We are very grateful to the Bone Cancer Research Trust for supporting our research.

This study had two aims: The first was to review published literature on incidence survival and aetiology of childhood bone tumours, and the second was to investigate incidence and survival trends in Northern England and the West Midlands. The main objective of the study was to identity putative environmental risk factors which may contribute to the aetiology of bone tumours in children and young adults and could be investigated in more detail in further studies.

Main Findings

Literature Review

The review covered both descriptive epidemiology and aetiology of bone tumours, including all studies published on PubMed in English from 1970 to date.

Descriptive epidemiology focussed on gender differences, age at diagnosis, geographical variation, temporal trends in incidence, space-time clustering, seasonal variation and survival trends. We observed that children aged 0-14 show equal incidence of bone tumours by gender, but in adolescents aged 15-19 they are more common in boys. Bone tumours are rarely diagnosed in children under the age of 5 years and are most commonly diagnosed around the time of puberty, which coincides with peak bone growth. Geographical variation in malignant bone tumours is seen worldwide, particularly between different ethnic groups. Despite an overall increase in childhood cancer over the last 40 years, incidence of bone tumours has not increased. An environmental aetiological factor has been suggested for osteosarcoma with the presence of space-time clustering, although no seasonal variation has been seen for either osteosarcoma or Ewing sarcoma. Five year survival from bone tumours has increased over the last 40 years, although there has been little improvement since 1990. Survival in the UK is lower than in the West, North and South regions of Europe although higher than in the East. Survival is higher in the USA than in Europe. Survival for bone tumours decreases with age of diagnosis, with adolescents showing lower five year survival rates than children.

We explored both genetic and environmental factors which may play a role in the aetiology of bone tumours in children and young adults. Although it is difficult to draw conclusions from the results, we found several factors to be consistently implicated with the development of bone tumours. Hernias, farming, a younger age at puberty and family history of cancer have been identified as potential risk factors for Ewing sarcoma in this age group. Chicken farming, a younger age at puberty, fluoride exposure and family history of cancer have been identified as potential risk factors for osteosarcoma. Although no aetiologic associations were firmly established by the study we feel the results warrant continued research to confirm or refute the hypotheses generated.

Incidence and Survival Analyses

We conducted two incidence and survival analyses: one focussing on bone tumours in children aged 0-14, and another broader analysis of all cases in patients aged 0-49.

We used information from five UK cancer registries to carry out these analyses. Four of these were used in the 0-14 analysis and one in the 0-49. Data from the Northern Region Young Persons’ Malignant Disease Registry (NRYPMDR), the Yorkshire Specialist Register of Cancer in Children and Young People (YSRCCYP), the West Midlands Regional Children’s Tumour Registry (WMRCTR) and the Manchester Children’s Tumour Registry (MCTR) were used for the 0-14 paper, as these are specialist registries which record cases of cancer in children and young adults. Data from The Northern and Yorkshire Cancer Registry and Information Service (NYCRIS) were used in the 0-49 analyses.

In the 0-14 analyses we confirmed previously published data on childhood bone tumours. For the incidence data we found a similar incidence rate to those reported in countries with predominantly white populations, an increasing incidence with age, a male:female ratio close to 1, a predominance of osteosarcoma and Ewing’s sarcoma and incidence increasing with age to give highest rates in the 10-14 year age group – all typical patterns previously reported. We also observed a decrease in Ewing’s sarcoma over the study period whilst incidence of the other diagnostic groups remained steady; however it is possible the decrease may be due to artefact. For the survival data we observed the lowest survival rates in older children and observed rates similar to previous UK data. We observed survival in Northern England and the West Midlands to be lower than all other regions in Europe aside from the East. The most significant finding of this study was a lack of improvement in five-year survival for osteosarcoma over the study period, despite an improvement for Ewing’s sarcoma. Further research is needed to fully understand this.

Analyses of bone tumours in patients over the age of 24 are rare. Therefore the 0-49 analysis allowed us to gain a greater insight into bone tumour trends across a larger age spectrum than those covered by most previous studies. Our analysis was however consistent with the small number of studies in existence for this extended age group, and our findings of a predominance of osteosarcoma and Ewing’s sarcoma, a larger number of males diagnosed than females and highest incidence in the 15-29 age group have all been previously reported. We also observed incidence rates similar to those seen in other studies. In the survival analysis we observed survival differences by age for Ewing sarcoma (with survival being lower in patients aged 15-49 than those aged 0-14) but not for the other subgroups. Ewing sarcoma also had a lower five-year survival than the other subgroups. In all groups there was no difference in survival rates by gender. As with the 0-14 study, we observed an improvement in survival for Ewing sarcoma over the study period without improvement for osteosarcoma. Again, further research is needed to determine the reasons for the lack of improvement in survival in this subgroup.

Publications

1. Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981–2002. Eyre et al. British Journal of Cancer. Volume 100, Issue 1. Wednesday 7 January, 2009. Click here to read this paper

Publications in progress

1. The aetiology of bone tumours in children and young adults: a review
2. Incidence and survival for bone tumours diagnosed in 0-49 year olds from the Northern and Yorkshire Regions, 1981-2002

Presentations

• Overview presentation given at BCRT patients and supporters conference in June 2008.
• Abstract: “Incidence and survival for bone tumours diagnosed in children from Northern England and the West Midlands, 1981-2002” presented at National Cancer Research Institute (NCRI) and International Society of Pediatric Oncology (SIOP) conferences in October 2008.

Staff employed

Emmanuel Mubwandarikwa: July 2007 – January 2008
Rachel Eyre: February 2008 – September 2008

Further Research

Further research will investigate the possible role of fluoride in the development of bone tumours in children and young adults.

Richard McNally & Rachel Eyre