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  • Review Article
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Systemic treatment of soft-tissue sarcoma—gold standard and novel therapies

Nature Reviews Clinical Oncology volume 11, pages 187–202 (2014)Cite this article

Subjects

Key Points

  • Soft-tissue sarcoma (STS) is a rare disease that encompasses over 50 separate histological subtypes with varying sensitivity to systemic treatment

  • Chemotherapy has been based on historical experience but there is now increasing evidence for treatment with chemotherapy in large phase II and III trials

  • While ifosfamide and doxorubicin remain important treatment options in STS, therapy is increasingly tailored towards different histological subtypes

  • Clinical trials remain a challenge due to the rarity and heterogeneity of STS and international collaboration is critical to achieve high quality clinical trials stratified by histological subtype

  • Targeted therapies such as tyrosine kinase inhibitors and immunotherapy will become increasingly important as we further define the molecular basis of sarcomagenesis

Abstract

Soft-tissue sarcoma (STS) is a rare and heterogeneous group of tumours that comprise approximately 1% of all adult cancers, and encompass over 50 different subtypes. These tumours exhibit a wide range of differing behaviours and underlying molecular pathologies, and can arise anywhere in the body. Surgical resection is critical to the management of locoregional disease. In the locally advanced or metastatic disease settings, systemic therapy has an important role in the multidisciplinary management of sarcoma. Cytotoxic therapy that usually consists of doxorubicin and ifosfamide has been the mainstay of treatment for many years. However recent advances in molecular pathogenesis, the development of novel targeted therapies, changes in clinical trial design and increased international collaboration have led to the development of histology-driven therapy. Furthermore, genomic profiling has highlighted that some STS are driven by translocation, mutation or amplification and others have more complex and chaotic karyotypes. In this Review, we aim to describe the current gold standard treatment for specific STS subtypes as well as outline future promising therapies in the pipeline.

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Figure 1: Gold standard treatment paradigms for advanced STS.
Figure 2: Kinase interaction maps for kinase inhibitors in sarcoma.
Figure 3: Immunotherapy in sarcoma.

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Acknowledgements

We would like to thank the Royal Marsden Hospital/Institute of Cancer Research Biomedical Research Centre for supporting this work and to the members of the Sarcoma Unit, Royal Marsden Hospital for critical reading of the manuscript.

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  1. Department of Medical Oncology, Sarcoma Unit, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK

    Mark Linch, Ian R. Judson & Charlotte Benson

  2. Department of Clinical Oncology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK

    Aisha B. Miah

  3. Department of Histopathology, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK

    Khin Thway

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M.L., K.T. and C.B. researched data for the article and wrote the article. M.L., I.R.J. and C.B. made a substantial contribution to the discussion of the article content. M.L., A.B.M., I.R.J. and C.B. reviewed and edited the manuscript before submission and all authors revised the article after peer review.

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Correspondence to Charlotte Benson.

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M.L., A.B.M., I.R.J. & C.B. have all received research support from Bayer, GlaxoSmithKline, Eisai, Novartis, AstraZeneca and Ziopharm Oncology. K.T. Declares no competing interests.

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Linch, M., Miah, A., Thway, K. et al. Systemic treatment of soft-tissue sarcoma—gold standard and novel therapies. Nat Rev Clin Oncol 11, 187–202 (2014). https://doi.org/10.1038/nrclinonc.2014.26

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