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Supplementary Table 1 describes the clinical characteristics of patients.

Supplementary Table 4 provides the precise description of all STAG2 mutations in Ewing sarcoma.

Supplementary Figure 1. Representative CIRCOS plots. Supplementary Figure 2. Scheme of copy number alterations. Indicates the copy number alterations in Ewing sarcoma. Supplementary Figure 3. Mutation spectrum in Ewing sarcoma. Indicates the proportion of each somatic base changes in Ewing sarcoma. Supplementary Figure 4. CDKN2A analysis across cell lines. RT-QPCR and western blot results in cell lines. Supplementary Figure 5. CDKN2A analysis across the extended cohort. QPCR analysis of the CDKN2A locus across the whole series of patients.

Supplementary Table 3. Analysis of the statistical significance of mutations.

Supplementary Table 2 provides a summary (a), list of structural variants (b), list of copy number alterations (c), list of Tier 1 single nucleotide variants (d), indels (e), and purity analyses (f).

Ewing sarcoma is a primary bone tumor initiated by EWSR1–ETS gene fusions. To identify secondary genetic lesions that contribute to tumor progression, we performed whole-genome sequencing of 112 Ewing sarcoma samples and matched germline DNA. Overall, Ewing sarcoma tumors had relatively few single-nucleotide variants, indels, structural variants, and copy-number alterations. Apart from whole chromosome arm copy-number changes, the most common somatic mutations were detected in STAG2 (17%), CDKN2A (12%), TP53 (7%), EZH2, BCOR, and ZMYM3 (2.7% each). Strikingly, STAG2 mutations and CDKN2A deletions were mutually exclusive, as confirmed in Ewing sarcoma cell lines. In an expanded cohort of 299 patients with clinical data, we discovered that STAG2 and TP53 mutations are often concurrent and are associated with poor outcome. Finally, we detected subclonal STAG2 mutations in diagnostic tumors and expansion of STAG2-immunonegative cells in relapsed tumors as compared with matched diagnostic samples.Significance: Whole-genome sequencing reveals that the somatic mutation rate in Ewing sarcoma is low. Tumors that harbor STAG2 and TP53 mutations have a particularly dismal prognosis with current treatments and require alternative therapies. Novel drugs that target epigenetic regulators may constitute viable therapeutic strategies in a subset of patients with mutations in chromatin modifiers. Cancer Discov; 4(11); 1342–53. ©2014 AACR.This article is highlighted in the In This Issue feature, p. 1243

List of supplementary tables and figures.

STAG2 mutation in three cases that show a reduction of STAG2-immunopositive cells at disease recurrence.

International audience; In Euro-EWING99-R1 randomized trial, cyclophosphamide was shown to be noninferior to ifosfamide in the consolidation of standard-risk Ewing sarcoma (SR-EWS) after a common induction with VIDE (vincristine-ifosfamide-doxorubicin-etoposide). We present the results of the late effects analysis of VAC (vincristine-dactinomycin-cyclophoshamide) vs VAI (vincristine-dactinomycin-ifosfamide) conducted in Euro-EWING99-R1 French cohort. Of 267 French randomized patients, 204 were alive and free-of-relapse at 5-years including 172 with available long-term follow-up data concerning cardiac, renal and/or gonadal functions (sex-ratio M/F = 1.3, median age at diagnosis = 14 years): 84 randomized in VAC (median cumulative doses: cyclophosphamide = 9.7 g/m2, ifosfamide = 59.4 g/m2) and 88 in VAI (ifosfamide = 97.1 g/m2). With a median follow-up of 10 years (range = 5-17), five late relapses and five second malignancies were recorded. The 10-year event-free survival among 5-year free-of-relapse survivors was similar between VAC and VAI (93% vs 95%, P =.63). We estimated the 10-year cumulative probabilities of cardiac and kidney toxicities at 4.4% (95% confidence interval [95% CI] = 1.1%-7.6%) and 34.8% (95% CI = 26.8%-42.0%), respectively. Cardiac toxicity cumulative probability was similar in both arms, whereas kidney toxicity was higher in VAI (at 10 years, 43.0% vs 25.7%, P =.02), resulting from significant difference in glomerular toxicity (31.1% vs 13.1%, P

