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Treatment of extremity rhabdomyosarcomas (RMS) includes chemotherapy, surgery, and radiotherapy. Lymph node irradiation is recommended in the presence of regional node involvement at diagnosis. The aim of this study was to analyze the correlation between the pattern of relapse of non-metastatic extremity RMS and the initial therapies delivered. All patients with localized extremity RMS prospectively treated in France in the MMT-95 and RMS-05 protocols were selected. Extent of disease and pattern of relapse were evaluated by clinical examination and imaging. We identified 59 patients with clinical characteristics corresponding to unfavorable prognostic factors. Twenty patients (34%) were considered to have lymph node involvement at diagnosis. Regional node biopsy was performed in 32 patients (54%) and modified the lymph node stage in 8 of the 59 patients (14%). Seventy-three percent of patients received radiotherapy. Fifty-two patients achieved first remission. Overall, 26 patients underwent complete tumor resection, 17 had R1 margins, and 5 were not operated due to early tumor progression. With a median follow-up of 82 months (range: 5–287), 18 relapses had occurred, at least locoregional in 12 cases. The 5‑year local and nodal control rates were 73% (63–86%) and 86% (77–95%), respectively. Five-year progression-free and overall survival were 57% (95%CI [45–72%]) and 70% (95%CI [58–84%]), respectively. The main sites of extremity RMS relapse are locoregional. Nodal failures in non-irradiated fields are not uncommon. We recommend systematic biopsy of in-transit nodes, especially in alveolar RMS and/or RMS with regional positive nodes at diagnosis to ensure their negativity.

Background. The initial management of patients with sarcoma is critical. We used the French National Cancer Institute-funded nationwide sarcoma database NETSARC to report the management and oncologic outcomes in children, adolescents and young adults (AYAs) patients with sarcoma at the national level. Patients and methods. Data from patients with sarcoma are collected, regularly monitored and updated using NETSARC. NETSARC was searched for pediatric (Results. We collected data from 3,972 pediatric and AYA patients with sarcoma diagnosed between 2010 and 2017, including 714 children, 1,290 AYAs treated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed regarding pre-treatment biopsy (Children: 83.5%; AYA in RSC: 85.9%; AYA in non-RSC 48.1%), pre-treatment imaging (Children: 81.2%; AYA in RSC: 86.8%; AYA in non-RSC: 56.5%) and R0 margins (Children: 52%; AYA in RSC 57.6%; AYA in non-RSC: 20.2%) (pConclusions. This study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists.

Complete surgical resection constitutes the mainstay of treatment for locally aggressive, rarely metastazing tumor and low-grade soft tissue sarcomas (LAS). Local relapse is the most common tumor event, especially in the presence of positive margins (R1 margins). The aims of this study are to assess the impact of the national network on patient care and to evaluate the role of immediate re-excision in children, adolescents and young adults with incompletely resected LAS.National retrospective multicenter study of all young patients (≤25 years) included in the Sarcoma "ConticaBase" treated for LAS between 2005 and 2017 for whom pathology/biology review was available via the national NETSARC + network.A total of 96 patients were identified (median age: 16 years). Tumors were localized in 99% of cases (1 N+ tumor). With a median follow-up of 4.7 years (range: 0.1-11.9), eight local relapses and two distant metastases were observed. No patient died. Overall 5-year event-free survival (EFS) was 90.4% [95%CI, 84.3-97]. Five year EFS for R1 patients (n = 51) with (n = 24) and without (n = 27) immediate re-excision was 90.5% [95%CI, 78.8-100.0] and 80.3% [95%CI, 64.7-99.9], respectively (p = 0.34). The 37 patients directly treated in a reference center more commonly had a diagnostic biopsy (78% vs. 21%; p 0.001), more complete surgery (R0: 65% vs. 14%; p 0.001) and less commonly underwent re-excision (16% vs. 54%; p 0.001).This large series indicates that LAS are rare in young patients and have a favorable prognosis. Immediate management in reference centers is associated with better standard of care. The main tumor events are local relapses.

Simple Summary Osteosarcoma is the most common primary malignant bone tumour in adolescents and young adults. The survival of osteosarcoma patients has not improved for four decades. The purpose was to describe first and subsequent relapses in patients from the OS2006/Sarcome-09 trial, to help future trial design. Among the 434 patients with a confirmed osteosarcoma who achieved CR1 during first line treatment, 157 patients experienced at least one relapse. The 3-year progression-free and overall survival rates were 21% and 37%, respectively. Only a quarter of the patients were included in clinical trials at first recurrence. We want to promote randomised phase-II trials in osteosarcoma relapses, with broad inclusion criteria at study entry in terms of age and disease status, and PFS as primary endpoint. Surgery/local treatment of all residual lesions should be allowed when feasible. Single-arm trial design could be used for subsequent relapses. Abstract The purpose was to describe first and subsequent relapses in patients from the OS2006/Sarcome-09 trial, to help future trial design. We prospectively collected and analysed relapse data of all French patients included in the OS2006/Sarcome-09 trial, who had achieved a first complete remission. 157 patients experienced a first relapse. The median interval from diagnosis to relapse was 1.7 year (range 0.5–7.6). The first relapse was metastatic in 83% of patients, and disease was not measurable according to RECIST 1.1 criteria in 23%. Treatment consisted in systemic therapy (74%) and surgical resection (68%). A quarter of the patients were accrued in a phase-II clinical trial. A second complete remission was obtained for 79 patients. Most of them had undergone surgery (76/79). The 3-year progression-free and overall survival rates were 21% and 37%, respectively. In patients who achieved CR2, the 3y-PFS and OS rates were 39% and 62% respectively. Individual correlation between subsequent PFS durations was poor. For osteosarcoma relapses, we recommend randomised phase-II trials, open to patients from all age categories (children, adolescents, adults), not limited to patients with measurable disease (but stratified according to disease status), with PFS as primary endpoint, response rate and surgical CR as secondary endpoints.

