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Idiopathic normal pressure hydrocephalus has a complex multifactorial pathogenesis and is associated with Alzheimer’s disease in many patients. To date, it is not well known if a similar association exists with behavioural variant of frontotemporal lobar degeneration. In a first step, we compare the prevalence of idiopathic normal pressure hydrocephalus in two groups of patients, one with behavioural variant of frontotemporal lobar degeneration (n = 69) and the other with Alzheimer’s disease (n = 178). In the second step, we describe more precisely the phenotype of patients with the association of idiopathic normal pressure hydrocephalus and behavioural variant of frontotemporal lobar degeneration. Firstly, we report that the prevalence of idiopathic normal pressure hydrocephalus was far higher in the group of patients with behavioural variant of frontotemporal lobar degeneration than in the group of patients with Alzheimer’s disease (7.25% and 1.1%, respectively, P = 0.02). Secondly, we show that patients with the double diagnosis share common clinical and para-clinical features of both idiopathic normal pressure hydrocephalus and behavioural variant of frontotemporal lobar degeneration patients, including CSF shunting efficacy in real-life experience. Overall, our results suggest a link between these two conditions and should encourage neurologists to look for idiopathic normal pressure hydrocephalus in their behavioural variant of frontotemporal lobar degeneration patients in the event of gait disturbances; the benefit/risk balance could indeed be in favour of shunt surgery for selected patients with this newly described entity.

In patients with novel coronavirus disease 2019 (COVID-19) referred for lung scintigraphy for suspected pulmonary embolism (PE), there has been an ongoing debate within the nuclear medicine community as to whether and when the ventilation study should be performed. Indeed, while PE diagnosis typically relies on the recognition of ventilation/perfusion (V/P) mismatched defects, the ventilation procedure potentially increases the risk of contamination to the healthcare workers. The primary aim of this study was to assess the role of ventilation imaging when performing lung scintigraphy for suspected PE in COVID-19 patients. The secondary aim was to describe practices and imaging findings in this specific population. Methods: A national registry was created in collaboration with the French Society of Nuclear Medicine to collect lung scans performed in COVID-19 patients for suspected PE. Practices of departments were assessed regarding imaging protocols and aerosol precautions. A retrospective review of V/P SPECT/CT scans was then conducted. Two physicians blinded to clinical information reviewed each case by sequentially using P SPECT, P SPECT/CT and V/P SPECT/CT images. Scans were classified in one of the four following categories: patients for whom PE could reasonably be excluded based on 1) perfusion SPECT only, 2) P SPECT/CT, 3) V/P SPECT/CT; or 4) patients with mismatched defects suggestive of PE according to the EANM criteria. Results: Data from 12 French nuclear medicine departments were collected. Lung scans were performed between 03/2020 and 04/2021. Personal protective equipment and dedicated cleaning procedures were used in all departments. Out of the 145 V/Q SPECT/CT included in the central review, PE could be excluded using only P SPECT, P SPECT/CT and V/P SPECT/CT in 27 (19%), 55 (38%) and 45 (31%) patients, respectively. V/P SPECT/CT was positive for PE in 18 (12%) patients, including 12 (67%) with a low burden of PE (≤10%). Conclusion: In this population of COVID-19 patients assessed with lung scintigraphy, PE could be confidently excluded without ventilation in only 57% of patients. Ventilation imaging was required to confidently rule out PE in 31% of patients. Overall, the prevalence of PE was low (12%).

Dementia with Lewy bodies remains underdiagnosed in clinical practice mainly because of the low sensitivity of existing diagnostic criteria and a strong overlap with Alzheimer’s pathology that can mask the Lewy phenotype. The objective of this study was therefore to develop and validate a new clinical scale designed to detect signs of Lewy body disease, called LeSCoD for Lewy body Screening scale in Cognitive Disorders. 128 patients who fulfilled the clinical criteria of dementia with Lewy bodies (DLB; n = 32), Alzheimer’s disease (AD; n = 77) or both (n = 19) was prospectively enrolled. 18F-DOPA PET imaging and/or CSF biomarkers were available in some patients. LeSCoD scale was systematically administered and the potential correlation with 18F-DOPA PET imaging was evaluated in a subgroup of patients. LeSCoD scale showed robust internal and external validity. We determined a cut-off of 10 above which the sensitivity and specificity for Lewy body disease diagnosis were 86% and 95%, respectively. The LeSCoD scale correlated with striatal dopamine uptake in 18F-DOPA PET. LeSCoD scale is a simple and reliable tool for the evaluation of Lewy body disease in routine clinical practice, with a higher sensitivity and specificity than the existing criteria. It might be an alternative to the use of dopamine-specific imaging.

Background and ObjectivesGRNvariants are a frequent cause of familial frontotemporal dementia (FTD). Monitoring disease progression in asymptomatic carriers of genetic variants is a major challenge in delivering preventative therapies before clinical onset. This study aimed to assess the usefulness of fluorodeoxyglucose (FDG)–PET in identifying metabolic changes in presymptomaticGRNcarriers (PS-GRN+) and to trace their longitudinal progression.MethodsParticipants were longitudinally evaluated over 5 years in a prospective cohort study focused onGRNdisease (Predict-PGRN). They underwent cognitive/behavioral assessment, plasma neurofilament measurement, brain MRI, and FDG-PET. Voxel-wise comparisons of structural and metabolic imaging data between 2 groups were performed for each time point. Longitudinal PET changes were evaluated with voxel-wise comparisons and the metabolic percent annual changes method. The association of regional brain metabolism with plasma neurofilament and cognitive changes was analyzed.ResultsAmong the 80 individuals enrolled in the study, 58 (27 PS-GRN+ and 31 noncarriers) were included in the analyses. Cross-sectional comparisons between PS-GRN+ and controls found a significant hypometabolism in the left superior temporal sulcus (STS) region (encompassing the middle and superior temporal gyri), approximately 15 years before the expected disease onset, without significant cortical atrophy. The longitudinal metabolic decline over the following 5 years peaked around the right STS in carriers (p< 0.001), without significantly greater volume loss compared with that in controls. Their estimated annualized metabolic decrease (−1.37%) was higher than that in controls (−0.21%,p= 0.004). Lower glucose uptake was associated with higher neurofilament increase (p= 0.003) and lower frontal cognitive scores (p= 0.014) in PS-GRN+.DiscussionThis study detected brain metabolic changes in the STS region, preceding structural and cognitive alterations, thus contributing to the characterization of the pathochronology of preclinicalGRNdisease. Owing to the STS involvement in the perception of facially communicated cues, it is likely that its dysfunction contributes to social cognition deficits characterizing FTD. Overall, our study highlights brain metabolic changes as an early disease-tracking biomarker and proposes annualized percent decrease as a metric to monitor therapeutic response in forthcoming trials.

