Confirmatory Adaptive Designs for Clinical Trials With Multiple Time-to-Event Outcomes in Multi-state Markov Models.

The analysis of multiple time-to-event outcomes in a randomized controlled clinical trial can be accomplished with existing methods. However, depending on the characteristics of the disease under investigation and the circumstances in which the study is planned, it may be of interest to conduct interim analyses and adapt the study design if necessary. Due to the expected dependency of the endpoints, the full available information on the involved endpoints may not be used for this purpose.

[Nursing and medical delegable measures for children and adolescents with cancer as outpatient outreach care - The pilot project KIK HomeCare].

Background: In the period from 2019 to 2022, pediatric hemato-oncological patients were cared for in a pilot project in North Rhine-Westphalia (NRW). The project delivered care at the homes of the patients as opposed to care at the clinics and included both general nursing as well as specific treatments that were delegated from physicians. Patients were admitted to this form of care upon referral by a physician.

A subset of image-defined risk factors predict completeness of resection in children with high-risk neuroblastoma: An international multicenter study.

Background: Image-defined risk factors (IDRFs) were promulgated for predicting the feasibility and safety of complete primary tumor resection in children with neuroblastoma (NB). There is limited understanding of the impact of individual IDRFs on resectability of the primary tumor or patient outcomes. A multicenter database of patients with high-risk NB was interrogated to answer this question.

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.

Upward Lightning at Wind Turbines: Risk Assessment From Larger-Scale Meteorology.

Upward lightning (UL) has become a major threat to the growing number of wind turbines producing renewable electricity. It can be much more destructive than downward lightning due to the large charge transfer involved in the discharge process. Ground-truth lightning current measurements indicate that less than 50% of UL could be detected by lightning location systems (LLS).

Upward Lightning at the Gaisberg Tower: The Larger-Scale Meteorological Influence on the Triggering Mode and Flash Type.

Upward lightning is rarer than downward lightning and requires tall (100+ m) structures to initiate. It may be either self-initiated or triggered by other lightning discharges. While conventional lightning location systems (LLSs) detect most of the upward lightning flashes superimposed by pulses or return strokes, they miss a specific flash type that consists only of a continuous current.

[Hospital-based Home Care for Children with Cancer from the Parents̓ Point of View - A Qualitative Exploration of Family Members].

Background: About 2,200 children and adolescents in Germany per year are diagnosed with oncological diseases. Through now, there are almost no offers for home care services for these patients. There is a pilot program offering hospital-based home care for children and adolescents with cancer in Germany.

Amplification of annual and diurnal cycles of alpine lightning.

The response of lightning to a changing climate is not fully understood. Historic trends of proxies known for fostering convective environments suggest an increase of lightning over large parts of Europe. Since lightning results from the interaction of processes on many scales, as many of these processes as possible must be considered for a comprehensive answer.

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.

Image-defined risk factors in localized thoracic neuroblastoma and ganglioneuroma.

Background: The pretreatment International Neuroblastoma Risk Group Staging System (INRGSS) discriminates localized tumors L1/L2 depending on the absence/presence of image-defined risk factors (IDRFs) at diagnosis. Referring to this new staging system, we assessed initial imaging of localized thoracic neuroblastoma (NB) and ganglioneuroma (GN) and the extent of initial tumor resection.

Methods: Patients with localized thoracic NB/GN from the German clinical trials NB97 and NB2004 were included.

The Diagnosis and Treatment of Osteosarcoma and Ewing's Sarcoma in Children and Adolescents.

Background: Osteosarcoma and Ewing's sarcoma in children and adolescents require age-specific interdisciplinary diagnosis and treatment to achieve optimal therapeutic outcomes.

Methods: The diagnosis and treatment of malignant bone tumors in childhood and adolescence are presented in the light of publications retrieved by a selective search, pertinent guidelines, and the authors' extensive experience in an interdisciplinary cancer center.

Results: Bone sarcomas make up approximately 5% of all malignancies in children and adolescents; the most common types are Ewing's sarcoma and osteosarcoma.

Differentiated Thyroid Cancer in Adolescents: Single Center Experience and Considerations for Surgical Management and Radioiodine Treatment.

Objective: Differentiated thyroid cancer (DTC) in adolescents rare but with a favorable outcome, despite higher rates of cervical lymph node and pulmonary metastasis compared to adults. The aim of this study was to critically evaluate treatment of adolescents with DTC at a single center.

Methods: Patients receiving postoperative radioiodine treatment (RAIT) for DTC between 2005 and 2020 at our institution were screened to identify adolescents according to the World Health Organization definition (10-19 years of age).

Independent Validation of a Deep Learning nnU-Net Tool for Neuroblastoma Detection and Segmentation in MR Images.

Objectives: To externally validate and assess the accuracy of a previously trained fully automatic nnU-Net CNN algorithm to identify and segment primary neuroblastoma tumors in MR images in a large children cohort.