Treatment of extremity rhabdomyosarcomas (RMS) includes chemotherapy, surgery, and radiotherapy. Lymph node irradiation is recommended in the presence of regional node involvement at diagnosis. The aim of this study was to analyze the correlation between the pattern of relapse of non-metastatic extremity RMS and the initial therapies delivered.All patients with localized extremity RMS prospectively treated in France in the MMT-95 and RMS-05 protocols were selected. Extent of disease and pattern of relapse were evaluated by clinical examination and imaging.We identified 59 patients with clinical characteristics corresponding to unfavorable prognostic factors. Twenty patients (34%) were considered to have lymph node involvement at diagnosis. Regional node biopsy was performed in 32 patients (54%) and modified the lymph node stage in 8 of the 59 patients (14%). Seventy-three percent of patients received radiotherapy. Fifty-two patients achieved first remission. Overall, 26 patients underwent complete tumor resection, 17 had R1 margins, and 5 were not operated due to early tumor progression. With a median follow-up of 82 months (range: 5-287), 18 relapses had occurred, at least locoregional in 12 cases. The 5‑year local and nodal control rates were 73% (63-86%) and 86% (77-95%), respectively. Five-year progression-free and overall survival were 57% (95%CI [45-72%]) and 70% (95%CI [58-84%]), respectively.The main sites of extremity RMS relapse are locoregional. Nodal failures in non-irradiated fields are not uncommon. We recommend systematic biopsy of in-transit nodes, especially in alveolar RMS and/or RMS with regional positive nodes at diagnosis to ensure their negativity.

Background Hepatoblastoma tumor rupture is a high-risk criterion in the SIOPEL 3/4 protocol. Little is known about the outcome of these children. Methods Radiological signs of possible tumor rupture, defined as peritoneal effusion, peritoneal nodules, or hepatic subcapsular hematoma, were reported in 24 of 150 patients treated for hepatoblastoma in France from January 2000 to December 2014 after central radiological expert review. Results Twenty-two patients with available clinical data were included (nine PRETEXT-I/II, six PRETEXT-III, seven PRETEXT-IV, and five had lung metastases). Five patients had a subcapsular hematoma only, and 17 patients had intraperitoneal rupture (subcapsular hematoma and peritoneal effusion). A hepatic biopsy was performed in 19 patients. Intraperitoneal rupture occurred before biopsy in 12 and after biopsy in three (including one with prebiopsy subcapsular hematoma) (missing data: two). All patients were treated with chemotherapy, with high-risk regimens including cisplatin or carboplatin and doxorubicin in 19 and cisplatin or carboplatin alone in three. Liver surgery was performed in 20 patients (including three liver transplants). Fifteen patients (68%) achieved complete remission. With a median follow-up of 5.5 years, 11 events occurred (six progressions and three relapses, including three peritoneal progressions/relapses, one surgical complication, and one second cancer) and eight patients died. One of eight patients with no other high-risk criterion had a relapse. The three-year event-free survival and overall survival rates were 49.6% (95% CI = 30-69) and 68.2% (40-84), respectively. Conclusions Tumor rupture is predictive of poor prognosis with risk of peritoneal progression/relapse. However, it should not be a contraindication for liver transplantation.

International audience; Background: With recent conservative strategies, prognosis of patients with desmoid-type fibromatosis (DTF) is about function preservation. We analyzed the long-term quality of life (QoL) of pediatric patients with DTF.Methods: All French young patients (

Introduction: This study evaluates the management of patients aged 0 to 30 years treated for sarcoma with data registered in the NETSARC French national database and compared the survival of adolescents and young adults (AYA) patients managed in reference sarcoma national centers (AYA in NC) and in non-NC (AYA outside NC). Patients and Methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers funded by the French National Cancer Institute. Patients’ characteristics and follow-up are prospectively collected in a database regularly monitored and updated. Patients’ survival was compared between groups. The primary endpoint was overall survival (OS). Secondary endpoints were local progression-free survival (LPFS), progression-free survival (PFS), and the quality of initial surgery. Results: Among 3,972 patients aged 0 to 30 years diagnosed between 2010 and 2017, 714 children, 1,290 AYAs in NC and 937 AYAs outside NC were included. Compliance to guidelines between AYAs treated in versus outside reference centers was significantly different (p

// Gabrielle Lui 1, 2 , Naim Bouazza 1, 2, 3 , Francoise Denoyelle 4 , Marion Moine 1 , Laurence Brugieres 5 , Pascal Chastagner 6 , Nadege Corradini 7 , Natacha Entz-Werle 8 , Cecile Verite 9 , Judith Landmanparker 10 , Helene Sudour-Bonnange 11 , Marlene Pasquet 12 , Arnauld Verschuur 13 , Cecile Faure-Conter 14 , Francois Doz 15, 16, * , Jean-Marc Treluyer 1, 2, 3, 17, * and On behalf of the SFCE (Societe Francaise des Cancers de l’Enfant et l’Adolescent) 1 University of Paris Descartes, EA 7323, Sorbonne Paris-Cite, France 2 CIC-1419 Inserm, Cochin-Necker, Paris, France 3 Clinical Research Unit of Paris Descartes Necker Cochin, AP-HP, Paris, France 4 Department of Pediatric Otolaryngology, Necker Children’s Hospital, Paris, France 5 Department of Children and Adolescents Oncology, Gustave Roussy, Villejuif, France 6 Department of Pediatric Onco-Hematology, Children’s Hospital, Vandoeuvre Les Nancy, France 7 Pediatric Oncology Department, Mother-Children Hospital, Nantes, France 8 Pediatric Onco-Hematology Unit, CHU of Strasbourg, Strasbourg, France 9 Pediatric Hematology Department, Bordeaux University Hospital, Bordeaux, France 10 Sorbonne University, Department of Pediatric Hematology Oncology, APHP, Trousseau Hospital, Paris, France 11 Pediatric Oncology Unit, Children, Adolescents and Young Adults Unit, Oscar Lambret Center, Lille, France 12 Children’s Hospital, University Hospital of Toulouse, Toulouse, France 13 Pediatric Oncology Department, La Timone Children’s Hospital, Marseilles, France 14 Institute of Pediatric Hemato-Oncology, Lyon, France 15 Oncology Center SIREDO, Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Curie Institute, Paris, France 16 Paris Descartes University, Paris, France 17 Department of Clinical Pharmacology, Cochin Hospital AP-HP, Paris, France * These authors have contributed equally to this work Correspondence to: Gabrielle Lui, email: gabrielle.lui@aphp.fr Keywords: platinum; pharmacogenetics; ototoxicity; children; cancer Received: March 26, 2018 Accepted: June 25, 2018 Published: July 20, 2018 ABSTRACT Platinum is extensively used in the treatment of several childhood cancers. However, ototoxicity is one of the most notable adverse effects, especially in children. Several studies suggest that genetics may predict its occurrence. Here, polymorphisms associated with platinum-induced ototoxicity were selected from the literature and were investigated in a pediatric population treated with platinum-based agents. In this retrospective study, patients treated with cisplatin and/or carboplatin were screened. The patients with pre- and post-treatment audiogram (Brock criteria) available were included. We selected polymorphisms that have previously been associated with cisplatin ototoxicity with a minor allele frequency ≥30%. Deletion of GSTM1 and GSTT1 , rs1799735 ( GSTM3 ), rs1695 ( GSTP1 ), rs4880 ( SOD2 ), rs2228001 ( XPC ), rs1799793 ( XPD ) and rs4788863 ( SLC16A5 ) were investigated. Data of one hundred and six children matching the eligible criteria were analyzed. Thirty-three patients (31%) developed ototoxicity (with a Brock grade ≥2). The probability of hearing loss increased significantly in patients carrying the null genotype for GSTT1 (P = 0.03), A/A genotype at rs1695 (P = 0.01), and C/C genotype at rs1799793 (P = 0.008). We also showed an association of the cumulative doses of carboplatin with cisplatin ototoxicity (P