The most appropriate criteria and timing for palliative care referral remain a critical issue, especially in patients with metastatic breast cancer for whom long-term chemosensibility and survival are observed. We aimed to compare the impact of early palliative care including formal concertation with oncologists on decision for an additional line of chemotherapy compared with usual oncology care.This randomized prospective study enrolled adult women with metastatic breast cancer and visceral metastases with a 3rd- or 4th-line chemotherapy (CT). Patients received usual oncology care with a palliative care consultation only upon patient or oncologist request (standard group, S) or were referred to systematic palliative care consultation including a regular concertation between palliative care team and oncologists (early palliative care group, EPC). The primary endpoint was the rate of an additional CT (4th or 5th line) decision. Quality of life, symptoms, social support and satisfaction were self-evaluated at 6 and 12 months, at treatment discontinuation or 3 months after discontinuation.From January 2009 to November 2012, two authorized cancer centers included 98 women (EPC: 50; S: 48). Thirty-seven (77.1%, 95%CI 62.7-88%) patients in the EPC group had a subsequent chemotherapy prescribed and 36 (72.0%, 95%CI 57.5-83.8%) in the S group (p = 0.646). No differences in symptom control and global quality of life were observed, but less deterioration in physical functioning was reported in EPC (EPC: 0 [- 53-40]; S: - 6; 7 [- 60 to - 20]; p = 0.027). Information exchange and communication were significant improved in EPC (exchange, EPC: - 8.3 [- 30 to + 7]; S: 0.0 [- 17 to + 23]; p = 0.024; communication, EPC: 12.5 [- 8 to - 37]; S: 0.0 [- 21 to + 17]; p = 0.004).EPC in metastatic breast cancer patients did not impact the prescription rate of additional chemotherapy in patients a 3rd- or 4th-line chemotherapy for metastatic breast cancer; however, EPC may contribute to alleviate deterioration in physical functioning, while facilitating communication.ClinicalTrial.gov identifier: NCT00905281, May 20, 2009.

International audience; Eribulin is widely used in the treatment of metastatic breast cancer, with a manageable toxicity profile. This aggressive disease often requires systemic and local treatments, comprising surgery or radiotherapy. However, eribulin is usually discontinued during radiation therapy due to the lack of data concerning the safety of this combination, especially in the setting of repeat locoregional radiation therapy. Our patient was diagnosed with ER positive invasive ductal carcinoma of the left breast initially treated by surgery, radiation therapy, chemotherapy, and hormone therapy. She then received various lines of chemotherapy for multiple triple-negative relapses in the left axillary region. Since October 2020, she has been treated by eribulin. In order to improve local control, it was decided to add local radiation therapy to the region of recurrence in addition to systemic therapy. She underwent radiation therapy concomitantly with eribulin from February to March 2021. Treatment was very well tolerated, and no acute toxicity was reported. This is the first published case of repeat locoregional radiation therapy in combination with eribulin.

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.

Sarcomas are a rare heterogeneous group of malignant neoplasms that can arise in almost any anatomic site and any age. Close collaboration among adult and pediatric cancer specialists in the management of these tumors is of foremost importance. In this review, we present the current multidisciplinary organization in care of patients with sarcoma in France and we review the main advances made in the last decades in systemic and radiotherapy treatment in the main sarcoma types diagnosed in children, adolescents and young adults (AYA), thanks to the international collaboration.

Orthopaedic surgery I has a key role on the medical pathway of adolescent and young-adult (AYA) patients with musculo-skeletal tumor from diagnosis, tumor resection, musculo-skeletal immediate or delayed reconstruction, to dealing with late complications and sequelae following reconstruction during childhood. Administrative authorizations, organization by health authorities as well as training courses are quite different for adult and pediatric surgery. However, surgery for musculo-skeletal tumors in AYA patients have neither adult nor pediatric specifities; resection-reconstruction rules and technics are the same for adult or pediatric patients, with nevertheless lower complication rate and more biologic reconstructions for the youngest, and more prosthetic reconstructions for the oldest. Late complications after bone and soft-tissue reconstructions in childhood and musculo-skeletal deformation after surgery and/or radiotherapy in childhood need the vision from "adult" orthopaedic teams for long and very long term success of the surgical project with a good knowledge of pediatric technics previously used. Thus, formal shared time and transition care are necessary between pediatric and adult surgical teams to prepare long-term follow-up of these childhood cancer survivors. Participation to the same specialized Multi-Disciplinary Board, scientific society gathering adult and pediatric surgeons, clinical trials with no age-limitation might help to erase barriers and to ease collaboration between adult and pediatric ortho-oncologic teams.

Purpose: The French standard chemotherapy for osteosarcoma combines high-dose methotrexate (HDM) and etoposide–ifosfamide (EI) in children and adolescents, and API-AI (doxorubicin–cisplatin–ifosfam...

