Survival in Teenagers and Young. Adults with Cancer in the UK

Transcription

1 Survival in Teenagers and Young Adults with Cancer in the UK

2 Survival in Teenagers and Young Adults (TYA) with Cancer in the UK A comparative report comparing TYA cancer survival with that of children aged 0 to 14 years and adults aged 25 to 49 years and looking at differences in survival by gender Authors: C O Hara, A Moran (NWCIS) and the TYA National Cancer Intelligence Advisory Group 1 August Details of the membership and role of this group can be found at I

3 Table of Contents Summary... 1 Introduction... 3 Methods... 4 Study Subjects... 5 Results... 7 Comparative overview of five year survival by diagnosis and five year age band Results by Diagnosis ) Acute Lymphoblastic Leukaemia (ALL) ) Acute Myeloid Leukaemia ) Non Hodgkin Lymphoma (HL) ) Hodgkin Lymphoma (HL) ) CNS tumours (including borderline and benign) ) Bone tumours ) Soft tissue sarcomas (STS) ) Germ Cell Tumours of the Ovary ) Germ Cell Tumours of the Testis ) Extra gonadal Germ Cell Tumours ) Melanoma of the Skin ) Carcinoma of the Thyroid ) Carcinoma of the Breast (females) ) Carcinoma of the Ovary ) Carcinoma of the Uterine Cervix ) Carcinoma of the Colon or Rectum Discussion Acknowledgements References Appendix II

4 Summary There is evidence that outcomes in TYA cancer patients, as measured by survival rates, are sometimes not as good as those for children. Poorer survival for males than females have also been reported for certain types of cancer. In the light of this evidence, we decided to undertake a detailed study of survival rates in TYA with cancer in the UK, comparing these with outcomes in children and in adults diagnosed between 25 and 49 years of age. Outcomes are also compared by gender. This report has been written by NWCIS and the TYA National Intelligence Advisory Group, which is an informal group of interested clinicians and epidemiologists who support NWCIS in their TYA work. It has been produced under the auspices of the NCIN and the Childhood and TYA Clinical Reference Group. Age The pattern of survival rates with age varied markedly by type of cancer for patients diagnosed in in the UK. The most important findings were: Five year survival rates decreased markedly from 0 to 49 years in patients with ALL, and to a lesser extent AML. Large differences were present one year after diagnosis showing that early deaths made a major contribution to the drop in survival with age. Patients aged years with STS and with bone tumours had lower five year survival than either the 0 14 or age groups. TYA patients with CNS tumours had better survival rates than either younger or older patients. Gender Females aged had statistically significantly better five year survival than males for STS and melanoma. Rates for females aged were more than 5% higher than for males for NLL, ALL and colorectal carcinoma, though these were not statistically significant. In the age group females had better survival than males for melanoma and colorectal carcinoma though neither were statistically significant. For STS males aged had poorer survival, but with little difference from 30 years onwards, suggesting that the health behaviour of men in their 20s may be worth investigating. Females had better survival than males for melanoma at all ages examined. 1

5 Way forward Additional analyses are being undertaken for ALL, CNS, STS and bone tumours to help explain these results. Further research is indicated in TYA patients into the biology of their cancers, delays in diagnosis and treatment and the optimal management. 2

6 Introduction There is increasing recognition that teenagers and young adults (TYA) are a distinct group as regards cancer, differing from children, and middle aged and older adults in many important aspects including response to treatment, health behaviour and wider needs. We defined TYA as those who are diagnosed with cancer from their 15 th to 25 th birthday. Choice of age range to report is influenced by several factors. We chose this age range to reflect commissioning arrangements for clinical services in England and to span delivery of care between services for children and those for adults; one could argue for the expansion of the age range to include 13 and 14 years olds and those up to aged 29 or even 39. Approximately 2,000 individuals aged between years are diagnosed with cancer each year in the UK. About 300 TYA patients die from cancer each year. Cancers in TYA are classified mainly by tumour morphology rather than the part of the body in which the tumour arises. The relative frequency of different cancers in TYA is markedly different from that in middle aged and older adults. It more closely resembles the distribution of cancers seen in childhood, though there are many important differences. The Improving Outcome Guidance (IOG) for Children and Young People with cancer (2005) recommends that patients aged are managed at a Principal Treatment Centre (PTC) for TYA cancers and that those aged are given the choice of being managed at a PTC. The National Cancer Intelligence Service (NCIN) has emphasised the importance of TYA by making it a lead registry role; this is undertaken by the North West Cancer Intelligence Service (NWCIS). There is evidence that outcomes in TYA cancer patients, as measured by survival rates, are sometimes not as good as those for children. Poorer survival for males than females have also been reported for certain types of cancer. In the light of this evidence, we decided to undertake a detailed study of survival rates in TYA with cancer in the UK, comparing these with outcomes in children and in adults diagnosed between 25 and 49 years of age. Outcomes are also compared by gender. This report has been written by NWCIS and the TYA National Intelligence Advisory Group, which is an informal group of interested clinicians and epidemiologists who support NWCIS in their TYA work. It has been produced under the auspices of the NCIN and the Childhood and TYA Clinical Reference Group. 3

