Epidemiological study to quantify risks for paediatric computerized

tomography and to optimise doses (EPI-CT)

Kristina KjærheimCancer Registry of Norway

HelsIT, Trondheim, 29.09.2011

Content

> Brief overview of project > Background, aims, partners> Design and analyses> Ethical approval

> Collection of RIS data

The project is supported by the EU FP7 Euratom grant agreement n°269912 (EU countries) and the Norwegian Research Council (Norway)

Background

> CT scans contribute with approx. 80 % of population dose from medical diagnostics and treatment

> We assume children to be the most vulnerable to damage, due to larger susceptibility, and to a longer time span for negative effects to occur

> So far, the knowledge of risk related to low dose exposure is limited and mostly model based

> Large need for empirical knowledge> The aim is to estimate risk of leukaemia, other cancer

disease and possibly other health effects related to CT scans during childhood andadolescence

Partners 1. International Agency for Research on Cancer (IARC): co-ordinator2. The University Medical Centre of the Johannes Gutenberg

University Mainz, Germany3. Federal Office for Radiological Protection, Germany4. Radiation and Nuclear Authority of Finland (STUK), Finland5. Karolinska Institute (KI), Sweden6. Danish Cancer Society (DCS), Denmark7. University of Newcastle upon Tyne (UNEW), UK8. The Centre for Research in Environmental Epidemiology, Spain9. Institute Gustave Roussy INSERM (IGR), France10. Institut de Radioprotection et de Sûreté Nucléaire (IRSN), France11. Institut Curie (IC), France12.Centre d’Assurance de qualité des Applications Technologiques

dans le domaine de la Santé (CAATS), France13.The Netherlands Cancer Institute (NKI), Holland14.The Belgian Nuclear Research Centre (SCK.CEN)15.University of Ghent (UGhent), Belgium16.Public Research Centre Henri Tudor (CRP), Luxemburg 17.Norwegian Radiation Protection Authority (NRPA)18.Cancer Registry of Norway (CRN)

Design & analyses> Combined retrospective/prospective cohort study > External and internal comparisons

> SIR-analyses > Cox regression, splines and generalised additive

models> Qualitative (RIS based) and quantitative (PACS based)

exposure variables > Number of scans, scan types, age at scan, dose

estimates,…> Dose optimization exercises

> (Biological sub studies: DNA damage, gene expression, cytokines)

Power calculations

> Based on estimated number of person-years and the expected number of leukaemia cases

> If each CT (of head, chest, abdomen) gives 5 mGy and

> If 50 mGy (i.e. 10 scans) gives an RR of 1.75 - 2.25

Then:> A cohort of 1.1 million children gives 80 % probability

of finding an RR of 1.75 for 10 CT scans

> A cohort of 500 000 children gives 95 % probability of finding an RR of 2.5 for 10 CT scans

Description of data materialCohort/countr

y Age span Start of f‐up Data source PACS from Cohort size

EU

Belgium 0‐15 2002 PACS 2001 30.000

Denmark 0‐18 2000 PACS 1999/01 30.000

France‐IRSN 0‐5 2000 Rad.dept. var. 90.000

France‐INSERM 0‐15 2000 PACS 2000 50.000

Germany 0‐15 1990 RIS/PACS 2000 140.000

Holland 0‐18 1998 PACS 2000 40.000

Spain 0‐20 2005 Rad.dept. var. 200.000

Sweden 0‐18 1984 Rad.dept. 2000 95.000

UK 0‐21 1985 Rad.dept. var. 400.000Non‐EU

Norge 0‐20 1985? RIS/PACS 2003? 20.000?

