Advertisement

Is There Value in Molecular Profiling of Soft-Tissue Sarcoma?

  • Antoine Italiano
Sarcoma (SH Okuno, Section Editor)
  • 11 Downloads
Part of the following topical collections:
  1. Topical Collection on Sarcoma

Opinion statement

Soft-tissue sarcomas represent a heterogeneous group of diseases accounting for up to 1% of cancer in adults and 15% of cancer in children. Introduction of next-generation sequencing (NGS) technologies has allowed to gain additional insight into the genetic diversity and complexity of sarcomas, including the potential therapeutic implications of some genetic alterations.

Two large studies have investigated the role of targeted NGS to identify actionable mutations in patients with soft-tissue sarcomas. In these two studies, actionable alterations were identified in up to 50% of patients. Retrospective data suggest that genomically guided treatments may be associated with substantial clinical benefit in sarcoma patients with advanced disease. However, prospective data are lacking. The MULTISARC is a randomized phase 3 investigating the potential of NGS implementation to improve outcome of metastatic sarcoma patients.

Overall, a significant proportion of soft-tissue sarcoma bears potential targetable genomic alteration that can be identified through NGS. There is still a lack of evidence to support routine implementation of NGS for the management of sarcoma patient. The MULTISARC randomized trial which randomized patients to tumor genetic profiling or not might confirm the role of NGS to improve outcome of metastatic sarcoma patients through the identification of additional genomically guided lines of treatment.

Keywords

Sarcoma Next-generation sequencing Targeted therapies 

Notes

Compliance with Ethical Standards

Conflict of Interest

The author declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    O’Leary M, Krailo M, Anderson JR, Reaman GH. Progress in childhood cancer: 50 years of research collaboration, a report from the Children’s Oncology Group. Semin Oncol. 2008;35:484–93.CrossRefPubMedCentralGoogle Scholar
  2. 2.
    National Cancer Institute. SEER Cancer Statistics Review 1975–2004 [online], http://seer.cancer.gov/csr/1975_2004/(2007).
  3. 3.
    Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F. WHO Classification of tumours of soft tissue and bone. 4th edn; 2013.Google Scholar
  4. 4.
    Italiano A, Mathoulin-Pelissier S, Cesne AL, Terrier P, Bonvalot S, Collin F, et al. Trends in survival for patients with metastatic soft-tissue sarcoma. Cancer. 2011;117:1049–54.Google Scholar
  5. 5.••
    Comprehensive and integrated genomic characterization of adult soft tissue sarcomas. Cell. 2017;171:950–965.e28. First large and comprehensive genomic characterization of soft-tissue sarcomas.Google Scholar
  6. 6.
    Italiano A, Kind M, Stoeckle E, Jones N, Coindre JM, Bui BN, et al. Temsirolimus in advanced leiomyosarcomas: patterns of response and correlation with the activation of the mammalian target of rapamycin pathway. Anti-Cancer Drugs. 2011;22:463–7.Google Scholar
  7. 7.
    Schwartz GK, Tap WD, Qin LX, Livingston MB, Undevia SD, Chmielowski B, et al. Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, phase 2 trial. Lancet Oncol. 2013;14:371–82.Google Scholar
  8. 8.
    Chakravarty D, Gao J, Phillips S, et al. OncoKB: a precision o ncology knowledge base. JCO Precis Oncol. 2017;1:1–16. https://www.ncbi.nlm.nih.gov/pubmed/29801054.
  9. 9.••
    Lucchesi C, Khalifa E, Laizet Y, Soubeyran I, Mathoulin-Pelissier S, Chomienne C, Italiano A. Targetable alterations in adult patients with soft-tissue sarcomas: insights for personalized therapy. Jama Oncol. 2018;4(10):1398–1404. https://www.ncbi.nlm.nih.gov/pubmed/29801054.
  10. 10.
    Cousin S, Grellety T, Toulmonde M, Auzanneau C, Khalifa E, Laizet Y, et al. Clinical impact of extensive molecular profiling in advanced cancer patients. J Hematol Oncol. 2017;10:45.Google Scholar
  11. 11.
    Gounder MM, Ali SM, Robinson V, et al. Impact of next-generation sequencing (NGS) on diagnostic and therapeutic options in soft-tissue and bone sarcoma. J Clin Oncol. 2017;(suppl; abstr 11001).Google Scholar
  12. 12.
    Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;2002(347):472–80.CrossRefGoogle Scholar
  13. 13.
    Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21:4342–9.Google Scholar
  14. 14.
    McArthur GA, Demetri GD, van Oosterom A, et al. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: imatinib target exploration consortium study B2225. J Clin Oncol. 2005;23:866–73.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical OncologyInstitut BergoniéBordeauxFrance
  2. 2.University of BordeauxBordeauxFrance
  3. 3.Institut BergoniéBordeauxFrance

Personalised recommendations