Transcript Introduction to Public Health and Epidemiology

NCSI-CYP – Risk Stratification Investigation
Overview of presentation
1.
Context
2.
Objectives
3.
Methods
4.
What has been achieved
5.
What has to be done
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1. Context
British Childhood Cancer Survivor Study (BCCSS)
(available evidence)
The BCCSS comprises the population–based cohort of 18000 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 15000
survivors aged at least 16 years. The questionnaire was concerned with
a wide spectrum of health and social outcomes and 10500 survivors
returned a completed questionnaire, 70% of those eligible.
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1. Context
BCCSS – future evidence
In 2011 the BCCSS will be extended to comprise the population-based
cohort of 34000 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 1200 5-year survivors
(diagnosed in 2006, 2007, 2008, 2009 and 2010) will be added to the
BCCSS database producing an overall total of 40000 5-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.
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1. Context
Teenage and Young Adult Cancer Survivor Study
(TYACSS)
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).
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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.
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3. Methods
1.
Use the entire BCCSS cohort of 18000 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 10500 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.
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4. What has been achieved
Entire cohort – causes of death
JAMA (2010) 304: 172-179
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4. What has been achieved
10500 returned questionnaires – health status (SF-36)
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; 633-40 Reulen et al
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4. What has been achieved
10500 returned questionnaires – health status (SF-36)
% limited in bathing and dressing
UK no rms
5%
all survivo rs
12%
leukaemia
6%
Ho dgkin's disease
6%
no n-Ho dgkin's
8%
CNS
21%
neuro blasto ma
10%
retino blasto ma
9%
Wilms' tumo ur
6%
bo ne tumo ur
19%
so ft tissue sarco ma
9%
o ther
9%
0%
10%
20%
30%
40%
50%
60%
70%
80%
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4. What has been achieved
10500 returned questionnaires – health status (SF-36)
% limited in climbing stairs
UK no rms
8%
all survivo rs
18%
leukaemia
8%
Ho dgkin's disease
13%
no n-Ho dgkin's
15%
CNS
27%
neuro blasto ma
19%
retino blasto ma
10%
Wilms' tumo ur
11%
bo ne tumo ur
37%
so ft tissue sarco ma
15%
o ther
13%
0%
10%
20%
30%
40%
50%
60%
70%
80%
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4. What has been achieved
10500 returned questionnaires – health status (SF-36)
%limited in w alking 100 yards
UK no rms
5%
all survivo rs
14%
leukaemia
6%
Ho dgkin's disease
7%
no n-Ho dgkin's
12%
CNS
22%
neuro blasto ma
13%
retino blasto ma
8%
Wilms' tumo ur
9%
bo ne tumo ur
36%
so ft tissue sarco ma
11%
o ther
9%
0%
10%
20%
30%
40%
50%
60%
70%
80%
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4. What has been achieved
10500 returned questionnaires – educational attainment
EDUCATIONAL ATTAINMENT
AMONG SURVIVORS
J. Natl. Cancer Inst.
Lancashire et al (2010); 102: 254-270
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4. What has been achieved
10500 returned questionnaires – educational attainment
Comparison with general population data, all survivors
(controlling for age and gender)
ALL CANCER TYPES
OR
99% CIs
P value
University degree
0.77
0.68 – 0.87
<0.001
Teaching qualification
0.85
0.77 – 0.94
<0.001
A’level
0.85
0.78 – 0.93
<0.001
O’level (grade A to C)
0.81
0.74 – 0.90
<0.001
At all stages of educational attainment that were
considered survivors of childhood cancer were found to
perform worse than the general population.