International audience; Purpose: This study aimed at determining the diagnostic implications of indirect signs of infection at FDG-PET-i.e., hypermetabolisms of the spleen and/or bone marrow (HSBM)-when documented in patients with known or suspected infective endocarditis (IE).Methods: HSBM were defined by higher mean standardized uptake values comparatively to that of the liver on FDG-PET images from patients with a high likelihood of IE and prospectively included in a multicenter study.Results: Among the 129 included patients, IE was ultimately deemed as definite in 88 cases. HSBM was a predictor of definite IE (P = 0.014; odds ratio (OR) 3.2), independently of the criterion of an abnormal cardiac FDG uptake (P = 0.0007; OR 9.68), and a definite IE was documented in 97% (29/30) of patients showing both HSBM and abnormal cardiac uptake, 78% (7/9) of patients with only abnormal cardiac uptake, 67% (42/63) of patients with only HSBM, and 37% (10/27) of patients with neither one.Conclusion: In this cohort with a high likelihood of IE, HSBM is an additional albeit indirect sign of IE, independently of the criterion of an abnormal cardiac uptake, and could reinforce the suspicion of IE in the absence of any other infectious, inflammatory, or malignant disease.

Background: The frontal variant of Alzheimer’s disease (fAD) is poorly understood and poorly defined. The diagnosis remains challenging. The main differential diagnosis is the behavioral variant of frontotemporal degeneration (bvFTD). For fAD, there is some dissociation between the clinical frontal presentation and imaging and neuropathological studies, which do not always find a specific involvement of the frontal lobes. DAPHNE is a behavioral scale, which demonstrated excellent performance to distinguish between bvFTD and AD. Objective: The aim of the present study was to assess the reliability of this new tool to improve the clinical diagnosis of fAD. Methods: Twenty fAD patients and their caregivers were prospectively included and were compared with 36 bvFTD and 22 AD patients. Results: The three main behavioral disorders in the fAD patients were apathy, loss of empathy, and disinhibition. Three disorders were discriminant because they were less frequent and less severe in the fAD patients than in the bvFTD patients, namely hyperorality, neglect, and perseverations. This specific pattern of behavioral disorders was corroborated by SPECT or 18FDG PET-CT scan that showed that patients with fAD could have a medial frontal hypoperfusion, whereas in bvFTD patients the orbitofrontal cortex was the main involved region, with more diffuse hypoperfusion. Conclusion: We demonstrated that DAPHNE had good sensitivity and good specificity to discriminate between the three groups and in particular between fAD and bvFTD patients. DAPHNE is a quick tool that could help clinicians in memory clinics not only to differentiate bvFTD from typical AD but also from fAD.

Purpose To assess the rate and pattern of incidental interstitial lung abnormalities suggestive of COVID-19 on 18F-FDG PET/CT in asymptomatic cancer patients during the period of active COVID-19 circulation between March and April 2020 in a geographic area of low prevalence of the virus. Methods 1396 18F-FDG PET/CT performed between January 1, 2020, and February 21, 2020, and between March 16, 2020, and April 17, 2020 for routine oncological indication were retrospectively analyzed. No patients had symptoms suggestive of COVID-19 at the time of the 18F-FDG PET/CT. Incidental interstitial pneumonias suggestive of COVID-19 were identified, and the 18F-FDG PET/CT patterns were described. We compared the incidence of these lesions in the pre-COVID and pandemic phases. Results We observed a 1.6% increase in interstitial lung abnormalities during the period of COVID-19 circulation. All had

Introduction L’association de l’hydrocephalie chronique de l’adulte (HCA) et de la degenerescence lobaire fronto-temporale comportementale (DLFTc) est peu rapportee dans la litterature. Objectifs Cette etude retrospective observationnelle vise a decrire cliniquement et radiologiquement (imageries morphologique et fonctionnelle) l’association DLFTc-HCA. Patients et methodes Parmi les patients vus en 2019 au CMRR de Nantes pour une DLFTc repondant aux criteres possible et probable de Rascovsky, nous avons recense ceux ayant egalement un diagnostic d’HCA. Le diagnostic d’HCA etait pose sur la triade de Hakim et l’imagerie (hydrocephalie associee a un effacement des sillons au vertex). Les imageries morphologiques et fonctionnelles ont ete comparees en aveugle avec 10 patients HCA sans DLFTc. Resultats Une HCA etait evoquee chez 9 des 81 patients DLFTc. Ils presentaient tous un trouble du controle executif cognitif et comportemental (Rascovsky ≥ 4/6) auquel s’ajoutaient des troubles de la marche, ameliores chez 7 des 8 patients ayant eu des ponctions lombaires soustractives, puis chez 1 des 2 patients derives. Huit DLFTc-HCA et 1 HCA avaient un gradient d’atrophie anteroposterieur, 3 des 9 DLFTc-HCA et aucun des 4 HCA ayant eu une imagerie fonctionnelle presentaient un hypometabolisme a predominance anterieure. Discussion Il s’agit a notre connaissance de la premiere serie clinique de patients DLFTc-HCA. L’absence de neuropathologie ou de genetique est la principale limite. L’atrophie a predominance anterieure chez 8 des 9 patients conforte cependant l’hypothese qu’il s’agit bien de DLFTc, et non de presentations comportementales d’HCA. La moindre detection d’un gradient en imagerie fonctionnelle pourrait etre due a l’hypometabolisme sous-cortical diffus. Conclusion L’association DLFTc-HCA n’est pas rare (11,1 % des DLFTc), et est a evoquer devant des troubles du comportement frontaux, des troubles de la marche, et une hydrocephalie sur l’imagerie.

The aim of this retrospective multicentric study was to develop and evaluate a prognostic

Introduction La pathologie a corps de Lewy reste sous diagnostiquee en pratique courante du fait d’un manque de sensibilite des criteres diagnostiques et d’une intrication tres frequente avec une pathologie d’Alzheimer. Objectifs Validation de LeSCoD, un outil de depistage des signes de pathologie de Lewy et correlation a l’imagerie TEP a la Fluoro-DOPA. Patients et Methodes Nous avons elabore LeSCoD, une echelle composite semi-quantitative, issue d’echelles validees dans la maladie de Parkinson ou la MCL. Pour l’etude de validation, 3 groupes de patients (maladie d’Alzheimer (MA), maladie a corps de Lewy (MCL) et suspicion de co-pathologie Alzheimer–Lewy) ont ete inclus de maniere prospective en consultation memoire. L’echelle LeSCoD et un bilan neuropsychologique etaient realises ainsi qu’une TEP a la Fluoro-DOPA de facon optionnelle. Resultats Au total, 133 patients ont ete inclus : 77 MA, 34 MCL et 22 co-pathologie MA-MCL. Deux seuils ont ete obtenus : un seuil de 5, en dessous duquel une MA est diagnostiquee avec une sensibilite de 100 % et une specificite de 57 % ; un seuil de 10, au-dessus duquel le diagnostic de pathologie de Lewy est retenu avec une sensibilite de 86 % et une specificite de 95 %. L’echelle LeSCoD s’est averee egalement correlee a la denervation dopaminergique striatale evaluee en TEP. Discussion L’interet de cette echelle reside a la fois dans son caractere semi-quantitatif et dans son recouvrement des signes moteurs et non moteurs de la pathologie de Lewy, ameliorant ainsi la sensibilite pour le diagnostic de MCL. Les correlations entre le score LeSCoD et la denervation dopaminergique renforcent la validite de l’echelle. Conclusion L’echelle LeSCoD constitue donc un outil simple de detection de la pathologie de Lewy en pratique clinique et pourrait etre en fonction du score obtenu, une alternative a la realisation d’une imagerie dopaminergique.