Background Disorders of sex development (DSD) are rare conditions. Although they are known to predispose to germ cell tumors (GCT), there is a paucity of information regarding the circumstances of DSD discovery. Design/methods All patients with DSD registered in two French pediatric GCT protocols (TGM95 and 13) were analyzed. Results Sixteen patients were identified among 276 ovarian, 160 testicular, and 24 mediastinal GCT. Eleven phenotypic females (median age 15 years) exhibited gonadal GCT, including 10 with a 46,XY karyotype and gonadal dysgenesis and one with 46XX,45X0 mosaicism. None had genital anomalies, seven had spontaneous pubertal changes, and one had spontaneous menarche. The tumors were bilateral in four cases. DSD was diagnosed after the GCT diagnosis in seven cases. The reasons for karyotyping were bilateral tumors (3), gonadoblastoma/streak gonad/absence of egg follicles (3), or systematic for GCT (1). The karyotyping was performed before the GCT diagnosis in four cases: for polymalformative syndrome (2) or primary amenorrhea (2). Four males (median age 14 years) exhibited mediastinal GCT (metastatic in two cases) indicative of Klinefelter syndrome, despite typical phenotypes in all cases. The remaining patient had severe hypospadias, leading to the discovery of 46,XY/45,X0 mosaicism before the diagnosis of testicular nonseminomatous GCT at 16 years of age. Conclusion DSD are often uncovered at the time of GCT diagnosis (11/16 cases). This should prompt oncologists to rule out a DSD in patients with GCT, even in case of pubertal development. Earlier recognition of Klinefelter syndrome could potentially lead to GCT detection at an earlier stage.

Because of the rarity of Chronic Myeloid Leukemia (CML) in children and adolescents, only few studies reported on efficacity and tolerance of imatinib in the pediatric population and scant data are available regarding long-term follow-up. The aim of our analysis was to assess, the long-term efficacity and safety of imatinib in children with CML in early chronic phase included in the French multicentric prospective Glivec Phase IV trial (Millot et al, J Clin Oncol 2011). Methods: Children aged 0 to 18 years with newly diagnosis CML in chronic phase were eligible to received daily imatinib 260 mg/m² according the trial. Long-term analysis included overall survival (OS), progression-free survival (PFS), response to treatment and adverse events. Results: Between March 2004 and December 2008, 44 patients (median age 13.4 years; range 0.8 - 16.7 years) were included in the trial. As of April 2019, with a median follow-up of 10.6 years (range 1.8 - 13.4 years), 2 patients (pts) progressed to blastic crisis and only one death was recorded. The median age was 21.8 years (range 9.3 - 28.8 years) at the last follow-up. The median duration of imatinib therapy was 10.5 years (range 0.2 - 12.5 years) for the entire cohort. To date, 13 pts (29.5%) are still treated with imatinib. Thirty-one pts (70.5%) had discontinued first line treatment with imatinib after a median time of treatment of 2.4 years (range 0.2 - 10.6 years) for the following reasons: 10 pts did not achieve major molecular response (MMR), 1 pt developed blast crisis, 2 pts had unsatisfactory level of molecular response (MR) according to the clinician, 10 pts lost their response (loss of complete hematological response n=1, complete cytogenetic response [CCR] n=6 and MMR n=3), 4 pts attempted treatment free remission (TFR), 3 pts were intolerant to imatinib and 1 pt stopped because of pregnancy. Among these 31 pts who discontinued imatinib, 2 pts are still in TFR, and 29 pts switched to a second line therapy: second generation tyrosine kinase inhibitors (2TKI) (n=25), allogeneic hematopoietic stem cell transplantation (HSCT) (n=3), polychemotherapy (n=1). Sixteen of these 31 pts (51.6%) required subsequent lines of therapy including a second pt who transformed to blastic crisis under a second line therapy with dasatinib. Overall 11 pts (25%) underwent HSCT. Overall, regarding the best response, during the study follow-up 11 pts (25%) achieved MMR after a median time of 2.3 years (range 0.8-5.1), 7 pts (13.6%) achieved MR4 after a median time of 5.1 years (range 2.5-7.8), 25 pts (56.8%) achieved MR4.5 after a median time of 2.92 years (range 1.1-10.4) and 1 pt (2.3%) achieved CCR only. At last follow-up, 43 out the 44 pts were alive : 3 pts (7%) were in CCR, 12 pts (27.9%) in MMR, 6 pts (13.9%) in MR4 and 22 pts (51.2%) in MR4.5. Among the 13 pts still treated with imatinib, 1 pt (7.7%) was in CCR, 6 pts (14%) in MMR, 3 pts (23.1%) were in MR4 and 3 pts (23.1%) in MR4.5. Among the 11 transplanted patients, all pts except one are alive, in at least MR4.5. The death was related to post transplant infection. On an intention to treat basis, the 10-year OS of 44 patients treated was 97.7% (CI 95% 93.3-100). The 10-year PFS was 95.5% (CI 95% 89.3-100). We collected also the long-term safety of imatinib in the 25 pts who have received this therapy for more than 4 years. Newly occurring or worsening grade 3 or 4 hematologic or biochemical adverse events were infrequent after 4 years of imatinib. There is a decrease in the frequency of hematologic and extra hematologic sides effects reported during the first year and those reported after the fourth year of treatment with imatinib: musculoskeletal events 80 vs 24% (p Conclusion: With more than 10 years of follow-up, we showed that imatinib remains effective in one third of children included in the Glivec phase IV study with acceptable adverse effects and a low impact over time. Despite the notable proportion of switches, the OS and the PFS remain satisfactory in this pediatric cohort. Disclosures No relevant conflicts of interest to declare.

