Event-free survival of infants and toddlers enrolled in the HR-NBL-1/SIOPEN trial is associated with the level of neuroblastoma mRNAs at diagnosis
| العنوان: | Event-free survival of infants and toddlers enrolled in the HR-NBL-1/SIOPEN trial is associated with the level of neuroblastoma mRNAs at diagnosis |
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| المؤلفون: | Sandro Dallorso, Ulrike Poetschger, Yania Yáñez, Genevieve Laureys, Ales Vicha, Dominique Valteau-Couanet, Adela Cañete, Tim Lammens, Claudia Pasqualini, Catarina Träger, Maria Valeria Corrias, Andrei Tchirkov, Roberto Luksch, Susan A. Burchill, Stefano Parodi, Luigi Varesio, Ruth Ladenstein |
| المساهمون: | Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Operative Unit of Pediatrics, Fondazione IRCCS Istituto Nazionale dei Tumori, Département de Pédiatrie, Institut Gustave Roussy (IGR), Paediatric Oncology Unit, Hospital Infantil Universitario La Fe, Children’s Cancer Research Institute [Vienna, Austria], IRCCS Istituto Nazionale dei Tumori [Milano] |
| المصدر: | Pediatric Blood and Cancer Pediatric Blood and Cancer, Wiley, 2018, 65 (7), pp.e27052. ⟨10.1002/pbc.27052⟩ Pediatric Blood and Cancer, 2018, 65 (7), pp.e27052. ⟨10.1002/pbc.27052⟩ PEDIATRIC BLOOD & CANCER r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe instname |
| بيانات النشر: | HAL CCSD, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Male, Kaplan-Meier Estimate, 0302 clinical medicine, Stage (cooking), toddlers, RTqPCR, infants, Hazard ratio, Event free survival, Hematology, Prognosis, Progression-Free Survival, 3. Good health, Real-time polymerase chain reaction, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Area Under Curve, outcome, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.medical_specialty, Tyrosine 3-Monooxygenase, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sensitivity and Specificity, 03 medical and health sciences, neuroblastoma, Internal medicine, Neuroblastoma, medicine, Biomarkers, Tumor, Humans, RNA, Messenger, neoplasms, Proportional Hazards Models, Homeodomain Proteins, business.industry, Infant, Newborn, Infant, medicine.disease, Minimal residual disease, Peripheral blood, 030104 developmental biology, ROC Curve, Pediatrics, Perinatology and Child Health, Bone marrow, business, Transcription Factors |
| الوصف: | 1 Background: The purpose of this study was to evaluate whether levels of neuroblastoma mRNAs in bone marrow and peripheral blood from stage M infants (≤12 months of age at diagnosis, MYCN amplified) and toddlers (between 12 and 18 months, any MYCN status) predict event‐free survival (EFS). 2 Methods: Bone marrow aspirates and peripheral blood samples from 97 infants/toddlers enrolled in the European High‐Risk Neuroblastoma trial were collected at diagnosis in PAXgene™ blood RNA tubes. Samples were analyzed by reverse transcription quantitative polymerase chain reaction according to standardized procedures. 3 Results: Bone marrow tyrosine hydroxylase (TH) or paired‐like homeobox 2b (PHOX2B) levels in the highest tertile were associated with worse EFS; hazard ratios, adjusted for age and MYCN status, were 1.5 and 1.8 respectively. Expression of both TH and PHOX2B in the highest tertile predicted worse outcome (p = 0.015), and identified 20 (23%) infants/toddlers with 5‐year EFS of 20% (95%CI: 4%–44%). Prognostic significance was maintained after adjusting for over‐fitting bias (p = 0.038), age and MYCN status. In peripheral blood, PHOX2B levels in the highest tertile predicted a two‐fold increased risk of an event (p = 0.032), and identified 23 (34%) infants/toddlers with 5‐year EFS of 29% (95%CI: 12%–48%). Time‐dependent receiver operating characteristic analysis confirmed the prognostic value of combined TH and PHOX2B in bone marrow and of PHOX2B in peripheral blood during the first year of follow‐up. 4 Conclusions: High levels of bone marrow TH and PHOX2B and of peripheral blood PHOX2B at diagnosis allow early identification of a group of high‐risk infant and toddlers with neuroblastoma who may be candidates for alternative treatments. Integration with additional biomarkers, as well as validation in additional international trials is warranted. |
| اللغة: | English |
| تدمد: | 1545-5009 1545-5017 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eb16095557368183bfedec4558495cdd https://hal.archives-ouvertes.fr/hal-01927100 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....eb16095557368183bfedec4558495cdd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15455009 15455017 |
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