International audience; See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant (18)F-misonidazole ((18)F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The (18)F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In (18)F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral α = 0.05, power 1-β = 0.95). Results: Seventy-nine patients were preincluded, 54 were included, and 34 were (18)F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the (18)F-FMISO-positive group). DFS and overall survival at 1 y were 0.86 (95% CI, 0.77-0.96) and 0.63 (95% CI, 0.49-0.74), respectively. DFS was longer in the (18)F-FMISO-negative patients (P = 0.004). The radiotherapy dose was not associated with DFS when adjusting for the (18)F-FMISO status. One toxic death (66 Gy) and 1 case of grade 4 pneumonitis (>66 Gy) were reported. Conclusion: Our approach results in a response rate of 40% or more, with acceptable toxicity. (18)F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy.

BACKGROUND: Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated radioimmunotherapy using anti-CD22 (90)Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma. METHODS: We did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals. Eligible patients were aged 60-80 years with bulky stage 2-3 or stage 3-4 CD20-positive diffuse large B-cell lymphoma, previously untreated, and not eligible for transplantation. Patients received six cycles of R-CHOP (rituximab [375 mg/m(2)], cyclophosphamide [750 mg/m(2)], doxorubicin [50 mg/m(2)], and vincristine [1·4 mg/m(2), up to 2 mg] all on day 1, and prednisone [40 mg/m(2)] daily for 5 days), administered every 14 days. 6-8 weeks after R-CHOP, responders received two doses of 15 mCi/m(2) (555 MBq/m(2)) (90)Y-epratuzumab tetraxetan administered 1 week apart. The primary endpoint was 2 year event-free survival in all registered eligible patients who received at least 1 day of study treatment; the safety analysis was done in the same population. This trial is registered with ClinicalTrials.gov, number NCT00906841. FINDINGS: Between Oct 22, 2008, and Dec 16, 2010, we recruited 75 patients, of whom four (5%) were excluded after central pathology review; hence, 71 (95%) patients were included in the analysis. All patients started induction treatment; 57 (80%) received radioimmunotherapy. With a median follow-up of 37 months (IQR 30-44), the estimated 2 year event-free survival was 75% (95% CI 63-84). Radioimmunotherapy toxicity consisted of grade 3-4 thrombocytopenia in 48 (84%) of 57 patients and neutropenia in 45 (79%) of 57 patients. One patient developed myelodysplastic syndrome 28 months after receiving radioimmunotherapy and one patient developed acute myeloid leukaemia 5 months after receiving radioimmunotherapy. INTERPRETATION: Fractionated radioimmunotherapy with (90)Y-epratuzumab tetraxetan might be appropriate for response consolidation after induction chemotherapy in older patients with advanced diffuse large B-cell lymphoma, but further comparative studies are needed. FUNDING: Immunomedics, Amgen, Canceropole Grand Ouest, the GOELAMS/LYSA group and the French National Agency for Research (Investissements d'Avenir).

Radioimmunotherapy (RIT) has been developed for more than 30 years. Two products targeting the CD20 antigen are approved in the treatment of non-Hodgkin B-cell lymphoma (NHBL): iodine 131-tositumomab and yttrium 90-ibritumomab tiuxetan. RIT can be integrated in clinical practice for the treatment of patients with relapsed or refractory follicular lymphoma (FL) or as consolidation after induction chemotherapy. High-dose treatment, RIT in first-line treatment, fractionated RIT, and use of new humanized monoclonal antibodies (MAbs), in particular targeting CD22, showed promising results in NHBL. In other hemopathies, such as multiple myeloma, efficacy has been demonstrated in preclinical studies. In solid tumors, more resistant to radiation and less accessible to large molecules such as MAbs, clinical efficacy remains limited. However, pretargeting methods have shown clinical efficacy. Finally, new beta emitters such as lutetium 177, with better physical properties will further improve the safety of RIT and alpha emitters, such as bismuth 213 or astatine 211, offer the theoretical possibility to eradicate the last microscopic clusters of tumor cells, in the consolidation setting. Personalized treatments, based on quantitative positron emission tomography (PET), pre-therapeutic imaging, and dosimetry procedures, also could be applied to adapt injected activity to each patient.

See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant

Introduction et but de l’etude L’objectif de cette etude etait de developper et d’evaluer une signature radiomique en utilisant l’imagerie tomographique par emission de positons (TEP/TDM) chez des patients atteints d’un cancer du poumon non a petites cellules traites par irradiation stereotaxique. Materiel et methodes Il s’agit d’une etude retrospective multicentrique portant sur 87 patients atteints d’un atteints d’un cancer du poumon non a petites cellules de stade T1-T2 traite dans quatre centres du Grand Ouest. Les patients des trois premiers centres (n = 27, 29 et 8) constituaient le groupe d’apprentissage, et ceux du quatrieme (n = 23) le groupe de validation. Le critere d’evaluation principal etait le controle local. En tout, 184 parametres radiomiques ont ete extraits (92 de chaque modalite) et sept parametres cliniques, histologiques et therapeutiques ont ete consideres. En raison des differents scanographes et protocoles d’acquisition des institutions, nous avons utilise la methode ComBat pour harmoniser les parametres de texture. Resultats et analyse statistique En analyse unifactorielle, deux parametres issus de la TEP et deux de la scanographie etaient significativement predictifs du controle local, a l’inverse des variables cliniques. Le meilleur modele predictif du groupe d’apprentissage etait obtenu en associant deux parametres TEP (IC2 et strength), avec une sensibilite de 100 % et une specificite de 88 %, et un hazard ratio indefini (p Conclusion Notre etude a permis d’identifier deux parametres de textures derives de la TEP/scanographie comme facteurs predictifs independants associes a la recidive locale chez les patients atteints d’un cancer du poumon non a petites cellules traites par irradiation stereotaxique. Ce modele merite d’etre confirme sur une cohorte plus consequente et pourrait etre utilise en clinique pour guider une eventuelle escalade de dose.

