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UK childhood cancer survival falling behind rest of EU?
Keynote Comment
UK childhood cancer survival falling behind rest of EU?
Hidajet Delic/AP/PA Photos
One of the main driving forces behind the initiation of the UK National Cancer Plan was the unfavourable comparison of cancer outcomes between adults in England and adults in parts of mainland Europe. This plan is already beginning to have a major effect on outcome, by centralisation and better organisation of care. Childhood cancer has long been seen as the model for organisation of care, with most children being treated on national protocols and in specialist-care centres since the establishment of the UK Children’s Cancer Study Group (UKCCSG; now called the Children’s Cancer and Leukaemia Group) 30 years ago. Between 1978 and 1982, 57% of children were referred to a specialist-care centre, and this percentage rose to 89% between 1998 and 2002. Therefore, the results of two major comparative studies, which showed that survival from childhood cancer is low compared with other European countries, are somewhat concerning.1,2 However, caveats should be placed around such comparisons, especially as cancer registry data are collected differently across Europe. First, only a few countries have good linkage between registration data and mortality data, to allow complete follow-up for survival. The UK and Scandinavia probably have the best registration systems. Second, there are problems of definition, especially for brain tumours. Third, if multiple comparisons are made then some results will be deemed significant by chance.
Survival rates differ for children across Europe
662
However, the consistency of the relative ranking of UK survival rates compared with those of some northern and western European countries merits further scrutiny. To try to understand the possible reasons for the low cancer survival rate in the UK, we have chosen to focus on two childhood cancers that usually present with clinical features that are alarming to parents and should, therefore, lead them to seek early contact with health professionals. A common presentation is an abdominal mass, usually either a nephroblastoma (Wilms’ tumour) or a neuroblastoma. Reported survival was worse in the UK compared with some other parts of Europe, in studies spanning the period 1978–1997.1,2 Complete ascertainment of the specific disease type is an important issue, as is knowing the true incidence of the disease. Considerable variation between different European countries exists in the incidence of neuroblastoma, especially in those diagnosed under the age of 1 year. We now know that the likely reason for this variability is that there are at least two types of neuroblastoma, one of which regresses spontaneously and the other being a truly malignant tumour. In populations where screening for neuroblastoma was undertaken, the incidence almost doubled.3 If population survival data include these spontaneously regressing tumours, then survival will be artificially increased. Countries that have active childhealth surveillance programmes for children in their first year of life also have an increased incidence. In the UK, a greater proportion of children with neuroblastoma have metastatic disease at presentation,4 suggesting they are diagnosed somewhat later in the course of their disease. This finding might explain the differences in overall survival from neuroblastoma even for those diagnosed after the second year of life (British Isles 30% [95% CI 26–35] vs western Europe (mainly Germany, Belgium, Netherlands, Luxembourg, and Switzerland) 46% [42–50]).5 Wilms’ tumour is a common solid tumour of childhood and one where there should be little difficulty in comprehensive ascertainment or pathological definition, and no spontaneous regression. Even though, for the past 15 years, over 94% of children with Wilms’ tumour have been referred to specialist centres in the British Isles, their overall survival of 83% is slightly, but significantly, worse than the rate of 89% reported for northern (Scandinavia) and western Europe.6 This difference in survival is unlikely http://oncology.thelancet.com Vol 8 August 2007
Keynote Comment
to be caused by access to specialist-care centres or to the speed and delivery of treatment once a referral has been made. Access to clinical trials is widely available across Europe, but, until recently, there was no European-wide standard clinical protocol and children from the UK were receiving a different treatment protocol to many of those in other parts of Europe. Therefore, the possibility exists that children from the UK have been receiving suboptimum first-line treatment or less-intensive salvage treatment at relapse. Evidence supports this idea, by showing that survival is improving with the latest treatment protocol and introduction of a national relapse strategy. A nihilistic versus an aggressive approach to relapse could make a real difference to overall survival and such an approach