Introduction The preservation of fertility is an integral part of care of children requiring gonadotoxic treatments for cancer or non-malignant diseases. In France, the cryopreservation of ovarian tissue has been considered and has been offered as a clinical treatment since its inception. The aim of this study is to review 20 years of activity in fertility preservation by ovarian tissue cryopreservation (OTC) for children and the feasibility of oocyte isolation and cryopreservation from the ovarian tissue at a single center. Material and methods Retrospective study including patients aged 15 years or younger who underwent OTC, combined for some with oocyte cryopreservation of isolated oocytes, before a highly gonadotoxic treatment for malignant or non-malignant disease was initiated. We describe the evolution of activities in our program for fertility preservation and patient characteristics at the time of OTC and follow up. Results From April 1998 to December 2018, 418 girls and adolescents younger than 15 years of age underwent OTC, representing 40.5% of all females who have had ovarian tissue cryopreserved at our center. In all, 313 patients had malignant diseases and 105 had benign conditions. Between November 2009 and July 2013, oocytes were isolated and also cryopreserved in 50 cases. The mean age of patients was 6.9 years (range 0.3-15). The most frequent diagnoses in this cohort included neuroblastoma, acute leukemia and hemoglobinopathies; neuroblastoma being the most common diagnosis in very young patients. During follow up, three patients requested the use of their cryopreserved ovarian tissue. All had undergone ovarian tissue transplantation, one for puberty induction and the two others for restoring fertility. So far, no pregnancies have been achieved. Eighty-four patients who had OTC died. Conclusions Ovarian tissue cryopreservation is the only available technique for preserving fertility of girls. To our knowledge this is the largest series of girls and adolescents younger than 15 years so far reported on procedures of OTC before highly gonadotoxic treatment in a single center.

Introduction Li-Fraumeni syndrome (LFS) resulting from monoallelic germline TP53 gene mutation is a rare hereditary cancer predisposition. Breast cancer (BC) is the most common cancer among women with TP53 germline mutation with a risk ranging from 49% to 85% by the age of 60 years old. Most of these cancers are early onset. Few patients' cases have been reported so far in the literature. Our aim was to describe the medical history of a cohort of LFS women diagnosed with BC recruited from a single institution. The characteristics combined were genetic alteration diagnosis, tumor characteristics, treatment, outcome, and LFS associated cancers. Methods We retrospectively identified breast cancer patients with TP53 germline mutation from the Institut Curie (Paris, France) database and described their cancer characteristics and medical history. Results From 1989 to 2015, 25 patients affected with BC (31 tumors) and TP53 germline mutation carrier were identified, with a median follow up of 6.5 years. Median age at BC diagnosis was 30.5 years. All patients were women. 33% had a previously identified TP53 mutation in their family. 70% of them had BC as their first cancer event. 60% of the patients presented with another LFS associated cancer or non-related cancers: osteosarcoma (22%), glioblastoma (18%), pulmonary carcinoma (13%), gastric linitis plastica (9%), malignant hemopathy (9%), soft tissue sarcoma (9%), adrenocortical carcinoma (4%), ovarian cystadenocarcinoma (4%), renal tumor (4%), choroid plexus carcinoma (4%). 92% of the breast tumors were ductal carcinoma (28% DCIS and 64% IDC), 7% were sarcoma (1 phyllodesarcoma, 1 pleiomorphic liposarcoma); there were no lobular carcinoma. Among the IDC, 50% were HER2 positive, 72% were hormone-receptor positive. Most patients had a mastectomy (64%), and most of them received radiation (55%). However, when TP53 mutation had been identified prior to the treatment, none of the patients received radiotherapy (5 patients). Most patients received chemotherapy (70%) (37% in neoadjuvant setting, 33% in adjuvant setting, 25% for metastatic setting). 40% of the patients received hormone therapy (37% as adjuvant treatment, 7% for metastatic disease) Most of the patients did not relapse from BC (75%). Overall, only 17% of the patients had metastatic BC. To date, 12 patients of our series have died (48%), 6 patients (24%) from other LFS-associated cancers and 4 patients from BC (16%). Conclusion To the best of our knowledge, this descriptive series is the largest study of tumor characteristics and medical history of LFS-women with BC, the most frequent cancer among women with TP53 germline mutation. It confirms the higher HER2 overexpression rate observed in LFS-patients BC, as suggested in the literature and showed a high rate of DCIS at initial presentation. Most of the patients developed other LFS-associated cancers. In depth molecular analysis of these BC will be performed in order to gain insight into their biological specificities and to adapt the therapeutic management of this poor prognosis syndrome. Citation Format: Tran M, Loirat D, Colas C, Bozec L, Laurence V, Lerebours F, Cabel L, Bidard F-C, Stoppa-Lyonnet D, Vincent-Salomon A, Gauthier-Villars M, Lavigne M, De Pauw A. Breast cancer characteristics and outcomes in patients with TP53 germline mutation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-07.

