Sensitive liquid biopsy monitoring correlates with outcome in the prospective international GPOH-DCOG high-risk neuroblastoma RT-qPCR validation study.

Background: Liquid biopsies offer less burdensome sensitive disease monitoring. Bone marrow (BM) metastases, common in various cancers including neuroblastoma, is associated with poor outcomes. In pediatric high-risk neuroblastoma most patients initially respond to treatment, but in the majority the disease recurs with only 40% long-term survivors, stressing the need for more sensitive detection of disseminated disease during therapy.

Noncompliance of pediatric cancer patients with chemotherapy: A single-center experience in a lower-middle income country.

Noncompliance with therapy is a big obstacle to successful therapy. We aimed to evaluate the prevalence and risk factors affecting the compliance of pediatric cancer patients with therapy in a tertiary care center far away from the capital in a lower-middle income country (LMIC). A retrospective cohort study of reports of all pediatric cancer patients who were diagnosed and started treatment between 2006 and 2010 at South Egypt Cancer Institute (SECI) was done.

Comparing presentations and outcomes of children with cancer: a study between a lower-middle-income country and a high-income country.

Background: Substantial progress has been achieved in managing childhood cancers in many high-income countries (HICs). In contrast, survival rates in lower-middle-income countries (LMICs) are less favorable. Here, we aimed to compare outcomes and associated factors between two large institutions; Egypt (LMIC) and Germany (HIC).

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.

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.

Confirmatory adaptive group sequential designs for single-arm phase II studies with multiple time-to-event endpoints.

Existing methods concerning the assessment of long-term survival outcomes in one-armed trials are commonly restricted to one primary endpoint. Corresponding adaptive designs suffer from limitations regarding the use of information from other endpoints in interim design changes. Here we provide adaptive group sequential one-sample tests for testing hypotheses on the multivariate survival distribution derived from multi-state models, while making provision for data-dependent design modifications based on all involved time-to-event endpoints.

Hypercalcemia is a frequent side effect of 13-cis-retinoic acid treatment in patients with high-risk neuroblastoma.

Purpose: 13-cis-Retinoic acid (13-cisRA) is used as a postconsolidation treatment in patients with high-risk neuroblastoma. Hypercalcemia is a known side effect of retinoids. Frequency, symptoms, treatment, and risk factors for hypercalcemia were analyzed.

Genetic Alterations and Resectability Predict Outcome in Patients with Neuroblastoma Assigned to High-Risk Solely by Amplification.

Background: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of oncogene amplification (MNA).

Methods: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group).

Results: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39-54%) and 56% (95%-CI 49-63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18-31%, < 0.

Neuroblastoma Screening at 1 Year of Age: The Final Results of a Controlled Trial.

Background: Neuroblastoma screening aims to reduce neuroblastoma-related mortality. A controlled trial showed no reduction in stage 4 disease incidence and preliminary mortality data. This article presents epidemiologic and clinical data 20 years after cessation of the screening program.

Clinical and molecular characterization of patients with stage 4(M) neuroblastoma aged less than 18 months without MYCN amplification.

Introduction: The survival of children with stage 4(M) neuroblastoma without MYCN amplification and below the age of 18 months is considered better than the still dismal outcome of older high-risk neuroblastoma patients. This study analyzes the impact of clinical and molecular characteristics on the long-term outcome.

Patients And Methods: Clinical presentation, survival, and recurrence patterns of patients enrolled onto trials NB90, NB97, and NB2004 were retrospectively analyzed.

The reliability of bone marrow cytology as response criterion in metastatic neuroblastoma.

Background: The quantitative assessment of neuroblastoma cell content in bone marrow aspirates for response evaluation has been introduced recently. Data on the concordance of interobserver reports are lacking so far.

Methods: Investigators of seven European countries representing national reference or large oncological centers convened in 2016.

A nomogram of clinical and biologic factors to predict survival in children newly diagnosed with high-risk neuroblastoma: An International Neuroblastoma Risk Group project.

Background: Long-term outcome remains poor for children with high-risk neuroblastoma (five-year overall survival [OS] ∼50%). Our objectives were to (a) identify prognostic biomarkers and apply them in a nomogram to identify the subgroup of ultra-high-risk patients at highest risk of disease progression/death, for whom novel frontline therapy is urgently needed; and (b) validate the nomogram in an independent cohort.

Methods: A total of 1820 high-risk patients (≥18 months old with metastatic neuroblastoma), diagnosed 1998-2015, from the International Neuroblastoma Risk Groups (INRG) Data Commons were analyzed in a retrospective cohort study.

[Quadruple negative SARS-CoV-2-PCR: still COVID-19 pneumonia!].

