CARDIOVASCULAR PROBLEMS IN SURVIVORS OF CHILDHOOD CANCER AND THEIR SIBLINGS

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1 Swiss Childhood Cancer Registry (SCCR) CARDIOVASCULAR PROBLEMS IN SURVIVORS OF CHILDHOOD CANCER AND THEIR SIBLINGS Julien Caccia, Corina S. Rueegg, Eva-Maria Hau, Nicolas X. von der Weid, Gisela Michel, Claudia E. Kuehni Institute of Social and Preventive Medicine University of Bern 15 August 2013, Swiss Public Health Conference 1

2 Childhood cancer: burden of disease CH: 250 children Actual (<15 10-years years) diagnosed survival rates every >80% year > 80% 10-year survival 2/3 of survivors develop late effects Cardiovascular diseases (CVD) are among the main causes of non-malignant late death (after second tumours and relapse) 2

3 Main mechanisms of cardiovascular damage Radiotherapy: chest Cancer Chemotherapy: Anthracyclines Direct damage to the heart Vascular dysfunction - Heart failure - Arrhythmia - Valvular disease - Pericarditis Time - Hypertension - Stroke - Coronary artery disease - Thrombosis Image adapted from: 3

4 Aims 1. To assess prevalence of cardiovascular disease (CVD) in childhood cancer survivors compared to their siblings 2. To identify risk factors for CVD in childhood cancer survivors 4

5 Study design Swiss Childhood Cancer Registry Swiss Childhood Cancer Registry (SCCR) Cancer survivors: - Survived 5 years - Diagnosed <15 years at diagnosis - 16 years at study Siblings of the same age range (control group) Swiss Childhood Cancer Survivor Study (SCCSS) Cardiovascular health? Questionnaire survey: Cancer history (survivors only) Quality of life Physical and mental health Medication and medical care Health behaviours Socio-economic status 5

6 Outcome and exposures Outcome: Cardiovascular disease (CVD), defined as 1 of the following: 1. Hypertension 2. Arrythmia 3. Heart failure 4. Myocardial infarction 5. Stroke 6. Deep vein thrombosis/pulmonary embolism (DVT/PE) 7. Valvular problems Exposures: From registry: sex, age, age at Dx, year of Dx, cancer, treatments, relapse From questionnaire: parents education, smoking, physical activity, BMI 6

7 Study population Response rate: - Survivors: 69%, N= Siblings: 55%, N= 713 Characteristics - Mean age at diagnosis: 7.6 years - Mean time since diagnosis: 17 years - Mean age at survey: 25 years 7

8 Prevalence of CVDs in survivors & siblings % Survivors (N=1607) Siblings (N=713) CVDs Overall ( 1) Hypertension Arrhythmia Heart failure Myocardial infarction Stroke DVT/PE Valvular problems Note: age and sex standardized proportion are given for siblings 8

9 Risk for CVDs in survivors compared to siblings OR 1 95%CI global p 2 Survivors vs. siblings Sibling 1 <0.001 Survivor By Diagnosis No cancer (siblings) 1 <0.001 Leukaemia Lymphoma CNS tumor Bone & soft tissue sarcomas Neuroblastoma & hepatic tumor Renal tumor Retinoblastomas &miscellaneous Langherans cell histiocytosis By treatment no treatment (siblings) 1 <0.001 surgery only Chemotherapy +/- surgery Radiotherapy +/- surgery Chemo+Radio +/- surgery Bone marrow Transplantation adjusted for age, sex, BMI, smoking status, parental education 9

10 Risk for CVDs in survivors compared to siblings (2) OR 1 95%CI global p-value 2 BMI non-obese obese Age at survey by category <20 1 < > OR from second model (diagnosis), similar in all 3 models, 2 global p-values calculated using a likelyhood ratio test 10

11 Summary 1. Higher prevalence of cardiovascular diseases in cancer survivors compared to siblings, even at a young age 2. Risk factors: survivors of Lymphomas and neuroblastomas and those treated with chemotherapy, radiotherapy and (particularly) bone marrow transplantation. 3. The absolute risk increases with age and obesity in survivors and siblings. 11

12 Conclusion and discussion Prevalence of CVDs after childhood cancer is comparable to international data Self-reported data risk to be biased by over reporting (survivors are also more likely to undergo screening procedures) Validation self-reported CVDs is on-going (survivors) Quantification of the treatments received (i.e. Rx to the chest and anthracyclines) will give more precise estimates Finally, we hope, with this analysis, to define groups of survivors who will profit from regular cardiovascular follow-up in Switzerland 12

13 Thank you for your attention!?/! 13

14 Main diagnostic groups SCCR 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% < I Leukaemias I II II Lymphomas III III CNS CNS neoplasms IV IV Neuroblastoma Neuroblastoma V Retinoblastoma V Retinoblastoma VI Renal tumours VI Renal tumours VII Hepatic tumours VII Hepatic tumours VIII Malignant bone tumours VIII Malignant bone tumours IX Soft tissue sarcomas IX Soft tissue sarcomas X Germ cell tumours X Germ cell tumours XI Other malignant epithelial neoplasms XI Other malignant epithelial XII neoplasms Other specified and unspecified malignant neoplasms Langerhans XII Other specified cell histiocytosis and unspecified malignant neoplasms Age at diagnosis (years) 14

15 The Swiss Childhood Cancer Survivor Study investigates late effects Type of study Time since diagnosis Population-based questionnaire survey nested in the SCCR 5 years Year of diagnosis Since 1976 Age at diagnosis Place of diagnosis < 21 years (on-going) Paediatric oncology clinics or other N (participated) 2,190 survivors Abbreviations: SCCR, Swiss Childhood Cancer Registry; N, number Adapted for different age groups German, French and Italian 15

16 Swiss Childhood Cancer Registry Introduction Methods Results Conclusion/Discussion Study procedure Survivors Extraction SCCR Address update Contact via clinic Mailing of Questionnaire Mailing of Reminder Telephone call Data entry Dataset generation Analysis & Publication Siblings Population from Survivor Questionnaires Contact via Survivor Address request via Survivor Mailing of Questionnaire via Survivor Mailing of Questionnaire to Siblings No Reminder Mailing of Reminder Data entry Dataset generation Analysis & Publication 16

17 SCCSS questionnaire: Cardiovascular chapter 17

18 Comparison of self-reported cardiovascular problems between childhood cancer survivors and their siblings Survivors (n=1'607) siblings 1 (n=713) SCCSS question N % N % OR 95% CI p-value Hypertension no 1' yes [ ] Arrythmia no 1' yes [ ] 0.05 Heart failure or cardiomyopathy no 1' yes [ ] Myocardial infarction Stroke no 1' yes [ ] no 1' yes [ ] Venous thrombosis /pulmonary embolism no 1' yes [ ] <0.001 Valvular problems no 1' CVD yes [ ] no yes [ ] <

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