Bevacizumab-containing treatment for relapsed or refractory Wilms tumor.

INTRODUCTION: Angiogenesis is critical for tumor growth and metastasis. Bevacizumab is an antiangiogenic drug used to treat various adult and childhood solid tumors. Its potential efficacy in Wilms tumor (WT) with poor prognosis is not established. AREAS COVERED: The response to bevacizumab-containing regimens in relapsed or refractory WT was reviewed in available literature. Searches were conducted using PubMed, Scopus, and ClinicalTrials.gov databases. Eight papers were identified, published between 2007 and 2020, including six treatment regimens, predominantly vincristine, irinotecan, and bevacizumab (VIB) ± temozolomide (VITB). Among 16 evaluable patients, there were two complete responses, seven partial responses, five patients achieved stable disease (SD), and two patients had progressive disease. Objective responses (OR) were observed in 56% of all cases. OR or SD was observed in 89% (8/9) patients who received VIB/VITB. Bevacizumab was generally well tolerated. Related toxicities included hypertension, proteinuria, and delayed wound healing. EXPERT OPINION: This review suggests potential effectiveness and good tolerability of bevacizumab in the setting of relapsed/refractory WT when used in combination with other drugs. Such combination therapies may serve as a bridging treatment option to other interventions and more personalized treatment options in the future; however, focused trials are needed to obtain additional evidence.

A Molecular Update and Review of Current Trials in Paediatric Low-Grade Gliomas.

BACKGROUND: Paediatric low-grade gliomas (pLGGs) are the most common primary brain tumour in children. Though considered benign, slow-growing lesions with excellent overall survival, their long-term morbidity can be significant, both from the tumour and secondary to treatment. Vast progress has been made in recent years to better understand the molecular biology underlying pLGGs, with promising implications for new targeted therapeutic strategies. SUMMARY: A multi-layered classification system of biologic subgroups, integrating distinct molecular and histological features has evolved to further our clinical understanding of these heterogeneous tumours. Though surgery and chemotherapy are the mainstays of treatment for pLGGs, many tumours are not amenable to surgery and/or progress after conventional chemotherapy. Therapies targeting common genetic aberrations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway have been the focus of many recent studies and offer new therapeutic possibilities. Here, we summarise the updated molecular classification of pLGGs and provide a review of current treatment strategies, novel agents, and open trials. KEY MESSAGES: (1) There is a need for treatment strategies in pLGG that provide lasting tumour control and better quality of survival through minimising toxicity and protecting against neurological, cognitive, and endocrine deficits. (2) The latest World Health Organisation classification of pLGG incorporates a growing wealth of molecular genetic information by grouping tumours into more biologically and molecularly defined entities that may enable better risk stratification of patients, and consideration for targeted therapies in the future. (3) Novel agents and molecular-targeted therapies offer new therapeutic possibilities in pLGG and have been the subject of many recent and currently open clinical studies. (4) Adequate molecular characterisation of pLGG is therefore imperative in today's clinical trials, and treatment responses should not only be evaluated radiologically but also using neurological, visual, and quality of life outcomes to truly understand treatment benefits.

Clinical characteristics of children presenting with a suspicion or allegation of historic sexual abuse.