Medical History And Clinical Findings:  A 78-year-old man fell ill with weakness, coughing and fever 19 days after a cruise in early April 2020 and was admitted 4 days later with increasing shortness of breath.

Examination And Diagnosis:  On admission, the patient had subfebrile temperatures, exercise dyspnea, and right-basal rales. CRP was moderately elevated and oxygen saturation was slightly reduced.

The prognostic strength of serum LDH and serum ferritin in children with neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project.

Purpose: Age, MYCN status, stage, and histology have been used as neuroblastoma (NB) risk factors for decades. Serum lactate dehydrogenase (LDH) and serum ferritin are reproducible, easily obtained, and prognostic, though never used in risk stratification, except one German trial. We analyzed the prognostic strength of LDH and ferritin, overall, within high-risk NB, and by era, using the International Neuroblastoma Risk Group Data Commons.

Can we optimise doxorubicin treatment regimens for children with cancer? Pharmacokinetic simulations and a Delphi consensus procedure.

Background: Despite its cardiotoxicity doxorubicin is widely used for the treatment of paediatric malignancies. Current treatment regimens appear to be suboptimal as treatment strategies vary and do not follow a clear pharmacological rationale. Standardisation of dosing strategies in particular for infants and younger children is required but is hampered by scarcely defined exposure-response relationships.

Extended induction chemotherapy does not improve the outcome for high-risk neuroblastoma patients: results of the randomized open-label GPOH trial NB2004-HR.

Background: Long-term survival of high-risk neuroblastoma patients is still below 50% despite intensive multimodal treatment. This trial aimed to address whether the addition of two topotecan-containing chemotherapy courses compared to standard induction therapy improves event-free survival (EFS) of these patients.

Patients And Methods: An open-label, multicenter, prospective randomized controlled trial was carried out at 58 hospitals in Germany and Switzerland.

Telomerase Is a Prognostic Marker of Poor Outcome and a Therapeutic Target in Neuroblastoma.

Purpose: Telomere maintenance is a hallmark of high-risk neuroblastoma; however, the contribution of telomerase and alternative lengthening of telomeres (ALT) to clinical phenotypes has remained unclear. We aimed to determine the clinical relevance of telomerase activation versus ALT as biomarkers in pretreatment neuroblastoma and to assess the potential value of telomerase as a therapeutic target.

Materials And Methods: The genomic status of and was assessed in 457 pretreatment neuroblastomas by fluorescence in situ hybridization.

Biochemical testing for neuroblastoma using plasma free 3-O-methyldopa, 3-methoxytyramine, and normetanephrine.

Background: Neuroblastoma, the most common extracranial solid tumor of childhood, produces catecholamines that are metabolized within tumor cells. Homovanillic acid (HVA) and vanillylmandelic acid (VMA), the end products of catecholamine metabolism, have limited accuracy for testing of the tumors. This study assessed whether metabolites produced in earlier steps of catecholamine metabolism might offer improved diagnostic accuracy over urinary HVA and VMA.

A new risk score for patients after first recurrence of stage 4 neuroblastoma aged ≥18 months at first diagnosis.

Background: The prognosis of patients with recurrences from stage 4 neuroblastoma is not uniformly dismal. The evaluation of new therapies therefore needs to consider the individual risks of the treated patients. This study aims to define clinically useful risk criteria.

Correction: Long-term outcomes of the GPOH NB97 trial for children with high-risk neuroblastoma comparing high-dose chemotherapy with autologous stem cell transplantation and oral chemotherapy as consolidation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Inside or outside? A new collection of Gateway vectors allowing plant protein subcellular localization or over-expression.

Transient expression of proteins based on agro-infiltration techniques has proven very efficient and straightforward to study the intrinsic properties of proteins. The level of protein expression has been enhanced by the use of vector plasmids containing virus-derived sequences and the cloning step has been facilitated by recombination technologies. The pEAQ-HT-DEST series of vectors fulfilling these improvements are vectors of choice.

High-Density Molded Cellulose Fibers and Transparent Biocomposites Based on Oriented Holocellulose.

Ecofriendly materials based on well-preserved and nanostructured wood cellulose fibers are investigated for the purpose of load-bearing applications, where optical transmittance may be advantageous. Wood fibers are subjected to mild delignification, flow orientation, and hot-pressing to form an oriented material of low porosity. The biopolymer composition of the fibers is determined.

Are network growth and the contributions to congresses associated with publication success? A pediatric oncology model.

Background: The consistent focus of 'Advances in Neuroblastoma Research' congresses on the topic neuroblastoma sets it as a model for a circumscribed scientific community.

Methods: The contributions of authors, institutions and countries to congress abstracts and their collaborations were compared to the Hirsch index (h-index) calculated from the Web of Science publication output on the topic 'neuroblastoma'.

Results: From 1975 to 2016, 18 congresses were held.