Introduction Structural valve degeneration (SVD) of bioprostheses is a common and serious complication in patients undergoing aortic valve replacement. SVD pathophysiology remains unclear.18F-sodium fluoride (NaF) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) have respectively shown that an active metabolic phenomenon of calcification rather than an inflammatory process contribute to native aortic valve stenosis. We studied the respective value of NaF and FDG PET to explore the potential mechanisms involved in SVD. Method SVD patients underwent NaF PET to explore potential active calcification process, FDG PET to explore potential inflammatory process and thoracic CT. Tracer uptake was quantitatively measured by the bioprosthesis tissue-to-background ratio of standardized uptake values (TBR). Echocardiographic parameters, bioprosthesis calcium scoring on CT, and qualitative pattern of NaF and FDG activity on bioprostheses were analyzed. Results Twenty-one patients were included. Calcium score was higher in patients with significant NaF visual uptake versus patients without (1065 ± 505 vs. 462 ± 320, P = 0.015). The median NaF TBR (3.49, [2.33–5.04]) was significantly higher than FDG (1.34, [1.20–1.47]). Patients with NaF TBR greater than the median value had a higher calcium score (1059 ± 550 vs. 566 ± 363, P = 0.05), and showed a tendency to have more severe hemodynamic stenosis. Picture shows an example of patient with SVD (A); CT (B) established localizations of calcium deposits; NaF PET/CT (C) show intense uptake adjacent to calcifications; FDG PET/CT (D) show no uptake ( Fig. 1 ). Conclusion These results suggest a link between SVD severity and active calcification activity and opens new perspectives on the assessment of SVD pathophysiology through NaF PET quantification of ongoing mineral burden.

Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated radioimmunotherapy using anti-CD22We did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals. Eligible patients were aged 60-80 years with bulky stage 2-3 or stage 3-4 CD20-positive diffuse large B-cell lymphoma, previously untreated, and not eligible for transplantation. Patients received six cycles of R-CHOP (rituximab [375 mg/mBetween Oct 22, 2008, and Dec 16, 2010, we recruited 75 patients, of whom four (5%) were excluded after central pathology review; hence, 71 (95%) patients were included in the analysis. All patients started induction treatment; 57 (80%) received radioimmunotherapy. With a median follow-up of 37 months (IQR 30-44), the estimated 2 year event-free survival was 75% (95% CI 63-84). Radioimmunotherapy toxicity consisted of grade 3-4 thrombocytopenia in 48 (84%) of 57 patients and neutropenia in 45 (79%) of 57 patients. One patient developed myelodysplastic syndrome 28 months after receiving radioimmunotherapy and one patient developed acute myeloid leukaemia 5 months after receiving radioimmunotherapy.Fractionated radioimmunotherapy withImmunomedics, Amgen, Canceropôle Grand Ouest, the GOELAMS/LYSA group and the French National Agency for Research (Investissements d'Avenir).

Resume L’heterogeneite au sein d’une cohorte de patients a ete definie comme un defi majeur dans la pratique clinique et est probablement davantage mise en evidence dans le domaine de l’oncologie. Cela a ete l’impulsion d’etudes d’avant-garde de recherche preclinique et clinique au cours de ces dernieres annees, beaucoup d’entre elles ont cherche a stratifier les patients selon leur profil genetique, proteomique et metabolique, afin de selectionner le traitement le plus approprie au patient considere. L’imagerie moleculaire du cancer du sein peut etre potentiellement utilisee pour la stadification du cancer du sein, le bilan d’extension des recidives, l’evaluation de la reponse et dans le choix des therapies. Cet article se concentre sur l’imagerie tomographie par emission de positons (TEP) qui peut fournir des informations sensibles, iteratives, non invasives des caracteristiques de la tumeur. De plus en plus, des cibles plus specifiques du cancer du sein sont imagees telles que les recepteurs des œstrogenes (ER) et les facteurs de croissance. Bien que l’imagerie moleculaire du cancer du sein ne soit pas encore couramment utilisee en pratique clinique quotidienne, son champ d’applications est en pleine expansion.

Objectives To report cases of cat scratch disease with vertebral osteomyelitis. Methods We describe clinical features, diagnostic, treatment, and outcome of 2 patients with vertebral osteomyelitis due to Bartonella henselae and provide a review of the relevant literature. Results A 47-year-old man was investigated for fever, splenomegaly, and cervical adenopathy. A lymphoma was suspected on the clinical picture, the laboratory tests, and the computed tomographic scan. [ 18 F]-fluoro-2-deoxy-d-glucose-positron emission tomography detected splenic nodules and a hypermetabolic focus of C7 vertebral body compatible with a vertebral osteomyelitis on magnetic resonance imaging. B henselae infection was confirmed by polymerase chain reaction performed on lymph node biopsy. A 34-year-old woman was investigated for fever and right upper quadrant abdominal pain. She had consulted 2 weeks before for a unique lesion of right index and an axillar adenopathy that have improved spontaneously. A technetium bone scan performed 1 week later because of a thoracic backache demonstrated an increased uptake of the T6 vertebra. Vertebral magnetic resonance imaging was compatible with a T6 osteomyelitis. B henselae infection was confirmed by serology (seroconversion). Both patients were treated with rifampin and doxycycline and recovered within 3 months. Conclusions B henselae vertebral osteomyelitis can involve immunocompetent adults. In the case of vertebral osteomyelitis with negative blood cultures, recent history of local lymphadenopathy and cat exposure must be investigated and B henselae serology must be performed. Nevertheless, even if serology is positive, vertebral biopsy is required to rule out other pathogens or malignancy. B henselae infection can be confirmed by polymerase chain reaction performed on vertebral or lymph node biopsy.

Resume Bien que l’efficacite de la radiotherapie vectorisee ait ete demontree dans plusieurs indications, le developpement de cette approche therapeutique originale reste limite. Des resultats prometteurs ont cependant ete obtenus ces dernieres annees, en particulier avec differents analogues de la somatostatine marques pour les tumeurs neuro-endocrines ou la radio-immunotherapie pour les lymphomes. La toxicite reste limitee, notamment si les patients sont selectionnes en fonction de leurs antecedents. L’utilisation de nouveaux vecteurs (bombesine, anticorps anti-PMSA), de systeme de preciblage et de radioelements innovants (Cuivre 67, Astate 211) laissent envisager des perspectives interessantes, en particulier pour cibler les petites masses tumorales ou la maladie residuelle.