7 Methods We identified all patients resident in the UK who were diagnosed with a malignant neoplasm or a benign or borderline CNS tumour between the ages of 0 and 49 years. We used the TYA cancer database held by the North West Cancer Intelligence Service (NWCIS), populated with annual updates from the National Cancer Data Repository (NCDR), which is an amalgamated dataset of all cancer registrations for the UK between 1985 and We classified patients into those diagnosed at 0 14, and years, including only the first malignancy recorded for each individual. The age group were divided into and year olds for more detailed analyses. Analyses were also undertaken for each five year age group from 0 4 to years. Cancers cases that were registered only as a result of a cancer being recorded on a death certificate (DCOs) were excluded as were individuals whose date of death was the same as date of diagnosis (zero survivors). Any five year age group was excluded from the analysis if the total number of new cases of any diagnosis group per year was less than 5. The 0 14 year age group was excluded if the number of new cases per year was less than 10. Cases are grouped by diagnoses using the TYA classification scheme (Birch et al 2002). Details of the classifications are found in the Appendix. Survival up to 5 years was estimated for each age group including all cases with a first diagnosis of cancer between 1st January 2001 and 31st December Each case was censored at 31st December 2010 or at death (from any cause) if earlier. Relative survival was estimated using the STATA STRS programme (Dickman et al 2004) which estimates survival as the ratio of the observed survival of the patients (where all deaths are considered events) to the survival that would be expected if each cancer patient experienced the same survival (life expectancy) as observed in the general population. Using national life tables stratified by age, sex and time, expected survival was estimated using the Ederer II method. Differences in five year relative survival by age and gender were modelled by using a multiple regression approach based on generalized linear models, assuming a Poisson distribution for the observed number of deaths. The excess hazard ratios (EHRs) of death derived from these models quantifies the extent to which the risk of death in one group differs from that of another or others after considering the background risk of death in the general population (after Dickman et al 2004). Differences were considered statistically significant if P values were <0.05 (two sided). All statistical analyses were conducted using STATA version

8 Study Subjects Table I. Number of cases in UK diagnosed that have been included in the survival analyses by gender, age and diagnosis*. MALES FEMALES PERSONS 0 to 14 years 15 to 24 years 25 to 49 years 0 to 14 years 15 to 24 years 25 to 49 years 0 to 14 years 15 to 24 years 25 to 49 years ALL 1, , AML ,333 NHL , , ,993 HL , , ,345 2,973 CNS tumours 1, , ,442 1,980 1,245 8,935 Bone tumours STS , , ,581 testicular germ cell tumours -- 1,260 7, ,260 7,179 ovarian germ cell tumours extra-gonadal germ cell tumours melanomas , , ,083 12,598 thyroid carcinomas , ,269 breast carcinomas , ,111 ovarian carcinomas , ,401 cervical carcinomas , ,405 colorectal carcinomas , , ,295 *Note these figures may differ slightly from published incidence figures for the same time period as some cases are excluded for the purpose of survival analyses (see methods) 5

9 Table II. Number of cases in UK diagnosed that have been included in the survival analyses by gender, age and diagnosis*. MALES FEMALES PERSONS 0 to 14 years 15 to 24 years 25 to 49 years 0 to 14 years 15 to 24 years 25 to 49 years 0 to 14 years 15 to 24 years 25 to 49 years ALL , AML ,366 NHL , , ,428 HL , , ,474 3,281 CNS tumours 1, , ,063 2,040 1,398 9,870 Bone tumours STS , , ,936 testicular germ cell tumours -- 1,382 7, ,382 7,558 ovarian germ cell tumours extra-gonadal germ cell tumours melanomas , , ,196 14,941 thyroid carcinomas , ,326 breast carcinomas , ,815 ovarian carcinomas , ,447 cervical carcinomas , ,478 colorectal carcinomas , , ,599 *Note these figures may differ slightly from published incidence figures for the same time period as some cases are excluded for the purpose of survival analyses (see methods) 6

