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Page 4 of 5 Judson. J Cancer Metastasis Treat 2021;7:28 https://dx.doi.org/10.20517/2394-4722.2021.110

[17]
The study by Baker et al. concerns survivorship. Doxorubicin remains a staple component of
chemotherapy for metastatic sarcoma and those tumours for which intensive multi-agent chemotherapy is
given with curative intent, such as Ewing sarcoma and osteosarcoma. A recent study in the pre-operative
setting indicated that for a number of different high grade extremity soft tissue sarcoma histotypes,
supposedly histotype-tailored chemotherapy regimens proved inferior to a combination of ifosfamide and
an anthracycline (epirubicin) in terms of disease-free and overall survival, although the paper was unable to
draw definitive conclusions owing to its statistical design . The reason for the superior efficacy of
[18]
anthracycline/doxorubicin in the treatment of sarcomas remains unclear.

Given that treatment with doxorubicin remains necessary, it is extremely valuable to examine the long term
consequences of anthracycline use in survivors and to study ways in which the adverse effects can be
mitigated. Historically the focus has been on the cardiomyopathy associated with doxorubicin, the risk of
which relates to the cumulative dose and can be ameliorated by cumulative dose restriction and the use of
[19]
dexrazoxane, as confirmed by randomised clinical trials and a number of studies in different diseases,
including osteosarcoma . These studies not only demonstrated significant cardioprotection but no
[20]
reduction in disease control nor an increased incidence of secondary malignancy. Note in their paper on
GSK3β Abe et al. fail to mention dexrazoxane in their discussion of the potential for GSK3β inhibitors to
[10]
exert a cardioprotective effect, which is an important omission.

However, cardiomyopathy is not the only problem. Cancer survivors treated with anthracyclines have a
much increased risk of coronary artery disease (CAD) and also of a number of the chronic diseases which
are known risk factors for CAD, such as hypertension, obesity, diabetes and dyslipidaemia. In a prospective
5-year study, Baker et al. followed 61 cancer survivors with a median age of 42 years who had received
[17]
adjuvant or neoadjuvant doxorubicin. Data on known risk factors were collected at baseline and
prospectively, including high body mass index, smoking and alcohol use, exercise, hypertension, elevated
cholesterol, increased high-sensitivity C-reactive protein, an index of inflammation and known CAD risk
factor, type 2 diabetes, depression and anxiety, and impaired renal function. The findings indicate a much
higher incidence of risk factors for CAD than in the general population, even in patients < 40 years of age,
and the need for active intervention to mitigate known risk factors where possible. The authors strongly
recommend that cancer survivors be followed in oncology clinics. This may not always be feasible and will
vary in different healthcare jurisdictions, but perhaps shared care arrangements with primary care together
with clear guidance from the cancer service as to what to monitor and the types of intervention required
could be developed. As more and more patients survive cancer this need is bound to increase and there is an
obligation to treat not just the cancer itself but also the chronic effects of therapy.

Sarcoma care remains under-resourced and under-researched and it is gratifying to see it highlighted by this
interesting collection of papers.

DECLARATIONS
Authors’ contribution
Judson I contributed solely to the article.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.