Orthopaedic surgery I has a key role on the medical pathway of adolescent and young-adult (AYA) patients with musculo-skeletal tumor from diagnosis, tumor resection, musculo-skeletal immediate or delayed reconstruction, to dealing with late complications and sequelae following reconstruction during childhood. Administrative authorizations, organization by health authorities as well as training courses are quite different for adult and pediatric surgery. However, surgery for musculo-skeletal tumors in AYA patients have neither adult nor pediatric specifities; resection-reconstruction rules and technics are the same for adult or pediatric patients, with nevertheless lower complication rate and more biologic reconstructions for the youngest, and more prosthetic reconstructions for the oldest. Late complications after bone and soft-tissue reconstructions in childhood and musculo-skeletal deformation after surgery and/or radiotherapy in childhood need the vision from "adult" orthopaedic teams for long and very long term success of the surgical project with a good knowledge of pediatric technics previously used. Thus, formal shared time and transition care are necessary between pediatric and adult surgical teams to prepare long-term follow-up of these childhood cancer survivors. Participation to the same specialized Multi-Disciplinary Board, scientific society gathering adult and pediatric surgeons, clinical trials with no age-limitation might help to erase barriers and to ease collaboration between adult and pediatric ortho-oncologic teams.

Purpose: This study aimed to explore and identify the factors associated with problematic substance use (alcohol, tobacco, and cannabis) and behavioral addictions (internet and eating disorders) over time in adolescents and young adults (AYAs) treated for cancer. Methods: AYAs newly diagnosed with cancer, 15-25 years of age, completed a questionnaire during their hospitalization (T1), assessing their consumption of alcohol, tobacco, and cannabis (The Alcohol Use Disorders Identification Test; The Smoking Behavior Questionnaire; and The Cannabis Abuse Screening Test), their internet use (The Internet Addiction Test), their body preoccupations (The Eating Attitudes Test), as well as their coping strategies (Brief COPE) and emotional adjustment (The Hospital Anxiety and Depression Scale). Questionnaires were completed again 6 months later (T2). Results: Seventy-three AYAs were included at T1 and 21 AYAs at T2. Nearly one out of two (46.58%) AYAs had a problematic substance use or behavioral addiction after cancer diagnosis (T1). Problematic use of internet was frequently reported (23.29%), as well as harmful alcohol consumption or addiction (16.44%) and cannabis dependence (12.33%). The main factor related to problematic substance use was being older, while the main factor related to behavioral addiction was having a higher anxiety score. Substance use as a coping strategy was used more frequently by AYAs with problematic substance use and emotional support as a coping strategy was used more frequently by AYAs with a behavioral addiction. Conclusions: High rates of problematic substance use and behavioral addiction were reported in our sample. AYAs surveyed had high problematic use of cannabis and high internet use. Attention to substance use and addictive behaviors is recommended to ensure optimal care.

