Subsequent primary neoplasms among bone sarcoma survivors; increased risks remain after 30 years of follow-up and in the latest treatment era, a nationwide population-based study



The long-term risks and time trends of subsequent primary neoplasms (SPNs) among Ewing (ES) and osteosarcoma (OS) survivors are not fully understood.


We performed a nationwide study of all ES and OS patients identified in the Swedish Cancer Registry from 1958 to 2015 with up to 58 years of follow-up. The risk of SPN was compared with that of the general population using standardised incidence ratios (SIRs) and absolute excess risks (AERs).


One hundred and fifteen SPNs were diagnosed among 1779 patients with ES or OS, yielding an overall SIR of 2.3 (95% confidence interval (CI), 1.9–2.7). The risk remained significantly increased in the latest treatment era (SIR2000-2015 2.0; 95% CI, 1.1–3.5). The highest absolute excess risks (AER) was due to breast cancer (AER 15.2/10,000 person-years; 95% CI, 5.0–29.8) followed by female genital malignancies (AER 9.5/10,000 person-years; 95% CI, 2.4–21.5). The excess breast cancer risk among ES survivors was noted also after 30 years of follow-up with 127 extra breast cancers/10,000 person-years (95% CI, 6.6–419).


Breast- and female genital malignancies contribute most to the excess risk of SPN among ES and OS survivors. Importantly, excess risks did not decline over calendar time or long-term follow-up.

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The authors would like to thank Professor Robert Harris at the Karolinska Institute for language support. Furthermore, the authors would like to thank the Stella Power Foundation (kontakt@StellaPower.se), which made a financial donation to the Karolinska Institute. The donation was used to pay for statistical expertise in this study.

Author information

A.H. conceived and designed the study. He also collected the data, contributed to the data analysis and wrote the manuscript. Critical review and final approval of the manuscript was also done by A.H. A.D. contributed by analysing the data and performed all the statistics in the study. He also took part in writing the manuscript, critically reviewed and approved the final version of the manuscript. P.T. took part in designing the study as well as writing the study. He also contributed to the analysis, took part in writing the article, critically reviewed and approved the final version of the manuscript. KES conceived and designed the study. She also interpreted the data and took part in writing the manuscript. She critically reviewed and approved the final version of the manuscript.

Correspondence to Asle Charles Hesla.

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The study was approved by the Regional ethical review board in Stockholm, registration number 2016/953-32. The Regional ethical review board waived the requirement to obtain informed consent. The study was conducted according to the Declaration of Helsinki.

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The data that support the findings of this study are available from the Cancer Registry at Socialstyrelsen (https://www.socialstyrelsen.se/en/search-results/?q=cancer+registry). Restrictions apply to the availability of these data, which were used under license for this study. Data are available from the authors with permission from Socialstyrelsen (National Board of Health and Welfare).

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Hesla, A.C., Discacciati, A., Tsagkozis, P. et al. Subsequent primary neoplasms among bone sarcoma survivors; increased risks remain after 30 years of follow-up and in the latest treatment era, a nationwide population-based study. Br J Cancer (2020). https://doi.org/10.1038/s41416-020-0748-3

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