Therapy and Outcomes of Patients with Relapsed Nonmetastatic Rhabdomyosarcoma: A Report from the French Society of Pediatric Oncology Malignant Mesenchymal Tumor Committee.

Background: The prognosis for patients with relapse of localized rhabdomyosarcoma (RMS) remains poor, with limited evidence for optimal second-line therapy. This study describes the management and outcomes of relapsed RMS patients in France.

Methods: We retrospectively reviewed all nonmetastatic RMS patients enrolled in France in the RMS 2005 study who relapsed between 2006 and 2019 after achieving complete local control, defined as complete remission or stable residue ≥ 6 months after treatment completion.

A germline PDGFRB splice site variant associated with infantile myofibromatosis and resistance to imatinib.

Purpose: Infantile myofibromatosis is characterized by the development of myofibroblastic tumors in young children. In most cases, the disease is caused by somatic gain-of-function variants in platelet-derived growth factor (PDGF) receptor beta (PDGFRB). Here, we reported a novel germline intronic PDGFRB variant, c.

Centralized Investigator Review of Radiological and Functional Imaging Reports in Real-World Oncology Studies: The SACHA-France Experience.

SACHA-France (NCT04477681) is a prospective real-world study that collects clinical safety and efficacy data of novel anticancer therapies prescribed off-label or on compassionate use to patients <25 years. From March 2020 until February 2024, 640 patients with solid tumors or lymphomas were included, with 176 (28%) reported objective tumor responses. Centralized medical monitoring of local radiological/functional imaging reports by the SACHA coordinating investigator led to response modification in 45 out of 176 cases (26%), highlighting the relevance of the medical review of study data.

Li-Fraumeni-associated osteosarcomas: The French experience.

Purpose: Describe clinical characteristics and outcome of Li-Fraumeni syndrome (LFS)-associated osteosarcomas.

Methods: TP53 germline pathogenic/likely pathogenic variant carriers diagnosed with osteosarcoma in France between 1980 and 2019 were identified via the French Li-Fraumeni database at Rouen University Hospital. Sixty-five osteosarcomas in 52 patients with available clinical and histological data were included.

Targeted therapies in children with renal cell carcinoma (RCC): An International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG)-related retrospective descriptive study.

Introduction: Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC.

Treatment at relapse for synovial sarcoma of children and adolescents: A multi-institutional European retrospective analysis.

Purpose: Though the prognosis for pediatric patients with localised synovial sarcoma (SS) is generally good, the chances of being cured after relapse are limited. This study describes a retrospective multi-institutional series of relapsing SS patients treated at six selected European referral centers for pediatric sarcoma.

Patients And Methods: The study included 41 patients <21 years with relapsing SS, treated between 2002 and 2022.

Therapeutic benefit of larotrectinib over the historical standard of care in patients with locally advanced or metastatic infantile fibrosarcoma (EPI VITRAKVI study).

Background: Patients with infantile fibrosarcoma (IFS) have shown strong and long-lasting responses to larotrectinib, a tropomyosin receptor kinase inhibitor (TRKi), in single-arm clinical trials. Conventional chemotherapy has also shown important efficacy. But, until now, no comparative data exist.

FGFR1 fusions as a novel molecular driver in rhabdomyosarcoma.

The wide application of RNA sequencing in clinical practice has allowed the discovery of novel fusion genes, which have contributed to a refined molecular classification of rhabdomyosarcoma (RMS). Most fusions in RMS result in aberrant transcription factors, such as PAX3/7::FOXO1 in alveolar RMS (ARMS) and fusions involving VGLL2 or NCOA2 in infantile spindle cell RMS. However, recurrent fusions driving oncogenic kinase activation have not been reported in RMS.

Chemo-immunotherapy with dinutuximab beta in patients with relapsed/progressive high-risk neuroblastoma: does chemotherapy backbone matter?

Background: Addition of anti-GD2 antibodies to temozolomide-based chemotherapy has demonstrated increased antitumor activity and progression-free survival in patients with relapsed/progressive high-risk neuroblastoma. However, chemo-immunotherapy is not yet approved for this indication. This study presents the chemo-immunotherapy experience in patients with relapsed/progressive high-risk neuroblastoma treated within the off-label use program of the Neuroblastoma Committee of the French Society of Pediatric Oncology (SFCE).

Adenoid cystic carcinoma of the parotid and submandibular glands in children and young adults: A population-based study.

Objectives: This study aims to analyze the behavior and treatment of adenoid cystic carcinoma (AdCC) in the pediatric and young adult population and to identify factors affecting overall survival (OS).

Materials And Methods: The study analyzed salivary gland malignancies in patients aged 0-21 with AdCC histology using the National Cancer Database from 2004 to 2018.

Results: A total of 72 patients (59.

Clinical trial inclusion in patients with relapsed/refractory neuroblastoma following the European Precision Cancer Medicine trial MAPPYACTS.

Introduction: Despite poor survival for patients with relapsed or refractory neuroblastoma, only 10-16% of patients are reported to be included in early phase trials. This study aimed to explore the impact of molecular profiling within the prospective precision cancer medicine trial MAPPYACTS (NCT02613962) on subsequent early phase trial recruitment and treatment by matched targeted therapies in this population.