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4. What has been achieved
10500 returned questionnaires – educational attainment
Comparison with general population data by cancer type
University degree
–
–
Leukaemia (RT = Yes)
Hodgkin’s disease
NHL
CNS neoplasm (RT = Yes)
(RT = No)
Neuroblastoma
Retinoblastoma
Wilms tumour
Bone sarcomas
Soft tissue sarcomas
Other neoplasm
OR
99% CI
P value
0.60
1.00
1.01
0.31
0.58
0.72
1.17
0.87
1.22
1.02
1.12
0.49 – 0.75
0.77 – 1.29
0.74 – 1.38
0.23 – 0.43
0.42 – 0.80
0.46 – 1.14
0.89 – 1.55
0.68 – 1.14
0.88 – 1.69
0.77 – 1.35
0.87 – 1.44
<0.001
0.97
0.93
<0.001
<0.001
0.07
0.14
0.18
0.11
0.86
0.24
Deficits are observed in survivors of CNS neoplasm and
leukaemia
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4. What has been achieved
10500 returned questionnaires – educational attainment
Comparison with general population data by cancer type
O’level
– Leukaemia (RT = Yes)
Hodgkin’s disease
NHL
– CNS neoplasm (RT = Yes)
(RT = No)
Neuroblastoma
+ Retinoblastoma
Wilms tumour
+ Bone sarcomas
Soft tissue sarcomas
Other neoplasm
OR
99% CI
P value
0.72
1.11
1.31
0.37
0.72
0.91
1.40
0.98
1.69
1.08
1.19
0.61 – 0.85
0.88 – 1.41
0.98 – 1.75
0.31 – 0.45
0.57 – 0.90
0.67 – 1.24
1.08 – 1.82
0.79 – 1.21
1.19 – 2.41
0.85 – 1.37
0.95 – 1.50
<0.001
0.25
0.02
<0.001
<0.001
0.45
0.001
0.79
<0.001
0.42
0.05
Deficits are observed in survivors of CNS neoplasm and
leukaemia. Excesses are observed for survivors of bone
sarcoma and retinoblastoma.
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4. What has been achieved
10500 returned questionnaires – CTCAE grading of physical
conditions is complete
FPT Diag (grouped)
Category
LEUK (1)
539
HODGKINS
(2)
76
NHL (3)
82
CNS (4)
1377
NEURO (5)
45
RETINO (6)
986
WILMS (7)
85
BONE (8)
36
STS (9)
188
OTHER (10)
173
Speech (3)
256
71
52
496
33
44
55
19
71
104
1201
Cardiovascular (4)
320
156
91
345
81
66
261
85
124
161
1690
Pulmonary (5)
224
91
51
225
52
45
118
52
62
74
994
Gastrointestinal (6)
133
40
57
71
24
18
74
14
56
39
526
Renal (7)
163
59
44
249
81
48
168
33
117
95
1057
Vision and Eye (1)
Musculoskeletal (8)
Neurological (9)
Endocrine (10)
Total
Total
3587
14
9
2
18
11
6
9
193
47
9
318
1333
292
230
4026
289
202
357
265
311
424
7729
730
299
113
1090
60
46
128
46
147
297
2956
3712
1093
722
7897
676
1461
1255
743
1123
1376
20058
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4. What has been achieved
2000 individuals with very detailed treatment
Leukaemia
99
(
Hodgkin’s disease
251
( 12.2%)
Non-Hodgkin lymphoma
149
(
CNS tumour
435
( 21.2%)
Neuroblastoma
178
(
8.7%)
Retinoblastoma
146
(
7.1%)
Wilms’ tumour
283
( 13.8%)
Bone sarcoma
106
(
Soft tissue sarcoma
225
( 11.0%)
Other
177
(
2049
4.8%)
7.3%)
5.2%)
8.6%)
(100.0%)
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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:
Alkylating agents
601
Anthracyclines
368
Anti-metabolites
400
Epipodophyllotoxins
162
Vinca-alkaloids
758
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4. What has been achieved
2000 individuals with very detailed treatment
Levels of exposure to radiotherapy (I):
Number
Mean dose (Gy)
Cranium
Directly Exposed
Adjacent
Outside Field
171
204
293
668
27.8
6.2
0.2
Head
Directly Exposed
Adjacent
Outside Field
96
281
291
668
15.4
9.1
0.3
Neck
Directly Exposed
Adjacent
Outside Field
167
254
247
668
18.1
5.9
0.3
Cervical spine
Directly Exposed
Adjacent
Outside Field
176
238
254
668
17.1
5.3
0.4
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4. What has been achieved
2844 individuals entered into MRC ALL trials
260 (9%) had BMT.
2080 (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
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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)
18000 - 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)
10500 - 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.
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