10 Results Overview of five-year survival by diagnosis and age 2 for patients diagnosed in the UK year survival (%) ALL AML HL NHL Figure I: Haematological Malignancies Acute Lymphoblastic Leukaemia (ALL), Acute Myeloid Leukaemia (AML), Non Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL) year survival (%) CNS tumours Bone tumours STS Figure II: CNS Tumours, Bone Tumours and Soft Tissue Sarcomas (STS) 2 Data for 0 to 14 year age group where number of cases is too small have been excluded. 7

11 year survival (%) Extragonadal germ cell tumours Figure III: Germ Cell Tumours Ovarian germ cell tumours Testicular germ cell tumours year survival (%) Breast carcinoma Cervical carcinoma Colorectal carcinoma Ovarian carcinoma Thyroid carcinoma Melanoma Figure IV: Carcinomas and Melanoma 8

12 Results by Diagnosis The following section provides detailed comparative analyses of 5 year survival for 16 diagnostic groups, looking at differences in outcomes by age and gender for individual diagnostic types. Tabulated data for each of the diagnostic groups examined here are also provided in the Appendix (Tables A.1 and A.2). 1) Acute Lymphoblastic Leukaemia (ALL) 2) Acute Myeloid Leukaemia 3) Non Hodgkin Lymphoma (HL) 4) Hodgkin Lymphoma (HL) 5) CNS Tumours 6) Bone Tumours 7) Soft Tissue Sarcomas (STS) 8) Germ Cell Tumours of the Ovary 9) Germ Cell Tumours of the Testis 10) Extra gonadal Germ Cell Tumours 11) Melanoma of the Skin 12) Carcinoma of the Thyroid 13) Carcinoma of the Breast (females) 14) Carcinoma of the Ovary 15) Carcinoma of the Uterine Cervix 16) Carcinoma of the Colon or Rectum 9

13 1) Acute Lymphoblastic Leukaemia (ALL) % Survival Acute Lymphoblastic Leukaemia survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 1.1: 0 to 5 year relative survival for patients diagnosed in with ALL in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For patients diagnosed between 2001 and 2005, we observed a trend of decreasing survival with age that starts to appear within the first year after diagnosis (Fig 1.1). Five year relative survival was 20% lower among the TYA age group (15 to 24 years) than among the paediatric age group aged 0 to 14 years but 23% higher than the 25 to 49 year olds (Table 1.1). Even within the TYA age group itself, survival was observed to be lower for the older TYA patients (19 to 24 years) having 17% lower 5 year survival that the 15 to 18 year olds (Table 1.1). Table 1.1: Five year survival for those diagnosed with ALL in by age group, comparing survival among 15 to 24 year olds with the younger and older age groups, and 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years ( ) to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

14 The decreasing trend in 5 year survival was observed for both sexes, although the age differentiation appears to start at a slightly later age in females than males (Fig 1.2). No significant differences were observed between males and females with ALL for any of the age groups examined (Table 1.2 and Fig 1.2). Table 1.2: Five year survival for those diagnosed with ALL in , comparing survival for males with females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 0 to 14 years M Ref -- F ( ) to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) 0.91 Acute Lymphoblastic Leukaemia % Survival to 4 5 to 9 10 to to to to to to to to 99 Males Females Figure 1.2: Five year survival for those aged 0 to 49 years diagnosed with ALL in by fiveyear age group and gender. Significant differences in 5 year survival between males and females for each age band are indicated by stars above each bar: *Significant at P< 0.05, **Significant at P< 0.01,***Significant at P< 0.001, No stars = no significant difference. 11

15 2) Acute Myeloid Leukaemia % Survival Acute Myeloid Leukaemia survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 2.1: 0 to 5 year relative survival for patients diagnosed with AML in in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For patients diagnosed with AML between 2001 and 2005, we again observed a trend of decreasing survival with age that starts to arise within the first year of diagnosis (Fig 2.1). Five year relative survival was 9% lower among the TYA age group (15 to 24 years) than among the paediatric age group aged 0 to 14 years but 6% higher than the 25 to 49 year olds (Table 1.1). differences were observed within the TYA age group itself (Table 2.1). No significant Table 2.1: Five year survival for those diagnosed with AML in by age group, comparing 5 year survival among 15 to 24 year olds with the younger and older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years ( ) to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