INTRODUCTION: Police-recorded sexual offences against children and young people (CYP) increased 85% in the UK between 2010/2011 and 2014/2015. Many children delay disclosure, but little data are available regarding characteristics of CYP presenting with historic child sexual abuse (CSA). AIM: To identify the clinical and CSA-related characteristics of CYP presenting with a suspicion or allegation of historic CSA. METHOD: Data were collected on all CYP<17 years presenting with suspected or alleged historic CSA (ie, >3 days since last sexual assault in prepubertal children, >7 days pubertal girls) between October 2009 and November 2014. DATA COLLECTED: source and indication for referral, alleged perpetrator, physical findings. Findings supportive of CSA were peer reviewed for consensus agreement. ANALYSIS: χ2 test, Fisher's exact test and logistic regression. RESULTS: Among 249 CYP, presentation with physical/behavioural symptoms was associated with age <13 years (p<0.01), and alleged penetration with ages 13-17 years (p<0.01). Where known, time since alleged CSA ranged from 1 week to 13 months. Anogenital findings supportive of CSA were present in 7% of examined children (16/233), significantly associated with alleged penetration (p<0.01) and more likely with increasing age (OR 1.46, 95% CI 1.23 to 1.72). Additionally, where tested, sexually transmitted infections (STI) were detected in 2.6% CYP (3/116). Alleged perpetrators were intrafamilial in 66% (126/190). No associations were identified between perpetrator type and gender (p=1.0), age (p=0.7) or indication for referral (p=0.35). CONCLUSIONS: Despite significant time delay since the alleged CSA, this study highlights the persistence of anogenital findings supportive of CSA in 7% and STIs in 2.6% of CYP.

The value of paediatric assessment in historic child sexual abuse.

INTRODUCTION: A perception exists that there are few benefits of a paediatric assessment in historic child sexual abuse (CSA), as the likelihood of finding forensic evidence is low. AIM: To determine the value of a comprehensive paediatric assessment in a dedicated clinic for children and young people who present following suspicion or allegation of historic CSA. METHOD: All children with suspected or alleged historic CSA, defined as >7 days after the last episode of sexual assault in pubertal girls, or >3 days for prepubertal girls and all boys, were assessed in a specialised paediatric clinic. Clinic data were collected prospectively between October 2009 and November 2014 and through retrospective case note review. RESULTS: Among the 249 children who presented with possible historic CSA, ages ranged from 0 to 17 years (median 7, SD 4.3). Of these children, 141 (57%) had a medical concern(s) related to the referral reason, 78 (31%) had an unrelated medical concern(s) and 55 (22%) had emotional or behavioural concerns requiring onward referral, while 18 (7%) children had physical signs supportive of CSA. Findings referable to social care were identified in 26 cases (10%), the police in 6 cases and 15 (6%) parents required professional help for anxiety symptoms. CONCLUSIONS: This study highlights the value of a comprehensive paediatric assessment in a dedicated clinic for cases of suspected or alleged historic CSA, by identifying a broad variety of unmet health needs in this group. The findings have important implications for the child, their families and the multiagency team.

The effect of case management on childhood pneumonia mortality in developing countries.

BACKGROUND: With the aim of populating the Lives Saved Tool (LiST) with parameters of effectiveness of existing interventions, we conducted a systematic review of the literature assessing the effect of pneumonia case management on mortality from childhood pneumonia. METHODS: This review covered the following interventions: community case management with antibiotic treatment, and hospital treatment with antibiotics, oxygen, zinc and vitamin A. Pneumonia mortality outcomes were sought where available but data were also recorded on secondary outcomes. We summarized results from randomized controlled trials (RCTs), cluster RCTs, quasi-experimental studies and observational studies across outcome measures using standard meta-analysis methods and used a set of standardized rules developed for the purpose of populating the LiST with required parameters, which dealt with the issues of comparability of the studies in a uniform way across a spectrum of childhood conditions. RESULTS: We estimate that community case management of pneumonia could result in a 70% reduction in mortality from pneumonia in 0-5-year-old children. In contrast treatment of pneumonia episodes with zinc and vitamin A is ineffective in reducing pneumonia mortality. There is insufficient evidence to make a quantitative estimate of the effect of hospital case management on pneumonia mortality based on the published data. CONCLUSION: The available evidence reinforces the effectiveness of community and hospital case management with World Health Organization-recommended antibiotics and the lack of effect of zinc and vitamin A supportive treatment for children with pneumonia. Evidence from one trial demonstrates the effectiveness of oxygen therapy but further research is required to give higher quality evidence so that an effect estimate can be incorporated into the LiST model. We identified no trials that separately evaluated the effectiveness of other supportive care interventions. The summary estimates of effect on pneumonia mortality will inform the LiST model.