[Background] Although there have been multiple randomised trials in newly diagnosed Ewing sarcoma family of tumours (ESFT) and these have been conducted over many years and involved many international cooperative groups, the outcomes for all stages of disease have plateaued. Internationally, the standard treatment of ESFT is not defined, and there is a need to add new agents other than conventional chemotherapy to improve outcomes. This trial will compare two different induction/consolidation chemotherapy regimens: (1) vincristine, ifosfamide, doxorubicin and etoposide (VIDE) induction and vincristine, actinomycin D, ifosfamide or cyclophosphamide, or busulfan and mephalan (VAI/VAC/BuMel) consolidation and (2) vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC/IE) induction and ifosfamide and etoposide, vincristine and cyclophosphamide, vincristine, actinomycin D and ifosfamide, or busulfan and mephalan (IE/VC/VAI/BuMel) consolidation (randomisation 1, or R1). A second randomisation (R2) will determine whether the addition of zoledronic acid to consolidation chemotherapy, as assigned at R1, is associated with improved clinical outcome., [Methods] EURO EWING 2012 is an international, multicentre, phase III, open-label randomised controlled trial. There are two randomisations: R1 and R2. Patients are randomly assigned at two different time points: at entry to the trial (R1) and following local control therapy (R2). The primary outcome measure is event-free survival. The secondary outcome measures include overall survival, adverse events and toxicity, histological response of the primary tumour, response of the primary tumour, regional lymph nodes or metastases (or both), and achievement of local control at the end of treatment., [Discussion] This study will establish which is the “standard regimen” of chemotherapy, taking into account both clinical outcomes and toxicity. This will form the chemotherapy backbone for future interventional studies where we may want to add new targeted agents. It will also determine the role of zoledronic acid in conjunction with the separate EE2008 trial. Any trial in ESFT needs to take into account the rarity of the tumour and consider that international cooperation is needed to provide answers in a timely manner., [Trial registration] Registered with EudraCT number 2012-002107-17 on 26 February 2012. Registered with ISRCTN number 92192408 on 4 November 2013., This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement n°602856. The NCC in France, CLB, receives additional funding from SFCE and Ligue contre le cancer. The coordinating sponsor (the University of Birmingham, Birmingham, UK) is funded by Cancer Research UK (grant award reference C5952/A14745).

PLOS ONE 15(9), e0237792 (2020). doi:10.1371/journal.pone.0237792, Published by PLOS, San Francisco, California, US

Background, Methods To describe the characteristics, treatments (systemic/local), and outcome (oncological/functional) of French patients with head and neck Ewing's sarcomas (HNES) registered in the Euro‐Ewing 99 (EE99) database. Specific patient‐level data were reviewed retrospective. Results Forty‐seven HNES patients in the EE99 database had a median age of 11 years, 89% had bone tumors (skull 55%, mandible 21%, maxilla 11%), 89% had small tumors (

Ewing sarcoma (EWS) is a pediatric cancer characterized by the EWSR1-FLI1 fusion. We performed a genome-wide association study of 733 EWS cases and 1346 unaffected individuals of European ancestry. Our study replicates previously reported susceptibility loci at 1p36.22, 10q21.3 and 15q15.1, and identifies new loci at 6p25.1, 20p11.22 and 20p11.23. Effect estimates exhibit odds ratios in excess of 1.7, which is high for cancer GWAS, and striking in light of the rarity of EWS cases in familial cancer syndromes. Expression quantitative trait locus (eQTL) analyses identify candidate genes at 6p25.1 (RREB1) and 20p11.23 (KIZ). The 20p11.22 locus is near NKX2-2, a highly overexpressed gene in EWS. Interestingly, most loci reside near GGAA repeat sequences and may disrupt binding of the EWSR1-FLI1 fusion protein. The high locus to case discovery ratio from 733 EWS cases suggests a genetic architecture in which moderate risk SNPs constitute a significant fraction of risk., Ewing sarcoma (EWS) is a rare pediatric bone cancer typically involving the EWSR1-FLI1 fusion. Here the authors perform a genome-wide association study and report three new EWS risk loci that reside near GGAA repeat sequences, and identify candidate genes (RREB1 and KIZ) from eQTL analysis.

Resume Introduction Les tumeurs malignes rares de l’ovaire regroupent les tumeurs borderline complexes, les tumeurs germinales, les tumeurs des cordons sexuels et les tumeurs epitheliales rares. Les indications et modalites de preservation de la fertilite, la prise en charge d’une infertilite, les possibilites de contraception et de traitement hormonal de la menopause sont des questions frequentes en pratique clinique. Un groupe d’experts du reseau national dedie aux cancers gynecologiques rares (TMRG/TMRO) associe a des experts nationaux de la fertilite, des traitements hormonaux et de la contraception se sont reunis pour proposer des recommandations nationales. Methodes Un panel de 39 experts de differentes specialites a participe a l’elaboration des recommandations, en suivant la methode DELPHI (consensus formalise d’experts). Apres revue systematique de la litterature, des recommandations ont ete redigees puis soumises a deux tours successifs de cotations. Resultats Trente-cinq recommandations ont ete retenues, precisant les indications de preservation de la fertilite, les situations contre-indiquant une stimulation ovarienne (en preservation de la fertilite ou dans la prise en charge d’une infertilite), les possibilites de contraceptions (notamment hormonales) et de traitement hormonal de la menopause pour chaque type tumoral. De facon generale, une prudence a ete retenue pour les tumeurs potentiellement hormonosensibles comme les tumeurs des cordons sexuels, les adenocarcinomes sereux et endometrioides de bas grade, ainsi que pour les tumeurs borderline avec criteres histologiques pejoratifs. Discussion Dans le contexte d’une litterature pauvre, ces recommandations etablies via consensus formalise d’experts devraient constituer une aide aux cliniciens dans la prise en charge de ces patientes.