Resume Objectifs Le curage standard est actuellement remis en question dans la prise en charge du cancer de la prostate. Le but de cette etude prospective est d’evaluer les performances de la technique du ganglion sentinelle (GS) par cœlioscopie chez des patients porteurs d’un cancer localise de prostate candidats a un traitement local. Patients et methodes Les patients etaient injectes par voie transrectale echoguidee avec 0,3 mL/100MBq de 99 m Tc-sulfure de rhenium colloidal dans chaque lobe prostatique la veille de l’intervention. Une lymphoscintigraphie etait realisee deux heures apres. La radiodetection peroperatoire etait realisee avec une sonde cœlioscopique (Clerad ® Gamma Sup) suivie d’un curage extensif. Les comptages des GS etaient realises in vivo et confirmes ex vivo. L’analyse anatomopathologique etait realisee par HPS, suivie d’un immunomarquage si GS indemnes. Resultats Soixante-dix patients, porteurs d’un cancer de la prostate a risque intermediaire ou eleve de metastases ganglionnaires (D’Amico), PSA median 9,5 ng/mL [6–130] ont ete inclus dans l’etude. Le taux de detection lymphoscintigraphique a ete de 94,2 % (66/70) et peroperatoire de 97,0 % (68/70). Quatorze patients presentaient des metastases ganglionnaires, six uniquement dans les GS. Le taux de faux negatifs etait de 2/14 (14,0 %). La region iliaque interne est le premier site metastatique (40,9 %). Un curage limite ou standard aurait ignore respectivement 72,7 % et 59,0 % des metastases ganglionnaires. Conclusion La voie cœlioscopique est adaptee a un large reperage des GS et un curage cible de ces ganglions limiterait significativement le risque chirurgical du curage etendu tout en maintenant la precision de l’information.

Resume But Une etude de phase II promue par le GOELAMS, multicentrique, non randomisee, est en cours, evaluant l’efficacite et la tolerance de l’administration fractionnee de l’ 90 Y-epratuzumab (deux injections a sept jours d’intervalle), dans le traitement de consolidation de patients de plus de 60 ans atteints de lymphomes diffus a grandes cellules de forte masse tumorale, en reponse complete (RC), RC non confirmee (RCu) ou reponse partielle (RP) apres un traitement d’induction comportant six cures de R-CHOP14. Nous rapportons des resultats preliminaires chez 41 des 75 patients inclus et en cours de suivi. Patients et methodes La toxicite etait evaluee selon des criteres NCI-CTC version 3. Le taux de RC et de RCu ainsi que le taux de conversion des RP en RC/RCu six semaines apres les injections de 90 Y-epratuzumab ont ete evalues selon les criteres IWRC. Resultats Trente-trois patients ont recu les deux injections d’ 90 Y-epratuzumab. La toxicite de l’ 90 Y-epratuzumab etait essentiellement hematologique, caracterisee par une neutropenie grade 3/4 chez 81,8 % des patients et une thrombopenie grade 3/4 chez 78,8 % des patients, reversibles. Deux patients (6,1 %) ont presente une toxicite non hematologique de grade 3/4. Six semaines apres les injections de 90 Y-epratuzumab, 40,0 % des patients amelioraient leur reponse et le taux de RC/RCu etait de 83,9 %. Conclusion Ces resultats preliminaires montrent une toxicite importante mais essentiellement hematologique, attendue en consolidation. Le taux de reponse apparait encourageant et reste a confirmer par un nombre d’inclusions et un recul suffisants.

The aim of this retrospective study was to evaluate the contribution of (18)F-FDG PET to the clinical management and survival outcome of patients suspected of recurrent cervical carcinoma and in line with the hypothesis that early diagnosis of recurrent cervical cancer may improve overall survival.A total of 40 patients underwent conventional imaging (CI) and FDG PET/CT for suspected cervical cancer. Clinical management decisions were recorded with CI and additional PET/CT. Discordances and concordances between CI and PET/CT results were compared to the final diagnosis as based on histopathology analysis or follow-up considered as the gold standard.The final diagnosis was established pathologically (n = 25) or by median clinical follow-up for 48 months after the PET (n = 15). The PET/CT was positive in 76% (20/26) of patients compared to 19% (6/26) with CI. Globally PET/CT modified the treatment plan in 55% (22/40) of patients and in 75% (18/24) when the CI was negative prior to PET/CT. These changes led to the use of previously unplanned therapeutic procedures in 37.5% (15/40). When FDG PET was positive for recurrence (3 foci), the median overall survival was 12 months (2-70) compared to patients with PET findings withor = 1 focus for which the median survival was not attained (p = 0.007). A multivariate analysis of prognostic factors demonstrated that abnormal FDG uptake (3 foci) was the most significant factor (p0.03) for death from cervical cancer.FDG PET is a valuable tool in the case of suspected recurrence of cervical cancer on account of its impact on treatment planning and especially in predicting patient outcome.

Down syndrome (DS) is caused by trisomy of chromosome 21. The average age of onset of Alzheimer's disease (AD) ranged from 50 to 55 years in DS, with early symptoms usually characterised by changes in behaviour and executive dysfunction. On the other hand, posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome characterised by progressive impairment of visual functions in the absence of visual deficits and a pattern of atrophy involving posterior cortex. This syndrome is mostly caused by AD pathology. We report the case of patient with DS who developed PCA. While atypical variants of AD are commonly associated with an early age at onset, all focal forms of AD may potentially appear in DS. Specifying the phenotype has an impact on the care of DS patients and could help us to know the evolution. It could also provide a better understanding of the underlying mechanisms of focal forms.

The pathological process affects the peripheral autonomic nervous system in the vast majority of sporadic PD patients. Recent reports have shown that patients with a familial form of the disease caused by mutation of the gene encoding LRRK2 and alpha-synuclein also display autonomic abnormalities, especially cardiac sympathetic denervation. In the present report, we have studied the involvement of the peripheral autonomic system in a patient with Gaucher disease-associated parkinsonism. Using colonic biopsies and quantitative 123I-MIBG scintigraphy respectively, we show that both Lewy pathology and cardiac denervation were present in this case of Gaucher-associated Parkinsonism. We discuss the consequence of these findings on the pathophysiology of the disease.

International audience; La démence à corps de Lewy (DCL) est la deuxième cause de démence dégénérative du sujet âgé, dans les grandes séries autopsiques. Dans la réalité quotidienne des centres mémoire pourtant, la DCL représente une faible proportion des diagnostics cliniques, avec une forte disparité entre les centres. Plusieurs raisons peuvent rendre compte de la faible sensibilité du diagnostic de DCL : l’imprécision et la subjectivité des critères diagnostiques existants ; la place insuffisante donnée à certains signes non-moteurs (troubles du comportement en sommeil paradoxal, dysautonomie) ; enfin et surtout l’association quasi constante de la pathologie de Lewy à une pathologie de type Alzheimer, qui domine rapidement le phénotype clinique. À l’heure de l’essor des thérapies ciblées contre les agrégats protéiques, de nouvelles échelles cliniques permettant d’appréhender la coexistence de la pathologie de Lewy dans la maladie d’Alzheimer sont plus que jamais nécessaires.

