Variation in Cancer Outcomes Amongst Children and Young Adults in Yorkshire

This study set out to improve upon the quality of research addressing variation in cancer outcomes amongst children and young adults (CYAs) through the novel application of multiple imputation (MI) to the population based Yorkshire cancer register. The study also sought to determine whether there were inequalities in disease severity according to age, ethnicity or deprivation for CYAs with cancer for the first time in the UK and to quantify cardiovascular late effects amongst survivors of CYA cancer based on a unique data linkage approach to hospital admission data. Key survival inequalities for CYAs with central nervous system (CNS) tumours (n=795), leukaemia (n=912) and germ cell tumours (GCTs) (n=846) between 1990 and 2009 were identified. Teenagers and young adults (TYA) compared to children across all three groups and those of non-white and non-Asian ethnicity diagnosed with CNS tumours had significantly poorer survival. Importantly, these survival inequalities could not be explained by differences in the stage at diagnosis according to age, ethnicity or deprivation. Survival rates from CNS tumours and leukaemia continued to improve over time. These improvements only became evident after using MI to adjust for missingness, which is often ignored by researchers. Despite no observed improvement for GCTs over time, the number of advanced stage tumours at diagnosis decreased significantly for this diagnostic group. For all cancers combined, the long term cardiovascular effects of cancer exist not only for children, but also for TYAs surviving their cancer. Continued efforts should be made to ensure equal access to clinical trials and improved treatment protocols for TYAs. In addition, children as well as TYAs should be monitored for early signs of cardiovascular disease to maximise cardiovascular health. Finally, ignoring missing data can result in reduced study power and biased estimates, thus researchers should strive to use advanced techniques such as MI to account for missing data

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 <it>a priori </it>for analysis: ependymoma; astrocytoma; primitive neuroectodermal tumours (PNETs); other gliomas; total CNS tumours. We applied the <it>K</it>-function method for testing global space-time clustering using fixed geographical distance thresholds. Tests were repeated using variable nearest neighbour (NN) thresholds.</p> <p>Results</p> <p>There was statistically significant global space-time clustering for PNETs only, based on time and place of diagnosis (<it>P </it>= 0.03 and 0.01 using the fixed geographical distance and the variable NN threshold versions of the <it>K</it>-function method respectively).</p> <p>Conclusions</p> <p>There was some evidence for a transient environmental component to the aetiology of PNETs. However, a possible role for chance cannot be excluded.</p

Cortical pencil lining on SWI MRI in NBIA and healthy aging

BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) is characterized by pathological iron accumulation in the subcortical nuclei and the cortex. As age-related iron accumulation studies in these structures are lacking in healthy aging, we aimed to characterize the dynamics of age-dependent iron accumulation in subcortical nuclei in healthy aging and selected NBIA cases. This is fundamental to understand the natural age-related iron deposition in the healthy brain prior to using this marker as a potential prognostic or diagnostic tool in neurodegenerative disorders. METHODS: Susceptibility-weighted imaging (SWI) scans from 81 healthy volunteers (0-79 years) and four genetically confirmed patients suffering from NBIA (2-14 years) were obtained. We scored the presence or absence of pencil lining of the motor cortex and putamen and analyzed the normalized SWI signal intensity ratio (NSIR) in five subcortical nuclei. RESULTS: In healthy subjects, an age-dependent increase of pencil lining occurred starting from the second decade of life and was present in all cases at the age of 50. In their first decade, NBIA patients showed no cortical pencil lining, but we did observe putaminal pencil lining at this stage. In healthy subjects, age and NSIR of all nuclei correlated positively and was particularly dynamic in early childhood until young adulthood in the globus pallidus, dentate nucleus and red nucleus, but not in the caudate nucleus and putamen. NBIA patients showed an increased NSIR in the globus pallidus only and not in the other subcortical nuclei compared to age-matched healthy subjects. CONCLUSIONS: Cortical pencil lining is part of healthy aging. This should be considered when assessing this as a potential marker in NBIA diagnosis and prognosis. Putaminal pencil lining has the potential to become a specific marker for some subtypes of NBIA in the first decade of life, as it was only observed in NBIA and not in age-matched healthy subjects. NSIR in the subcortical nuclei during healthy aging was shown to be dynamic, accentuating the importance of having an age-dependent baseline

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 =0.96-0.98 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