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Background: Despite aggressive multimodal therapy, >50% of children with high-risk neuroblastoma (HRNB) relapse. Survival after relapse is rare, and no consensus currently exists on the most effective therapy., Objective: To conduct a systematic review of the literature on effectiveness of re-induction chemotherapy in children with relapsed HRNB., Methods: Database searches were performed to identify studies looking at response to 1st line chemotherapy for children >12 months at diagnosis with first relapse of HRNB. Studies not reporting separate outcomes for HRNB patients or of refractory patients only were excluded. Two independent reviewers extracted the data and assessed study quality using a modified Newcastle-Ottawa tool., Results: Nine studies were identified fitting the inclusion criteria. All except one were single arm cohorts, and two were retrospective database reviews from single centres. One was a multicentre randomised controlled trial. All used a version of the validated International Neuroblastoma Response Criteria with 8 recording best ever response and 1 at a specified time, and 5 had central review. The proportion of relapsed patients varied from 24 to 100% with 30-93% receiving upfront myeloablative therapy. The response rate varied from 6 to 64%; however, because of heterogeneity, studies were not directly comparable, and no single treatment emerged as the most effective re-induction therapy., Conclusions: To date, there is no clear superior re-induction therapy for 1st relapse of HRNB. Randomised controlled trials with separate arms for relapsed versus refractory disease are needed to determine optimal re-induction chemotherapy to act as a backbone for testing newer targeted agents., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A previous study found a thyroid cancer excess in Cumbria following the Chernobyl explosion, but did not analyse sex-specific effects. This study examines sex differences in the incidence of thyroid cancer. Ninety-five primary thyroid carcinomas (69 females, 26 males) diagnosed in those aged 0-24 during 1968-2005 were identified from the Northern Region Young Persons' Malignant Disease Registry. Age-standardised incidence rates (ASRs), rate ratios (RRs) and 95% confidence intervals (CIs) were calculated. For males, the ASR was 0.6 per million person-years during the pre-Chernobyl period (1968-1986), and was 1.8 per million person-years during the post-Chernobyl period (1987-2005). For females, the ASR was 2.4 pre-Chernobyl and was 3.9 post-Chernobyl. The previously noted excess in Cumbria was entirely confined to females (Cumbrian females: RR for post-Chernobyl compared with pre-Chernobyl=10.8; 95% CI: 1.4-85.3). These findings may be consistent with sex-specific differences in susceptibility to an environmental exposure, such as fallout from the Chernobyl nuclear accident.

Aim: We aimed to describe and contrast the epidemiology of haematological malignancies among 0-14 and 15-24-year-olds in northern England from 1990 to 2002 and compare clinical trial entry by age group., Patients and Methods: Incidence rates were examined by age, sex and period of diagnosis and differences were tested using Poisson regression. Differences and trends in survival were assessed using Cox regression., Results: 1680 subjects were included comprising 948 leukaemias and 732 lymphomas. Incidence rates for acute lymphoblastic leukaemia were significantly higher for 0-14 compared to 15-24-year-olds, whilst Hodgkin lymphoma showed the reverse. No significant changes in incidence were observed. 60% of leukaemia patients aged 15-24 years entered trials compared to 92% of 0-14-year-olds. Survival rates were significantly lower and improved less markedly over time for 15-24 compared to 0-14-year-olds, particularly for leukaemia., Conclusions: Trial accrual rates need to be improved amongst 15-24-year-olds and a more structured follow-up approach adopted for this unique population.

We previously demonstrated significant space-time clustering amongst cases of childhood leukaemia (in particular acute lymphoblastic leukaemia (ALL)), central nervous system (CNS) tumour (especially astrocytoma), soft tissue sarcoma and Wilms' tumour. We hypothesised that there may be common aetiological mechanisms between some of these diagnostic groups. To test this hypothesis we analysed for cross-space-time clustering between these diagnostic groups, using population-based data from north-west England. Data were examined by a second-order procedure based on K-functions. Reference points in time and space were dates and addresses at birth and diagnosis. The results showed statistically significant (P < 0.05) cross-clustering between cases of leukaemia and CNS tumour and between cases of ALL and astrocytoma. There was no statistically significant cross-clustering of Wilms' tumours and soft tissue sarcomas with any other malignancy. In conclusion, these findings are consistent with common, possibly infectious, aetiological mechanisms for childhood leukaemia (particularly ALL) and CNS tumours (particularly astrocytoma).

Previously, we reported space-time clustering and seasonal variation in childhood central nervous system (CNS) tumours for the period 1954-1998. These previous studies provided evidence that infections may be involved in aetiology. To determine whether there were also localised spatial factors involved in aetiology we analysed the geographical distribution of CNS tumours in children aged 0-14 years using Manchester Children's Tumour Registry (MCTR) data for the period 1976-2000. Specifically, the Potthoff-Whittinghill test for spatial clustering was applied and Poisson regression was used to analyse the relationship between incidence rates and small-area population density, ethnic composition and deprivation index. No relationships were seen for all CNS tumours together and only a few for the subgroups. The previous findings of space-time clustering and seasonal variation, involving astrocytoma and ependymoma, together with the lack of spatial clustering and ecological relationships for these tumours provide evidence that astrocytoma and ependymoma may be associated with a highly mobile transient aetiological agent. An example of such an agent is an infection that occurs in mini-epidemics.

The aim of this paper was to study the geographical distribution of Wilms' tumours (WT) and soft-tissue sarcomas (STS) for 0-14 year olds included in a population-based registry from North West England during 1976-2000. Standardised morbidity ratios (SMRs) were calculated. Relationships between incidence rates and small area (ward) population density, ethnic composition, deprivation index and urban-rural status were examined using Poisson regression. There was a non-linear relationship between WT incidence and population density (P=0.008), with a higher incidence associated with wards with low deprivation scores (P=0.02); and which included a greater proportion of whites (P=0.01). For STS, a higher incidence was associated with wards with low deprivation scores (P=0.04); and which were 'more rural/less urban' (P=0.03). These results are consistent with a role for localised environmental exposures, in combination with lifestyle factors, in the aetiology of WT. For STS, there is some evidence for the involvement of environmental and/or lifestyle factors.