BACKGROUND: Current outcome of very early relapse of acute lymphoblastic leukemia (ALL) in children remains poor. As a single agent, clofarabine provided a response rate of 26% in childhood ALL second relapse and, in combination with cyclophosphamide and etoposide, a 44% complete remission and complete remission without platelet recovery (CR+CRp) rate. Further multi-drug combinations need to be investigated. We used the VANDA regimen as a template, cytarabine being replaced by clofarabine. PATIENTS AND METHODS: A phase I study combining escalating doses of clofarabine (25% increments from 20 to 40 mg/m(2) /d) with fixed doses of mitoxantrone, etoposide, asparaginase, and dexamethasone was undertaken in children presenting with very early or second or post-transplant ALL relapse. RESULTS: Twenty patients were enrolled, 19 were evaluable. Four patients had previously been allografted. Dose-limiting toxicity (DLT) appeared at dose level 3 (32 mg/m(2) ), one out of six patients experienced a liver DLT. At dose level 4 (40 mg/m(2) ), four DLT occurred (two fungal infection and two liver DLT). The maximum tolerated dose (MTD) of clofarabine was thus determined to be 32 mg/m(2) . There was no toxic death. Eleven (57.9%) patients achieved a CR. Six patients proceeded to allogeneic stem cell transplantation. CONCLUSION: Clofarabine MTD was 32 mg/m(2) /d in this combination which appeared feasible and effective in this population. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc

Background We present the results of the TGM-95 study for gonadal sex-cord stromal tumors (SCT). Methods Between 1995 and 2005, children (

Purpose The aim is to study statural growth in a large cohort of children with chronic myeloid leukaemia (CML) treated with front-line imatinib. Methods Retrospective data from 81 children less than 18 years of age with CML identified in the French pediatric registry were analysed. Height was expressed as standard deviation score (SDS). Results A gradual decrease in height SDS was observed over time since starting imatinib. The height SDS was significantly lower 12 months and 24 months after the start of imatinib overall ( p −4 ) irrespective of gender and pubertal age. The height SDS was significantly ( p −4 ) lower 12 months after the start of imatinib in boys and girls, and in the prepubertal age group as well as in the postpubertal age group, respectively. A similar finding was observed in the subgroups of boys and girls starting imatinib at a prepubertal or postpubertal age. Loss in height SDS 12 months after the start of imatinib was of the same range in boys when compared to girls and in patients who started imatinib at a prepubertal age compared to those who started at a postpubertal age. Conclusion Growth velocity was altered during the first years of imatinib treatment in boys as well as in girls and in prepubertal age patients as well as in adolescents.

Methods French patients (≤18years) treated for dysgerminoma between 1985 and 2005 in TGM-85, 90, 95 protocols were included. Treatment was based on primary unilateral oophorectomy followed by prophylactic lymph node irradiation (1985–1998) or a wait-and-see strategy (1998–2005) for localised completely resected tumours (pS1) or by platinum-based chemotherapy for advanced diseases. Results Forty-eight patients (median age 12.8 years) were included. Six patients had gonadal dysgenesis. Two had bilateral dysgerminoma. Twenty-eight patients had loco-regional dissemination, seven with para-aortic lymph nodes. None had distant metastases. Primary surgery was performed in 47/48 patients. Among the 15 patients with pS1 tumour: seven did not receive adjuvant treatment, six had lymph node irradiation and two received chemotherapy. Among the 32 patients with advanced tumour, 31 received cisplatinum-based (n = 25) or carboplatin-based (n = 8) regimen with lymph node irradiation for one of them and one did not receive adjuvant treatment. With a median follow-up of 14 years, all patients are alive in complete remission. Five events occurred: 2 contralateral dysgerminomas, 1 peritoneal relapse and 2 second neoplasms (teratoma and melanoma). Bilateral oophorectomy was necessary for 12 patients. Desire of pregnancy was expressed for 17/36 patients with unilateral oophorectomy, which succeeded in 13 cases (5 medically assisted). 2/17 had ovarian failure. The renal function was normal in 24/25 evaluated patients treated with platinum, ifosfamide or irradiation. The hearing function was evaluated on 17/36 patients treated with platinum: 12 Brock grade-0, 3 brock grade-1 and 2 grade-4. Conclusion Dysgerminoma has an excellent prognosis even in advanced cases with conservative surgery and platinum-based chemotherapy. However the disease and/or treatment resulted in a high rate of bilateral oophorectomies and a significant impact on future fertility.

International audience; Background: The role of tumor molecular profiling in directing targeted therapy utilization remains to be defined for pediatric tumors. We aimed to evaluate the feasibility of a sequencing and molecular biology tumor board (MBB) program, and its clinical impact on children with solid tumors. Procedure: We report on a single-center MBB experience of 60 pediatric patients with a poor prognosis or relapsed/refractory solid tumors screened between October 2014 and November 2015. Tumor molecular profiling was performed with panel-based next-generation sequencing and array comparative genomic hybridization. Results: Mean age was 12 ± 5.7 years (range 0.1–21.5); main tumor types were high-grade gliomas (n = 14), rare sarcomas (n = 9), and neuroblastomas (n = 8). The indication was a poor prognosis tumor at diagnosis for 16 patients and relapsed (n = 26) or refractory disease (n = 18) for the remaining 44 patients. Molecular profiling was feasible in 58 patients. Twenty-three patients (40%) had a potentially actionable finding. Patients with high-grade gliomas had the highest number of targetable alterations (57%). Six of the 23 patients subsequently received a matched targeted therapy for a period ranging from 16 days to 11 months. The main reasons for not receiving targeted therapy were poor general condition (n = 5), pursuit of conventional therapy (n = 6), or lack of pediatric trial (n = 4). Conclusions: Pediatric molecular profiling is feasible, with more than a third of patients being eligible to receive targeted therapy, yet only a small proportion were treated with these therapies. Analysis at diagnosis may be useful for children with very poor prognosis tumsors.

