Management of Ganglioneuroma and Ganglioneuroblastoma Intermixed: A United Kingdom Children's Cancer and Leukaemia Group (UK CCLG) Nationwide Study Report.

Background: Ganglioneuroblastoma intermixed (GNBi) and ganglioneuroma (GN) represent benign variants of peripheral neuroblastic tumours. While historically surgical resection was recommended, watchful active observation has become the accepted management for a subset of patients.

Objectives: To review clinical features, biology, natural history and management of a retrospective UK CCLG study cohort of GN and GNBi, and compare outcomes of patients treated with surgical resection or watchful active observation.

Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.

Background: Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20 years. Limited data exist on CMMRD-associated lymphomas and their outcome.

Cost-effectiveness analysis alongside the inter-B-NHL ritux 2010 trial: rituximab in children and adolescents with B cell non-Hodgkin's lymphoma.

Objectives: The randomized controlled trial Inter-B-NHL ritux 2010 showed overall survival (OS) benefit and event-free survival (EFS) benefit with the addition of rituximab to standard Lymphomes Malins B (LMB) chemotherapy in children and adolescents with high-risk, mature B cell non-Hodgkin's lymphoma. Our aim was to assess the cost-effectiveness of rituximab-chemotherapy versus chemotherapy alone in the French setting.

Methods: We used a decision-analytic semi-Markov model with four health states and 1-month cycles.

BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL.

Anaplastic large-cell lymphoma (ALCL) is a T-cell malignancy driven in many cases by the product of a chromosomal translocation, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). NPM-ALK activates a plethora of pathways that drive the hallmarks of cancer, largely signalling pathways normally associated with cytokine and/or T-cell receptor-induced signalling. However, NPM-ALK is also located in the nucleus and its functions in this cellular compartment for the most part remain to be determined.

Memory recovery in relation to default mode network impairment and neurite density during brain tumor treatment.

Objective: The aim of this study was to test brain tumor interactions with brain networks, thereby identifying protective features and risk factors for memory recovery after resection.

Methods: Seventeen patients with diffuse nonenhancing glioma (ages 22-56 years) underwent longitudinal MRI before and after surgery, and during a 12-month recovery period (47 MRI scans in total after exclusion). After each scanning session, a battery of memory tests was performed using a tablet-based screening tool, including free verbal memory, overall verbal memory, episodic memory, orientation, forward digit span, and backward digit span.

Prognostic Factors in Childhood Anaplastic Large Cell Lymphoma: Long Term Results of the International ALCL99 Trial.

With the aim of describing the long-term follow-up and to define the prognostic role of the clinical/pathological/molecular characteristics at diagnosis for childhood, adolescent and young adults affected by anaplastic large cell lymphoma (ALCL), we analyzed 420 patients aged up to 22 years homogeneously treated within the international ALCL99 trial. The 10-year progression free survival (PFS) was 70% and overall survival was 90%, rare late relapses occurred but no secondary malignancies were reported. Among clinical/pathological characteristics, only patients presenting a small cell/lymphohistiocytic (SC/LH) pattern were independently associated with risk of failure (hazard ratio = 2.

Stem Cell Transplantation and Vinblastine Monotherapy for Relapsed Pediatric Anaplastic Large Cell Lymphoma: Results of the International, Prospective ALCL-Relapse Trial.

Purpose: To analyze the efficacy of a risk-stratified treatment of children with relapsed anaplastic large cell lymphoma (ALCL). The ALCL-Relapse trial (ClinicalTrials.gov identifier: NCT00317408) stratified patients according to the time of relapse and CD3 expression to prospectively test reinduction approaches combined with consolidation by allogeneic or autologous hematopoietic stem cell transplantation (SCT) and vinblastine monotherapy.

Neuro-meningeal relapse in anaplastic large-cell lymphoma: incidence, risk factors and prognosis - a report from the European intergroup for childhood non-Hodgkin lymphoma.

Relapses involving the central nervous system (CNS) are rare in children and adolescents with ALK+ anaplastic large cell lymphoma (ALCL) treated with regimens including CNS prophylaxis. Early identification of patients at high-risk for CNS relapse would enable stratification and better adaptation of initial treatment especially in the light of the upcoming targeted therapies with limited CNS penetration. We analyzed clinical and histological data of all ALK+ALCL patients with CNS relapse registered in ALCL99-database with the aim to describe risk factors and outcome.

The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status.

Resistance to anaplastic lymphoma kinase (ALK)-targeted therapy in ALK-positive non-small cell lung cancer has been reported, with the majority of acquired resistance mechanisms relying on bypass signaling. To proactively identify resistance mechanisms in ALK-positive neuroblastoma (NB), we herein employ genome-wide CRISPR activation screens of NB cell lines treated with brigatinib or ceritinib, identifying PIM1 as a putative resistance gene, whose high expression is associated with high-risk disease and poor survival. Knockdown of PIM1 sensitizes cells of differing MYCN status to ALK inhibitors, and in patient-derived xenografts of high-risk NB harboring ALK mutations, the combination of the ALK inhibitor ceritinib and PIM1 inhibitor AZD1208 shows significantly enhanced anti-tumor efficacy relative to single agents.

ACCELERATE and European Medicine Agency Paediatric Strategy Forum for medicinal product development for mature B-cell malignancies in children.

Paediatric Strategy Forums have been created by the multistakeholder organisation, ACCELERATE, and the European Medicines Agency to facilitate dialogue between all relevant stakeholders and suggest strategies in critical areas of paediatric oncology drug development. As there are many medicines being developed for B-cell malignancies in adults but comparatively few in children with these malignancies, a Paediatric Strategy Forum was held to discuss the best approach to develop these products for children. It was concluded that as current frontline therapy is highly successful, despite associated acute toxicity, de-escalation of this or substitution of presently used drugs with new medicines can only be undertaken when there is an effective salvage regimen, which is currently not available.

