Cancer différencié de la thyroïde chez les enfants et les moins de 21 ans (revue de la littérature et expérience de l'Institut Bergonié (47 cas))

Les patients de moins de 21 ans comptent pour moins de 10% de cette affection. Au diagnostic, la présentation clinique et anatomapathologique diffère de celles des adultes : extension estra thyroïdienne et multifocalité fréquente, envahissement ganglionnaire cervical dans 60% des cas et métastases à distance jusqu'à 25% des cas. L'évolution se complique fréquemment de récidive (jusqu'à 40%). Pourtant dans cette tranche d'âge le pronostic est excellent (faible mortalité). La progression de la maladie est lente. Le traitement standard de cette maladie rare est controversé. Faut-il entreprendre une thérapeutique initiale agressive, au vu du risque de récidive, mais au prix d'une morbidité opératoire (hypoparathyroïdie définitive et paralysie récurrentiel) ? Y'at-il des facteurs pronostiques fiables clinique, biologique, immuno histochimique ou de biologie moléculaire capable de prédire le devenir à long terme afin de sélectionner des populations ç risque au diagnostic ? Nous avons évalué à long terme (morbidité, survie globale et sans récidive) en fonction des différentes stratégies thérapeutiques en tenant compte des caractéristiques cliniques et anatomopathologiques, dans les séries de la littérature comportant plus de 10 patients et à partir de notre expérience personnelle d'une série de 47 patients de moins de 21 ans traités à l'institut bergonié depuis 1950. Le taux de mortalité est inférieur à 5%. La survie sans maladie varie de 60 à 80% à 10 ans. L'âge < 10 ans, un stade avancé, une résection incomplère sont des facteurs prédictif de récidive ou de maladie persistante. Les facteurs immuno histochimique et de biologie moléculaire sont en cours d'évaluation. La morbidité opératoire chute dans les mains d'un chirurgien entraîné et lorsqu'est réalisé une transplantation hétérotopique des parathyroïdes. Une thyroïdectomie total associée à , au minimum, un curage entral et aux éventuels chaînes envahies complété par une dose thérapeutique d'Iode 131 et un traitement hormonal freinateur semble être l'attitude la plus sure et efficace, en attendant la validation de facteur pronostique biologique.BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.

The Gastrin-Releasing Peptide Receptor (GRPR) is over-expressed in estrogen receptor (ER) positive breast tumors and related metastatic lymph nodes offering the opportunity of imaging and therapy of luminal tumors. 68Ga-RM2 binding and 18F-FDG binding in tumoral zones were measured and compared using tissue micro-imaging with a beta imager on 14 breast cancer samples (10 primaries and 4 associated metastatic lymph nodes). Results were then assessed against ER expression, progesterone receptor (PR) expression, HER2 over-expression or not and Ki-67 expression. GRPR immunohistochemistry (IHC) was also performed on all samples. We also retrospectively compared 68Ga-RM2 and 18F-FDG bindings to 18F-FDG SUVmax on the pre-therapeutic PET/CT examination, if available. 68Ga-RM2 binding was significantly higher in tumors expressing GRPR on IHC than in GRPR-negative tumors (P = 0.022). In ER+ tumors, binding of 68Ga-RM2 was significantly higher than 18F-FDG (P = 0.015). In tumors with low Ki-67, 68Ga-RM2 binding was also significantly increased compared to 18F-FDG (P = 0.029). Overall, the binding of 68Ga-RM2 and 18F-FDG displayed an opposite pattern in tumor samples and 68Ga-RM2 binding was significantly higher in tumors that had low 18F-FDG binding (P = 0.021). This inverse correlation was also documented in the few patients in whom a 18F-FDG PET/CT examination before surgery was available. Findings from this in vitro study suggest that GRPR targeting can be an alternative to 18F-FDG imaging in ER+ breast tumors. Moreover, because GRPR antagonists can also be labeled with lutetium-177 this opens new avenues for targeted radionuclide therapy in the subset of patients with progressive metastatic disease following conventional treatments

Assessment of the French colistin action plan

International audienceThe discovery of the plasmid resistance gene to colistin mcr-1 in 2015, profoundly changed the way this widely used molecule in veterinary medicine in France was considered. National management measures have been set up to reduce its use in animals, in line with European recom-mendations. Two objectives were defined: that of the AMEG in 2016, to reach a consumption of less than 5mg/kg in 3 to 4 years and that defined by the Ecoantibio2 national plan of a 50% reduction in the cattle, pig and poultry sectors in 5 years compared to the 2014-2015 use. In order to assess the effectiveness of these measures, French sales, usages and resistance surveillance data were analysed