16 The decreasing trend by age was observed for both sexes (Fig 1.2). No significant differences were observed between males and females with AML for the paediatric or TYA age groups. However, significant differences were observed between males and females of the 25 to 49 year age group with males having 6% lower 5 year survival than females (Table 1.2) differences appear to occur between 25 and 34 years of age (Fig 2.2). Most of these gender Table 1.2: Five year survival for those diagnosed with AML in , comparing 5 year survival for males with survival for females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 0 to 14 years M Ref -- F ( ) to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) 0.04 Acute Myeloid Leukaemia % Survival ** * 0 to 4 5 to 9 10 to to to to to to to to 49 Males Females Figure 2.2: Five year survival for those aged 0 to 49 years diagnosed with AML in by five year age group and gender. Significant differences in 5 year survival between males and females for each age band are indicated by stars above each bar: * Significant at P< 0.05, **Significant at P< 0.01, ***Significant at P< 0.001, No stars = no significant difference. 13

17 3) Non-Hodgkin Lymphoma (HL) % Survival Non-Hodgkin Lymphoma survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 3.1: 0 to 5 year relative survival for patients diagnosed with NHL in in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For patients diagnosed with NHL between 2001 and 2005, we observed only small differences in survival between the three age groups. However, the paediatric age group showed marginally better relative survival between 2 and 5 years after diagnosis than the two other age groups (Fig 3.1), and had statistically significantly better five year survival of 85% compared with 78% and 79% for the TYA and 25 to 49 year age groups respectively. We also observed significantly higher 5 year survival among the 15 to 18 years (83%) compared with the 19 to 24 year olds (75%) (Table 3.1). Table 3.1: Five year survival for those diagnosed with NHL in by age group, comparing 5 year survival among 15 to 24 year olds with the younger and older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years ( ) to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

18 No significant differences were observed between males and females with NHL for the paediatric or TYA age groups (Fig 3.2). Significant differences were observed between males and females of the 25 to 49 year age group with males having 3% lower 5 year survival than females (Table 3.2) Most of these gender differences appear to occur towards at the upper end of this age group (Fig 3.2). Table 3.2: Five year survival for those diagnosed with NHL in , comparing 5 year survival for males with survival for females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 0 to 14 years M Ref -- F ( ) to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) 0.02 Non-Hodgkin Lymphoma % Survival * * 0 to 4 5 to 9 10 to to to to to to to to 49 Males Females Figure 3.2: Five year survival for those aged 0 to 49 years diagnosed with NHL in by five year age group and gender. Significant differences in 5 year survival between males and females for each age band are indicated by stars above each bar: *Significant at P< 0.05, **Significant at P< 0.01, ***Significant at P< 0.001, No stars = no significant difference. 15

19 4) Hodgkin Lymphoma (HL) % Survival Hodgkin Lymphoma survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 4.1: 0 to 5 year relative survival for patients diagnosed with HL in in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For patients diagnosed with HL between 2001 and 2005, we observed no difference in survival between the paediatric and TYA age groups (Fig 4.1 and Table 4.1) and no difference in 5 year survival within the TYA age group itself (Table 4.1); patients up to 24 years of age experienced an average of 94% survival at 5 years. However, survival among the older age group (25 to 49 years) was observed to be slightly lower than the TYA age group at 91% (Table 4.1). differences were observed between males and females (Table 4.2 and Fig 4.2). No significant Table 4.1: Five year survival for those diagnosed with HL in by age group, comparing 5 year survival among 15 to 24 year olds with the younger and older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years ( ) to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

20 Table 4.2: Five year survival for those diagnosed with HL in , comparing 5 year survival for males with survival for females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 0 to 14 years M Ref -- F ( ) to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) 0.68 Hodgkin Lymphoma % Survival to 9 10 to to to to to to to to 49 Males Females Figure 4.2: Five year survival for those aged 0 to 49 years diagnosed with HL in by fiveyear age group and gender. Significant differences in 5 year survival between males and females for each age band are indicated by stars above each bar: *Significant at P< 0.05, **Significant at P< 0.01, ***Significant at P< 0.001, No stars = no significant difference. The number of cases for the 0 to 4 age group is too small to include. 17

21 5) CNS tumours (Central Nervous System & other Intracranial & Intraspinal Neoplasms including borderline and benign) % Survival CNS Tumours survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 5.1: 0 to 5 year relative survival for patients diagnosed with a CNS tumour in in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For patients diagnosed with a CNS tumour between 2001 and 2005, we observed higher survival among the TYA age group (82%) than both the paediatric age group (75 %) and the older age group of 25 to 49 years (73%) (Fig 5.1 and Table 5.1). No significant difference was observed within TYA age group itself (Table 5.1). Table 5.1: Five year survival for those diagnosed with CNS tumours in by age group, comparing 5 year survival among 15 to 24 year olds with the younger and older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years ( ) to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