Objectifs L’hypoxie tumorale est responsable d’une chimio- et radioresistance. La TEP au F-Miso permet d’etudier l’hypoxie tumorale in vivo. Notre objectif a ete d’etudier prospectivement des pts atteints d’un cancer pulmonaire non a petites cellules stade III qui devaient beneficier d’une radio-chimiotherapie (RCT) a visee curative. L’analyse de l’hypoxie par TEP-FMiso a ete realisee par 3 experts via le reseau SFMNnet et les volumes FDG et F-Miso ont ete definis de maniere centralisee. Les patients ayant une TEP-F-Miso positive ont beneficie d’un complement de dose de RT sur les volumes hypoxiques. Nous presentons les resultats preliminaires. Materiels et methodes Les patients ont beneficie d’une TEP-FDG avant et apres la CT d’induction. Les patients qui avaient une TEP-FDG positive apres la CT d’induction ont eu une TEP-F-Miso. Si la TEP-F-Miso etait positive, les patients ont eu une delineation des volumes cibles FDG et F-Miso, transmis ensuite au radiotherapeute local, qui prescrivait un boost a la dose maximale sur les zones hypoxiques. Si la TEP-F-Miso etait negative, les patients avaient une RCT standard de 66 Gy. Les examens ont ete recales, puis differents volumes cibles ont ete definis par seuillage relatif pour le FDG (40, 50, 60, 70, 80, 90 % des SUVmax) et par seuillage absolu pour le Fmiso (SUV a 1,4). Les volumes des traceurs ont ete compares (Dice et Jaccard). La tolerance et le controle local (RECIST1.1) ont ete evalues a 3 et 1 an post-RT. Resultats Soixante-dix-neuf patients (60a) ont ete inclus. Cinquante-quatre patients sur 79 evaluables en pre-RT ont beneficie d’une TEP-F-Miso. Trente-quatre patients sur 54 (62 %) avaient au moins 1 lesion hypoxique et 20/54 etaient non hypoxiques. Vingt-quatre patients sur 34 (70 %) hypoxiques ont pu beneficier d’une augmentation de dose de 70 a 86 Gy. Aucune toxicite grade 4 n’a ete observee et seulement 1 toxicite grade 3. Le SUVmax Fmiso etait de 2,6 pour les patients hypoxiques et de 1,5 pour les patients normoxiques (p Conclusions Les resultats preliminaires de l’etude multicentrique RTEP5 montrent que la realisation d’un complement de dose de RT basee sur la TEP-F-Miso est faisable. Aucune toxicite grade 4 n’a ete observee et le controle local des patients ayant eu une augmentation de dose est de 59 % a 3 mois. Les sous-volumes les plus hypermetaboliques et les volumes hypoxiques sont deux zones tumorales distinctes.

Introduction Les criteres diagnostiques actuels de maladie a corps de Lewy (MCL) ne tiennent pas compte du chevauchement clinique et histopathologique entre MCL et maladie d’Alzheimer (MA). Objectifs L’objectif est d’augmenter la sensibilite du diagnostic clinique de pathologie de Lewy a l’aide d’un questionnaire correle a la perte dopaminergique dans le spectre MA-MCL. Patients et methodes Les donnees d’un questionnaire (LESCOD) etabli a Nantes, regroupant 9 caracteristiques de la maladie a corps de Lewy (parkinsonisme, hallucinations, depression, dysautonomie vasculaire et vesico-sphincterienne, declin cognitif, fluctuations, hyposmie, troubles du comportement en sommeil paradoxal) ont ete comparees a la fonction dopaminergique evaluee en TEP a la 18F-DOPA, au niveau du noyau caude (NC) et du putamen (PUT), chez des patients consultant pour une plainte cognitive attribuee a une MCL ou a une MA. Resultats Sur les 10 patients inclus, deux presentaient une MA et huit une MCL. Le score de dissemination de la pathologie Lewy et le score de severite definis par le score LESCOD etaient significativement inversement correles a la fixation dopaminergique au niveau du NC ( p p p p Discussion L’alteration de la substance noire, specifique et precoce dans la pathologie de Lewy apparait correlee aux signes cliniques de cette pathologie. Le score LESCOD pourrait permettre de maniere simple d’identifier une pathologie de Lewy dominante ou associee chez des patients atteints de MA. Ceci aurait un interet therapeutique permettant d’eviter la prescription de neuroleptiques chez les patients MA suspects d’une pathologie de Lewy associee. Conclusion Ces resultats preliminaires demandent a etre confirmes, mais ouvrent en pratique courante des perspectives nouvelles concernant l’evaluation de la charge de la pathologie de Lewy dans le spectre MA-MCL. Informations complementaires Financements publics.

Purpose FDG-positron emission tomography (PET) has high diagnostic accuracy in cardiac sarcoidosis (CS). Beyond CS, the non invasive diagnosis of inflammatory cardiomyopathies (IC) is challenged by a lower diagnostic performance of usual tools as magnetic resonance imaging (MRI). Methods 17 consecutive patients with suspected IC had a FDG-PET to detect myocardial inflammation. From all clinical data including PET, we classified patients in either CS or non-CS and respective PET data were compared. The clinical impact of adding PET in the non-CS group was evaluated by comparing diagnosis and management proposed by an expert blind to PET with final diagnosis and management actually held in practice. Results 6 patients had CS, all with positive PET. In the 11 non-CS patients, 7 had a positive PET. All had MRI late gadolinium enhancement in FDG uptake areas, suggesting a true positivity of PET for the presence of inflammation. PET data were all significantly different between CS and nonCS patients with positive PET, particularly the coefficient of variation of cardiac SUV which is an index of heterogeneity of FDG uptake was significantly greater in CS patients (0,4 vs 0,17 p Conclusion Some patients with suspected IC had a positive FDG-PET in favour of myocardial inflammation, with a different pattern from that observed in CS. Adding PET to usual diagnostic tools led to a decrease of possible IC diagnosis that turned in excluded IC. These preliminary data suggest a potential role of PET for the non-invasive diagnosis of IC that will need further investigations. Download : Download high-res image (89KB) Download : Download full-size image Abstract 0049 – Figure: FDG uptake concordant with MRI-LGE

Radioimmunotherapy (RIT) efficacy has been demonstrated in hematology, in particular in B cell non-Hodgkin lymphoma (NHL). RIT can be applied in clinical practice using non-ablative activity of murine anti-CD20 131I-tositumomab and 90Y-ibritumomab tiuxetan. Today, different approaches are explored to improve efficacy of RIT in NHL: myeloablative RIT, RIT as consolidation after chemotherapy, RIT in first-line treatment, fractionated RIT, RIT using other antigen targets or other monoclonal antibody. This chapter reviews current advances in the fractionated radioimmunotherapy, in particular the use of Epratuzumab Tetraxetan, a 90-Y-labeled anti-CD22 antibody in the treatment of non-Hodgkin lymphoma. We present especially the result of a phase I/II, multi center, dose-escalation trial assessing 90Y-hLL2 administered once weekly for 2 or 3 weeks, achieving high rates of durable complete responses with manageable hematological toxicity in NHL relapsing patients.

