Neuroblastoma in Infants: Long-Term Survival From INES Protocols A SIOPEN Study.

Objectives: Neuroblastoma is the most common extracranial solid tumor in infants, with a possibility of spontaneous regression even in disseminated disease. Despite an overall good prognosis, relapse can worsen the outcome for some patients. A long-term analysis is crucial to identify subgroups of patients with poorer prognosis, assessing the risks of late relapse, progression or long-term toxicity associated with multimodal treatment in very young children.

Sensitive detection of minimal residual disease and immunotherapy targets by multi-modal bone marrow analysis in high-risk neuroblastoma - a multi-center study.

Background: Bone marrow dissemination of tumor cells, common in various cancers, including neuroblastoma, is associated with poor outcome, necessitating sensitive detection methods for bone marrow minimal residual disease (MRD) and offer detection of biomarkers for therapy stratification. Current standard-of-care diagnostics, involving cytomorphological and histological assessment of bone marrow aspirates and trephine biopsies, lack sensitivity, leading to undetected MRD in many patients, and do not allow molecular biomarker assessment.

Methods: This study evaluates advanced multi-modal high-sensitivity MRD detection techniques in 509 bone marrow specimens from 108 high-risk neuroblastoma patients across two centers.

Fcγ Receptor Polymorphism in Patients with Relapsed/Refractory High-Risk Neuroblastoma Correlates with Outcomes in the SIOPEN Dinutuximab Beta Long-Term Infusion Trial.

Purpose: To identify a tolerable dinutuximab beta long-term infusion (LTI) schedule with immunomodulatory activity for relapsed/refractory high-risk neuroblastoma (HRNBL).

Patients And Methods: In this phase I/II trial, dinutuximab beta LTI (five 35-day cycles) with subcutaneous interleukin-2 (IL-2) was evaluated in HRNBL cohorts (1× exploratory and 2× confirmatory). The composite primary endpoint was >80% patients free of intravenous morphine by day 5/cycle 1 plus ≥100 natural killer (NK) cells/μL and ≥1 μg/mL dinutuximab beta concentration by day 15/cycle 1.

Risk stratification in neuroblastoma patients through machine learning in the multicenter PRIMAGE cohort.

Introduction: Neuroblastoma, the most prevalent solid cancer in children, presents significant biological and clinical heterogeneity. This inherent heterogeneity underscores the need for more precise prognostic markers at the time of diagnosis to enhance patient stratification, allowing for more personalized treatment strategies. In response, this investigation developed a machine learning model using clinical, molecular, and magnetic resonance (MR) radiomics features at diagnosis to predict patient's overall survival (OS) and improve their risk stratification.

Do national cancer control plans address care and research for children, adolescents, and young adults? A review of status, priorities, and recommendations across 41 European countries.

Paediatric cancers, although rare, are the leading cause of disease-related mortality in European children above one year. A key pillar of the European Health Union, Europe's Beating Cancer Plan (EBCP) puts a spotlight on childhood cancer. National Cancer Control Plans (NCCPs) have a key role but did not address childhood cancers sufficiently previously.

Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study.

Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these.

Primary Mediastinal Ewing's Sarcoma: Post Hoc Analysis from Two International Multicenter Prospective Randomized Trials.

Objective: Ewing sarcoma (EWS) of the mediastinum is extremely rare, with only a few cases reported in the literature. We aimed to gain a better understanding of primary mediastinal EWS, describing patients treated within two international, multicenter, prospective, randomized EWS trials.

Methods: Data from patients with primary mediastinal EWS were retrieved from the database of the EURO-E.

Prognostic factors in patients with localized and metastatic alveolar rhabdomyosarcoma. A report from two studies and two registries of the Cooperative Weichteilsarkom Studiengruppe CWS.

