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Introduction Adolescents and young adults (AYA) with cancer undergo physical transformations due to disease and treatments occurring alongside puberty and adolescence. Although physical activity is recommended for its benefits, its practice among AYA with cancer remains insufficient. The aim of the Éducation Thérapeutique et Activité Physique: Engagement des Adolescents et Jeunes Adultes atteints de cancer study is to identify the evolution of AYA with cancer medical knowledge and powers (power to act, to express oneself) over life and cancer care, and their role in commitment in adapted physical activity (APA) and therapeutic patient education during and after oncological treatments.Methods and analysis This prospective mixed methods monocentre study will be conducted in a French comprehensive cancer centre. Observations will be conducted two times a week during medical consultations, APA interventions and therapeutic education sessions for AYA with cancer. Semidirective interviews will involve 70 participants, including AYA with cancer aged 15–25, health professionals, APA teachers and parents. Quantitative data will be collected on AYA’s social characteristics and participation in physical activity intervention and therapeutic education sessions. A correspondence factor analysis will supplement inductive analysis of ethnographic qualitative data, involving patient coresearchers. The results will help to improve the understanding of AYAs’ medical knowledge and powers, their commitment in physical activity and to develop strategies to increase their participation.Ethics and dissemination This study complies with reference methodology MR004 of the French National Data Protection Authority and was registered by the Data Protection Officer of the Leon Berard Cancer Center on the activity registry of the institution (Ref. N°R201-004-259; 5 July 2022). Ethics approval has been obtained from the Centre Léon Bérard ethics board (Ref. N°2022–006; 20 July 2022). Oral informed consent will be obtained from all participants before data collection. The results of this study will be published in peer-reviewed scientific journals, national and international conferences.

Ovarian transposition (OT) has been proposed as a protective measure against radiation-induced damage to ovarian function and fertility. Despite its historical use, limited research has focused on evaluating endocrine and exocrine ovarian function after OT performed in adolescents and young adults (AYAs) before or during puberty. The purpose of our study was to investigate the fertility, pubertal development, and ovarian function of women with a previous history of OT during childhood, adolescence or young adulthood. In an observational bicentric retrospective study, we included 32 young female cancer patients who underwent OT before the age of 26 between 1990 and 2015 at Lyon Léon Bérard Cancer Center or Nancy University Hospital. The mean age at the time of OT was 15.6 years with a cancer diagnosis at 15 ± 4.8 years. Among the 10 women attempting pregnancy post-treatment, 60% achieved successful pregnancies. After a mean follow-up of 9.6 ± 7 years, 74% (17 out of 23) of women recovered spontaneous menstrual cycles (seven out of eight evaluable women with OT before or during puberty). Notably, 35% of women who did not attempt pregnancy demonstrated adequate ovarian reserve. Ovarian reserve and function recovery were influenced by the specific chemotherapy received. Importantly, our findings suggest that OT’s effectiveness on ovarian activity resumption does not significantly differ when performed before or during puberty compared to pubertal stages. This study contributes valuable insights into the long-term reproductive outcomes of young women undergoing OT, emphasizing its potential efficacy in preserving ovarian function and fertility across different developmental stages.

Abstract Background Ifosfamide is a major anti-cancer drug in children with well-known renal toxicity. Understanding the mechanisms underlying this toxicity could help identify children at increased risk of toxicity. Methods The IFOS01 study included children undergoing ifosfamide-based chemotherapy for Ewing sarcoma or rhabdomyosarcoma. A fully evaluation of renal function was performed during and after chemotherapy. Proton nuclear magnetic resonance (NMR) and conventional biochemistry were used to detect early signs of ifosfamide-induced tubulopathy. The enzymatic activity of aldehyde dehydrogenase (ALDH) was measured in the peripheral blood lymphocytes as a marker of ifosfamide-derived chloroacetaldehyde detoxification capacity. Plasma and urine concentrations of ifosfamide and dechloroethylated metabolites were quantified. Results The 15 participants received a median total ifosfamide dose of 59 g/m2 (range: 24–102), given over a median of 7 cycles (range: 4–14). All children had acute proximal tubular toxicity during chemotherapy that was reversible post-cycle, seen with both conventional assays and NMR. After a median follow-up of 31 months, 8/13 children presented overall chronic toxicity among which 7 had decreased glomerular filtration rate. ALDH enzymatic activity showed high inter- and intra-individual variations across cycles, though overall activity looked lower in children who subsequently developed chronic nephrotoxicity. Concentrations of ifosfamide and metabolites were similar in all children. Conclusions Acute renal toxicity was frequent during chemotherapy and did not allow identification of children at risk for long-term toxicity. A role of ALDH in late renal dysfunction is possible so further exploration of its enzymatic activity and polymorphism should be encouraged to improve the understanding of ifosfamide-induced nephrotoxicity.

PurposeThe R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases.MethodsFrom 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method.ResultsOf 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm.ConclusionIn ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

Background: Desmoid type fibromatosis (DTF) are rare intermediate malignancies with unpredictable outcome. Series containing children and young adults (YA) are lacking. Methods: The aim of this retrospective study was to describe the French population of patients

RATIONALE:CSF1R tyrosine kinase inhibitors (TKI) and antibodies yield response rates and tumor control in patients with diffuse type tenosynovial giant cell tumors (dTGCT). The long term management of patients with dTGCT treated with TKI is however not known. PATIENTS AND METHODS:We conducted a retrospective single center study on the 39 patients with advanced and/or inoperable dTGCT referred to the Centre Leon Berard for a medical treatment. The clinical characteristics and treatments of patients who had received at least one line of CSF1R TKI or Ab was collected from the electronic patient records and analyzed, after this study was approved by the Institutional Review Board of the Centre Leon Berard. Statistics were conducted using SPSS 23.0. RESULTS:Thirty-nine patients received at least one line of TKI among the 101 patients with histologically confirmed dTGCT refered to this center. Imatinib, nilotinib, pexidartinib, emactuzumab were the most frequently used agents. First line treatment was given for a median duration of 7 months. With a median follow-up from the initiation of TKI of 30 months, the progression-free rate at 30 months is 56% for the 39 patients. 15 patients had recurrent disease after first line CSF1R inhibitor: 12 (80%) received a 2nd line treatment for a median duration of 6 months and a median time to progression (TTP) of 12 months. Six patients had afterwards a recurrent disease and 5 (83%) received a 3rd line treatment for a median duration of 5 months and a median TTP of 9 months. Progression-free rate at 30 months was observed in 3 of 12 (25%) after line 2 and 1 of 5 (20%) after line 3. None of the patients refered died with a median follow-up of 67 months. CONCLUSIONS:CSF1R TKI or Ab provide prolonged tumor control and symptom relief for a majority of patients with inoperable or relapsing dTGCT, in first and subsequent lines. Multiple lines are required for close to 50% of patients with relapsing dTGCT.

Primary malignant bone tumours, osteosarcomas, and Ewing sarcomas are rare diseases which occur mainly in adolescents and young adults. With the current therapies, some patients remain very difficult to treat, such as tumour with poor histological response to preoperative CT (or large initial tumour volume for Ewing sarcomas not operated), patients with multiple metastases at or those who relapsed. In order to develop new therapies against these rare tumours, we need to unveil the key driving factors and molecular abnormalities behind the malignant characteristics and to broaden our understanding of the phenomena sustaining the metastatic phenotype and treatment resistance in these tumours. In this paper, starting with the biology of these tumours, we will discuss potential therapeutic targets aimed at increasing local tumour control, limiting metastatic spread, and finally improving patient survival.