Avec l’augmentation croissante des taux de guerison des cancers de l’enfant et de l’adolescent, la question de la fertilite et de sa preservation represente aujourd’hui une preoccupation majeure pour les equipes d’oncohematologie. Le statut de la fertilite a l’âge adulte constitue un secteur important de la qualite de vie des anciens patients, et en ce sens, les recommandations preconisent qu’une cryopreservation de sperme soit proposee a tout adolescent pubere avant le debut d’un traitement potentiellement gonadotoxique. Cette recherche possede deux volets. Le premier a permis de faire l’etat des lieux des pratiques medicales pediatriques en oncologie concernant la transmission des informations au sujet des risques pour la fertilite ainsi qu’au sujet de la proposition de cryopreservation de sperme. Le second vise a explorer l’experience subjective d’anciens patients autour de ces questions. Notre etude a inclus les anciens patients âges de 14 a 18 ans au moment du diagnostic, traites et en remission complete depuis au moins un an. Dix-sept entretiens ont ete realises avec ces adolescents et jeunes adultes. Les objectifs principaux etaient de pouvoir degager des recommandations pour les equipes medicales et soignantes et de creer un livret d’information a destination des adolescents et jeunes adultes. L’analyse thematique des entretiens montre l’importance de l’annonce des risques, la prise de decision, la medicalisation de la preservation du sperme et les interactions parentales. L’experience subjective des anciens patients permet une prise de conscience de la necessite de certains amenagements. Les jeunes ont eux-memes participe a l’elaboration des projets d’amelioration issus de notre etude. Le desir d’etre recus seuls, en priorite et en dehors de la presence de leurs parents, l’amenagement d’un accueil specifique dans la structure de recueil et de conservation du sperme, les echanges avec le medecin referent ou le medecin biologiste sur les resultats du recueil de sperme, afin de conserver des informations sur le statut de la fertilite, forment les demandes principales issues des entretiens avec les jeunes.

Aujourd’hui en France, pres d’une personne sur 850 âgee de 20 a 45 ans a ete soignee pour un cancer pendant l’enfance ou l’adolescence. Les perspectives actuelles doivent donc s’orienter vers la reduction des sequelles et des effets secondaires a long terme. L’hypofertilite ou la sterilite en font partie. Cette preoccupation a inspire et motive cette recherche. Elle concerne d’une part les pratiques medicales pediatriques pour transmettre l’information au sujet des risques pour la fertilite et proposer une cryopreservation de sperme pour les adolescents puberes, et d’autre part, l’experience subjective d’anciens patients concernant cette information et cette proposition. Etat des lieux des pratiques medicales confrontees a l’experience des patients afin de degager des recommandations et de developper un livret d’information pour les adolescents. Un questionnaire anonyme, portant les indications de sexe et d’âge, a ete adresse aux 79 pediatres seniors exercant au sein des services d’oncohematologie pediatrique. Cinquante-six observations de 27 centres ont pu etre exploitees au niveau statistique, soit 70,9 % de taux de participation individuelle et 84,4 % de taux de participation des centres. Quatre-vingt-seize pour cent des praticiens interroges proposent une cryoconservation de sperme dans plus de 50 % des cas aux patients atteints par la maladie de Hodgkin. En revanche, pres de 62 % la proposent « jamais–rarement » ou « parfois » aux patients atteints de tumeurs du systeme nerveux central (SNC). Seuls 29 % feront cette proposition « tres souvent–toujours » a ces patients. La grande majorite des pediatres informe les parents en priorite et leur demande leur avis avant d’evoquer la question avec l’adolescent, alors que 85 % de ces medecins jugent que c’est a l’adolescent de prendre une decision. Peu de ressources semblent mobilisables pour les medecins en difficulte. En effet, seulement 24,1 % d’entre eux travaillent en collaboration avec une personne formee a la question de la preservation de la fertilite, et ce sont en grande majorite des pediatres de sexe feminin. 85,2 % n’ont aucun document a remettre a l’adolescent en soutien a la consultation. Pres de 60 % des medecins pensent qu’une consultation avec un psychologue ou un pedopsychiatre devrait etre proposee de facon systematique. Les enjeux se situent donc dans la formation continue des medecins-pediatres ainsi que dans le travail pluridisciplinaire et transdisciplinaire pour optimiser les pratiques.

