Lymphome de Burkitt après transplantation d organe en pédiatrie (une étude rétrospective multicentrique)

Les syndromes lymphoprolifératifs post-transplantation sont une complication connue de la transplantation d organe en pédiatrie. Il n existe pas de recommandations thérapeutiques et peu d auteurs individualisent les lymphomes. Le but de cette étude est d étudier la faisabilité et l efficacité d une chimiothérapie intensive en traitement du lymphome de Burkitt post-transplantation en pédiatrie. Nous avons interrogé l Agence de Biomédecine et le Registre national des hémopathies malignes de l enfant, pour recenser les cas survenus avant 2007.11 cas étaient éligibles, greffés hépatiques ou rénaux. Le lymphome était survenu 30 mois (médiane) après la transplantation. Il y avait 4 tumeurs de stade III, 1 de stade IV et 4 leucémies de Burkitt. La charge virale sanguine EBV était élevée pour 10 patients. L immunosuppression a été réduite pour 9 patients. 3 patients ont reçu du rituximab sans efficacité prolongée. 10 patients ont été traités selon le protocole LMB. Un patient est décédé précocement de défaillance multi-viscérale. Nous avons relevé des septicémies documentées, des infections fongiques et un abcès pulmonaire. Nous n avons pas observé de rejet aigu. Les 9 patients effectivement traités selon le protocole LMB sont en 1ère rémission complète avec un suivi médian de 6 ans. La patiente traitée selon un protocole de chimiothérapie à faible dose n a jamais été mise en rémission complète et est décédée.Notre étude a montré qu une chimiothérapie intensive de type LMB est efficace dans le traitement de lymphome de Burkitt survenant chez des enfants greffés hépatiques ou rénaux, sans toxicité majeure sur le greffon.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Care management for foreign children, adolescents, young adults with cancer, and their families

International audienceBACKGROUND: Little is known about care management for foreign patients in pediatric oncology in European centers. We aimed to describe care given to children, adolescents, and young adults who came to France for cancer treatment, and to determine whether their geographical origin had an influence on decision making. PROCEDURE: We conducted a monocentric retrospective study on all foreign patients aged 0-25 years and hospitalized for at least one night in Institut Curie (Paris, France) from 2009 to 2013. We analyzed the potential advantages of receiving treatment in France as well as their social and familial consequences. RESULTS: A total of 93 foreign patients' files were retrieved. Most of these patients came from Africa (70%). In accord with the specific expertise of the institution, retinoblastoma was the most frequent tumor type (39%). An antitumor treatment had already been administrated in the native country in 44% of patients. We considered that 66% of patients received a significant medical advantage from care in our institution. The treatment provided in France was considered impossible in the native country in 44% of cases. The social and familial impact on the patients' families was high (59%). Almost all patients (96%) received the treatment that would have been proposed to their French counterparts. CONCLUSIONS: There were notable medical advantages for foreign patients who come to France for their oncologic treatment despite important familial consequences. Patients' geographical origin did not have an influence on medical decisions

A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion

Comment in [Birth notice: a new bone sarcoma has been born]. [Bull Cancer. 2012]International audienceThe identification of subtype-specific translocations has revolutionized the diagnostics of sarcoma and has provided new insight into oncogenesis. We used RNA-seq to investigate samples from individuals diagnosed with small round cell tumors of bone, possibly Ewing sarcoma, but which lacked the canonical EWSR1-ETS translocation. A new fusion was observed between BCOR (encoding the BCL6 co-repressor) and CCNB3 (encoding the testis-specific cyclin B3) on the X chromosome. RNA-seq results were confirmed by RT-PCR and through cloning of the tumor-specific genomic translocation breakpoints. In total, 24 BCOR-CCNB3-positive tumors were identified among a series of 594 sarcoma cases. Gene profiling experiments indicated that BCOR-CCNB3-positive cases are biologically distinct from other sarcomas, particularly Ewing sarcoma. Finally, we show that CCNB3 immunohistochemistry is a powerful diagnostic marker for this subgroup of sarcoma and that overexpression of BCOR-CCNB3 or of truncated CCNB3 activates S phase in NIH3T3 cells. Thus, the intrachromosomal X-chromosome fusion described here represents a new subtype of bone sarcoma caused by a newly identified gene fusion mechanism

End of life care in children and adolescents with cancer: perspectives from a French pediatric oncology care network

