Summary

This is an international EU-FP7 funded project to investigate important somatic late effects (cardiovascular diseases, second malignant neoplasm and late mortality) of childhood and adolescent cancer in long-term survivors (≥5 years). Results of this study will help to develop new guidelines for international follow-up care.   

Study description

Background: With improving therapy, overall survival of childhood cancer increased dramatically and 5-year survival rates now exceed 80%. However, as a consequence of cancer and treatment, two third of survivors develop chronic conditions and all-cause mortality increased. In the first 10 years after diagnosis the main cause of death is recurrence of the primary cancer, but thereafter deaths from second primary cancers and circulatory causes predominate. Beyond 45 years past diagnosis, recurrence accounts only for 7% of the absolute excess mortality, while second primary cancers and circulatory deaths together account for 77%. This underlines the need to identify avoidable risk factors for these late effects. In single countries, only few childhood cancer survivors have already attained middle or late adulthood. Thus, combination of datasets in international studies is essential to tackle these questions.

Objectives:
I)   To establish a cohort of 5-year survivors of childhood and adolescent cancer
II)  To analyse in this “PanCareSurFup” cohort study incidence and risk factors for:
       a.  total and cause-specific late mortality
       b.  second primary cancers, particularly sarcomas, gastrointestinal
            and genitourinary carcinomas
       c.  late cardiovascular disease
III) To perform nested case-control studies on:
       a.  secondary malignant sarcomas and secondary carcinomas
       b.  late cardiovascular disease
IV) To develop evidence-based, standardised guidelines for the clinical follow-up of survivors and to establish a pan-European follow-up system.

Methods: I) Cohort of 5-year survivors: To obtain a representative cohort of all 5-year survivors of child and adolescent cancer in Switzerland, we will complement the existing Swiss Childhood Cancer Survivor Study (SCCSS; which includes children treated by the Swiss Paediatric Oncology Group) with children and adolescents treated elsewhere, who will be identified via the National Institute of Cancer Epidemiology and Registration (NICER). Overall, we estimate to recruit about 4900 5-year survivors in Switzerland. The cohorts of the11 participating European countries will be combined to a pan-European “PanCareSurFup cohort”.

II) “PanCareSurFup” cohort studies: For all cohort members, we will assess current address, live status and date of death via community registries and obtain cause of death via linkage with the Swiss mortality statistics. Cardiovascular late effects and second primary cancers will be identified via: a) a questionnaire to all survivors; b) mortality records (for deceased); c) linkage with NICER (for second primary cancers). All patient-reported diseases from the questionnaire will be validated with medical records.

III) Nested case-control studies: From the cohort, Switzerland will sample 50 cases with severe cardiovascular disease, 55 cases with secondary sarcoma or carcinoma and 105 controls. For these we will: a) extract details of radio- and chemotherapy from initial medical records; and b) assess by interview current health problems and environmental, social and lifestyle risk factors;.

IV) Systematic reviews of all available evidence will be written to develop evidence-based, standardised guidelines. These reviews will be completed in close collaboration with experts from across Europe and the Cochrane Childhood Cancer Group in Amsterdam, The Netherlands.

Rationale and significance: This research project, partly funded by the EU, is a unique opportunity to study the most serious and life threatening late effects of childhood and adolescent cancer in an international setting that maximises statistical power and generalisability of results. The identification of avoidable causes for cardiovascular late effects and second primary cancers will allow adapting treatment in new patients, aiming at maximal cure rates with minimal long-term side effects.   

Study Team

- Kuehni, Claudia (PL). Institute of Social and Preventive Medicine, University of Bern
- Gisela Michel. Institute of Social and Preventive Medicine, University of Bern
- Hau-Grosch Eva-Maria. Institute of Social and Preventive Medicine, University of Bern
- Von der Weid, Nicolas. Pediatric Oncology, CHUV Lausanne
- Niggli, Felix. Centre of clinical research, University of Zurich
- Bergsträsser Eva. Centre of clinical research, University of Zurich
 

Applicants

- Kuehni, Claudia. Institute of Social and Preventive Medicine, University of Bern
- Michel Gisela. Institute of Social and Preventive Medicine, University of Bern

Partners

- Swiss Paediatric Oncology Group (SPOG)
- PanCare SurFup (PCSF)

Funding

European Union  FP 7: HEALTH.2010.2.4.1-7: Predicting long-term side effects to cancer therapy.
Recherche Suisse Contre le Cancer (Grant KFS 02783-02-2011)

Project duration

02.2011- 02.2016

State

ongoing