Resume Les carcinomes sont des tumeurs rares de l’adolescent–jeune adulte (AJA) au spectre different de ceux de l’adulte. Les localisations les plus frequentes en dehors de la thyroide sont le nasopharynx, les glandes salivaires, le colon-rectum et les ovaires. Si les carcinomes du nasopharynx ou des glandes salivaires sont des tumeurs de bon pronostic, d’autres sont de pronostic plus reserve, comme les carcinomes digestifs, gynecologiques ou de la ligne mediane. Les modes de revelation sont aspecifiques et dependent de la localisation : masse, syndrome tumoral, douleur, alteration de l’etat general. Le caractere inhabituel des carcinomes a l’âge pediatrique conduit a proposer une exploration oncogenetique systematique. La genealogie, les signes cliniques associes et le type de carcinome doivent guider les analyses. En l’absence d’orientation, l’analyse du gene TP53 et, pour les carcinomes du spectre elargi du syndrome hereditary non-polyposis colorectal cancer (HNPCC), la recherche de mutation des genes MMR ( mismatch repair ) semble essentielle. En raison de la rarete de ces maladies et de l’absence de recommandations homogenes, les membres du comite tumeurs rares de la SFCE recommandent pour la prise en charge de ces AJA, une relecture histologique par un pathologiste habitue aux carcinomes de l’adulte, un double avis en oncologie pediatrique et adulte, une analyse des referentiels adultes avec adaptation au caractere pediatrique de la maladie, en particulier en termes de risque d’effets secondaires. Un recours a un avis national (par un membre du groupe FRACTURE) ou europeen (groupe EXPERT) est parfois necessaire dans les situations les plus complexes.

ObjectivesBCOR-CCNB3 sarcoma (BCS) is an undifferentiated tumor that has some clinical and morphologic similarity to classic Ewing sarcoma, but it is characterized by a distinct BCOR-CCNB3 gene fusion. There are no reports describing its cytomorphologic findings.MethodsWe describe cytologic findings of five molecularly proven BCS cases (four males and one female, aged 8.5-22 years).ResultsSmears showed mainly round cells, but some spindle cells and rhabdoid-like cells were also observed. Dispersed cells dominated in smears, but also distinct pseudopapillary structures with vascular cores were noted in four cases. Scant connective tissue fragments were found in four cases. There was no rosette formation in any case.ConclusionsBCS should be differentiated from other round cell tumors. Some cytologic features, especially rhabdoid-like cells, connective tissue fragments, and pseudopapillary formations, combined with immunohistochemical and molecular studies, may be helpful in making the appropriate diagnosis.

BACKGROUND The skills of adult versus pediatric neuro-oncologists are not completely similar though additive. Because the tumors and their protocols are different and the tolerance and expected sequelae are specific. Multidisciplinary meetings including adult and pediatric neuro oncologists are warranted to share expertise. MATERIAL AND METHODS Since 2008, on behalf of ANOCEF, GO-AJA and SFCE societies, a weekly national web based conference was held in France. Any patient with the following criteria could be discussed: Adolescent and Young Adults aged between 15 and 25 years, and any adult with a pediatric type pathology, including medulloblastoma, germ cell tumors, embryonic tumors, ependymoma, pilocytic astrocytoma. RESULTS Number of cases discussed increased from 8 to 202/year, with a mean number of 3 cases (1 to 7) discussed at each meeting. In 2018, 36 meetings were held, with a mean of 8 participants (2 to 14) issued from various French centers. 168 cases were discussed in 2018. Mean age was 30 years old (7 to 67). 45% were discussed at diagnosis; The patients had mostly medulloblastomas (n=47), ependymomas (n=24), low (n=21) or high grade gliomas (n=11), pineal tumors (n=20), germ cell tumors (n=9) and embryonal tumors (n=6). The rate of inclusion in protocols was increased since the opening of this web conference, especially for the germ cell tumor GCT SIOP protocol that is opened without age restriction, and in RSMA standard risk or MEVITEM relapse adult medulloblastoma protocols. CONCLUSION Multidisciplinary Web conference for AYAs is feasible and fruitful. It shares knowledge and increases the inclusion rate in protocols. It should be developped further.

