TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk (71 % and TMTV0 ≤225 ml (n = 37, 63 %), ΔSUVmaxPET0-2 = 225 ml (n = 17, 29 %), and ΔSUVmaxPET0-2 = 225 ml (n = 5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % (p

International audience; UNLABELLED: In newly diagnosed diffuse large B-cell lymphoma (DLBCL), the sensitivity of bone marrow biopsy (BMB) for the detection of bone marrow involvement (BMI) can be low because of sampling error if the BMI is focal and not diffuse. Although (18)F-FDG PET/CT is now recommended for initial staging of DLBCL, its role regarding BMI is not well defined. This study evaluated whether (18)F-FDG PET/CT, in comparison with BMB, is useful for the detection of BMI and predictive of outcome. METHODS: From the 142 patients who were referred to our institution for newly diagnosed DLBCL from June 2006 to October 2011, 133 were retrospectively enrolled in our study. All patients underwent whole-body (18)F-FDG PET/CT and a BMB from the iliac crest before any treatment. (18)F-FDG PET/CT was considered positive for BMI in cases of uni- or multifocal bone marrow (18)F-FDG uptake that could not be explained by benign findings on the underlying CT image or history. A final diagnosis of BMI was considered if the BMB was positive or if the positive (18)F-FDG PET/CT was confirmed by guided biopsy or targeted MR imaging or in cases of disappearance of focal bone marrow uptake concomitant with the disappearance of uptake in other lymphoma lesions on (18)F-FDG PET/CT monitoring. Progression-free survival and overall survival were analyzed using the Cox proportional hazards regression model. RESULTS: Thirty-three patients were considered to have BMI. Of these, 8 were positive according to the BMB and 32 were positive according to (18)F-FDG PET/CT. (18)F-FDG PET/CT was more sensitive (94% vs. 24%; P < 0.001), showed a higher negative predictive value (98% vs. 80%), and was more accurate (98% vs. 81%) than BMB. Median follow-up was 24 mo (range, 1-67 mo). Twenty-nine patients (22%) experienced recurrence or disease progression during follow-up, and 20 patients died (15%). In multivariate analysis, only the International Prognostic Index and the (18)F-FDG PET/CT bone marrow status were independent predictors of progression-free survival (P = 0.005 and 0.02, respectively), whereas only the International Prognostic Index remained an independent predictor of overall survival (P = 0.004). CONCLUSION: Assessment of BMI with (18)F-FDG PET/CT provides better diagnostic performance and prognostic stratification in newly diagnosed DLBCL than does BMB.

7509Background: 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)...