Background: The histologic classification of rhabdomyosarcoma (RMS) as alveolar (aRMS) or embryonal (eRMS) is of prognostic importance, with the aRMS being associated with a worse outcome. Specific gene fusions (PAX3/7::FOXO1) found in the majority of aRMS have been recognized as markers associated with poor prognosis and are included in current risk stratification instead of histologic subtypes in localized disease. In metastatic disease, the independent prognostic significance of fusion status has not been definitively established.

Maintenance therapy with trofosfamide, idarubicin and etoposide in patients with rhabdomyosarcoma and other high-risk soft tissue sarcomas (CWS-2007-HR): a multicentre, open-label, randomised controlled phase 3 trial.

Background: Rhabdomyosarcoma and other soft tissue sarcomas (STS) with high-risk features are still associated with an unsatisfactory outcome. We evaluated the efficacy of oral maintenance therapy added at the end of standard therapy in patients with high-risk rhabdomyosarcoma and STS.

Methods: CWS-2007-HR was a multicentre, open-label, randomised controlled, phase 3 trial done at 87 centers in 5 countries.

Childhood Cancer Survivorship Passport Challenges in the European Health Data Space.

Innovation in cancer therapy has increased childhood cancer survival rates. However, survivors are still at risk of developing late effects. In the digital transformation of the health sector, the Survivorship Passport (SurPass) can support long-term follow-up care plans.

Assessment of HL7 FHIR Interoperability Between EHR Systems and the Survivorship Passport v2.0 Platform to Generate Treatment Summaries for Childhood Cancer Survivors in Six Clinics: Preliminary Testing Results.

The Survivorship Passport (SurPass) for childhood cancer survivors provides a personalized treatment summary together with a care plan for long-term screening of possible late effects. HL7 FHIR connectivity of Electronic Health Record (EHR) systems with the SurPass has been proposed to reduce the burden of collecting and organizing the relevant information. We present the results of testing and validation efforts conducted across six clinics in Austria, Belgium, Germany, Italy, Lithuania, and Spain.

Use Cases Requiring Privacy-Preserving Record Linkage in Paediatric Oncology.

Large datasets in paediatric oncology are inherently rare. Therefore, it is paramount to fully exploit all available data, which are distributed over several resources, including biomaterials, images, clinical trials, and registries. With privacy-preserving record linkage (PPRL), personalised or pseudonymised datasets can be merged, without disclosing the patients' identities.

Irinotecan and temozolomide in combination with dasatinib and rapamycin versus irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma (RIST-rNB-2011): a multicentre, open-label, randomised, controlled, phase 2 trial.

Background: Neuroblastoma is the most common extracranial solid tumour in children. Relapsed or refractory neuroblastoma is associated with a poor outcome. We assessed the combination of irinotecan-temozolomide and dasatinib-rapamycin (RIST) in patients with relapsed or refractory neuroblastoma.

Reproducibility Analysis of Radiomic Features on T2-weighted MR Images after Processing and Segmentation Alterations in Neuroblastoma Tumors.

Purpose To evaluate the reproducibility of radiomics features extracted from T2-weighted MR images in patients with neuroblastoma. Materials and Methods A retrospective study included 419 patients (mean age, 29 months ± 34 [SD]; 220 male, 199 female) with neuroblastic tumors diagnosed between 2002 and 2023, within the scope of the PRedictive In-silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers (ie, PRIMAGE) project, involving 746 T2/T2*-weighted MRI sequences at diagnosis and/or after initial chemotherapy. Images underwent processing steps (denoising, inhomogeneity bias field correction, normalization, and resampling).

A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations.

Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB).

IT-Related Barriers and Facilitators to the Implementation of a New European eHealth Solution, the Digital Survivorship Passport (SurPass Version 2.0): Semistructured Digital Survey.