Methods And Materials: Clinical data from all French patients with relapsed/refractory neuroblastoma enrolled in MAPPYACTS were analyzed for subsequent matched/non-matched targeted treatment based on clinical tumor board (CMTB) recommendations.

Imaging characterization of paediatric tumours with the neurotrophic tyrosine receptor kinase fusion transcript.

Objectives: The neurotrophic tyrosine receptor kinase (NTRK) fusion transcript (FT) is a major genetic landmark of infantile fibrosarcoma (IFS) and cellular congenital mesoblastic nephroma (cCMN) but is also described in other tumours. The recent availability of NTRK-targeted drugs enhances the need for better identification. We aimed to describe the anatomic locations and imaging features of tumours with NTRK-FT in children.

Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of- heterozygosity and common and transcriptional silencing across advanced pediatric solid cancers.

The human leukocyte antigen (HLA) system is a major factor controlling cancer immunosurveillance and response to immunotherapy, yet its status in pediatric cancers remains fragmentary. We determined high-confidence HLA genotypes in 576 children, adolescents and young adults with recurrent/refractory solid tumors from the MOSCATO-01 and MAPPYACTS trials, using normal and tumor whole exome and RNA sequencing data and benchmarked algorithms. There was no evidence for narrowed HLA allelic diversity but discordant homozygosity and allele frequencies across tumor types and subtypes, such as in embryonal and alveolar rhabdomyosarcoma, neuroblastoma and 11q subtypes, and high-grade glioma, and several alleles may represent protective or susceptibility factors to specific pediatric solid cancers.

Oncological and endocrinological outcomes for children and adolescents with testicular and ovarian sex cord-stromal tumors. Results of the TGM13 National Registry.

Rationale: Sex cord-stromal tumors (SCST) are hormonally active and rare. The aim was to describe their endocrinological presentation and outcomes.

Method: Patients (< 19 years) registered in the TGM13 registry between 2014 and 2021 for SCST were selected.

Treatment adherence in retinoblastoma: A retro-prospective cohort study in Ivory Coast and the Democratic Republic of Congo.

Background: In high-income countries, retinoblastoma is curable in more than 95% of cases, whereas in low-income countries, mortality remains high, especially when the diagnosis is made late or the treatment is discontinued.

Aims: To determine the factors associated with adherence to the treatment of retinoblastoma in the Ivory Coast and the Democratic Republic of Congo (DRC).

Methods And Results: A retro-prospective cohort study was carried out.

Fusion-negative rhabdomyosarcoma 3D organoids to predict effective drug combinations: A proof-of-concept on cell death inducers.

Rhabdomyosarcoma (RMS) is the main form of pediatric soft-tissue sarcoma. Its cure rate has not notably improved in the last 20 years following relapse, and the lack of reliable preclinical models has hampered the design of new therapies. This is particularly true for highly heterogeneous fusion-negative RMS (FNRMS).

Phase I/II Study of the WEE1 Inhibitor Adavosertib (AZD1775) in Combination with Carboplatin in Children with Advanced Malignancies: Arm C of the AcSé-ESMART Trial.

Purpose: AcSé-ESMART Arm C aimed to define the recommended dose and activity of the WEE1 inhibitor adavosertib in combination with carboplatin in children and young adults with molecularly enriched recurrent/refractory malignancies.

Patients And Methods: Adavosertib was administered orally, twice every day on Days 1 to 3 and carboplatin intravenously on Day 1 of a 21-day cycle, starting at 100 mg/m2/dose and AUC 5, respectively. Patients were enriched for molecular alterations in cell cycle and/or homologous recombination (HR).

Treatment at Relapse for Synovial Sarcoma of Children, Adolescents and Young Adults: From the State of Art to Future Clinical Perspectives.

While the overall prognosis is generally quite satisfactory in children, adolescents and young adults with localised synovial sarcoma at first diagnosis, the outcome remains poor for patients after relapse. Conversely to the front-line standardised treatment options, patients with relapse generally have an individualised approach and to date, there is still a lack of consensus regarding standard treatment approaches. Studies on relapsed synovial sarcoma were able to identify some prognostic variables that influence post-relapse survival, in order to plan risk-adapted salvage protocols.

Inflammatory Myofibroblastic Tumor With Gene Fusions in Children and Young Adolescents.

Purpose: Inflammatory myofibroblastic tumors (IMTs) are often driven by anaplastic lymphoma kinase fusions and less frequently by alternative fusions such as . We describe the clinical characteristics, treatment approach, and outcome for a series of young patients with IMTs and alterations.

Methods: This was a retrospective, international, multicenter study analyzing young patients (younger than 21 years) with -altered IMTs treated in 10 European referral centers between 2014 and 2022.

Indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcoma: A study of the European paediatric Soft Tissue Sarcoma Study Group.

Background: The aim of this study was to assess the clinical impact of indeterminate pulmonary nodules (no more than four pulmonary nodules of less than 5 mm or one nodule measuring between 5 and less than 10 mm by computed tomography [CT]) in children and adolescents with adult-type non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) at diagnosis.

Methods: Patients with NRSTS treated in 11 centers as part of the European paediatric Soft Tissue Sarcoma Study Group (EpSSG) were retrospectively assessed. Local radiologists, blinded to clinical information except for patients' age and tumor histotype, reviewed the chest CT at diagnosis and filled out a case report form.