Purpose We report the results of a French multicenter retrospective study based on a period of more than 30 years and a review of the literature in order to more clearly define the surgical approach and specific pediatric risk factors. Methods Clinical data of children comprising all histologic subtypes of thymic epithelial tumors (TET) treated between 1979 and 2009 in French pediatric oncology centers were retrospectively analyzed and discussed in the light of a review of all pediatric cases reported in the literature. Results Nine cases were identified, corresponding to five females and four males with a median age of 13 years (range: 7.5–17). Histologic subtypes were type AB (n = 1), type B (n = 5) and type C (n = 3). Treatment consisted of tumor resection (4 R0, 4 R1, 1 R2) via right anterior thoracotomy, posterolateral thoracotomy, left thoracoscopy, sternotomy and cervicosternotomy, and/or chemotherapy, mainly cyclophosphamide-doxorubicin-cisplatin (CAP; n = 5), and/or radiotherapy (n = 4). Two patients with TET type C died. All other patients are alive with a median follow-up of 4 years (range: 1.5–20). Review of a total of 93 pediatric cases reported in the literature showed statistically significant associations between less favorable histologic subtypes and male gender (P = 0.012), advanced Masaoka stage (P

Purpose Some children with extracranial germ cell tumors (GCT) relapse after or do not respond to first-line treatment combining chemotherapy and surgery, of whom very few experience long-term survival despite multimodal salvage treatment. Methods This prospective study, part of the French TGM95 Protocol for non-seminomatous GCT (NSGCT), included 19 (7%) children with malignant refractory or recurrent extracranial NSGCT who were studied to identify prognostic factors and determine the best salvage treatment. Results At the end of the first-line treatment, 10 and 9 children were in complete and incomplete remission, respectively. Events occurred within 2 years (5–23 months) after initial diagnosis. A progression was observed in 13 patients at least in one site initially involved. Two patients had a purely biological relapse (increase in isolated markers), and four patients had a purely metastatic relapse (brain location in three cases). After salvage treatment combining surgery and various types of chemotherapy (including high-dose chemotherapy (HDCT) in 10 cases), the 5-year event-free survival and overall survival rates were of 26% (95%CI: 9.6–46.8%) and 32% (95%CI: 12.9–52.2%), respectively. Patients who underwent complete surgery (or without any detectable tumor) had higher survival rate than patients who underwent partial surgery or for whom surgery was not feasible (P = 0.0003) at first relapse while this rate was similar between patients treated or not with HDCT. Conclusion In pediatric recurrent or refractory NSGCT, complete excision of the tumor appears essential. The role of HDCT remains debated. Pediatr Blood Cancer 2014;61:253–259. © 2013 Wiley Periodicals, Inc.

Germ cell tumours include a group of highly heterogeneous tumours regarding to their clinical and histological appearance. Altogether, they represent 3% of cancers diagnosed in children and adolescent younger than 15 years. A bimodal age distribution is observed with a small peak during infancy and a larger peak after puberty. Non-seminomateous germ cell tumours are largely predominant as compared to seminomateous tumours, rarely seen before puberty. During infancy, sacrococcygeal locations predominate with either teratomas in neonates or yolk sac tumours in infants above three months. In adolescents, mixed germ cell tumours predominate with either gonadal, mediastinal or intracranial tumour. Surgical resection of the tumour is fundamental and must be carcinologic and conservative at the same time. Neoadjuvant chemotherapy may help to decrease the volume of the tumour making possible a delayed sparing surgery. Indeed, except for teratomas, these tumours are highly sensitive to chemotherapy, in particular to platinum salts. Prognosis is good even in metastatic diseases. This raises the question of a therapeutic de-escalation in an attempt to decrease long-term toxicity, in particular audiologic and renal impairment. On the opposite, recurrent or refractory diseases after chemotherapy carry a dismal prognosis and therapeutic strategies remain to be defined in such situations.

Objectif de l’etude Le sarcome d’Ewing de la cote represente la tumeur thoracique primitive la plus frequente de l’enfant et du jeune adulte, cependant les etudes et donnees specifiques sont rares. Les objectifs principaux de cette etude etaient d’evaluer la survie en fonction du traitement local et de definir des facteurs pronostiques. Materiel et methode Les patients inclus dans l’etude Euro-EWING99 (EE99) etait atteints d’un sarcome d’Ewing localise de la cote, avec ou sans epanchement pleural au diagnostic etaient eligibles. Les donnees ont ete recueillies de maniere prospective grâce a l’etude EE99 et completees retrospectivement. Resultats Les dossiers de 82 patients pris en charge de decembre 1999 a avril 2013 ont ete analyses. Le suivi median etait de 8,4 mois. Cinquante et un pour cent etaient atteints d’un epanchement pleural au moment du diagnostic. Le traitement local comportait une chirurgie d’exerese chez 81/82 patients, le plus frequemment apres une chimiotherapie d’induction. Soixante patients (73 %) ont ete irradies, 28 % dans le lit operatoire, 13 % dans l’hemithorax et 32 % sur les deux. Les probabilites de survie sans recidive et globale a 5 ans etaient respectivement de 69 % et 71 %. Vingt-six tumeurs (31 %) ont recidive en mediane 19 mois apres le diagnostic. La presence d’un epanchement pleural et des marges chirurgicales non saines (R1 ou R2) etaient des facteurs pronostiques independants defavorables de survies globale et sans recidive. L’irradiation de l’hemithorax ameliorait significativement la probabilite de survie globale en cas d’epanchement pleural : 27 % contre 68 % (p = 0,01). L’irradiation du lit operatoire ameliorait significativement la probabilite de survie en cas de mauvaise reponse histologique. Conclusion La presence d’un epanchement pleural au diagnostic et la qualite de l’exerese chirurgicale sont des facteurs pronostiques defavorables independants des sarcomes d’Ewing localises de la cote. L’irradiation hemithoracique ameliore significativement la probabilite de survie en cas d’epanchement pleural initial.

This study investigates invasive fungal infections (IFIs) in patients with acute myelogenous leukemia who were included in the Enfant Leucemie Aigue 02 protocol between 2005 and 2011. Among 387 patients, 15 had aspergillosis, 9 had candidiasis, and 2 had mucormycosis. The most frequent localization of IFIs was in the lungs. It was found that after a median of 34 months, 2 deaths were attributable to IFI without any difference in survival between the groups with and without IFI.