22 No significant differences were observed between males and females within the paediatric or TYA age groups (Table 5.2). However, among patients aged 25 to 49 years, significant differences were observed in 5 year survival between males and females (Table 5.2) with females having between 10% and 20% higher 5 year survival than males across the age group (Fig 5.2). Table 5.2: Five year survival for those diagnosed with a CNS tumour in , comparing 5 year survival for males with survival for females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 0 to 14 years M Ref -- F ( ) to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) 0.00 CNS Tumours % survival *** *** *** *** *** 5 to 9 10 to to to to to to to to 49 Males Females Figure 5.2: Five year survival for those aged 0 to 49 years diagnosed with a CNS tumour in by five year age group and gender. Significant differences in 5 year survival between males and females for each age band are indicated by stars above each bar: *Significant at P< 0.05, **Significant at P< 0.01, ***Significant at P< 0.001, No stars = no significant difference. 19

23 6) Bone tumours (Osseous and Chondromatous Neoplasms, Ewing tumour and other Neoplasms of Bone) % Survival Bone Tumours survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 6.1: 0 to 5 year relative survival for patients diagnosed with a bone tumour in in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For patients diagnosed with a bone tumour between 2001 and 2005, survival among TYA patients was significantly lower (56%) than that of both paediatric patients (63%) and the older age group (65%) (Table 6.1) a difference that appears to start to arise between 1 and 2 years following diagnosis (Fig 6.1). No significant difference in survival was observed within the TYA age group itself (Table 6.1). Table 6.1: Five year survival for those diagnosed with a bone tumour in by age group, comparing 5 year survival among 15 to 24 year olds with the younger and older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years ( ) to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

24 No significant differences were observed between males and females except within the older age group, aged 25 to 49 years (Table 6.2) where males had 9% lower 5 year survival than females. The only 5 year age band in which the difference between males and females was shown to be statistically significant was the 30 to 34 year age band (Fig 6.2). Table 6.2: Five year survival for those diagnosed with a bone tumour in , comparing 5 year survival for males with survival for females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 0 to 14 years M Ref -- F ( ) to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) 0.02 Bone Tumours % Survival * 0 to 4 5 to 9 10 to to to to to to to to 49 Males Females Figure 6.2: Five year survival for those aged 0 to 49 years diagnosed with a bone tumour in by five year age group and gender. Significant differences in 5 year survival between males and females for each age band are indicated by stars above each bar: *Significant at P< 0.05, **Significant at P< 0.01, ***Significant at P< 0.001, No stars = no significant difference. 21

25 7) Soft tissue sarcomas (STS) % Survival Soft Tissue Sarcomas survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 7.1: 0 to 5 year relative survival for patients diagnosed with STS in in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For patients diagnosed with a STS between 2001 and 2005, we observed lower survival in the TYA age group than in both the paediatric and the older age group, that appears to arise between one and two years following diagnosis (Fig 7.1). Five year survival for TYA patients was 6% lower at 61% than for paediatric patients and 25 to 49 year olds both which had 67% 5 year survival (Table 7.1). The 19 to 24 year olds also had higher 5 year survival at 64% than the 15 to 18 year olds (55%) although this did not reach statistical significance. Table 7.1: Five year survival for those diagnosed with STS in by age group, comparing 5 year survival among 15 to 24 year olds with the younger and older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years ( ) to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

26 Significant differences were observed between males and females within the TYA age group (Table 7.2) with females having higher 5 year survival rates (68%) than males (55%). These gender differences are particularly marked in the 20 to 24 year age group (Fig 7.2). Females also have better survival in some of the 5 year age bands under 15 years of age but these were not found to be statistically significant (Fig 7.2). No gender differences were evident for ages 25 to 49 years. Table 7.2: Five year survival for those diagnosed with STS in , comparing 5 year survival for males with survival for females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 0 to 14 years M Ref -- F ( ) to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) 0.85 Soft Tissue Sarcomas % Survival ** 0 to 4 5 to 9 10 to to to to to to to to 49 Males Females Figure 7.2: Five year survival for those aged 0 to 49 years diagnosed with a STS in by five year age group and gender. Significant differences in 5 year survival between males and females for each age band are indicated by stars above each bar: *Significant at P< 0.05, **Significant at P< 0.01, ***Significant at P< 0.001, No stars = no significant difference. 23