could be either professionally or parent driven. The original care pathway might also contribute to differences in survival. Early diagnosis is likely to be important and the National Institute of Health and Clinical Excellence referral guidelines of 2 weeks from suspicion of cancer by a general practitioner (GP) to specialist referral, applies to children as well as to adults. No evidence exists to suggest that these guidelines are not being followed. Indeed, if a GP detects an abdominal mass in a child, the likelihood is that the child will be seen by a paediatrician the same day. However, routine health-surveillance systems for children differ considerably across Europe. In Germany, most children have their own primary-care paediatrician, who undertakes regular health checks, including physical examination and often abdominal ultrasonography. Routine health-surveillance recommendations in the UK are guided by the publication Health for all Children,7 and these guidelines are not as thorough as previous recommendations, with few routine examinations. Most routine health checks are carried out by health visitors and only a few by GPs. In Germany, trials on Wilms’ tumour, held between 1994 and 2001, showed that 27·4% (260 of 947) of patients had a cancer that was first identified incidentally during a visit to a health professional for an unrelated problem or by routine surveillance.8 This percentage contrasts with that at our own two centres, where 11% (10 of 91) of patients presenting to the Royal Marsden Hospital in London and 4% of patients referred to the Newcastle Hospital or the Royal Victoria Infirmary in Newcastle were identified to have incidental tumours (unpublished). In Germany, the survival of those children who were identified only when they had symptoms of Wilms’ tumour was 84% compared with 90% for those http://oncology.thelancet.com Vol 8 August 2007
identified on routine or incidental examination. This difference in timing of diagnosis could account for much of the difference in survival between the UK and Germany. Intensive routine surveillance of children, especially using ultrasonography, might not be cost effective, but it could make a difference to survival from Wilms’ tumour. Suboptimum survival for childhood cancer is just one example of the worse state of children’s health care in the UK compared with many other countries. The perinatal mortality rate puts the UK in 15th position in Europe and there is clear evidence that children with diabetes are not receiving optimum care.9 Although there is a National Service Framework for children, which sets standards, there are no targets. Children continue to be a low priority for the NHS. So what can be done? Multinational clinical trials need to continue and be large enough to complete accrual in a reasonable period of time. Furthermore, routine surveillance and the primary care of children should be rigorously assessed. In the UK, we need to persuade politicians to take the health of children seriously and make an appropriate level of investment, ensuring that the UK improves by comparison with the bestperforming countries. Our children deserve nothing less.
For a discussion of recent improvements in paediatric oncology see Leading Edge page 661
*Alan W Craft, Kathy Pritchard-Jones Institute of Child Health, Newcastle upon Tyne, UK (AWC); Royal Marsden Hospital and Institute of Cancer Research, Surrey, UK (KP-J). [email protected] The authors declared no conflicts of interest. 1
2
3 4
5
6
7 8 9
Coebergh JW, Capocaccia R, Gatta G, Magnani C, Stiller CA. Childhood cancer survival in Europe 1978–1992: The EUROCARE study. Eur J Cancer 2001; 37: 671–816. Steliarova-Foucher E, Coebergh JW, Kaatsch P, Prichard-Jones K, Stiller C. Cancer in children and adolescents in Europe. Eur J Cancer 2006: 42: 1913–2190. Schilling FH, Spix C, Berthold F, Ertmann R. Neuroblastoma screening at 1 year of age. New Engl J Med 2002: 346: 1047–53. Powell JE, Esteve J, Mann JR, et al. Neuroblastoma in Europe: differences in the pattern of disease in the UK. SENSE. Study group for the Evaluation of Neuroblastoma Screening in Europe. Lancet 1998; 352: 682–87. Spix C, Pastore G, Sankila R, Stiller CA. Neuroblastoma incidence and survival in European children (1973–1997): report from the ACCIS project. Eur J Cancer 2006; 42: 2081–91. Pastore G, Znaor A, Spreafico F, Graff N, Pritchard-Jones K, SteliarovaFoucher E. Malignant renal tumours incidence and survival in European children (1978–1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42: 2103–14. Hall DMB, Elliman D. Health for all children, 4th edn. Oxford: Oxford University Press, 2003. Graf N, Reinhard H, Aliani S, et al. Wilms’ tumour with or without tumour related symptoms at diagnosis. Med Pediatr Oncol 2003: 41: 266. Danne T, Mortensen HB, Hougaard P, et al. Persistent differences among centers over 3 years in glycemic control and hypoglycaemia in a study of 3805 children and adolescents with Type 1 diabetes from the Hvidore Study Group. Diabetes Care 2001; 24: 1342–47.