Purpose To examine the clinical presentation, treatment and results in children and adolescents with primary mediastinal (PM) and retroperitoneal (RP) germ cell tumors (GCTs). Methods The TGM95 trial for malignant GCTs was conducted in France between 1995 and 2005 to evaluate a strategy adapted to prognostic factors with cisplatin-based chemotherapy and surgical management. We reviewed patients with TGCTs at PM and RP sites. Results Among 239 patients, there were 16 patients with PM and 5 with RP tumors, which represent 9% of all patients, highlighting the rarity of these extragonadal locations. A bimodal demographic distribution was observed (11/21 patients 12 years old). A majority of patients presented with bulky tumors that required urgent care with neoadjuvant chemotherapy. In all patients, elevation of alpha-fetoprotein indicated a yolk sac tumor component. Human chorionic gonadotrophin was elevated in five patients (four adolescents), suggesting a choriocarcinoma or seminoma component. The diagnosis was based on elevation of these tumor markers in addition to imaging. Chemosensitivity was observed for a majority of patients. An aggressive surgical approach allowed a microscopic complete resection in 12/15 patients with PM tumors and 4/5 with RP tumors. Overall, 14/16 and 4/5 patients survived, respectively. Three adolescents died of tumor progression. Conclusion In children with mediastinal or RP GCTs, the prognosis is favorable when a strategy of delayed aggressive surgery is performed after cisplatin-based chemotherapy. Younger patients have a better prognosis. Relapses were observed only in adolescents and could not be cured.

Germ cell tumours include a group of highly heterogeneous tumours regarding to their clinical and histological appearance. Altogether, they represent 3% of cancers diagnosed in children and adolescent younger than 15 years. A bimodal age distribution is observed with a small peak during infancy and a larger peak after puberty. Non-seminomateous germ cell tumours are largely predominant as compared to seminomateous tumours, rarely seen before puberty. During infancy, sacrococcygeal locations predominate with either teratomas in neonates or yolk sac tumours in infants above three months. In adolescents, mixed germ cell tumours predominate with either gonadal, mediastinal or intracranial tumour. Surgical resection of the tumour is fundamental and must be carcinologic and conservative at the same time. Neoadjuvant chemotherapy may help to decrease the volume of the tumour making possible a delayed sparing surgery. Indeed, except for teratomas, these tumours are highly sensitive to chemotherapy, in particular to platinum salts. Prognosis is good even in metastatic diseases. This raises the question of a therapeutic de-escalation in an attempt to decrease long-term toxicity, in particular audiologic and renal impairment. On the opposite, recurrent or refractory diseases after chemotherapy carry a dismal prognosis and therapeutic strategies remain to be defined in such situations.

Purpose Imatinib is the standard of care in adults with chronic myeloid leukemia (CML) in chronic phase (CP). Only a few studies to assess efficacy in children have been performed. We report on the results of the French prospective trial (ClinicalTrials.gov identifier NCT00845221) conducted in children and adolescents with newly diagnosed CML in CP. Patients and Methods A total of 44 patients from age 10 months to 17 years with newly diagnosed CML in CP received daily imatinib 260 mg/m2. Progression-free survival, responses, and tolerance were evaluated. Results With a median follow-up times of 31 months (range, 11 to 64 months), the estimated progression-free survival rate at 36 months was 98% (95% CI, 85% to 100%). A complete hematologic response was achieved in 98% of the patients. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were 61% and 31% at 12 months, respectively. During follow-up, CCyR and MMR were achieved in 36 children (77%) and 25 children (57%), respectively. Overall, 30% of the patients discontinued imatinib, mainly because of unsatisfactory response. The most common adverse events were neutropenia and musculoskeletal events. Conclusion Imatinib is effective in children with CML in CP with response rates similar to rates reported in adults. The adverse effects are acceptable, but longer follow-up studies are required to fully assess the long-term impact.

Background Rhabdoid tumours (RTs) are aggressive malignancies of childhood, mainly occurring in the kidney and brain. We describe a national multi-centre retrospective analysis of extra-renal non-cranial RTs (ERRTs). Procedure Diagnosis relied on central histological review and/or on hSNF5/INI1 defect, evidenced by immunohistochemistry or molecular screening. Clinical data were obtained from physicians. Results Twenty six patients fulfilled the inclusion criteria. Median age at diagnosis was 28 months [0–366], including late childhood and young adults cases. Surgery, either initial or secondary, was complete in three. All but three patients received chemotherapy, with variable regimens. Additional radiotherapy was used in six patients. Median time to recurrence or progression was 5 months [0–44], and one patient remained free of disease at 7 years. Conclusions ERRTs share the same chemosensitivity, early recurrence, and poor prognosis as renal and cerebral RTs. No chemotherapy regimen demonstrates a superior response. Pediatr Blood Cancer 2008;51:363–368. © 2008 Wiley-Liss, Inc.

International audience; OBJECTIVES: Investigating the role of parental smoking and maternal alcohol consumption in the etiology of childhood hematopoietic malignancies. METHODS: The national registry-based case-control study ESCALE was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and gender. Maternal smoking and alcohol consumption during pregnancy and paternal smoking since before conception were reported by the mothers in a structured telephone questionnaire. Odds ratios (OR) were estimated using unconditional regression models closely adjusted for potential confounders. RESULTS: A total of 765 cases of acute leukemia (AL), 130 of Hodgkin's lymphoma (HL), 165 of non-Hodgkin's lymphoma (NHL) and 1681 controls were included. Paternal smoking was significantly associated with childhood ALL (OR = 1.4 [1.1-1.7]), AML (OR = 1.5 [1.0-2.3]), Burkitt (OR = 2.0 [1.2-3.2]), and anaplastic large cell (OR = 3.2 [1.2-9.1]) NHL. For the four diseases, the ORs significantly increased with the number of cigarettes smoked. No association with HL or with other types of NHL was observed. The associations with maternal alcohol consumption and cigarette smoking during pregnancy were less consistent. CONCLUSION: The results support the hypothesis that only paternal smoking, and not maternal alcohol consumption or cigarette smoking, plays a role in childhood hematopoietic malignancies.

International audience; OBJECTIVES: We investigated the role of household exposure to pesticides in the etiology of childhood hematopoietic malignancies. METHODS: The national registry-based case-control study ESCALE (Etude sur les cancers de l'enfant) was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and sex. Maternal household use of pesticides during pregnancy and paternal use during pregnancy or childhood were reported by the mothers in a structured telephone questionnaire. Insecticides (used at home, on pets, or for garden crops), herbicides, and fungicides were distinguished. We estimated odds ratios (ORs) using unconditional regression models closely adjusting for age, sex, degree of urbanization, and type of housing (flat or house). RESULTS: We included a total of 764 cases of acute leukemia (AL), 130 of Hodgkin lymphoma (HL), 166 of non-Hodgkin lymphoma (NHL), and 1,681 controls. Insecticide use during pregnancy was significantly associated with childhood AL [OR = 2.1; 95% confidence interval (CI), 1.7-2.5], both lymphoblastic and myeloblastic, NHL (OR = 1.8; 95% CI, 1.3-2.6), mainly for Burkitt lymphoma (OR = 2.7; 95% CI, 1.6-4.5), and mixed-cell HL (OR = 4.1; 95% CI, 1.4-11.8), but not nodular sclerosis HL (OR = 1.1; 95% CI, 0.6-1.9). Paternal household use of pesticides was also related to AL (OR = 1.5; 95% CI, 1.2-1.8) and NHL (OR = 1.7; 95% CI, 1.2-2.6); but for AL the relationships did not remain after adjustment for maternal pesticide use during pregnancy. CONCLUSION: The study findings strengthen the hypothesis that domestic use of pesticides may play a role in the etiology of childhood hematopoietic malignancies. The consistency of the findings with those of previous studies on AL raises the question of the advisability of preventing pesticide use by pregnant women.

