Desmoid-Type Fibromatosis Tumors in Children After First-Line Failure: Clinical Aspects and Approaches for Subsequent Therapeutic Lines.

Background: Desmoid-type fibromatosis (DTF) is a rare intermediate malignancy with high local aggressiveness and recurrence in children after first-line methotrexate-vinblastine (Mtx-Vbl) regimen. The objective is to describe refractory DTF to standardize second-line therapy.

Methods: This national multicenter retrospective study included patients (<25 years) with progressive/refractory DTF after Mtx-Vbl first-line.

Maintenance therapy for pediatric sarcoma: full throttle ahead?

Purpose Of Review: Maintenance therapy (MT), particularly antiangiogenic approaches such metronomic chemotherapy (MC), correspond to the continuous administration of low-dose anticancer agents in a context of minimal residual disease. While widely used in pediatric acute lymphoblastic leukemia for decades, MT has recently shown promise in solid tumors. Additionally, antivascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) are increasingly explored in pediatric sarcomas.

[Recurrent or refractory Osteosarcoma and Ewing sarcoma-French guidelines from the FSG/NETSARC and GroupOs groups].

Osteosarcoma (OS) and Ewing Sarcoma (ES) are the two most frequent malignant bone tumors in children, adolescents and young adults. In case of disease recurrence, both are characterized by an aggressive behaviour and a relatively poor overall survival rate, with approximately a third of patients having a long-term disease-free survival. In case of recurrent or refractory (R/R) disease, the therapeutic strategy should be discussed in multidisciplinary staff meetings with expertise in bone sarcoma management.

Chondrosarcomas: Multidisciplinary review and practical recommendations, on behalf of GroupOs.

Chondrosarcomas are rare tumors occurring in middle age and older adults, defined by malignant cartilaginous matrix-producing neoplasms. Chondrosarcomas represent a heterogeneous group of tumors with diverse characteristics, management strategies and prognosis. The aim is to establish recommendations to support optimal practice for the diagnosis and treatment of chondrosarcomas within the framework of an expert group at the request of GroupOs and the French Sarcoma Group.

[Radiotherapy in Ewing sarcomas].

Ewing sarcomas are the 2nd cause of malignant bone tumors in children and young adults. After induction chemotherapy, local treatment is essential and most often includes surgery of the primary tumor. Radiotherapy may be necessary as an exclusive local procedure when surgery is not possible, or in an adjuvant situation when the surgical procedure must be completed (incomplete resection or poor histological response in particular).

A phase 1 dose-escalation study of LY3295668 erbumine as monotherapy and in combination with topotecan and cyclophosphamide in children with relapsed/refractory neuroblastoma.

Background: This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma.

Methods: Patients aged 2-21 years who had relapsed/refractory neuroblastoma were enrolled. LY3295668 erbumine was evaluated at two dose levels (12 and 15 mg/m) and administered orally twice daily continuously as monotherapy and in combination with intravenous topotecan and cyclophosphamide in 28-day cycles.

Bone sarcomas and cancer predisposition syndromes.

Bone sarcomas, constituting less than 1% of malignant neoplasms across all age groups, are rare tumours possibly associated with genetic susceptibility syndromes. This review aims to provide recommendations for the detection of cancer predisposition syndromes associated with bone sarcomas and managing affected patients. Recommendations were formulated by a multidisciplinary working and reviewing group from GroupOs and SFCE oncogenetic's group, including geneticists, oncologists, and radiologists.

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.

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.

[Of muscle and bone: Diagnostic challenge of an uncommonly located rhabdomyosarcoma].

Rhabdomyosarcomas form a heterogeneous group of malignant soft tissue tumors characterized by immature striated muscle differentiation. Epithelioid and spindle cell rhabdomyosarcoma is a recently described entity, mainly localized intraosseously and predominantly found in young patients. Its late diagnosis and high aggressiveness confer a grim prognosis to this tumor, highlighting the importance of early recognition and appropriate management.

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.

Alveolar soft part sarcomas in young patients: The French national NETSARC+ network experience.

Background And Aims: Alveolar soft part sarcoma (ASPS) is an ultra-rare chemo-resistant sarcoma in children, occurring preferentially in young adults. We aimed to describe and compare its clinical presentation and behaviour in children and young adults to determine whether the same therapeutic strategy should be addressed for both populations.

Methods: National retrospective multicentre study of children (0-18 years) vs.

Sequential Analysis of cfDNA Reveals Clonal Evolution in Patients with Neuroblastoma Receiving ALK-Targeted Therapy.

Purpose: The study of cell-free DNA (cfDNA) enables sequential analysis of tumor cell-specific genetic alterations in patients with neuroblastoma.

Experimental Design: Eighteen patients with relapsing neuroblastoma having received lorlatinib, a third-generation ALK inhibitor, were identified (SACHA national registry and/or in the institution). cfDNA was analyzed at relapse for nine patients and sequentially for five patients (blood/bone marrow plasma) by performing whole-genome sequencing library construction followed by ALK-targeted ddPCR of the hotspot mutations [F1174L, R1275Q, and I1170N; variant allele fraction (VAF) detection limit 0.

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.

Added value of whole-exome and RNA sequencing in advanced and refractory cancer patients with no molecular-based treatment recommendation based on a 90-gene panel.

Introduction: The objective was to determine the added value of comprehensive molecular profile by whole-exome and RNA sequencing (WES/RNA-Seq) in advanced and refractory cancer patients who had no molecular-based treatment recommendation (MBTR) based on a more limited targeted gene panel (TGP) plus array-based comparative genomic hybridization (aCGH).

Materials And Methods: In this retrospective analysis, we selected 50 patients previously included in the PROFILER trial (NCT01774409) for which no MBT could be recommended based on a targeted 90-gene panel and aCGH. For each patient, the frozen tumor sample mirroring the FFPE sample used for TGP/aCGH analysis were processed for WES and RNA-Seq.

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.

Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial.

Purpose: Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B).

Materials And Methods: Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B.

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).

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.