663
UK childhood cancer survival falling behind rest of EU?
Hidajet Delic/AP/PA Photos
One of the main driving forces behind the initiation of the UK National Cancer Plan was the unfavourable comparison of cancer outcomes between adults in England and adults in parts of mainland Europe. This plan is already beginning to have a major effect on outcome, by centralisation and better organisation of care. Childhood cancer has long been seen as the model for organisation of care, with most children being treated on national protocols and in specialist-care centres since the establishment of the UK Children’s Cancer Study Group (UKCCSG; now called the Children’s Cancer and Leukaemia Group) 30 years ago. Between 1978 and 1982, 57% of children were referred to a specialist-care centre, and this percentage rose to 89% between 1998 and 2002. Therefore, the results of two major comparative studies, which showed that survival from childhood cancer is low compared with other European countries, are somewhat concerning.1,2 However, caveats should be placed around such comparisons, especially as cancer registry data are collected differently across Europe. First, only a few countries have good linkage between registration data and mortality data, to allow complete follow-up for survival. The UK and Scandinavia probably have the best registration systems. Second, there are problems of definition, especially for brain tumours. Third, if multiple comparisons are made then some results will be deemed significant by chance.
Survival rates differ for children across Europe
662
However, the consistency of the relative ranking of UK survival rates compared with those of some northern and western European countries merits further scrutiny. To try to understand the possible reasons for the low cancer survival rate in the UK, we have chosen to focus on two childhood cancers that usually present with clinical features that are alarming to parents and should, therefore, lead them to seek early contact with health professionals. A common presentation is an abdominal mass, usually either a nephroblastoma (Wilms’ tumour) or a neuroblastoma. Reported survival was worse in the UK compared with some other parts of Europe, in studies spanning the period 1978–1997.1,2 Complete ascertainment of the specific disease type is an important issue, as is knowing the true incidence of the disease. Considerable variation between different European countries exists in the incidence of neuroblastoma, especially in those diagnosed under the age of 1 year. We now know that the likely reason for this variability is that there are at least two types of neuroblastoma, one of which regresses spontaneously and the other being a truly malignant tumour. In populations where screening for neuroblastoma was undertaken, the incidence almost doubled.3 If population survival data include these spontaneously regressing tumours, then survival will be artificially increased. Countries that have active childhealth surveillance programmes for children in their first year of life also have an increased incidence. In the UK, a greater proportion of children with neuroblastoma have metastatic disease at presentation,4 suggesting they are diagnosed somewhat later in the course of their disease. This finding might explain the differences in overall survival from neuroblastoma even for those diagnosed after the second year of life (British Isles 30% [95% CI 26–35] vs western Europe (mainly Germany, Belgium, Netherlands, Luxembourg, and Switzerland) 46% [42–50]).5 Wilms’ tumour is a common solid tumour of childhood and one where there should be little difficulty in comprehensive ascertainment or pathological definition, and no spontaneous regression. Even though, for the past 15 years, over 94% of children with Wilms’ tumour have been referred to specialist centres in the British Isles, their overall survival of 83% is slightly, but significantly, worse than the rate of 89% reported for northern (Scandinavia) and western Europe.6 This difference in survival is unlikely http://oncology.thelancet.com Vol 8 August 2007
Keynote Comment
to be caused by access to specialist-care centres or to the speed and delivery of treatment once a referral has been made. Access to clinical trials is widely available across Europe, but, until recently, there was no European-wide standard clinical protocol and children from the UK were receiving a different treatment protocol to many of those in other parts of Europe. Therefore, the possibility exists that children from the UK have been receiving suboptimum first-line treatment or less-intensive salvage treatment at relapse. Evidence supports this idea, by showing that survival is improving with the latest treatment protocol and introduction of a national relapse strategy. A nihilistic versus an aggressive approach to relapse could make a real difference to overall survival and such an approach could be either professionally or parent driven. The original