International audienceBackground: In developed countries, cancer remains the leading cause of pediatric death from illness after the neonatal period. Objective: To describe the end-of-life care characteristics of children and adolescents with solid tumors (ST) or hematologic malignancies (HM) who died from tumor progression in the Île-de-France area. Methods: This is a regional, multicentric, retrospective review of medical files of all children and adolescents with cancer who died over a 1-year period. Extensive data from the last 3 months of life were collected. Results: A total of 99 eligible patients died at a median age of 9.8 years (range, 0.3–24 years). The most frequent terminal symptoms were pain (n = 86), fatigue (n = 84), dyspnea (n = 49), and anorexia (n = 41). Median number of medications per patient was 8 (range, 3–18). Patients required administration of opioids (n = 91), oxygen (n = 36), and/or sedation (n = 61). Decision for palliative care was present in all medical records and do-not-resuscitate orders in 90/99 cases. Symptom prevalence was comparable between children and adolescents with ST and HM. A wish regarding the place of death had been expressed for 64 patients and could be respected in 42 cases. Death occurred in hospital for 75 patients. Conclusions: This study represents a large and informative cohort illustrating current pediatric palliative care approaches in pediatric oncology. End-of-life remains an active period of care requiring coordination of multiple care teams

Real‐world experience of tyrosine kinase inhibitors in children, adolescents and adults with relapsed or refractory bone tumours: A Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) study

Abstract Objectives We conducted a retrospective multi‐centre study to assess the real‐world outcome of regorafenib (REGO) and cabozantinib (CABO) in recurrent/refractory bone tumours (BTs) including osteosarcoma (OST), Ewing sarcoma (EWS) and chondrosarcoma (CS)/extra‐skeletal mesenchymal CS (ESMC). Methods After regulatory approval, data from patients with recurrent BT (11 institutions) were extracted from CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration) database. Patient characteristics, treatment and outcomes were collected. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results From July 2018 to May 2022, 66 patients received REGO or CABO; 39 OST, 18 EWS, 4 CS and 5 ESMC. Median age was 27.8 years (range 12–76); median starting dose was 60 mg for CABO (n = 37, range 40–60) and 120 mg for REGO (n = 29, range 40–160). Twenty‐eight (42.4%) patients required dose reduction: hand‐foot syndrome 7 (10.6%), nausea/vomiting 1 (1.5%), diarrhoea 1 (1.5%), 2 elevated LFTs (3%), elevated bilirubin 1 (1.5%) and mucositis 1 (1.5%). The median OS for patients with OST, EWS, CS and ESMC was 8.5 months (n = 39, 95% CI 7–13.1); 13.4 months (n = 18, 95% CI 3.4–27.2), 8.1 (n = 4, 95% CI 4.1–9.3) and 18.2 (n = 5, 95% CI (10.4–na), respectively. Median PFS for OST, EWS, CS and ECMS was 3.5 (n = 39, 95% CI 2.8–5), 3.9 (n = 18, 95% CI 2.1–5.9), 5.53 (n = 4. 95% CI 2.13–NA) and 11.4 (n = 5, 95% CI 1.83–14.7), respectively. Age, line of therapy, REGO versus CABO, or time from diagnosis to initiation of TKI were not associated with PFS on univariable analysis. Conclusion Our real‐world data show that TKIs have meaningful activity in recurrent BT with acceptable toxicities when started at modified dosing. Inclusion of TKIs in earlier lines of treatment and/or maintenance therapy could be questions for future research

Diagnostic classification of childhood cancer using multiscale transcriptomics.

Acknowledgements: The KiCS program is supported by the Garron Family Cancer Centre at The Hospital for Sick Children through funding from the SickKids Foundation. A.H. received funding from the Canadian Institutes for Health Research (grant no. 162267) and is the Tier 1 Canada Research Chair in Rare Childhood Brain Tumors. D.M. is supported by the CIBC Children’s Foundation Chair in Child Health Research. A.S. is partially supported by an Early Researcher Award from the Ontario Ministry of Research and Innovation; by the Canada Research Chair in Childhood Cancer Genomics; and by funding from the V Foundation and the Robert J. Arceci Innovation Award from the St. Baldrick’s Foundation. We would like to thank the Centre for Applied Genomics, The Hospital for Sick Children, for assistance with RNA sequencing and the Treehouse Childhood Cancer Initiative, University of California, Santa Cruz, for access to their public data repository.The causes of pediatric cancers' distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types