27 8) Germ Cell Tumours of the Ovary % Survival Germ Cell Tumours of the Ovary survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 8.1: 0 to 5 year relative survival for patients diagnosed in in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For female patients diagnosed with an ovarian germ cell tumour between 2001 and 2005, we observed no difference in survival between the TYA age groups and the younger or older age groups or within the TYA age group itself (Fig 8.1 and Table 8.1). It should be noted however that the number of cases within each of these age groups are small and particularly so in the 0 to 14 age group. Table 8.1: Five year survival for females diagnosed with an ovarian germ cell tumour in by age group, comparing 5 year survival among 15 to 24 year olds with the older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years ( ) to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

28 9) Germ Cell Tumours of the Testis % Survival Germ Cell Tumours of the Testis survival time (years) 15 to 24 years 25 to 49 years Figure 9.1: 0 to 5 year relative survival for male patients diagnosed in with a testicular germ cell tumour in the UK at ages 15 to 24 and 25 to 49 years*. The number of cases of testicular germ cell tumours in the 0 to 14 age group is too small to include in these analyses. For male patients diagnosed with a testicular germ cell tumour between 2001 and 2005, we observed no difference in survival between the TYA age groups and the older age groups or within the TYA age group itself (Fig 9.1 and Table 9.1). Table 9.1: Five year survival for males diagnosed with a testicular germ cell tumour in by age group, comparing 5 year survival among 15 to 24 year olds with the older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 15 to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

29 10) Extra-gonadal Germ Cell Tumours % Survival Extra-gonadal Germ Cell Tumours survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 10.1: 0 to 5 year relative survival for patients diagnosed in in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For patients diagnosed with an extra gonadal germ cell tumour between 2001 and 2005, we observed decreasing survival with age within the first year after diagnosis (Fig 10.1) with the paediatric patients have significantly higher 5 year survival of 90% compared with the TYA age group (80%). TYA patients had higher survival that the 25 to 49 year olds (74%) but this difference was not statistically significant (Table 10.1). Table 10.1: Five year survival for those diagnosed with an extra gonadal germ cell tumour in by age group, comparing 5 year survival among 15 to 24 year olds with the younger and older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years ( ) to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

30 No significant differences were observed between males and females in the paediatric or TYA age groups (Table 10.2). However in the 25 to 49 age group, males appear to have significantly lower 5 year survival (65%) than females (88%). An examination of these differences by 5 year age band shows some gender differences to be evident in most age bands over 25 years of age as well as to some extent in the 15 to 19 age band (Fig 10.2). However the number of cases within each age band is too small to confirm the statistical significance of these differences some differences may be due to chance. Table 10.2: Five year survival for those diagnosed with an extra gonadal germ cell tumour in , comparing 5 year survival for males with survival for females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 0 to 14 years M Ref -- F ( ) to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) Extra-gonadal Germ Cell Tumours % Survival to 9 10 to to to to to to to to 49 Males Females Figure 10.2: Five year survival for those aged 0 to 49 years diagnosed with an extra gonadal germ cell tumour in by five year age group and gender. The number of cases of extra gonadal germ cell tumours is too small to allow robust statistical analyses of survival by gender and 5 year age band. 27

31 11) Melanoma of the Skin % Survival Melanoma survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 11.1: 0 to 5 year relative survival for patients diagnosed with skin melanoma in in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For patients diagnosed with skin melanoma between 2001 and 2005 we observed higher survival among TYA patients than both paediatric patients aged 0 to 14 years and patients aged 25 to 49 years. These age related differences appear to begin to arise between and two years following diagnosis (Fig 11.1). Five year relative survival for patients aged 15 to 24 years was 93% compared with 82% for those aged 0 to 14 years although it should be noted that the number of cases for the younger age group is very small (Table 11.1). The difference in 5 year survival between TYA and the older age group is smaller than between TYA and the paediatric age group but the difference is still statistically significant (Table 11.1). No difference was observed within the TYA age group itself. Table 11.1: Five year survival for those diagnosed with HL in by age group, comparing 5 year survival among 15 to 24 year olds with the younger and older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years ( ) to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

32 Significant differences were observed between males and females across all age groups (Table 11.2 and Fig 11.2) (note: number of cases under the 15 years of age is too small for this analysis). Table 11.2: Five year survival for those diagnosed with skin melanoma in , comparing 5 year survival for males with survival for females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 15 to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) 0.00 Melanoma % Survival ** *** *** *** *** *** *** 15 to to to to to to to 49 Males Females Figure 11.2: Five year survival for those aged 0 to 49 years diagnosed with skin melanoma in by five year age group and gender. Significant differences in 5 year survival between males and females for each age band are indicated by stars above each bar: *Significant at P< 0.05, **Significant at P< 0.01, ***Significant at P< 0.001, No stars = no significant differences. Number of cases in patients under 15 years of age is too small for inclusion here. 29

33 12) Carcinoma of the Thyroid % Survival Carcinoma of the Thyroid survival time (years) under 15 years 15 to 24 years 25 to 49 years Figure 12.1: 0 to 5 year relative survival for patients diagnosed in in the UK at ages 0 to 14, 15 to 24 and 25 to 49 years. For patients diagnosed with a thyroid carcinoma between 2001 and 2005, we observed no difference in survival between the TYA age groups and those aged 0 to 14 years or those aged 25 to 49 years (Fig 12.1) and no difference in 5 year survival within the TYA age group itself (Table 12.1); patients up to 49 years of age experienced an average of 98% survival at 5 years Table 12.1: Five year survival for those diagnosed with a thyroid carcinoma in by age group, comparing 5 year survival among 15 to 24 year olds with the younger and older age groups and comparing 15 to 18 year olds with 19 to 24 year olds*. age group n relsurv LCL UCL EHR (CIs) P 0 to 14 years to 24 years Ref to 49 years ( ) to 18 years to 24 years * Number of cases and deaths in the under 15 years and in the 15 to 18 year age group are too small to undertake EHR analysis for these age groups. 30

34 No significant differences were observed between males and females in the TYA age group (Table 12.2) but were evident in the 25 to 49 year olds with females having slightly higher 5 year survival than males, particularly in the 35 to 44 year age groups (Fig 12.2). Table 12.2: Five year survival for those diagnosed with a thyroid carcinoma in , comparing 5 year survival for males with survival for females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 15 to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) % Survival Carcinoma of the Thyroid ** ** 15 to to to to to to to 49 Males Females Figure 12.2: Five year survival for those aged 0 to 49 years diagnosed with a thyroid carcinoma in by five year age group and gender. Significant differences in 5 year survival between males and females for each age band are indicated by stars above each bar: * Significant at P< 0.05, **Significant at P< 0.01, ***Significant at P< No stars = no significant difference. Number of cases in patients under 15 years of age is too small for inclusion here. 31

35 13) Carcinoma of the Breast (females) % Survival Carcinoma of the Breast (females) survival time (years) 15 to 24 years 25 to 49 years Figure 13.1: 0 to 5 year relative survival for patients diagnosed with breast carcinoma in in the UK at ages 15 to 24 and 25 to 49 years. Number of cases in the under 15 years age group is too small to be included. For females diagnosed with a breast carcinoma between 2001 and 2005, we observed no difference in survival between the TYA age groups and the 25 to 49 year olds (Fig 13.1 and Table 13.1) Table 13.1: Five year survival for those diagnosed with HL in by age group, comparing 5 year survival among 15 to 24 year olds with the older age group* age group n relsurv LCL UCL EHR (CIs) P 15 to 24 years Ref to 49 years ( ) *Number of cases within the 15 to 18 year age group is too small to include as comparison with the 19 to 24 age group. 32

36 14) Carcinoma of the Ovary % Survival Carcinoma of the Ovary survival time (years) 15 to 24 years 25 to 49 years Figure 14.1: 0 to 5 year relative survival for patients diagnosed in in the UK at ages 15 to 24 and 25 to 49 years. The number of cases in the under 15 years age group is too small to be included. For patients diagnosed with carcinoma of the ovary between 2001 and 2005, we observed higher survival among the TYA age group than among the 25 to 49 year olds that appears to start to arise from one year following diagnosis (Fig 14.1). Five year survival among the 15 to 24 year olds was 18% higher than for the older age group (Table 14.1) although the number of cases in this age group is considerably lower than in the older age group. within the TYA age group itself (Table 14.1). No difference in 5 year survival was evident Table 14.1: Five year survival for females diagnosed with a carcinoma of the ovary in by age group, comparing 5 year survival among 15 to 24 year olds with the older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 15 to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

37 15) Carcinoma of the Uterine Cervix % Survival Carcinoma of the Uterine Cervix survival time (years) 15 to 24 years 25 to 49 years Figure 15.1: 0 to 5 year relative survival for patients diagnosed with carcinoma of the cervix in in the UK at ages 15 to 24 and 25 to 49 years. Number of cases in the under 15 years age group are too small to be included. For females diagnosed with carcinoma of the cervix between 2001 and 2005, we observed no difference in survival between the TYA age groups and the 25 to 49 year olds (Fig 15.1 and Table 15.1). Table 15.1: Five year survival for females diagnosed with carcinoma of the cervix in by age group, comparing 5 year survival among 15 to 24 year olds with the older age groups*. age group n relsurv LCL UCL EHR (CIs) P 15 to 24 years Ref to 49 years ( ) *Number of cases within the 15 to 18 year age group is too small to include as comparison with the 19 to 24 age group. 34