Unrecognised Outbreak: Human parainfluenza virus infections in a pediatric oncology unit. A new diagnostic PCR and virus monitoring system may allow early detection of future outbreaks.

Human parainfluenza viruses (HPIVs) are significant causes of both upper and lower respiratory tract infections with type 3 (HPIV3) causing the most severe disease in the immunocompromised cohorts.  The objective of this study was to analyse the epidemiological nature of a cluster of cases of HPIV3 in a pediatric oncology unit of a major teaching hospital. In order to determine whether the activity observed represented a deviation from the norm, seasonal trends of HPIV3 in the surrounding geographical area as well as on the ward in question were analysed.

Uncommon low-grade brain tumors.

The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors includes numerous uncommon (representing ≤1% of tumors) low-grade (grades I-II) brain neoplasms with varying clinical behaviors and outcomes. Generally, gross tumor or maximal safe resection is the primary treatment. Adjuvant treatments, though their exact role is unknown, may be considered individually based on pathological subtypes and a proper assessment of risks and benefits.

Children's experiences of being diagnosed with cancer at the early stages of treatment; an interpretive phenomenological analysis.

Being given a diagnosis of cancer is a significant and highly distressing event for both children and their families, but little research has been done to explore and understand children's feelings. This study aims to understand from the child's perspective what it feels like to be told you have cancer, with the hope that increased understanding can lead to improved communication and support for children and families. The study uses qualitative methodology.

Pediatric precursor B-cell acute lymphoblastic leukemia with MYC 8q24 translocation - how to treat?

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Within ALL, precursor B-cell disease predominates and now has survival >90%. Mature B-cell, or Burkitt leukemia/lymphoma, is distinct from ALL and requires short intensive chemotherapy and with the addition of Rituximab, survival rates of >95% are achieved.

Prevention of radiotherapy-induced neurocognitive dysfunction in survivors of paediatric brain tumours: the potential role of modern imaging and radiotherapy techniques.

Neurocognitive dysfunction is the leading cause of reduced quality of life in long-term survivors of paediatric brain tumours. Radiotherapy is one of the main contributors to neurocognitive sequelae. Current approaches for prevention and reduction of neurocognitive dysfunction include avoidance of radiotherapy in young children and reduction of the radiotherapy dose and volume of brain irradiated.

Anti-ALK Antibodies in Patients with ALK-Positive Malignancies Not Expressing NPM-ALK.

Patients with Nucleophosmin (NPM)- Anaplastic Lymphoma Kinase (ALK) fusion positive Anaplastic Large Cell Lymphoma produce autoantibodies against ALK indicative of an immune response against epitopes of the chimeric fusion protein. We asked whether ALK-expression in other malignancies induces specific antibodies. Antibodies against ALK were detected in sera of one of 50 analysed ALK-expressing neuroblastoma patients, 13 of 21 ALK positive non-small cell lung carcinoma (NSCLC) patients, 13 of 22 ALK translocation-positive, but NPM-ALK-negative lymphoma patients and one of one ALK-positive rhabdomyosarcoma patient, but not in 20 healthy adults.

Antioxidant intake in paediatric oncology patients.

Background & Aims: Antioxidant intake can affect both free radical and the nutritional status of children receiving cancer treatment. The aim of this study was to investigate whether children with cancer met their antioxidant requirements.

Methods: A prospective observational study was performed at a single hospital in England from June 2008 to February 2010.

DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome.

Background: Constitutional DICER1 mutations were recently reported to cause familial pleuropulmonary blastoma (PPB).

Aim: To investigate the contribution and phenotypic spectrum of constitutional and somatic DICER1 mutations to cancer.

Methods And Results: The authors sequenced DICER1 in constitutional DNA from 823 unrelated patients with a variety of tumours and in 781 cancer cell lines.

Non-pineal supratentorial primitive neuro-ectodermal tumors (sPNET) in teenagers and young adults: Time to reconsider cisplatin based chemotherapy after cranio-spinal irradiation?

Background: Supratentorial PNET (sPNET) are rare CNS tumors of embryonal origin arising in children and adults. The treatment of sPNET for all age groups at our cancer center has been based on the management of medulloblastoma (MB), involving neurosurgical debulking followed by cranio-spinal irradiation (CSI) and systemic chemotherapy.

Methods: Medical records were reviewed to gather demographic and clinical data about all embryonal CNS tumors in children and adults from 2001 to 2007.

A rapidly advancing mediastinal mass--overcoming tracheobronchial obstruction.

We report the case of a 7-year-old boy who presented with rapidly advancing airway obstruction secondary to mediastinal T-cell non-Hodgkins lymphoma. His brisk deterioration required transfer to the pediatric intensive care unit and intubation of the trachea. Unforeseen unilateral bronchial involvement led to gas trapping and critical pulmonary hyperinflation.

Localized non-Hodgkin's lymphoma with B-cell histology: cure without cyclophosphamide? A report of the United Kingdom Children's Cancer Study Group on studies NHL 8501 and NHL 9001 (1985-1996).

We have examined the outcome for children treated on two consecutive United Kingdom Children's Cancer Study Group studies of localized B-cell non-Hodgkin's lymphoma (NHL). The first study (NHL 8501; 1985-1989) included cyclophosphamide in the treatment regimen at a total cumulative dose of 4 g/m2 whereas the regimen in the succeeding study (NHL 9001; 1990-1996) did not include cyclophosphamide. Ninety children with confirmed B-cell NHL were treated in the two studies (NHL 8501, n = 33 and NHL9001, n = 57).