International audience; The role of a family history of cancer in the etiology of childhood hematopoietic malignancies was investigated using the data from the ESCALE study. ESCALE, a population-based case-control study, was carried out in France over the period, 2003-2004. A total of 773 cases of acute leukemia (AL), 130 of Hodgkin's lymphoma (HL), 163 of non-Hodgkin's lymphoma (NHL) and 1,681 population-based controls were included. The controls were randomly selected from the French population and were frequency matched with the cases on age and gender. Cancer history in first- and second-degree relatives was reported by the mothers in a structured telephone questionnaire that was the same for the cases and controls. Odds ratios (ORs) were estimated using an unconditional regression model taking into account the stratification variables and potential confounders. A family history of cancer was associated with an increased risk of HL (OR = 1.5 [1.0-2.2]) and NHL (OR = 1.8 [1.3-2.5]), but not AL (OR = 1.0 [0.9-1.2]). The ORs were higher when at least 2 relatives had a history of cancer or when 1 case occurred before age 46 years. Only HL was significantly associated with a family history of hematopoietic malignancies (OR = 2.0 [1.0-3.8]), mainly because of a significant association with a history of HL (OR = 5.4 [1.3-22]). In conclusion, the study findings support the hypothesis of familial susceptibility to childhood lymphoma, but do not suggest familial susceptibility to childhood AL.

Aims The French pediatric CML working group conducted a retrospective study analysing the growth of patients under 18 years with CML treated with imatinib front-line. Patients and Methods Data from 78 patients receiving imatinib (260 mg/m2) for newly diagnosed CML in chronic phase between July 2001 and August 2012 were collected. Height was expressed as standard deviation score (SDS). Height SDS was calculated using French growth standard, as patient height minus mean height for age and sex, divided by standard deviation of height for age and sex. Pre-pubertal age was defined as being younger than 9 years for girls or 11 years for boys. Results A gradual decrease in the median of the height SDS score is observed over time since the start of imatinib. Sixty three patients were assessable for paired analysis at onset of imatinib and 12 months later. The median height-SDS in this group of patients was significantly lower (p < 10-4) 12 months after the start of imatinib. Variance analysis was performed in 36 children at onset of imatinib, 12 months and 24 months later. The median height-Z score in this group of patients was significantly lower 12 months and 24 months after the start of imatinib (p < 10-4) compared to initial diagnosis. The 63 patients assessable for paired data analysis at onset of imatinib and 12 months later were classified by sex and pubertal status. The median height Z score in boys and girls was significantly (p < 10-4) lower 12 months after the start of imatinib. When the patients were analysed according to the pubertal status at onset of imatinib, the median height SDS score was significantly (p < 10-4) lower 12 months after the start of imatinib in the prepurbertal group as well as in the postpubertal group. A similar finding was observed in the subgroups of boys and girls starting imatinib at a prebubertal or postpubertal age. No significant difference was observed when the median M12 height SDS score in patients who started imatinib at a prepubertal stage or a pospubertal stage were compared. Moreover, no significant difference was observed when the median M12 height-Z score in boys and girls were compared. Conclusion This retrospective analysis revealed a statistically significant deceleration in growth during the first 2 years of imatinib treatment in children and adolescents with CML and an absence of influence of sex and pubertal status on the depth of growth deceleration. Disclosures: No relevant conflicts of interest to declare.

Abstract 2570 Background. Current outcome of very early relapse of ALL in children remains poor. Clofarabine, a novel nucleoside analog has proven effective as a single agent in childhood ALL second relapse, providing a CR+CRp ratio of 20 to 28 % (Jeha 2006, Kearns 2006). Clofarabine in combination with cyclophosphamide and Etoposide provided a 44% overal response rate rate in children with advanced ALL (Hijiya 2011) and further multi-drug combinations need to be investigated. The VANDA regimen that has proven effective in high risk ALL and in ALL relapse (Domenech 2008) was used as a template, Cytarabine being replaced by Clofarabine in this combination. Procedure. A phase I study combining escalating doses of Clofarabine with fixed doses of Mitoxantrone, Etoposide, Asparaginase and Dexamethasone was undertaken in children presenting very early (18 months or less after initial diagnosis) medullary or combined ALL relapse or children with second relapse or post transplant relapse. A 3+3 rolling design was used for escalating clofarabine doses with 25% increments from 20 to 40mg/m2/d. Results. Sixteen patients were enrolled, eleven in first marrow relapse, four in second relapse. One patient with an initially refractory disease was secondary excluded as he didn't fulfill the inclusion criteria. Four patients had previously been allografted. Three patients were enrolled at dose level 1 (clofarabine 20 mg/m2), and 3 patients at dose level 2 (clofarabine 26 mg/m2) without any significant dose-limiting toxicity (DLT). Six patients were enrolled at dose level 3 (clofarabine 32 mg/m2), one patient experienced a liver DLT (gamma GT elevation) exceeding 7 days. At the last planned dose level (clofarabine 40 mg/m2), two patients had a grade 3 transaminase elevation exceeding 7 days and 2 patients had a severe fungal infection. Median duration of neutropenia was 20 days (15–31). Other expected toxicities included 3 documented bacterial infections, 3 mucosal toxicities needing parenteral support, one lung aspergillosis, one transient insulin dependant hyperglycemia. There was no toxic death. Out of 15 evaluable patients, 11 (73%) achieved a complete cytological remission (CR). 4 relapses occurred at 1, 1, 2 and 3 months. 6 patients proceeded to allo-SCT with 2 second allografts. One allografted patient died from EBV-PTLD, the others are alive at 2, 13, 13, 15, and 29 months post-transplant. Conclusion. Clofarabine in combination with four major antileukemic drugs appeared feasible and effective in inducing complete remission in those high risk patients. Clofarabine MTD was 32 mg/m2/d for five days and this dose step is currently being expanded to a total of 10 patients, before a phase II study will be proposed for early and very early ALL relapses. Study registered at ClinicalTrials.gov (http://clinicaltrials.gov/ct2/show/NCT01279096). Disclosures: Off Label Use: off label use of clofarabine.

