Incidence and survival of children and young people with central nervous system embryonal tumours in the North of England, 1990-2013.

BACKGROUND: Medulloblastoma and primitive neuroectodermal tumours (PNET) are the most common central nervous system (CNS) embryonal tumours diagnosed in childhood. Survival outcomes are worse for children diagnosed with CNS PNET compared to medulloblastoma. Less is known about survival outcomes in teenagers and young adults (TYA). METHODS: Data were extracted from two population-based cancer registries of children and young people (0-24 years) in the north of England for all diagnoses of medulloblastoma and CNS PNET between 1990 and 2013. Incidence and survival trends were analysed using Poisson and Cox regression. RESULTS: Between 1990 and 2013, 197 medulloblastomas and 58 CNS PNET were diagnosed, age-standardised incidence rates of 3.8 and 1.5 per million, respectively. Medulloblastoma incidence decreased over time while there was no significant change in trend for CNS PNET. The overall 5-year survival rate was 54%. The risk of death was 2.4 times higher (95% confidence interval [CI] 1.6, 3.7) for patients with CNS PNET compared to medulloblastoma, after adjustment for patient characteristics. There was a 39% reduction (95% CI 0.43, 0.87) in the risk of death for patients diagnosed between 2000 and 2013 compared to 1990-1999. Risk of death did not differ for TYA (15-24 years) compared to children aged 5-9 years. CONCLUSIONS: Medulloblastoma incidence decreased over time and differences in survival between medulloblastoma and PNET emerged within the first-year post diagnosis leading to poorer outcomes for children and young adults diagnosed with PNET; however, a significant improvement in survival over time was observed.

Trends in survival for teenagers and young adults with cancer in the UK 1992-2006.

BACKGROUND: Although relatively rare, cancer in teenagers and young adults (TYA) is the most common disease-related cause of death and makes a major contribution to years of life lost in this age group. There is a growing awareness of the distinctive needs of this age group and drive for greater understanding of how outcomes can be improved. We present here the latest TYA survival trends data for the United Kingdom (UK). METHODS: Using national cancer registry data, we calculated five-year relative survival for all 15-24 year olds diagnosed with cancer or a borderline/benign CNS tumour in the UK during the periods 1992-1996, 1997-2001 and 2002-2006. We analysed trends in survival for all cancers combined and for eighteen specified groups that together represent the majority of TYA cancers. We compared our data with published data for Europe, North America and Australia. RESULTS: Five-year survival for all cancers combined increased from 75.5% in 1992-1996 to 82.2% in 2002-2006 (P<0.001). Statistically significant improvements were seen for all disease groups except osteosarcoma, rhabdomyosarcoma, non-gonadal and ovarian germ cell tumours and ovarian and thyroid carcinomas. During the earliest time period, females had significantly better survival than males for five of the twelve non-gender-specific disease groups. By the latest period, only melanomas and non-rhabdomyosarcoma soft tissue sarcomas had differential survival by gender. Survival in the UK for the most recent period was generally similar to other comparable countries. CONCLUSION: Five-year survival has improved considerably in the UK for most cancer types. For some disease groups, there has been little progress, either because survival already approaches 100% (e.g. thyroid carcinomas) or, more worryingly for some cancers with poor outcomes, because they remain resistant to existing therapy (e.g. rhabdomyosarcoma). In addition, for a number of specific cancer types and for cancer as a whole males continue to have worse outcomes than females.

Real-time quantitative polymerase chain reaction (qPCR) analysis with fluorescence resonance energy transfer (FRET) probes reveals differential expression of the four ERBB4 juxtamembrane region variants between medulloblastoma and pilocytic astrocytoma.

AIMS: We report a comparative study on the mRNA expression of ErbB receptor tyrosine kinases, and in particular ERBB4 transcript variants, in two common paediatric brain tumours: medulloblastoma (MB) and pilocytic astrocytoma (PA). METHODS: While the conventional real-time quantitative polymerase chain reaction was used to measure the expression of ERRBs and ErbB4-processing protease genes, the LightCycler fluorescence resonance energy transfer probes were specifically designed to investigate all of the known ERBB4 juxtamembrane (JM) and cytoplasmic transcript variants. RESULTS: The overall expression of ERBBs suggests that ErbB2/ErbB4 heterodimers and ErbB4 homodimers may be major functional units of the ErbBs in MB, while ErbB2/ErbB3 heterodimers may play a more prominent role in addition to ErbB4-containing dimers in PA. Different expression patterns of ERBB4 JM transcripts in MB, PA and normal brain were observed. The JM-d variant was only detected in MBs, while JM-c was present in MB and PA but was not identified in normal brain. The expression of cleavable ERBB4 transcript variants was elevated in PAs and MBs compared with normal brain, while mRNA levels of ErbB4-processing proteases were similar in both tumour types and normal brain. This suggests that proteolytic cleavage of ErbB4 may be more common in MB and PA, which leads to signalling events divergent from those in normal brain. CONCLUSION: Taken together, these results suggest that ErbB4 processing and function may be altered in brain tumours, such as MB and PA, via differential expression of JM transcript variants.