Background: To overcome knowledge gaps and optimize long-term follow-up (LTFU) care for childhood cancer survivors, the concept of the Survivorship Passport (SurPass) has been invented. Within the European PanCareSurPass project, the semiautomated and interoperable SurPass (version 2.0) will be optimized, implemented, and evaluated at 6 LTFU care centers representing 6 European countries and 3 distinct health system scenarios: (1) national electronic health information systems (EHISs) in Austria and Lithuania, (2) regional or local EHISs in Italy and Spain, and (3) cancer registries or hospital-based EHISs in Belgium and Germany.

Scaling up and implementing the digital Survivorship Passport tool in routine clinical care - The European multidisciplinary PanCareSurPass project.

Background: Childhood cancer survivors (CCS), of whom there are about 500,000 living in Europe, are at an increased risk of developing health problems [1-6] and require lifelong Survivorship Care. There are information and knowledge gaps among CCS and healthcare providers (HCPs) about requirements for Survivorship Care [7-9] that can be addressed by the Survivorship Passport (SurPass), a digital tool providing CCS and HCPs with a comprehensive summary of past treatment and tailored recommendations for Survivorship Care. The potential of the SurPass to improve person-centred Survivorship Care has been demonstrated previously [10,11].

Comparative transcriptomics coupled to developmental grading via transgenic zebrafish reporter strains identifies conserved features in neutrophil maturation.

Neutrophils are evolutionarily conserved innate immune cells playing pivotal roles in host defense. Zebrafish models have contributed substantially to our understanding of neutrophil functions but similarities to human neutrophil maturation have not been systematically characterized, which limits their applicability to studying human disease. Here we show, by generating and analysing transgenic zebrafish strains representing distinct neutrophil differentiation stages, a high-resolution transcriptional profile of neutrophil maturation.

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.

Barriers and facilitators to the implementation of a new European eHealth solution (SurPass v2.0): the PanCareSurPass Open Space study.

Purpose: To identify barriers and facilitators for implementing the Survivorship Passport (SurPass) v2.0 in six long-term follow-up (LTFU) care centres in Europe.

Methods: Stakeholders including childhood cancer survivors (CCSs), healthcare providers (HCPs), managers, information and technology (IT) specialists, and others, participated in six online Open Space meetings.

Radiotherapy and long-term sequelae in pediatric patients with parameningeal rhabdomyosarcoma: Results of two Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry.

Background: Parameningeal location of rhabdomyosarcoma (PM RMS) is known to be an unfavorable prognostic factor. Scarce data are available on radiotherapy (RT) concepts with regard to outcome.

Methods: Treatment and outcome of 395 children with PM RMS registered within two Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1995-2021) were evaluated.

Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial.

Purpose: The phase III, open-label, prospective, multicenter, randomized Ewing 2008R1 trial (EudraCT2008-003658-13) was conducted in 12 countries to evaluate the effect of zoledronic acid (ZOL) maintenance therapy compared with no add-on regarding event-free survival (EFS, primary endpoint) and overall survival (OS) in standard-risk Ewing sarcoma (EWS).

Patients And Methods: Eligible patients had localized EWS with either good histologic response to induction chemotherapy and/or small tumors (<200 mL). Patients received six cycles of VIDE induction and eight cycles of VAI (male) or eight cycles of VAC (female) consolidation.

Multimodal Therapy with Consolidating Haploidentical Stem Cell Transplantation and Dinutuximab Beta for Patients with High-Risk Neuroblastoma and Central Nervous System Relapse.

Despite highly intensive multimodality treatment regimens, the prognosis of patients with high-risk neuroblastoma (HRNB) and central nervous system (CNS) relapse remains poor. We retrospectively reviewed data from 13 patients with HRNB and CNS relapse who received multimodal therapy with consolidating haploidentical stem cell transplantation (haplo-SCT) followed by dinutuximab beta ± subcutaneous interleukin-2 (scIL-2). Following individual relapse treatment, patients aged 1-21 years underwent haplo-SCT with T/B-cell-depleted grafts followed by dinutuximab beta 20 mg/m/day × 5 days for 5-6 cycles.