Introduction Differencier la maladie de Parkinson idiopathique (MPI) des autres syndromes parkinsoniens tels que atrophie multi-systematisee (AMS) ou paralysie supranucleaire progressive (PSP) peut etre difficile pour les cliniciens experts. Objectifs L’objectif de cette etude etait d’evaluer la correlation entre la conclusion des experts et celle des scintigraphies myocardiques au 123-I-MIBG pour le diagnostic differentiel entre MPI et PSP ou AMS. Methodes Les 10 patients qui ont beneficie d’une scintigraphie myocardique au CHU de Nantes entre fevrier 2012 et septembre 2013 pour un syndrome parkinsonien atypique ont ete inclus. L’examen d’imagerie etait interprete selon 3 plans d’analyse : taux de fixation cardiaque globale aux temps precoce et tardif, rapports cœur/mediastin aux 2 temps et taux de relargage du traceur. Un examen anormal etait en faveur d’une denervation dopaminergique post-ganglionnaire, compatible avec le diagnostic de MPI. Resultats La scintigraphie myocardique etait realisee entre un et dix huit ans apres le debut des symptomes. Deux de nos patients avaient une MPI, 3 une AMS et 4 une PSP. L’examen etait interprete comme normal chez 3 patients (aucun avec une MPI), pathologique chez 4 patients (dont 1 AMS et 1 PSP), et douteux chez 2 patients. La sensibilite de notre examen d’imagerie etait de 100 %. La specificite (calculee en incluant AMS et PSP) etait proche de 60 %. Elle etait meilleure pour differencier la MPI de la l’AMS. Discussion Nous avons retrouve une scintigraphie myocardique au 123-I-MIBG pathologique chez la totalite des patients parkinsoniens. Cet examen etait normal chez pres de 60 % des patients avec syndrome parkinsonien atypique. Ainsi un examen normal eliminerait formellement le diagnostic de MPI. Le nombre eleve de faux positifs peut s’expliquer par les differentes pathologies et medicaments qui peuvent alterer les neurones sympathiques post-ganglionnaires. Conclusion Au total, notre etude a retrouve des performances diagnostiques comparables a celles de la litterature concernant l’utilisation des scintigraphies myocardiques au 123-I-MIBG pour le diagnostic differentiel entre MPI et AMS ou PSP.

A cardiac magnetic resonance (CMR) imaging was performed 7 days after the admission of a 41-year-old woman referred for an acute coronary syndrome and normal coronary angiography, high-sensitive Tc troponin increase, and impaired left ventricle ejection fraction (LVEF). T2-weighted sequences showed increased sub-epicardial signal in anterior and inferior walls in favour of a myocardial …

Abstract 906 Background: Consolidation using radioimmunotherapy (RIT) is a promising approach for elderly patients with diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem-cell transplantation. RIT using fractionated injections of 90Y-epratuzumab tetraxetan (Immunomedics, Inc.), a radiolabeled humanized anti-CD22 antibody, has been evaluated in relapsed patients with indolent or aggressive non-Hodgkin lymphoma (NHL), providing long-term disease control with manageable hematologic toxicities (Morschhauser et al., J Clin Oncol. 2010;28(23);3709-16). A French phase II trial sponsored by the LYSA group now assessed front-line treatment using fractionated RIT with 90Y-epratuzumab tetraxetan as consolidation therapy after R-CHOP in previously untreated elderly (age >60 years) patients presenting with stage I/II bulky or stage III/IV DLBCL. Methods: The trial included 6 courses of R-CHOP delivered q2wks followed by 2 infusions of 90Y-epratuzumab tetraxetan (2 × 15 mCi/m2 [555 MBq/m2], 7 days apart), 8 wks later. Patients were enrolled at time of diagnosis. Results: From October 2008 to December 2010, 75 patients (41 males, 34 females) have been accrued prospectively at 19 French institutions. The median age was 69 (range, 60–79 years); 57 patients (76.0%) were Ann Arbor stage III/IV. Seventy-one of the 75 completed 6 courses of R-CHOP-14 and 61/75 (81.2%) were eligible for RIT. Thus, 14 patients were considered ineligible for RIT because of R-CHOP toxicity (N= 5), progressive disease (PD, N=3), patient refusal (N=3), or concomitant illness (N=3). RIT toxicity consisted of grade 3–4 hematologic toxicity in 51/61 patients (83.6%): grade 3–4 neutropenia in 46 (75.4%), grade 3–4 anemia in 15 (24.6%), and grade 3–4 thrombocytopenia in 47 (77.0%), with a nadir at 42, 48, and 43 days after RIT and a median duration of 18, 5, and 17 days, respectively. Following RIT, RBC and/or platelet transfusions were given to 31 patients (50.8 %). Serious febrile neutropenia was observed in 13 cases (17.3 %) after R-CHOP and in 3 patients (4.9%) following RIT. RIT's severe non-hematologic toxicity consisted of grade 4 gastrointestinal in 1 patient (1.6 %) and grade 4 infection in 3 (4.9%). No patient had mucositis after RIT. In the follow-up, 2 patients (2.6%) developed myelodysplastic syndrome 5 and 20 months after RIT. Using the 1999 International Workshop for Response Criteria for NHL (Cheson 1999), the overall response rate (ORR) after 6 × R-CHOP14 was 94.6% (71/75); 52 patients (69.3%) achieved CR/CRu and 19 (25.3%) had a partial response (PR). Among the 4 remaining patients, one had stable disease and 2 had PD; no assessment was obtained in the other. In an intention-to-treat analysis, CR/CRu rate after 6 × R-CHOP14 followed by RIT was 72.0% (N=54). Seven patients (9.3%) remained in PR and 8 (10.7%) progressed (2 patients previously in PR with PET-positive findings, 3 previously in CRu, including 1 PET-positive, and 3 in PD before RIT and then ineligible for RIT). No response assessment was obtained in the 6 others ineligible for RIT. At a median follow-up of 24 months (range, 1–46), 18 patients experienced lymphoma progression and/or a related death, yielding an estimated 2-year event-free-survival (EFS) of 73.3% (60.7-82.5%) and an estimated 2-year overall survival (OS) of 83.2% (71.4-90.4%). For the 61 patients who received 6 courses of R-CHOP followed by RIT consolidation, ORR was 91.8% (56/61); 50 patients (81.9%) achieved CR/CRu. Eight of 16 patients (50.0%) who had less than a CR/CRu with R-CHOP converted to CR/CRu after RIT. According to a PET analysis (Cheson 2007; N=55), 12 of the 24 patients (50.0%) who were not PET-negative after R-CHOP improved their metabolic response after RIT, resulting in a CR rate of 72.7%. Among these 61 patients, 12 experienced progression and/or a related death, yielding an estimated 2-year EFS of 78.7% (65.1–87.4%) and an estimated 2–year OS of 90.1% (77.7–95.8%). Conclusions: This phase II study clearly shows that fractionated RIT with 90Y-epratuzumab as a consolidation therapy after 6 × R-CHOP-14 is feasible and tolerable in elderly untreated DLBCL patients with advanced disease. RIT markedly improved response status observed after 6 × R-CHOP14. EFS data achieved with R-CHOP plus RIT compare favourably with those achieved with R-CHOP alone in the same patient population. Disclosures: Wegener: Immunomedics: Employment. Goldenberg:Immunomedics: Employment, Equity Ownership.