38 16) Carcinoma of the Colon or Rectum % Survival Carcinoma of the Colon or Rectum survival time (years) 15 to 24 years 25 to 49 years Figure 16.1: 0 to 5 year relative survival for patients diagnosed in in the UK at ages 15 to 24 and 25 to 49 years. The number of cases in the under 15 years age group are too small to be included. For patients diagnosed with colorectal carcinoma between 2001 and 2005, we observed higher survival among the TYA age group than for the 25 to 49 year olds (Fig 16.1), however the number of cases among the 15 to 24 year olds is much smaller than among the older age groups (Table 16.1). We also observed lower 5 year survival among the 19 to 24 year olds than the 15 to 18 year olds within the TYA age group itself. Again, however, it should be noted that these differences are based on very small number of cases and may be due to chance these results should be interpreted with caution. Table 16.1: Five year survival for those diagnosed with colorectal carcinoma in by age group, comparing 5 year survival among 15 to 24 year olds with the younger and older age groups and comparing 15 to 18 year olds with 19 to 24 year olds. age group n relsurv LCL UCL EHR (CIs) P 15 to 24 years Ref to 49 years ( ) to 18 years Ref to 24 years ( )

39 Males in the 15 to 24 year age group were observed to have 11% lower 5 year survival than their female counterparts but this did not reach statistical significance (Table 16.2). Gender differences were, however, statistically significant in the 25 to 49 year age group particularly in the 25 to 29 and the 45 to 49 year age groups (Fig 16.2). Table 16.2: Five year survival for those diagnosed with colorectal carcinoma in , comparing 5 year survival for males with survival for females for each age group. age group sex n relsurv LCL UCL EHR (CIs) P 15 to 24 years M Ref -- F ( ) to 49 years M Ref -- F ( ) Carcinoma of the Colon or Rectum % Survival * * 15 to to to to to to to 49 Males Females Figure 16.2: Five year survival for those aged 0 to 49 years diagnosed with colorectal carcinoma in by five year age group and gender. Significant differences in 5 year survival between males and females for each age band are indicated by stars above each bar: * Significant at P< 0.05, **Significant at P< 0.01, ***Significant at P< No stars = no significant difference. Number of cases in patients under 15 years of age is too small for inclusion here. 36

40 Discussion The pattern of five year survival rates between 0 14, and age groups in the UK varied markedly by type of cancer. For patients with acute leukaemia survival decreased with increasing age. For those with STS and bone tumours survival was worse for TYA patients than for either children or the age group, while TYA patients with CNS tumours had the best survival. In those aged years survival was significantly better for females than males for STS and melanoma. Caution needs to be taken in interpreting these results. Several of the diagnostic categories used, such as CNS, bone, STS and even NHL, are not single clinical entities but include different cancers with varying prognosis. Ovarian cancers are classified as either germ cell tumours or carcinomas based on the morphology codes recorded either by the pathology laboratory or during the cancer registration process. As such, there may be some variation in the usage of these morphology codes between regions and further work is needed to determine the level of consistency in the allocation of these morphology codes and the subsequent classification of ovarian cancers. Until that time, the results for these groups should be taken as provisional. Furthermore, many of the findings are based on relatively small number of cases and small numbers of deaths. With so many comparisons, it is likely that a few statistically significant results are due to chance. Relatively large differences that are not statistically significant, such as the 9% higher survival in females in the age group for colorectal carcinoma, should not be discounted but taken as interesting findings worthy of further investigation. For the less rare types of cancer relatively small differences may be statistically significant. Examples include the 3% and 2% differences in survival between TYA and older adults for HL and melanoma respectively. One needs to consider the clinical importance of such differences and also their validity, as there is considerable noise in the estimation of population based survival rates. Gatta et al (2009) reported that five year relative survival rates for patients with ALL were lower in year olds than in 0 14 year olds in the UK and Ireland, and in the rest of Europe for those diagnosed in Analyses based on the SEER database (which covers a proportion of the US population) for reported lower survival in year olds compared with the 0 14 age group for patients with soft tissue rhabdomyosarcomas and embryonal tumours (Bleyer et al 2006). They also showed that though survival for all bone sarcomas was similar across 0 14, and age groups, patients aged years with osteosarcoma did better than the age group. Birch et al (2008) presented survival rates in England for year olds diagnosed in and reported higher survival rates in females for STS and melanoma; the SEER publication showed the same pattern for melanoma. 37