Total 1.095.000

Ethical approval

> Given 29.04.2011

> Sent to leader of the diagnostic clinic, the radiological department and RIS/PACS responsible person at all hospitals

> Five page document in technical/legal Norwegian language, available from the CRN on request

Study logisticsHave done:> Letter of information to all hospitals

(to leader of diagnostic clinic, radiological dept and RIS/PACS responsible person)

> Appointment of contact personsWill do: > Telephone contact with appointed contact person> Written information to contact person with:

> Inclusion criteria> Variable list> Methods for sending data

Inclusion criteria

> All individuals who have undergone one or more CT scan before the age of 20 are to be included in the cohort

> Data extraction should go as far back in time as RIS is available at the hospital/department

> For all included individuals, data on CT scans also after the age of 20 would be desirable

Cohort description – inclusion and follow-up in Norway

Inclusion period

5

10

15

20

25

30

35

40

45

50

Age

2015

0

5

10

15

20

25

30

35

40

45

50At

tain

ed a

ge

1985 1990 1995 2000 2005 2010

1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015

Birth year

Variables to be included> For each person:

> First name, last name, personal identification number (11-digits) (*nødnummer?*), county of residence

> For each CT-scan:> RIS ID, Hospital ID, name/code of radiology department > Date of scan (ddmmyyyy) > Scanner type (producer and model) > Body part scanned /organ code > Use of contrast> Reason for scan (when available, free text)> Hospital department from which patient is referred (when

available, code and/or free text)> Height at the time of scan (when available) > Weight at the time of scan (when available)

Example of RIS data file

NAME PID Date Type NORAKO code Indication for scan

1 11111111111 06.15.05 CT Hip/thigh CT CX MN B Preoperative examination06.15.05 CT GE MN B

06.15.05 CT PSAR MN B

2 22222222222 06.20.05 CT Abdomen CT AB T1 Enlargement of liver?

06.20.05 CT AB ANG3 33333333333 06.20.05 CT Caput CT KC T1 Fracture? Bleeding

06.20.05 CT KC REK

4 44444444444 06.24.05 CT Hip/thigh CT CX MN B Preoperative examination

5 55555555555 06.20.05 CT Hip/thigh CT CX MN B Assumed deformity of right hip

6 66666666666 06.16.05 CT Caput CT KC T1

7 77777777777 06.23.05 CT Caput CT KC T1 Cerebral changes?

8 88888888888 06.12.05CT Abdomen/ Pelvis CT PE T1

Abdominal pain, pathology of liver/spleen?

Methods for sending data to CRN

> By post > on two CDs, where one contains name, personal ID and constructed ID

only, the other contains all other data and the constructed ID. > The constructed ID is a digital code unique for each individual (not for

each CT scan), and serves as a key to link the two files together at the CRN.

> By CRNs internett portal > This requires a certificate and a password, which will be available from

the CRN at request. The file may be cryptified if wanted, the key for de- cryptification may be communicated by telephone.

> A variable list and possible other descriptions of the data file may be sent to the CRN by e-mail.

PHASE 1 CRN

Cohort definition, Inclusion criteria, list of data elements →→→ HospitalRIS data collection RIS data extraction

Data management ←←← Pnr, sex, age, RIS, RIS IDPrelim ID1, sex, age, RIS, RIS ID 

→→→ NrpaRIS dose estimation

PHASE 2 Data management ←←← Prelim ID1, sex, age, RIS, RIS ID, RIS estimatesPACS data collection Prelim ID2, RIS estimates, RIS ID

→→→ Hospital PACS data extraction

Data management ←←← Prelim ID2, PACS, RIS ID Prelim ID3, PACS, RIS, RIS ID

→→→ NrpaPACS dose estimation

PHASE 3 Data management ←←← Prelim ID3, PACS, RIS, RIS ID, PACS estimatesCovariate linkage Pnr, Prelim ID4

→→→ Statistics NorwayData linkage

Data management ←←← Prelim ID4, SES of parents at the time of scan and at 16

Pnr, Prelim ID5→→→ Medical birth registry

Data linkagePHASE 4 Data management ←←← Prelim ID5, Down syndrome, congenital malformations

Outcome linkage Pnr, Prelim ID6→→→ Statistics Norway

Data linkageData management + linkage ←←← Prelim ID6, date of death, cause of death, emigration

Pnr, cancer date, diagnosis, hist/morf etc

In conclusion..

> This project will provide direct epidemiological evidence on the potential cancer risk due to low doses of ionising radiation exposure in a large multinational European cohort

> It will be the largest, and the most statistically powerful, study of paediatric CT scans undertaken until to date

> Results will contribute to radiation protection, dose optimisation and low dose radiation research and are awaited 2015

Thank you, all, for your attention!