Introduction Rare ovarian tumours include complex borderline ovarian tumours, sex-cord tumours, germ cell tumours and rare epithelial tumours. Indications and modalities of fertility preservation (FP), infertility management, contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and experts in reproductive medicine and gynaecology have built guidelines on FP, contraception and menopause hormone therapy in women treated for ovarian rare tumours. Material and methods A panel of 35 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review and then rated through two successive rounds. Results Thirty-five recommendations were identified, concerning indications for FP, contraindications for ovarian stimulation, contraceptive options and menopause hormone therapy for each tumour type. Discussion Overall, caution has been recommended in the case of potentially hormone-sensitive tumours such as sex-cord tumours, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumours. Conclusion In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

Growing evidence suggests that polymorphisms of genes coding for transporters or enzymes may partially explain the large between subject variability reported for methotrexate (MTX) pharmacokinetics (PK). This prospective study aimed to develop a population PK-pharmacogenetic model to evaluate the part of between-subject variability due to single-nucleotide polymorphisms (SNPs) in transporters and enzyme genes implicated in MTX distribution and elimination. MTX concentrations and 54 SNPs (located in ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCG2, SLC19A1, SLCO1B1, and UGT1A1 genes) were analyzed in patients treated with MTX included in the OS2006/sarcoma-09 trial (a multicenter, open-label, phase III trial, ClinicalTrials.gov. Identifier: NCT00470223). PK data were analyzed using the nonlinear mixed-effect modeling software program Monolix. The influence of each SNP was evaluated using a stepwise procedure under additive, recessive, or dominant genetic model. The likelihood ratio test was used to test the effect of each SNP on PK parameters. Overall, 187 patients with 7898 MTX blood concentrations were included in the PK-pharmacogenetic analysis. A 2-compartment model adequately described the data. Although high-dose MTX dosing recommendations in pediatric patients are currently based on body surface area, body weight was more predictive of clearance between-subject variability than body surface area. The most significant polymorphism associated with MTX clearance was rs13120400 (on the ABCG2 gene) under the recessive genetic model (P < .0001). GG genotype carriers for rs13120400 appeared to have a moderate decrease in MTX exposure compared to AA or GA carriers.

It is well recognised that adolescents and young adults (AYA) with cancer have inequitable access to oncology services that provide expert cancer care and consider their unique needs. Subsequently, survival gains in this patient population have improved only modestly compared with older adults and children with cancer. In 2015, the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE) established the joint Cancer in AYA Working Group in order to increase awareness among adult and paediatric oncology communities, enhance knowledge on specific issues in AYA and ultimately improve the standard of care for AYA with cancer across Europe. This manuscript reflects the position of this working group regarding current AYA cancer care, the challenges to be addressed and possible solutions. Key challenges include the lack of specific biological understanding of AYA cancers, the lack of access to specialised centres with age-appropriate multidisciplinary care and the lack of available clinical trials with novel therapeutics. Key recommendations include diversifying interprofessional cooperation in AYA care and specific measures to improve trial accrual, including centralising care where that is the best means to achieve trial accrual. This defines a common vision that can lead to improved outcomes for AYA with cancer in Europe.

11500 Background: In 2010, different chemotherapy regimens were standard in Europe and the USA for newly diagnosed ES. In the absence of novel agents to investigate, comparison of these two strategies was considered worthwhile. Methods: Newly diagnosed localised or metastatic ES patients aged 5-50 were eligible. Patients were randomized to receive either the European regimen (Arm A) of VIDE (vincristine [V], ifosfamide [I], doxorubicin [D] and etoposide [E]) induction and VAI or VAC (V, actinomycin D and I or cyclophosphamide [C]) consolidation or the USA regimen (Arm B) of compressed VDC/IE induction and IE/VC consolidation. The primary outcome measure was event-free survival (EFS); secondary outcomes included overall survival (OS) and toxicity. The design was Bayesian with interpretation based on posterior probabilities (with non-informative priors) – i.e. probability that true hazard ratio (HR) < 1.0 given the data [Pr(HR200 ml); country (37% UK, 31% France, 32% other). Median follow-up was 1.7 years. The HRs (95% CrI) were 0.70 (0.51, 0.95) for EFS and 0.64 (0.42, 0.96) for OS in favour of Arm B, with posterior probabilities of 98% for both that Arm B was better. Subgroup analyses showed no evidence that this benefit differed depending the baseline features, with no HT being close to significance (table). There were no major differences in acute toxicity: 68% of patients in Arm A experienced serious adverse events and 67% in Arm B. Conclusions: VDC/IE chemotherapy is superior to VIDE for both EFS and OS, with no excess toxicity. This benefit is consistent across all baseline stratification parameters. Clinical trial information: ISRCTN92192408 . [Table: see text]