Methods: An international multicenter, multivendor imaging repository of patients with neuroblastic tumors was used to validate the performance of a trained Machine Learning (ML) tool to identify and delineate primary neuroblastoma tumors. The dataset was heterogeneous and completely independent from the one used to train and tune the model, consisting of 300 children with neuroblastic tumors having 535 MR T2-weighted sequences (486 sequences at diagnosis and 49 after finalization of the first phase of chemotherapy).

Anti-GD2 Antibody Dinutuximab Beta and Low-Dose Interleukin 2 After Haploidentical Stem-Cell Transplantation in Patients With Relapsed Neuroblastoma: A Multicenter, Phase I/II Trial.

Purpose: Patients with relapsed high-risk neuroblastoma (rHR-NB) have a poor prognosis. We hypothesized that graft-versus-neuroblastoma effects could be elicited by transplantation of haploidentical stem cells (haplo-SCT) exploiting cytotoxic functions of natural killer cells and their activation by the anti-GD2 antibody dinutuximab beta (DB). This phase I/II trial assessed safety, feasibility, and outcomes of immunotherapy with DB plus subcutaneous interleukin-2 (scIL2) after haplo-SCT in patients with rHR-NB.

Genomic ALK alterations in primary and relapsed neuroblastoma.

Background: Genomic alterations of the anaplastic lymphoma kinase gene (ALK) occur recurrently in neuroblastoma, a pediatric malignancy of the sympathetic nervous system. However, information on their development over time has remained sparse.

Methods: ALK alterations were assessed in neuroblastomas at diagnosis and/or relapse from a total of 943 patients, covering all stages of disease.

Overcoming inter-observer planning variability in target volume contouring and dose planning for high-risk neuroblastoma - a European multicenter effort of the SIOPEN radiotherapy committee.

Background And Purpose: To establish an international quality standard for contouring and planning for high-risk neuroblastoma within the prospective High-Risk Neuroblastoma Study 2 of SIOP-Europe-Neuroblastoma (SIOPEN HR-NBL2), which includes a randomized question on dose escalation for residual disease.

Materials And Methods: Data on four patients with high-risk neuroblastoma were selected and distributed to the radiotherapy committee of the HR-NBL2 study for independent contouring and planning. Differences in contouring were analyzed using apparent and kappa-corrected agreement.

Epidemiology and Characteristics of Gastric Carcinoma in Childhood-An Analysis of Data from Population-Based and Clinical Cancer Registries.

(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood.

Efficacy and Feasibility of Proton Beam Therapy in Relapsed High-Risk Neuroblastoma-Experiences from the Prospective KiProReg Registry.

Background: Despite an intensive multimodal treatment approach, approximately 50% of high-risk (HR) neuroblastoma (NB) patients experience progression. Despite the advances in targeted therapy, high-dose chemotherapy, and other systemic treatment options, radiation therapy (RT) to sites of relapsed disease can be an option to reduce tumor burden and improve chance for disease control.

Methods: Patients who received salvage irradiation with proton beam therapy (PBT) for local or metastatic relapse of HR NB within the prospective registry trials KiProReg and ProReg were eligible for this retrospective analysis.

Presenting features of neuroblastoma with spinal canal invasion. A prospective study of the International Society of Pediatric Oncology Europe - Neuroblastoma (SIOPEN).

Introduction: Between 5 and 15% of children with neuroblastoma (NB) present with or develop spinal canal invasion (SCI). The majority of these children have symptoms of epidural compression of spinal cord and/or spinal nerves. Treatment of NB-SCI is considered an emergency but its modalities are not yet well-established.

Reliable assessment of telomere maintenance mechanisms in neuroblastoma.

Background: Telomere maintenance mechanisms (TMM) are a hallmark of high-risk neuroblastoma, and are conferred by activation of telomerase or alternative lengthening of telomeres (ALT). However, detection of TMM is not yet part of the clinical routine, and consensus on TMM detection, especially on ALT assessment, remains to be achieved.

Methods: Whole genome sequencing (WGS) data of 68 primary neuroblastoma samples were analyzed.

Adrenocortical Tumors and Pheochromocytoma/Paraganglioma Initially Mistaken as Neuroblastoma-Experiences From the GPOH-MET Registry.

In children and adolescents, neuroblastoma (NBL), pheochromocytoma (PCC), and adrenocortical tumors (ACT) can arise from the adrenal gland. It may be difficult to distinguish between these three entities including associated extra-adrenal tumors (paraganglioma, PGL). Precise discrimination, however, is of crucial importance for management.

Infants and Newborns with Atypical Teratoid Rhabdoid Tumors (ATRT) and Extracranial Malignant Rhabdoid Tumors (eMRT) in the EU-RHAB Registry: A Unique and Challenging Population.

Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment.