Children's Tumour Registry Research Articles

Reporting Incidences of Neuroblastoma in Various Resource Settings.

PURPOSEThe incidences of neuroblastoma (NB) differ significantly between various resource settings because of varying quality of cancer registries and underdiagnoses. This study aimed to evaluate current regional variations as reported by international cancer registries and the theoretical and reported differences in international NB incidences and to evaluate South Africa (SA) as a case for variable reporting.METHODSA comprehensive literature review on registries reporting on NB was performed to construct incidence tables. The SEER Program incidence of 10.5/million children was used to calculate the expected number of NB cases for each country. Registry data of NB cases between 2000 and 2016 were requested from The South African National Cancer registry (SA-NCR) and the South African Children's Tumour Registry (SACTR) for comparison and to perform a probabilistic linkage study.RESULTSInternationally, incidences varied between –97.1% and +80% compared with the SEER program. SA under-reported NB cases by an estimated 74.2%. Between 2000 and 2016, the SA-NCR reported between 23 and 51 cases/year, whereas the SACTR reported between 18 and 57 cases/year for the same period. The incidence reported by the SA-NCR varied between 1.5 and 2.8/million children under 15-year per year, whereas the SACTR reported 1.74-2.6 cases/million children. Both registries reported incidences less than high-income country. A probabilistic record linkage of the two registries resulted in a combined incidence of 2.9 cases/million children.CONCLUSIONAs with most low- and middle-income countries, SA has either a lower incidence or underdiagnoses of NB cases. The reasons for under-reporting are not clear, but can be due to undiagnosed NB cases with spontaneous regression, missed possible cases because of lack of autopsies, and diagnosed cases not recorded in registries.

Childhood cancer incidence in South Africa, 1987-2007.

Childhood cancer is an emerging problem in Africa. Its extent is hazy because data are scarce, but it should be addressed. This is the first report from the South African Children's Tumour Registry (SACTR), which covers the whole of South Africa (SA). It provides minimal estimates of cancer incidence and discusses the challenges of cancer surveillance and control in a child population in a middle-income country. Only about 2% of the African population is covered by cancer registries producing comparable incidence data. To present and interpret incidence patterns and trends of childhood cancer over a 21-year period. The results should raise awareness of the problem of childhood cancer in an African population and provide sensible data for taking this problem in hand. All eligible and validated cancer cases registered in the SACTR over the period 1987-2007 and classified according to the International Classification of Childhood Cancer were included. Population data were retrieved from official sources and estimated for the population subcategories. Incidence rates were standardised to the world standard and time trends were evaluated using joinpoint models, adjusting for sex and age. Based on the 11,699 cases, the overall age-standardised average annual incidence rate was 45 per million. Threefold differences in the overall incidence rates were observed between the ethnic groups, ranging from 116 for whites to 37 for black Africans, and they differed by diagnostic group. Differences between the nine provinces of SA relate to the ethnic composition and prevailing socioeconomic status. The overall incidence rate declined by 1.2% per year for the whole country (p<0.01). However, the decline was mainly observed during the first few years of the study period, after which rates stabilised or increased. Diagnosis and notification of childhood cancer should improve. The differences in incidence between ethnic groups suggest the priorities for cancer control.

The South African paediatric tumour registry – 25 years of activity

The South African Children's Tumour Registry was established 25 years ago as it was essential to collect data on malignant disease in the paediatric population that can be used for statistical research in an efficient and sustainable way. The Registry is a useful and significant repository of specific paediatric data, along with the recently revitalised National Cancer Registry, to serve the needs of the cancer research community.

Fifty years of paediatric malignant bone tumours in the West Midlands, UK, 1957-2006: incidence, treatment and outcome

Malignant bone tumours in the paediatric age group (0-14 years) are uncommon; various aetiological theories exist and few reports of incidence, age and sex distributions have been published. We examined the incidence of childhood malignant bone tumours in one large single region of the UK over an extended period of 50 years. The West Midlands specialist regional children's tumour registry holds data on all malignancies and benign brain tumours in children under 15 years in the West Midlands region, which has a population of around 1 million children. Demographic and clinical data have been abstracted and diagnoses reviewed by a panel of expert pathologists. During the period 1957-2006, 259 cases of malignant paediatric bone tumours were diagnosed. There were 153 osteosarcomas, 78 Ewing sarcomas and 28 other primary bone tumours. The overall age standardised rate was 4.66, with no increase over time, although there was a significant increase in the incidence of Ewing sarcomas in the period 1965-92. Sixty-eight per cent of tumours were in patients over 10 years, whereas the incidence in patients under 10 years showed a non-significant increase. Survival rates increased dramatically post-chemotherapy introduction, with Ewing sarcoma demonstrating better survival overall. This is a large study giving an overview of malignant bone tumours in the childhood population of a single region over an extended period, showing results consistent with national reports. It also examines late effects, which were mostly mobility/orthopaedic, although almost one-fifth of patients had cardiac problems and five went on to develop second malignancies.

Elevated breast cancer risk among mothers of a population-based series of 2668 children with cancer

Aims:Although a previous study found high risk of breast cancer in mothers of children with soft tissue sarcomas, breast cancer risks in mothers of sufferers of other childhood cancers largely remain unknown. The aetiology is not fully understood. The present study explored this excess by varying type of childhood solid cancer and formulated a hypothesis.Methods:Mothers of 2668 children with solid tumours included in the Manchester Children’s Tumour Registry, 1954–96, were traced and followed up to 31 December 2000 through the UK National Health Service Central Register. Standardized incidence ratio (SIR), p-values and 95% confidence intervals were calculated from age and calendar-year-specific female breast cancer incidence rates for England and Wales.Results:There was a significant excess of breast cancer in mothers overall (SIR=1.3, 95%CI=1.0–1.5) mainly due to mothers of children with rhabdomyosarcoma (RMS) (SIR=2.2, 95%CI=1.0–4.0), skin cancer (SIR=7.9, 95%CI=2.9–17.1) and central nervous system tumours (SIR=1.2, 95%CI=0.9–1.8). Maternal breast cancer risk was associated with late age at birth of the index child, and male sex and young age at diagnosis in the index child. Risk was highest in the ten years, following the birth of the index. The pattern was seen most strongly in mothers of children with embryonal RMS.Conclusion:There are excesses of breast cancer in mothers of children with solid tumours in general and specifically in RMS, skin and central nervous system (CNS). There appears to be a temporal relationship between certain tumours in children and breast cancer in their mothers, suggesting an origin of their respective pregnancy. We propose a mother–foetal interaction mechanism to explain this association.

Cervical paraganglioma—A case report and review of all cases reported to the Manchester Children's Tumour Registry 1954–2004

We report a 6-year-old male with left-sided ptosis, aniscoria and an initially missed slow growing left-sided neck mass, which was surgically excised when he was 9 years old and confirmed to be a paraganglioma. Seven years later he developed recurrent symptoms and was found to have a recurrence in the anterior mediastinum. We also report on all cases of cervical paragangliomas registered with the Manchester Children's Tumour Registry (MCTR) for the 50-year period 1954-2004. Paragangliomas are very rare tumours in the head and neck but should be considered in the differential diagnosis of neck masses especially when presenting with Horner syndrome. Recurrent symptoms and signs of hypertension herald recurrence. As these tumours can form part of a familial syndrome, long-term follow-up is necessary. Family members should be screened for early detection.

Incidence and survival of childhood Langerhans cell histiocytosis in Northwest England from 1954 to 1998

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of pathological Langerhans cells, for which the aetiology and pathogenesis remain largely unknown. Information on the 101 children with LCH registered with the population-based Manchester Children's Tumour Registry (MCTR) between 1954 and 1998 was extracted from the records of the MCTR. This included age, sex, date of diagnosis, systems affected at diagnosis and follow-up. The overall incidence rate for LCH was 2.6 cases per million child years. In those under 1 year of age the incidence rate was 9.0 cases per million child years, compared to 0.7 cases per million in those aged 10-14 years (P < 0.0001 for age trend). There was no evidence of seasonal variation in presentation by month of birth or first symptom. Bone was the most common site of disease involvement (67% of cases), followed by skin (37%) and soft tissue (22%). The overall survival rate has improved over time, from 57% in 1954-1968 to 74% in 1985-1998. Ninety percent of deaths were due to disease progression, the remainder were due to complications of intensive therapy. The site of LCH lesions and extent of disease present at diagnosis strongly predicted survival outcome. Patients with initial liver involvement had a 5-year survival rate of 25% compared with 93% for those with bone lesions alone at diagnosis. Incidence rates varied significantly by age at diagnosis, and have been stable over time. Survival has improved considerably over time, but varies strongly by age and systems affected at diagnosis.

Paediatric malignant tumours of the gastrointestinal tract in the West Midlands, UK, 1957-2000: a large population based survey.

To investigate the incidence, clinical characteristics and survival of malignant tumours of the gastrointestinal tract in children in the West Midlands in Britain over a 44-year span time, to identify any change over this period and to compare the data with the world literature. Retrospective population based study. Fifty-seven patients were identified from the records of the West Midlands Regional Children's Tumour Registry. Age-standardised incidence rates were calculated using the world standardised population method. Statistical tests used were the Log rank test and survival curves were produced using the Kaplan-Meier method. The age-standardised incidence of overall gut tumours during the period 1957-2000 was 1.10/million/year. The age standardised incidence of non-Hodgkin lymphoma (NHL) was calculated as 0.9/million/year and for adenocarcinoma 0.14/million/year. Malignant tumours of the gastrointestinal tract remain rare in children. No changing trends in incidence were observed over the 44-year period. NHL was the commonest malignancy overall and of the small bowel while equal number of adenocarcinoma and NHL were identified in the large bowel. There was no significant difference in survival between sexes, site and age groups in both NHL and adenocarcinoma. Survival has improved over the last four decades for NHL patients but remains poor for the adenocarcinoma patients.

Geographical and ecological analyses of childhood acute leukaemias and lymphomas in north-west England.

Childhood leukaemias and lymphomas have been associated with exposure to environmental factors, including infections, which show geographical variation. This study examined the geographical distribution of the incidence of acute leukaemia and lymphoma using Manchester Children's Tumour Registry (MCTR) data 1976-2000. A total of 910 children were included, all of whom had histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses, all the children were aged 0-14 years and were resident in the counties of Greater Manchester or Lancashire. Standardized morbidity ratios were calculated. Poisson regression was used to examine the relationship between incidence rates and small-area (census ward) population density, ethnic composition and deprivation index. There was a monotonic relationship between acute lymphoblastic leukaemia (ALL) incidence and population density (P = 0.05). Higher rates were seen in more densely populated areas. There was evidence for a monotonic relationship between the incidence of the mixed cellularity subtype of Hodgkin's disease (HD) and the Townsend deprivation score (P = 0.001). Markedly higher incidence was associated with greater levels of unemployment and household overcrowding. The results for ALL and mixed cellularity HD support the involvement of environmental factors, such as infections, in disease aetiology.

Neurofibromatosis type 1 and sporadic optic gliomas

Aims: To compare the natural history of sporadic optic glioma with those associated with neurofibromatosis type 1 (NF1). Methods: Optic glioma cases were identified using both the Manchester Children's Tumour...

Examination of temporal trends in the incidence of childhood leukaemias and lymphomas provides aetiological clues.

The age-sex distributions and temporal trends in incidence of leukaemia and lymphoma from the Manchester Children's Tumour Registry (MCTR), 1954-1998, are reported. This 45-year study includes 1795 children, all of whom had a histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses all the children were under 15 years of age and were resident in a geographically defined area of northwest England covered by the MCTR. Log-linear modelling identified significant linear increases in acute lymphoblastic leukaemia (ALL) (average annual increase 0.7%; P= 0.005) and in Hodgkin's disease (HD) (1.2%, P=0.04), but not in acute myeloid leukaemia (AML), nor in non-Hodgkin's lymphoma (NHL). The increase in ALL was most pronounced amongst males, aged 1-4 years, and is likely to be due to precursor B-cell leukaemias. The increases in ALL and HD are discussed in relation to current hypotheses suggesting a role for infection. Additionally, a non-linear cohort effect was identified for NHL (P= 0.008), which may indicate the involvement of environmental factors other than infection.

Incidence of childhood precursor B-cell acute lymphoblastic leukaemia in north-west England

A temporal increase in the incidence of childhood acute lymphoblastic leukaemia (ALL) in the UK has been noted. We present data from the Manchester Children's Tumour Registry which provide strong evidence that the increase is a result of an increase in the precursor B-cell subtype. In the childhood peak (age 1-4 years), the annual increase in precursor B-cell ALL between 1980 and 1998 was 3.0% (p=0.024). Recent findings are consistent with the causal involvement of infections in precursor B-cell ALL.

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Previous studies of space–time clustering in childhood leukaemia have produced equivocal and inconsistent results. To address this issue we have used Manchester Children's Tumour Registry leukaemia data in space–time clustering analyses. Knox tests for space–time interactions between cases were applied with fixed thresholds of close in space, < 5 km and close in time < 1 year apart. Addresses at birth as well as diagnosis were utilized. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also examined by a second order procedure based on K-functions. All methods showed highly significant evidence of space–time clustering based on place of birth and time of diagnosis, particularly for all leukaemias aged 0–14 and 0–4 years, and acute lymphoblastic leukaemia (ALL) 0–4 years. Some results based on location at diagnosis were significant but mainly gave larger P -values. The results are consistent with an infectious hypothesis. Furthermore, we found an excess of male cases over females involved in space–time pairs. We suggest this may be related to genetic differences in susceptibility to infection between males and females. These findings provide the basis for future studies to identify possible infectious agents. © 2000 Cancer Research Campaign

Paediatric presentation of type 2 neurofibromatosis

BACKGROUNDNeurofibromatosis type 2 (NF2) is a highly penetrant autosomal dominant condition predisposing affected individuals to schwannomas and meningiomas. The proportion of children presenting with meningioma or schwannoma who have NF2...

Seasonal variations in the onset of childhood leukaemia and lymphoma.

Infection has long been suspected as a possible factor in the aetiology of leukaemia and lymphoma. If seasonal variation in the onset of disease could be shown in any of the diagnostic subgroups of leukaemia or lymphoma, this would provide supportive evidence of an aetiology linked to exposure to infection. All cases in the Manchester Children's Tumour Registry (aged 0-14 years at diagnosis) with acute lymphoblastic leukaemia (ALL), acute non-lymphocytic leukaemia (ANLL), Hodgkin's disease (HD) or non-Hodgkin lymphoma (NHL) between 1 January 1954 and 31 December 1996 were included in an analysis of seasonal variation in the month of first symptom and the month of diagnosis. Cases of common acute lymphoblastic leukaemia (c-ALL) diagnosed from 1979 onwards were also analysed separately. The groups considered for analysis were: all cases of ALL (n = 1070), ALL diagnosed between 18 and 95 months of age (n = 730), ALL diagnosed over 95 months of age (n = 266), c-ALL (n = 309), ANLL (n = 244), all infant acute leukaemias (ALL and ANLL under 18 months; n = 107), HD (n = 166) and NHL (n = 189). Using the Edwards method, both c-ALL and HD demonstrated significant seasonal variation (P = 0.037 and 0.001 respectively) in date of first symptom, with peaks occurring in November and December respectively. Using this method, no indication of seasonal variation was found in the other diagnostic groups for date of first symptom or in any of the diagnostic groups for date of diagnosis. For comparison with a previous study, a further analysis based on date of diagnosis for all ALL cases, using summer-winter ratios, showed a significant summer excess. These results provide supportive evidence for an infectious aetiology for c-ALL and HD, and possibly for all ALL, which warrants further investigation.

The Tygerberg Hospital Children's Tumour Registry 1983-1993.

This study records the disease profile and outcome of all 492 children with confirmed cancer below the age of 15 who were admitted to Tygerberg Hospital, South Africa, from 1983 to 1993. The black (48.3%), so-called coloured (30.3%) and caucasian (21.3%) children did not represent a confined geographical area. Leukaemia (22.8%), brain tumours (20.5%), lymphomas (15.2%), nephroblastomas (10%), neuroblastomas (8.5%) and retinoblastomas (5.7%) were the most common tumours. All children were treated with standard protocols and included in the Kaplan-Meier survival analyses. 14 patients were lost to follow-up. Projected survival in (acute lymphoblastic leukaemia) ALL was 63% in white children, but only 17% in black children. Survival was 65% in stage 1 and 2 Wilms' tumour, and exceeded 50% in medulloblastoma and astrocytoma. So-called African Burkitt's lymphoma occurred in all population groups. Overall, 5-year survival in Hodgkin's disease was 70%. Black and coloured children with neuroblastoma presented mainly with stage 3 and 4 disease. All 26 black and coloured children with retinoblastoma had a negative family history and advanced disease which needed enucleation.

Childhood malignancies in the south‐west region of England, 1976–1985

The incidence and pattern of childhood cancer in the South-West Region of the United Kingdom was studied in the period 1976-1985 to see if there was any unevenness in distribution. This region consists of five counties with considerable variation in radon exposure and urbanisation. Cases were identified from multiple sources and the basis of the diagnosis reviewed. Internationally accepted diagnostic categories were used. Six hundred seventy-eight cases were found, giving an age standardised incidence rate of 114.2 per million childhood years. The incidence of different cancers by sex was strikingly similar to the Manchester Children's Tumour Registry, from a noncontiguous region, with three exceptions. In the South-West, there was a higher rate of soft tissue sarcoma in boys (P = 0.01) and lower rates of sympathetic nervous system and germ-cell tumours in girls (P = 0.01 and P = 0.04, respectively). There was no significant variation in cancer incidence among the five counties or with time. The incidence rate in counties of high radon exposure was not higher than with low radon exposure. The overall incidence in counties with urban districts was not significantly increased compared to those without, although there was a nonsignificant trend towards a higher incidence of leukaemia (P = 0.08). The incidence and type of childhood cancer are similar to those in a noncontiguous region. Geographical and temporal incidence are remarkably stable. Local environmental variation may not play a major role in the causality of childhood cancer.

Patterns and temporal trends in the incidence of malignant disease in children: I. Leukaemia and lymphoma

Patterns and trends in incidence of leukaemia and lymphoma in children aged under 15 years and resident in the North Western Regional Health Authority area of England at diagnosis, over the 35-year time period 1954–1988, were analysed. The study included 1407 cases registered with the Manchester Children's Tumour Registry, 100% of which had a histologically or cytologically verified diagnosis. Log-linear modelling identified significant linear increases in acute lymphocytic leukaemia (ALL) (average quinquennial increase 4%) and Hodgkin's disease (HD) (10%), but not in acute non-lymphocytic leukaemia nor non-Hodgkin's lymphoma. Additionally, the χ 2 test for trend identified a significant increase in the incidence of chronic myeloid leukaemia. The possibility that the increases seen in ALL and HD are linked to increases in prevalence of unknown infectious agents is discussed.

Congenital anomalies and genetic syndromes in 173 cases of medulloblastoma.

One hundred seventy-three consecutive cases of medulloblastoma recorded in the Manchester Children's Tumour Registry from 1954 to 1989 were studied. After review of case notes, X-rays, and health surveys the clinical outcome and incidence of congenital anomaly was determined. A previously unreported association with Rubinstein Taybi syndrome was found. Evidence of a genetic syndrome or congenital anomaly was found in 6.4%. These figures provide further evidence of the higher-than-expected incidence of congenital abnormalities.

Space-time clustering of childhood acute lymphoblastic leukaemia: indirect evidence for a transmissible agent.

Despite numerous anecdotal reports of small clusters of cases of childhood leukaemia, formal statistical analyses have yielded equivocal results (Linet, 1985). Incidence data from the UK national children's tumour registry (CCRG) for 1968-1983 have recently become available for small area analyses by location at diagnosis (OPCS, 1991). Extensive analyses using a variety of methodologies have shown consistent, though weak, evidence of the occurrence of both spatial clustering and space-time interactions. Results from one of these analyses (Alexander, 1991) are now extended to test specific prior hypotheses generated by an independent case-control study (Alexander et. al., 1992). These suggested that transmission of a specific, though unknown, agent (Z) plays some role in the development of childhood acute lymphoblastic leukaemia (ALL) with the times when children are susceptible to infection differing by age-of-onset and hence subtype of ALL. For cases with older onset (aged 5 years and over) it was suggested that persistent infection may have been established in utero or early infancy and, now, formal testing of appropriate space-time interactions provide indirect confirmation of this (P = 0.0002). More recent exposure to Z may contribute to ALL in the childhood peak years (Alexander et. al., 1992) but the confirmation provided here is less strong (P = 0.05). The results afford new impetus to a search for a transmissible aetiologic agent or agents; these need not be rare and the results should not be interpreted as evidence for direct case to case transmission.