1 Overview of presentation 1.Context 2.Objectives 3.Methods 4.What has been achieved 5.What has to be done NCSI-CYP – Risk Stratification Investigation

2 British Childhood Cancer Survivor Study (BCCSS) (available evidence) 1. Context The BCCSS comprises the population–based cohort of individuals diagnosed with cancer before aged 15 years, between 1940 and 1991 inclusive, in Britain, who survived at least 5 years from diagnosis. An on-going programme of population-based studies of: risks of specific underlying causes of deaths occurring beyond 5- year survival (3049 observed so far); risks and aetiology of subsequent primary neoplasms developing beyond 5-year survival (1354 observed so far). Whenever possible a postal questionnaire was sent to each of the survivors aged at least 16 years. The questionnaire was concerned with a wide spectrum of health and social outcomes and survivors returned a completed questionnaire, 70% of those eligible.

3 BCCSS – future evidence 1. Context In 2011 the BCCSS will be extended to comprise the population-based cohort of individuals diagnosed with cancer before aged 15 years, between 1940 and 2005 inclusive, in Britain, who survived at least 5 years from diagnosis. Annually in each of the next 5 years an additional year survivors (diagnosed in 2006, 2007, 2008, 2009 and 2010) will be added to the BCCSS database producing an overall total of year survivors. There will be a continuation of the programme of population-based investigations of: risks of specific causes of death; risks and aetiology of subsequent primary neoplasms. In addition the BCCSS database will be linked to the Hospital Episode Statistics (HES) for England, the Patient Episode Database for Wales (PEDW), the Information Services Division (ISD) linked database for Scotland and the Myocardial Ischaemia National Audit Project (MINAP) for England and Wales.

4 Teenage and Young Adult Cancer Survivor Study (TYACSS) 1. Context TYACSS comprises a cohort of 287, 164 individuals diagnosed with cancer when aged 15 to 39 years inclusive, in England and Wales, between 1971 and 2006 inclusive. 167,660 of these individuals survived at least 5 years from diagnosis and will form the basis of linkage to: 1) the national death registry to obtain underlying causes of death 2)the national cancer registry to obtain occurrences of subsequent primary neoplasms 3)Hospital Episode Statistics (HES), the Patient Episode Database for Wales (PEDW) and the Myocardial Ischaemia National Audit Project for England and Wales (MINAP).

5 2. NCSI-CYP – Risk Stratification Investigation Overall objectives: Use the BCCSS to provide estimates of the risk of specific adverse health and social outcomes for different groups of survivors defined in terms of types of cancer, aspects of treatment and other relevant factors. In particular, provide evidence-based risk profiles for different groups of survivors to inform planning of safe clinical follow-up of childhood cancer survivors in the UK. Assess risks associated with different proposed levels of care (1, 2 and 3) which are developments of the original Wallace et al levels of care.

6 3. Methods 1.Use the entire BCCSS cohort of individuals to assess the risks of specific causes of death and the risk of subsequent primary neoplasms for particular groups of survivors defined in terms of their type/site of cancer and treatment received. 2.Use the returned BCCSS questionnaires to assess risks of specific non-fatal non-cancer adverse outcomes including physical conditions graded using CTCAE, health status (SF36) including mental and physical component scores, and social outcomes including education and employment. 3.For 2000 individuals very detailed treatment exposure is available and this will be used to assess specific treatment exposure and associated adverse outcome risks. 4.For 2800 and 100 survivors of ALL and AML, respectively, treated within MRC randomised trials investigate risks of adverse outcomes in relation to treatment received, based on the assumption of treatment as per protocol for the relevant randomisation arm.

7 4. What has been achieved Entire cohort – causes of death JAMA (2010) 304:

8 Health status of adult survivors of childhood cancer (SF-36) Directly (age and sex) standardised prevalence of reporting being limited in specific activities Int. J. Cancer (2007): 121; Reulen et al 4. What has been achieved returned questionnaires – health status (SF-36)

9 4. What has been achieved returned questionnaires – health status (SF-36)

10 4. What has been achieved returned questionnaires – health status (SF-36)

11 4. What has been achieved returned questionnaires – health status (SF-36)

12 EDUCATIONAL ATTAINMENT AMONG SURVIVORS J. Natl. Cancer Inst. Lancashire et al (2010); 102: What has been achieved returned questionnaires – educational attainment

13 Comparison with general population data, all survivors (controlling for age and gender) At all stages of educational attainment that were considered survivors of childhood cancer were found to perform worse than the general population. 4. What has been achieved returned questionnaires – educational attainment

14 Comparison with general population data by cancer type Deficits are observed in survivors of CNS neoplasm and leukaemia 4. What has been achieved returned questionnaires – educational attainment

15 Comparison with general population data by cancer type Deficits are observed in survivors of CNS neoplasm and leukaemia. Excesses are observed for survivors of bone sarcoma and retinoblastoma. 4. What has been achieved returned questionnaires – educational attainment

16 4. What has been achieved returned questionnaires – CTCAE grading of physical conditions is complete

17 4. What has been achieved 2000 individuals with very detailed treatment

18 4. What has been achieved 2000 individuals with very detailed treatment Have computerised all cumulative doses and the number of patients exposed to particular agents were:

19 4. What has been achieved 2000 individuals with very detailed treatment Levels of exposure to radiotherapy (I):

20 4. What has been achieved 2844 individuals entered into MRC ALL trials 260 (9%) had BMT (73%) did not experience a relapse. Of the 2080 not relapsing, 1888 (91%) received cranial irradiation. Of the 764 relapsing, 540 (71%) did not receive a BMT

21 5. What has to be done All treatment exposure and adverse health and social outcome data is now computerised, with the exception of that relating to 100 patients treated within MRC-AML trials Firstly for physical adverse health outcomes, then secondly for health status and social outcomes: a) risks of specific causes of death and particular subsequent primary neoplasms for different groups of survivors defined in terms of type/site of cancer and aspects of treatment b) risks of non-fatal, non neoplastic adverse health outcomes for different groups of survivors defined in terms of type/site of cancer and aspects of treatment. c)2000 detailed treatment -investigation a) & b) as above, with the advantage of more detailed treatment, but disadvantage of lower frequency of specific outcomes. d)3000 in ALL/AML trials – investigations as a) & b) above.