Survival of childhood acute lymphoid leukaemia in Yorkshire by clinical trial era, 1990-2011.

Gender-specific differences in survival by clinical trial era in Yorkshire were assessed for children with acute lymphoid leukaemia (ALL) enrolled onto UKALLXI, ALL97/99 or UKALL2003 (n = 630; 1990-2011). For males, there was a non-significant improvement in survival for ALL97/99 [hazard ratio (HR) = 0·77; 95% confidence interval (CI) 0·43-1·42) and a significant improvement for UKALL2003 (HR = 0·50; 95%CI 0·25-0·99) compared to UKALLXI. For females, survival was significantly improved for ALL97/99 (HR = 0·33; 95%CI 0·14-0·78), and non-significantly improved for UKALL2003 (HR = 0·51; 95%CI 0·25-1·08) compared to UKALLXI. Modest overall survival improvements masked clinically important gender-specific changes over time by trial era, requiring confirmation in larger population-based studies.

Population mixing for leukaemia, lymphoma and CNS tumours in teenagers and young adults in England, 1996-2005.

BACKGROUND: Little aetiological epidemiological research has been undertaken for major cancers occurring in teenagers and young adults (TYA). Population mixing, as a possible proxy for infectious exposure, has been well researched for childhood malignancies. We aimed to investigate effects of population mixing in this older age group using an English national cancer dataset. METHODS: Cases of leukaemia, lymphoma and central nervous system (CNS) tumours amongst 15-24 year olds in England (diagnosed 1996-2005) were included in the study. Data were obtained by ward of diagnosis and linked to 1991 census variables including population mixing (Shannon index); data on person-weighted population density and deprivation (Townsend score) were also used and considered as explanatory variables. Associations between TYA cancer incidence and census variables were investigated using negative binomial regression, and results presented as incidence rate ratios (IRR) with 95% confidence intervals (CI). RESULTS: A total of 6251 cases of leukaemia (21%), lymphoma (49%) and CNS tumours (30%) were analysed. Higher levels of population mixing were associated with a significant decrease in the incidence of CNS tumours (IRR=0.83, 95% CI=0.75-0.91), accounted for by astrocytomas and 'other CNS tumours'; however, there was no association with leukaemia or lymphoma. Incidence of CNS tumours and lymphoma was 3% lower in more deprived areas (IRR=0.97, 95% CI=0.96-0.99 and IRR=0.97, 95% CI=.96-0.98 respectively). Population density was not associated with the incidence of leukaemia, lymphoma or CNS tumours. CONCLUSIONS: Our results suggest a possible role for environmental risk factors with population correlates in the aetiology of CNS tumours amongst TYAs. Unlike studies of childhood cancer, associations between population mixing and the incidence of leukaemia and lymphoma were not observed.

First description of seasonality of birth and diagnosis amongst teenagers and young adults with cancer aged 15-24 years in England, 1996-2005.

BACKGROUND: We aimed to examine evidence for an infectious aetiology among teenagers and young adults (TYA) by analysing monthly seasonality of diagnosis and birth amongst 15-24 year olds diagnosed with cancer in England. METHODS: Cases of leukaemia, lymphoma and central nervous system (CNS) tumours were derived from the national TYA cancer register (1996-2005). Incidence rates (IR) and trends were assessed using Poisson regression. Seasonality of diagnosis and birth was assessed using Poisson and logistic regression respectively with cosine functions of varying periods. RESULTS: There were 6251 cases diagnosed with leukaemia (n = 1299), lymphoma (n = 3070) and CNS tumours (n = 1882), the overall IR was 92 (95% CI 89-96) per 1,000,000 15-24 year olds per year.There was significant evidence of seasonality around the time of diagnosis for Hodgkin's lymphoma (P < 0.001) with a peak in February, and for 'other CNS tumours' (P = 0.010) with peaks in December and June. Birth peaks for those with 'other Gliomas' (Gliomas other than Astrocytoma and Ependymoma) were observed in May and November (P = 0.015). CONCLUSION: Our novel findings support an infectious aetiological hypothesis for certain subgroups of TYA cancer in England. Further work will examine correlation with specific infections occurring around the time of birth and diagnosis within certain diagnostic groups.

Space-time clustering of childhood central nervous system tumours in Yorkshire, UK.

BACKGROUND: We specifically tested the aetiological hypothesis that a factor influencing geographical or temporal heterogeneity of childhood central nervous system (CNS) tumour incidence was related to exposure to a transient environmental agent. METHODS: Information was extracted on individuals aged 0-14 years, diagnosed with a CNS tumour between the 1st January 1974 and 31st December 2006 from the Yorkshire Specialist Register of Cancer in Children and Young People. Ordnance Survey eight-digit grid references were allocated to each case with respect to addresses at the time of birth and the time of diagnosis, locating each address to within 0.1 km. The following diagnostic groups were specified a priori for analysis: ependymoma; astrocytoma; primitive neuroectodermal tumours (PNETs); other gliomas; total CNS tumours. We applied the K-function method for testing global space-time clustering using fixed geographical distance thresholds. Tests were repeated using variable nearest neighbour (NN) thresholds. RESULTS: There was statistically significant global space-time clustering for PNETs only, based on time and place of diagnosis (P = 0.03 and 0.01 using the fixed geographical distance and the variable NN threshold versions of the K-function method respectively). CONCLUSIONS: There was some evidence for a transient environmental component to the aetiology of PNETs. However, a possible role for chance cannot be excluded.

A systematic review of time to diagnosis in children and young adults with cancer.

PURPOSE: It is often assumed that prolonged time to diagnosis (TTD) for cancer negatively influences overall survival and survivorship through advanced stage disease at diagnosis. This systematic review assesses existing early diagnosis research in childhood and young adult cancer and aims to identify whether a consensus exists within the literature in relation to the terminology and methodologies used to investigate TTD in this population. METHODS: Medline, Embase, the Centre for Reviews and Dissemination database and Cochrane library were searched for papers on children and young adults (0-30 years) published from 1948 to the present. RESULTS: Of the 1665 potentially eligible citations identified, 32 papers met the inclusion criteria. The majority of work was in European (n=15) or North American (n=8) populations. Most work focused on brain tumours (n=10), retinoblastomas (n=5) and bone and soft tissue sarcomas (n=4). The majority of studies were in hospital-based settings (n=25), with only seven papers adopting a population-based setting. Summary statistics presented were mostly median TTD, the skewed distribution of the data meant comparisons between studies based on medians were difficult and combining studies within a meta-analysis was not appropriate. CONCLUSIONS: Within the childhood and young adult population, TTD for cancer varies between diagnostic groups and with age at diagnosis in the majority of studies. In order that clear conclusions can be drawn from early diagnosis research in children and young adults, specific criteria identifying circumstances in which delay has occurred should accompany a defined time line to diagnosis or treatment in every study.