The aim of this retrospective multicentric study was to develop and evaluate a prognostic 18F-FDG PET/CT radiomic signature in early-stage non-small cell lung cancer patients treated with stereotactic body radiotherapy (SBRT). Methods: Patients from 3 different centers (n = 27, 29, and 8) were pooled to constitute the training set, whereas the patients from a fourth center (n = 23) were used as the testing set. The primary endpoint was local control. The primary tumor was semiautomatically delineated in the PET images using the fuzzy locally adaptive Bayesian algorithm, and manually in the low-dose CT images. In total, 184 Image Biomarkers Standardization Initiative-compliant radiomic features were extracted. Seven clinical and treatment parameters were included. We used ComBat to harmonize radiomic features extracted from the 4 institutions relying on different PET/CT scanners. In the training set, variables found significant in the univariate analysis were fed into a multivariate regression model, and models were built by combining independent prognostic factors. Results: Median follow-up was 21.1 mo (range, 1.7-63.4 mo) and 25.5 mo (range, 7.7-57.8 mo) in training and testing sets, respectively. In univariate analysis, none of the clinical variables, 2 PET features, and 2 CT features were significantly predictive of local control. The best predictive models in the training set were obtained by combining one feature from PET (Information Correlation 2) and one feature from CT (flatness), reaching a sensitivity of 100% and a specificity of 96%. Another model combining 2 PET features (Information Correlation 2 and strength) reached sensitivity of 100% and specificity of 88%, both with an undefined hazard ratio (P < 0.001). The latter model obtained an accuracy of 0.91 (sensitivity, 100%; specificity, 81%), with a hazard ratio undefined (P = 0.023) in the testing set; however, other models relying on CT radiomic features only or the combination of PET and CT features failed to validate in the testing set. Conclusion: We showed that 2 radiomic features derived from 18F-FDG PET were independently associated with local control in patients with non-small cell lung cancer undergoing SBRT and could be combined in an accurate predictive model. This model could provide local relapse-related information and could be helpful in clinical decision making.

Abstract 2875 Background: Radioimmunotherapy (RIT) is under study as a consolidation treatment after chemotherapy induction in follicular lymphoma patients. This approach also appears interesting in diffuse large B-cell lymphoma (DLBCL) patients >60 years, who are not candidates for bone marrow transplantation. 90Y-epratuzumab tetraxetan (Immunomedics, Inc.) is a radiolabeled humanized anti-CD22 antibody that has been used for a fractionated RIT, showing high rates of durable complete responses with manageable hematologic toxicity in previously-treated indolent and aggressive non-Hodgkin lymphoma (NHL) patients (Morschhauser et al., J Clin Oncol. 2010;28(23);3709-16). A French phase II trial sponsored by the GOELAMS group is ongoing, assessing fractionated RIT using 90Y-epratuzumab tetraxetan as a consolidation therapy after first-line chemotherapy in disseminated DLBCL patients >60 years. The protocol has been designed to include 75 patients; 64 patients have been already enrolled. We report the initial results, in particular safety data, on the first 29 available patients. Design and Method: From October 2008 to November 2009, 29 untreated DLCBL patients >60 years were studied in several French institutions with an initial course of six cycles of R-CHOP14 followed 8 weeks later by two weekly infusions of 90Y-epratuzumab tetraxetan (15 mCi/m2 [555 MBq/m2]) 7 days apart. Hematologic and non-hematologic toxicities were evaluated using NCI-CTC v.3.0. Treatment responses were classified according to the 1999 International Workshop for Response Criteria for NHL. Results: Twenty-six patients underwent the entire course of R-CHOP and 23 received the 2 weekly RIT injections. Following R-CHOP, grade 3–4 neutropenia was observed in 20 patients (68.9%) and grade 3–4 thrombocytopenia in 4 (13.7%). During RIT infusions, 4 patients showed transient change of pulse or blood pressure, with 2 attributed to vasovagal reactions. RIT toxicity included grade 3–4 hematologic toxicity in 18 of 23 patients (78.3%); the most common grade > 3 toxicities were neutropenia (N=18, 78.3%) and thrombocytopenia (N=17, 73.9%). Serious febrile neutropenia was observed in 4 cases (13.8%) after R-CHOP and in 2 patients (8.7%) following RIT. Compared to R-CHOP, RIT non-hematologic toxicity was uncommon; moderate or severe gastrointestinal toxicity was observed in 10 patients (34.5%) after R-CHOP and in 2 (8.7%) following RIT; moderate or severe infection in 9 patients (31.0%) after R-CHOP and in 1 (4.3%) after RIT; and moderate or severe mucositis in 10 (34.4%) patients following R-CHOP, while no patient had mucositis after RIT. Following RIT, red cells and/or platelets transfusions were given to 12 patients (52,2%). Following R-CHOP, 10 of the 25 patients (40.0%) achieved a complete response (CR) or unconfirmed CR (CRu), 13 patients (52.0%) had a partial response (PR) and 2 patients (8.0%) had a stable disease. Six weeks after RIT, 13 patients (56.5%) achieved a CR or CRu, 9 patients (39.1%) had PRs, and 1 patient (4.3%) had progressive disease. Four of 13 patients (30.7%) who achieved less than a CR or CRu with R-CHOP improved their remission status 6 weeks after RIT. Conclusion: These preliminary results indicate the feasibility and safety of fractionated RIT with 90Y-epratuzumab as a consolidation therapy for elderly DLBCL patients. Additional data will be presented at the time of the communication. Disclosures: Off Label Use: monoclonal antibody epratuzumab labeled with yttrium 90 in phase II clinical trial. Wegener:Immunomedics, Inc.: Employment, shareholders. Goldenberg:Immunomedics, Inc.: Employment, shareholders.