Progressive chromatin rewiring by ETO2::GLIS2 revealed in a human iPSC model of pediatric leukemia initiation.

Pediatric acute myeloid leukemia frequently harbor fusion oncogenes associated with poor prognosis, including KMT2A, NUP98 and GLIS2 rearrangements. While murine models have demonstrated their leukemogenic activities, the steps from a normal human cell to leukemic blasts remain unclear. Here, we precisely reproduced the inversion of chromosome 16 resulting in ETO2::GLIS2 fusion in human induced pluripotent stem cells (iPSC).

Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial.

Importance: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

Objective: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

Design, Setting, And Participants: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America.

The landscape of Functional Outcome Measures Used in Patients with Bone Sarcoma of the Lower Extremity or Pelvis: A Systematic Review.

This systematic review provides a structured overview of the measurement instruments of functional outcome used in lower extremity and pelvic bone sarcoma patients. We identified 42 unique instruments covering 18 distinct functional outcome constructs with most studies measuring constructs within the activity domain of the International Classification of Functioning, disability, and health. The MusculoSkeletal Tumor Society 1993 and 1987 score, Toronto Extremity Salvage Score, and range of motion instruments were the measurement instruments most commonly used.

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.

A Review of GO-AJA's Impact on Adolescents and Young Adults with Cancer in France: A Decade of Progress and Challenges.

The "Groupe Onco-hématologie Adolescents Jeunes Adultes" (GO-AJA) born in 2012 is a French collaborative group. It focuses on heterogeneity and unmet needs for AYA with cancer. This article highlights GO-AJA's achievements and future prospects, emphasizing its role in structuring a professional national network, improving AYAs' comprehensive care and strengthening the roles of coordinating nurses.

An assessment of the attitudes, knowledge, and education regarding the health care needs of LGBTQ patients with cancer: results of an ESMO/SIOPE global survey.

Background: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals with cancer have specific and unique health issues and needs. Reports persist of inequalities in the care provided for these patients, making it important to assess the attitudes and knowledge of LGBTQ needs among those who provide care.

Materials And Methods: The European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOP Europe) Adolescents and Young Adults Working Group designed this survey comprising 67 questions covering demographics, knowledge, and education of LGBTQ health needs, and attitudes regarding LGBTQ patients with cancer.

A Novel Luciferase-Based Reporter Gene Technology for Simultaneous Optical and Radionuclide Imaging of Cells.

Multimodality reporter gene imaging combines the sensitivity, resolution and translational potential of two or more signals. The approach has not been widely adopted by the animal imaging community, mainly because its utility in this area is unproven. We developed a new complementation-based reporter gene system where the large component of split NanoLuc luciferase (LgBiT) presented on the surface of cells (TM-LgBiT) interacts with a radiotracer consisting of the high-affinity complementary HiBiT peptide labeled with a radionuclide.

Crystallization and the liquid-liquid critical point in nonbonded modified-WAC models.

For decades, it has been known that Liquid-Liquid Critical Points (LLCPs) can exist in one-component liquids, yet a comprehensive understanding of the conditions under which they arise remains elusive. To better comprehend the possible interplay between the LLCP and the crystalline phase, we conduct molecular dynamics simulations using the nonbonded family of modified-WAC (mWAC) models, which are known to exhibit a LLCP for certain parameter values. By comparing different versions of the mWAC model-those featuring a LLCP and those lacking one-we identify several key differences between the models relating to crystallization.

Impact of age on safety of Busulfan-Melphalan followed by autologous hematopoietic stem-cell transplantation versus standard chemotherapy in the patients of the EURO-E.W.I.N.G. 99 and Ewing 2008 clinical trials.

Introduction: Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.

CellsFromSpace: a fast, accurate, and reference-free tool to deconvolve and annotate spatially distributed omics data.

Motivation: Spatial transcriptomics enables the analysis of cell crosstalk in healthy and diseased organs by capturing the transcriptomic profiles of millions of cells within their spatial contexts. However, spatial transcriptomics approaches also raise new computational challenges for the multidimensional data analysis associated with spatial coordinates.

Results: In this context, we introduce a novel analytical framework called CellsFromSpace based on independent component analysis (ICA), which allows users to analyze various commercially available technologies without relying on a single-cell reference dataset.

