Risk of late health effects after soft-tissue sarcomas in childhood – a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia research programme

Abstract

Background

In the 1960s only 1/3 of children with soft-tissue sarcomas survived, however with improved treatments survival today has reached 70%. Given the previous poor survival and the rarity of soft-tissue sarcomas, the risk of somatic late effects in a large cohort of Nordic soft-tissue sarcoma survivors has not yet been assessed.

Methods

In this population-based cohort study we identified 985 five-year soft-tissue sarcoma survivors in Nordic nationwide cancer registries and late effects in national hospital registries covering the period 1964–2012. Information on tumour site and radiotherapy was available for Danish and Finnish survivors (N = 531). Using disease-specific rates of first-time hospital contacts for somatic diseases in survivors and in 4,830 matched comparisons we calculated relative rates (RR) and rate differences (RD).

Results

Survivors had a RR of 1.5 (95% CI 1.4–1.7) and an absolute RD of 23.5 (17.7–29.2) for a first hospital contact per 1,000 person-years. The highest risks in both relative and absolute terms were of endocrine disorders (RR = 2.5; RD = 7.6), and diseases of the nervous system (RR = 1.9; RD = 6.6), digestive organs (RR = 1.7; RD = 5.4) and urinary system (RR = 1.7; RD = 5.6). By tumour site, excess risk was lower after extremity tumours. Irradiated survivors had a 2.6 (1.2–5.9) times higher risk than non-irradiated.

Conclusions

Soft-tissue sarcoma survivors have an increased risk of somatic late effects in 5 out of 10 main diagnostic groups of diseases, and the risk remains increased up to 40 years after cancer diagnosis. Risks were slightly lower for those treated for tumours in the extremities, and radiotherapy increased the risk by more than two-fold.

Acknowledgements

We thank the ALiCCS board (Finn Wesenberg, Catherine Rechnitzer, Kirsi Jahnukainen, Anna Sällfors Holmqvist and Nea Malila) for their valuable help and guidance.

Ethical Approvals

The design of the ALiCCS study was approved by national bioethics committees, data protection authorities, or the national institutes for health and welfare in each country (Denmark: 2010-41-4334, Finland: THL/520/5.05.00/2016, Iceland: VSN 10-041 & VSN 12-084-V1 and Sweden: Ö 10-2010, 2011/19).

Author contributions

FNN and CB contributed to the study design, design of analyses, interpretation of results, and drafted the manuscript. CR, ASH, LT, L-MMH, HS, THS, HH, JFW and KKA contributed to the study design and interpretation of results. CR, HH, JFW and KKA contributed to the study design, design of analyses and interpretation of results. CB contributed to the design of the analyses and conducted statistical analyses. All authors revised the manuscript for intellectual content and approved the final version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

To request registry data from the four countries used in this study, contact the following authorities: Denmark: Research services at Sundhedsdatastyrelsen ([email protected]); Finland: TLH National Institute for Health and Welfare in Finland (Service telephone for research authorisation applications: tel. [phone]); Iceland: The Icelandic Cancer Registry ([email protected]); The Directorate of Health ([email protected]); Statistics Iceland www.statice.is/services ([email protected]); and Sweden: The National Board of Health and Welfare ([email protected]). The ALiCCS study group welcomes collaboration with other researchers in using our registry data. Study protocols can be planned in collaboration with us, and the study material can be analysed accordingly at the Danish Cancer Society Research Centre in Copenhagen, Denmark. For further information regarding collaborative ALiCCS projects, please contact Professor Jeanette Falck Winther, MD, DMSc. ([email protected]).

Additional information

Funding

This study was funded by a grant from the Danish Cancer Society’s Scientific Committee [R56-A3210-12-S2] and from the Danish Childhood Cancer Foundation (2011-44) and from the Danish Agency for Science, Technology and Innovation [4135-00106B]. Neither funder had any role in study design, data collection or analysis, the decision to publish, or preparation of the manuscript.