care pathway might also contribute to differences in survival. Early diagnosis is likely to be important and the National Institute of Health and Clinical Excellence referral guidelines of 2 weeks from suspicion of cancer by a general practitioner (GP) to specialist referral, applies to children as well as to adults. No evidence exists to suggest that these guidelines are not being followed. Indeed, if a GP detects an abdominal mass in a child, the likelihood is that the child will be seen by a paediatrician the same day. However, routine health-surveillance systems for children differ considerably across Europe. In Germany, most children have their own primary-care paediatrician, who undertakes regular health checks, including physical examination and often abdominal ultrasonography. Routine health-surveillance recommendations in the UK are guided by the publication Health for all Children,7 and these guidelines are not as thorough as previous recommendations, with few routine examinations. Most routine health checks are carried out by health visitors and only a few by GPs. In Germany, trials on Wilms’ tumour, held between 1994 and 2001, showed that 27·4% (260 of 947) of patients had a cancer that was first identified incidentally during a visit to a health professional for an unrelated problem or by routine surveillance.8 This percentage contrasts with that at our own two centres, where 11% (10 of 91) of patients presenting to the Royal Marsden Hospital in London and 4% of patients referred to the Newcastle Hospital or the Royal Victoria Infirmary in Newcastle were identified to have incidental tumours (unpublished). In Germany, the survival of those children who were identified only when they had symptoms of Wilms’ tumour was 84% compared with 90% for those http://oncology.thelancet.com Vol 8 August 2007
identified on routine or incidental examination. This difference in timing of diagnosis could account for much of the difference in survival between the UK and Germany. Intensive routine surveillance of children, especially using ultrasonography, might not be cost effective, but it could make a difference to survival from Wilms’ tumour. Suboptimum survival for childhood cancer is just one example of the worse state of children’s health care in the UK compared with many other countries. The perinatal mortality rate puts the UK in 15th position in Europe and there is clear evidence that children with diabetes are not receiving optimum care.9 Although there is a National Service Framework for children, which sets standards, there are no targets. Children continue to be a low priority for the NHS. So what can be done? Multinational clinical trials need to continue and be large enough to complete accrual in a reasonable period of time. Furthermore, routine surveillance and the primary care of children should be rigorously assessed. In the UK, we need to persuade politicians to take the health of children seriously and make an appropriate level of investment, ensuring that the UK improves by comparison with the bestperforming countries. Our children deserve nothing less.
For a discussion of recent improvements in paediatric oncology see Leading Edge page 661
*Alan W Craft, Kathy Pritchard-Jones Institute of Child Health, Newcastle upon Tyne, UK (AWC); Royal Marsden Hospital and Institute of Cancer Research, Surrey, UK (KP-J). [email protected] The authors declared no conflicts of interest. 1
2
3 4
5
6
7 8 9
Coebergh JW, Capocaccia R, Gatta G, Magnani C, Stiller CA. Childhood cancer survival in Europe 1978–1992: The EUROCARE study. Eur J Cancer 2001; 37: 671–816. Steliarova-Foucher E, Coebergh JW, Kaatsch P, Prichard-Jones K, Stiller C. Cancer in children and adolescents in Europe. Eur J Cancer 2006: 42: 1913–2190. Schilling FH, Spix C, Berthold F, Ertmann R. Neuroblastoma screening at 1 year of age. New Engl J Med 2002: 346: 1047–53. Powell JE, Esteve J, Mann JR, et al. Neuroblastoma in Europe: differences in the pattern of disease in the UK. SENSE. Study group for the Evaluation of Neuroblastoma Screening in Europe. Lancet 1998; 352: 682–87. Spix C, Pastore G, Sankila R, Stiller CA. Neuroblastoma incidence and survival in European children (1973–1997): report from the ACCIS project. Eur J Cancer 2006; 42: 2081–91. Pastore G, Znaor A, Spreafico F, Graff N, Pritchard-Jones K, SteliarovaFoucher E. Malignant renal tumours incidence and survival in European children (1978–1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42: 2103–14. Hall DMB, Elliman D. Health for all children, 4th edn. Oxford: Oxford University Press, 2003. Graf N, Reinhard H, Aliani S, et al. Wilms’ tumour with or without tumour related symptoms at diagnosis. Med Pediatr Oncol 2003: 41: 266. Danne T, Mortensen HB, Hougaard P, et al. Persistent differences among centers over 3 years in glycemic control and hypoglycaemia in a study of 3805 children and adolescents with Type 1 diabetes from the Hvidore Study Group. Diabetes Care 2001; 24: 1342–47.
663