Attention Deficit Hyperactivity Disorder: A Risk Factor for Premature Discontinuation of Inpatient Opioid Withdrawal Treatment.

: Substance use disorders present a tremendous challenge within contemporary healthcare systems. Specifically, in the domain of opioid use disorders (OUDs), several foundational elements are crucial for the efficacious management of afflicted individuals. Regrettably, the premature discontinuation of inpatient opioid withdrawal treatment is a prevalent phenomenon.

Prognostic value of hemogram parameters in osteosarcoma: The French OS2006 experience.

Background: Previous studies have shown that neutrophil-to-lymphocyte (NLR) ratio at diagnosis and early lymphocytes recovery on doxorubicin-based chemotherapy, may impact the outcome in patients with osteosarcoma (OST). This study aimed to evaluate the prognostic value of hemogram parameters in patients with OST treated with high-dose methotrexate and etoposide/ifosfamide (M-EI) chemotherapy.

Materials And Methods: We retrospectively analyzed the prognostic value of various hemogram parameters at diagnosis and during therapy in a large consecutive cohort of patients with OST included in the French OS2006 trial and treated with M-EI chemotherapy.

From biology to personalized medicine: Recent knowledge in osteosarcoma.

High-grade osteosarcoma is the most common paediatric bone cancer. More than one third of patients relapse and die of osteosarcoma using current chemotherapeutic and surgical strategies. To improve outcomes in osteosarcoma, two crucial challenges need to be tackled: 1-the identification of hard-to-treat disease, ideally from diagnosis; 2- choosing the best combined or novel therapies to eradicate tumor cells which are resistant to current therapies leading to disease dissemination and metastasize as well as their favorable microenvironment.

ctDNA quantification improves estimation of outcomes in patients with high-grade osteosarcoma: a translational study from the OS2006 trial.

Background: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification.

Patients And Methods: Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection.

Regorafenib in patients with advanced Ewing sarcoma: results of a non-comparative, randomised, double-blind, placebo-controlled, multicentre Phase II study.

Background: The REGOBONE multi-cohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the Ewing sarcoma (ES) cohort.

Methods: Patients with relapsed ES progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progression.

A systematic review of recent phase-II trials in refractory or recurrent osteosarcoma: Can we inform future trial design?

Background/objective: To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis.

Methods: A systematic review of trials registered on trial registries between 01/01/2017-14/02/2022. Comparison of 98 trials identified between 2003 and 2016.

DICER1-mutated rhabdomyosarcoma of the ovary with teratoid features.

DICER1-mutated rhabdomyosarcoma is a rare, emerging entity with a predilection for the gynecologic and genitourinary tracts. We report here a case of DICER1-mutated rhabdomyosarcoma of the ovary in a 14 years old girl which displayed interspersed mature teratoid glands, neuroectodermal rosettes and immature blastematous-like tubes. Morphologically the sarcomatous component predominated, corresponding to a high grade spindle cell rhabdomyosarcoma with botryoid features.

Longitudinal characterization of primary osteosarcoma and derived subcutaneous and orthotopic relapsed patient-derived xenograft models.

Osteosarcoma is a rare bone cancer in adolescents and young adults with a dismal prognosis because of metastatic disease and chemoresistance. Despite multiple clinical trials, no improvement in outcome has occurred in decades. There is an urgent need to better understand resistant and metastatic disease and to generate models from relapsed tumors.

Impact of age on survival according to molecular tumor findings in children and adolescents with soft-tissue and bone sarcoma: The BIOSCA project.

Background: Adolescents (15-19 years) with sarcoma are known to have significantly worse survival than children (0-14 years). One possible reason may be that the adolescent sarcomas exhibit specific biological characteristics resulting in differences in clinical presentation and treatment resistance behaviors. The BIOSCA project aims to further explore these age-related differences in survival accounting for molecular tumor characteristic in children and adolescents with sarcoma.

Isotretinoin-Induced Distal Ileitis Mimicking Crohn's Disease.

Terminal ileitis is a common condition defined as inflammation of the terminal portion of the ileum, which is typically associated with inflammatory bowel disease (IBD), classically Crohn's disease (CD). However, it can have other etiologies, including drug-induced ones. Isotretinoin is an effective and commonly used treatment for acne vulgaris, presenting multiple adverse effects.