Diagnostic accuracy and clinical impact of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in Positron Emission Tomography - Computed Tomography (PET-CT)-positive mediastinal lymphadenopathies in subjects with thoracic or extra-thoracic malignancy

BACKGROUND: The high sensitivity of PET-CT can identify hypermetabolic mediastinal adenopathies during cancer management, but specificity is low and a biopsy is sometimes required to eliminate benign adenopathies. METHODS: This prospective diagnostic accuracy study included patients with hypermetabolic mediastinal lymphadenopathies revealed on PET-CT, during either the initial management of a cancer, treatment evaluation, or monitoring. All patients underwent EUS-FNA. Diagnose of malignancy based on cytological analysis following EUS-FNA were compared with clinical and radiological follow-up informations. Treatment strategy decided before the results of the EUS-FNA pathology reports (Multidisciplinary Team Meeting [MTM-1]) was recorded and compared to the treatment strategy decided once pathological data from EUS-FNA were available (MTM-2). MAIN FINDINGS: Between 2013 and 2018, 75 patients were included with 47 eligible and evaluable patients. The sensitivity, specificity, and positive and negative predictive values of EUS-FNA were 93%, 100%, 100% and 90%, respectively. The concordance value between the therapeutic strategies determined for MTM-1 and MTM-2 was 44.7%. There were no significant differences in the intensity of fixation on PET-CT between malignant and benign lesions. CONCLUSION: The diagnostic accuracy of the minimally invasive EUS-FNA procedure is sufficiently robust to avoid surgical diagnosis. The combination of PET-CT and EUS-FNA may alter the therapeutic strategy that would be considered after PET-CT alone. REGISTRATION: NCT01892501

Safety and efficacy of temsirolimus as second line treatment for patients with recurrent bladder cancer

International audienceBACKGROUND:Bladder cancer is the 7th cause of death from cancer in men and 10th in women. Metastatic patients have a poor prognosis with a median overall survival of 14 months. Until recently, vinflunine was the only second-line chemotherapy available for patients who relapse. Deregulation of the PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and suggested the use of mTOR as a target for the treatment of urothelial cancers.METHODS:This trial assessed the efficacy of temsirolimus in a homogenous cohort of patients with recurrent or metastatic bladder cancer following first-line chemotherapy. Efficacy was measured in terms of non-progression at two months according to the RECIST v1.1 criteria. Based on a two-stage optimal Simon's design, 15 non-progressions out of 51 evaluable patients were required to claim efficacy. Patients were treated at a weekly dose of 25 mg IV until progression, unacceptable toxicities or withdrawal.RESULTS:Among the 54 patients enrolled in the study between November 2009 and July 2014, 45 were assessable for the primary efficacy endpoint. A total of 22 (48.9%) non-progressions were observed at 2 months with 3 partial responses and 19 stable diseases. Remarkably, 4 patients were treated for more than 30 weeks. Fifty patients experienced at least a related grade1/2 (94%) and twenty-eight patients (52.8%) a related grade 3/4 adverse event. Eleven patients had to stop treatment for toxicity. This led to recruitment being halted by an independent data monitoring committee with regard to the risk-benefit balance and the fact that the primary objective was already met.CONCLUSIONS:While the positivity of this trial indicates a potential benefit of temsirolimus for a subset of bladder cancer patients who are refractory to first line platinum-based chemotherapy, the risk of adverse events associated with the use of this mTOR inhibitor would need to be considered when such an option is envisaged in this frail population of patients. It also remains to identify patients who will benefit the most from this targeted therapy.TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT01827943 (trial registration date: October 29, 2012); Retrospectively registered

Additional file 1: Table S1. of Safety and efficacy of temsirolimus as second line treatment for patients with recurrent bladder cancer

Metabolic response evaluated by PET-scan Description: Global metabolic response evaluated by PET-scan at day 15, or at day 15 and 56 as compared to baseline and patients’ status at 2.8 months. R: Responder; NR: Non Responder. (DOCX 25 kb

Consolidation anti-CD22 fractionated radioimmunotherapy with 90 Y-epratuzumab tetraxetan following R-CHOP in elderly patients with diffuse large B-cell lymphoma: a prospective, single group, phase 2 trial

International audienceRadioimmunotherapy 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 90Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma