Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH

BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare childhood dysontogenetic intrathoracic neoplasm associated with an unfavourable clinical behaviour. CASES PRESENTATION: We report pathological and cytogenetic findings in two cases of PPB at initial diagnosis and recurrence. Both tumors were classified as type III pneumoblastoma and histological findings were similar at diagnosis and relapse. In both cases, conventional cytogenetic techniques revealed complex numerical and structural chromosomal abnormalities. Molecular cytogenetic analysis (interphase/metaphase FISH and multicolor FISH) identified accurately chromosomal aberrations. In one case, TP53 gene deletion was detected on metaphase FISH. To date, only few cytogenetic data have been published about PPB. CONCLUSION: The PPB genetic profile remains to be established and compared to others embryonal neoplasia. Our cytogenetic data are discussed reviewing cytogenetics PPBs published cases, illustrating the contribution of multicolor FISH in order to identify pathogenetically important recurrent aberrations in PPB

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways

Development and Validation of a Prediction Model of Overall Survival in High-Risk Neuroblastoma Using Mechanistic Modeling of Metastasis

International audiencePrognosis of high-risk neuroblastoma (HRNB) remains poor despite multimodal therapies. Better prediction of survival could help to refine patient stratification and better tailor treatments. We established a mechanistic model of metastasis in HRNB relying on two processes: growth and dissemination relying on two patient-specific parameters: the dissemination rate μ and the minimal visible lesion size S vis. This model was calibrated using diagnosis values of primary tumor size, lactate dehydrogenase circulating levels, and the metaiodobenzylguanidine International Society for Paediatric Oncology European (SIOPEN) score from nuclear imaging, using data from 49 metastatic patients. It was able to describe the data of total tumor mass (lactate dehydrogenase, R 2. 0.99) and number of visible metastases (SIOPEN, R 2 = 0.96). A prediction model of overall survival (OS) was then developed using Cox regression. Clinical variables alone were not able to generate a model with sufficient OS prognosis ability (P = .507). The parameter μ was found to be independent of the clinical variables and positively associated with OS (P = .0739 in multivariable analysis). Critically, addition of this computational biomarker significantly improved prediction of OS with a concordance index increasing from 0.675 (95% CI, 0.663 to 0.688) to 0.733 (95% CI, 0.722 to 0.744, P , .0001), resulting in significant OS prognosis ability (P = .0422)

Epistemological perspective in the modelling process of an industrial system integrating technical and organisational dimensions

Présentation orale (le résumé ainsi que la présentation peuvent être téléchargés à l'adresse suivante: http://sra-e-2006.ijs.si/Sessions_and_Contributions.htm)EDF and INERIS are collaborating on a project that aims at integrating technical and organisational dimensions together for assessing major hazard prevention of an industrial system. This means that the system is open and contains inherent complexity. The objective is to identify risks, evaluate and prioritize them to help decision making with the support of bayesian networks. We considered the risk analysis process as a particular case of modelling process and we decided to investigate the epistemological side of the modelling approach before implementing bayesian tools. Since the modelling question is not a traditional scientific question in the field of risk assessment, we had to immerse ourselves in a philosophical perspective for addressing issues such as : (1) Reality and truth : Should a model be a faithful and accurate image of reality, or rather be a representation that helps taking appropriate decisions ? (2) Subject-object relationship : Does the experience of the expert influence the final shape of the model ? How can we tackle inputs or opinions given by persons who are part of the system ? (3) The goal of a modelling process : Describing a system, explaining it, or predicting its behaviour ? (4) The values of the theories and languages used : How to translate and quantify influences between two events, especially in the organisational field where these influences may be subtle ? This paper presents the ideas that came to light in this epistemological stage of our project. We finally focused on the integration of uncertainty and suggested a distinction between quantification uncertainties, also referred to as technical uncertainties, and uncertainties linked to the modelling approach itself, that mostly cover methodological and epistemological uncertainties. This typology helped us in designing a conceptual frame for tackling both technical and organisational factors

Pediatric Patients With Solid or Hematological Tumor Disease: Vancomycin Population Pharmacokinetics and Dosage Optimization.

International audienceIn pediatric cancer patients, determination of optimal vancomycin dosage is essential because of high risk of inadequate concentrations and bacterial resistance. The aim of this study was to determine vancomycin pharmacokinetic parameters in this population and propose dosage optimization to achieve optimal concentration

Treatment of Childhood T-Cell Lymphoblastic Lymphoma-Long-Term Results of the SFOP LMT96 Trial

International audiencePURPOSE: Outcome of T-cell lymphoblastic lymphoma (T-LBL) in children is around 75-85% of event-free survival. The role of early intensification to improve outcome while using short infusions of high dose methotrexate (HDMTX) and shorter maintenance treatment was addressed by the French Society of Pediatric Oncology (SFOP) group. METHODS: From 1997 through 2003, 79 children (52 males; median age 10.5 years) were prospectively registered into the SFOP LMT 96 trial. The LMT96 protocol, with elements from the protocol of the Berlin-Frankfurt-Münster (BFM) Group included four main modifications: (a) 10 courses of HD-MTX (3 g/m(2) ) delivered over the first 44 weeks; (b) early intensification with cyclophosphamide together with the first course of HD-MTX; (c) a maintenance phase that included 6 monthly intensified chemotherapy pulses; and (d) treatment duration of 18 months for stages I-III. RESULTS: Eighty-nine percent of patients had an initial mediastinal involvement. With a median follow-up of 87 months, the 5-year event-free survival was 85% and overall survival 89%. Nine patients relapsed, eight during treatment. The early intensification did not change the pattern of relapses. Only 58% of patients experienced grade 3-4 neutropenia during the induction phase, 13% patients experienced grade 3 and 4 mucositis, and 5% patients experienced diabetes. The early intensification did not delay phases of chemotherapy. CONCLUSIONS: Early intensification in treatment for T-LBL in children is manageable. Three-hour infusion of HD-MTX did not jeopardize patient outcome. Our results are comparable with those of other international protocols in spite of shorter maintenance treatment for stages I-III. Pediatr Blood Cancer © 2015 Wiley Periodicals, In

The BNT162b2 mRNA COVID-19 vaccine in adolescents and young adults with cancer: A monocentric experience

International audienc