9539 Background: Our purpose was to identify prognostic factors in Ewing's sarcoma (ES) at diagnosis that could allow better treatment stratification. Methods: Between 1988 and 1999, 486 patients (pts) with localized (n=364) or metastatic (n=122) ES were enrolled in two French protocols EW88 and EW93. Characteristics at diagnosis of the patient (age, gender, fever) and of the tumor (initial tumor volume (ITV), primary location, presence and type of metastasis [METS]) were prospectively collected and their influence on disease-free survival (DFS) was assessed. Results: With a 8.5 years median FU, the number of events is 242 (49.8%). By univariate analysis, the following features were found to be associated with a poor prognosis: age 200 ml (p

Abstract 863 Aims: In order to investigate the efficacy and the safety of imatinib in children and adolescents with untreated Philadelphia-positive CML, the CML working party of the Société Française des Cancers de l'enfant (SFCE) conducted an open label, multicentric phase IV study trial (Clinical Trials.gov.NCT00845221). Patients and methods. Patients less than 18 yrs of age with newly diagnosed CP CML were eligible. Imatinib was administered orally at a dose of 260 mg/m2 which is equivalent in terms of drug exposure to the total dose of 400 mg in adults. Forty four children (64% boys) with a median age of 11.5 yrs (range 10 months-17 yrs) have been enrolled from 15 French pediatric centres between July 2004 and December 2008. Side effects were reported prospectively using the NIH CTCv2.0 criteria. Results. Median follow up is currently 17 months (range:1-67). The complete hematologic response rate was 86% and 98% (ITT) at 3 months and 6 months, respectively. The rate of complete cytogenetic response (CCyR) was 62% (ITT) at 12 months. The rate of major molecular response (MMR) defined as a BCR-ABL/ABL ratio ≤ 0.1% according to the International Scale was 34% (ITT) at 12 months. The median daily dose of imatinib was close to the intended doses, 250 mg/m2 (range 176-405) with a median treatment duration of 16 months (2 w to 67 mo). Three pts (7%) had a dose reduction of more than 25% of the theoretic dose. Nine pts (20%) interrupted imatinib temporarily at least once for a median duration of dose interruption of 12 days (range 2-70). Ten pts (23%) discontinued imatinib. The reasons for discontinuation were the following: allogeneic HSCT in CCyR or MMR (2 pts) according to the investigator choice, adverse event (2 pts: muscle pain 1 pt, liver enzyme elevation 1 pt), disease progression or failure (6 pts: loss of CHR [L248V mutation] 1pt, loss of CCyR [L384M mutation] 1pt, no cytogenetic response 1 pt, no molecular response 1 pt, loss of MMR 2 pts). One of them (loss of hematologic response) transformed to blastic phase shortly after coming off study and died. Grade III or IV toxicity was recorded in 14 pts (32%). GradeIII-IV hematologic toxicity was recorded in 8 pts (18%) including neutropenia in 18% and thrombocytopenia in 5%. Nine pts (21%) developed grade III or IV non-hematologic toxicity: muscle pain (2.5%), arthralgia (5%), weight gain (13%), liver enzyme (GOT/GPT) increase (6.5%). Change of body height was observed during the first year of treatment with imatinib in the 22 pts with a sufficient follow-up: a significant decrease of height standard deviation scores (SDS) was observed with a median of the difference of -0.37 (range, -1.09 to +0.14)(p Conclusion. Imatinib is efficient in children and adolescent with previously untreated CML in early chronic phase. However, we report for the first time, a negative impact of imatinib on the growth in a cohort of children and adolescents treated with imatinib. Disclosures: No relevant conflicts of interest to declare.

Introduction: MPNST are very rare and aggressive tumors, which affect children, adolescents, and young adults. These tumors appear frequently in NF1 context. These tumors are problematic for diagnosis, treatment, and survival. We decided to make this study to help to understand better MPNST. Methods: we made a multicentric retrospective study of pediatric patients treated in French Pediatric Oncology units, between 1995 and 2017. A pathologic review was compulsory for inclusion, at diagnosis or realized in our study if applicable. Results: we included 66 patients, with age from 0,1 to 18 years. 32 (48,5%) patients suffered from NF1. Overall survival was 39% and Event Free Survival was 39%. Poor prognosis factors were NF1 status, FNCLCC grade 3, size of tumor ≥ 10cm and metastases. The only effective treatment, in association with surgery, were radiotherapy. Conclusion: MPNST are very rare tumors, with a bad prognosis, even for localized forms. We need to make a better stratification of patients, with prognostic factors found in our study, and to develop new therapies to improve overall survival of these patients.; Introduction : les MPNST sont des tumeurs rares et agressives, qui touchent les enfants, adolescents et jeunes adultes. Ces tumeurs se développent en particulier dans un contexte de neurofibromatose de type 1. Ces tumeurs posent de nombreux problèmes aujourd’hui : diagnostique, thérapeutique et pronostique, qui nécessitent de réaliser des études pour mieux comprendre leur développement et évolution. Matériel et Méthodes : nous avons réalisé une étude multicentrique rétrospective des patients pédiatriques traités pour une MPNST en France entre 1995 et 2017. Une relecture anatomopathologique était nécessaire pour inclusion dans l’étude (au diagnostic ou dans le cadre de notre étude). Résultats : nous avons inclus 66 patients âgés de 0,1 à 18 ans. 32 (48,5%) patients présentaient une NF1. La survie globale était de 39% et la survie sans événement était de 39%. Les facteurs de mauvais pronostic retrouvés étaient le statut NF1, le grade tumoral FNCLCC à 3, une taille tumorale ≥ 10cm et le statut métastatique. La radiothérapie semble être le seul traitement permettant d’améliorer la survie, en plus de la chirurgie. Conclusion : les MPNST sont des tumeurs rares, au pronostic particulièrement sombre, y compris pour des formes localisées. Il est nécessaire de mieux stratifier les patients en fonction des facteurs pronostiques identifiés et de développer de nouveaux traitements pour améliorer la survie globale et sans rechute.