Skip to main content
SpringerLink
Log in

Sarcomas

  • Chapter
  • First Online:
Oncology in the Precision Medicine Era

  • 782 Accesses

Abstract

Soft tissue sarcomas (STSs) represent a rare and heterogeneous group of solid tumors that accounts for nearly 1% of all adult malignancies and comprise more than 50 different histological subtypes. For most STS subtypes, cytotoxic chemotherapy still remains the principal treatment for advanced and metastatic disease. In the past several decades, our expanding understanding of cancer biology has revealed distinct molecular alterations responsible for carcinogenesis of different subtypes of STS and allowed for the increased use of targeted therapies. In this review, we aim to describe the current treatments of STS based on subtype and advancements in molecular diagnostics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bramwell VH, et al. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft tissue sarcoma: a meta-analysis and clinical practice guideline. Sarcoma. 2000;4(3):103–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Judson I, et al. Results of a randomized phase III trial (EORTC 62012) of single agent doxorubicin versus doxorubicin plus ifosfamide as first line chemotherapy for patients with advanced or metastatic soft tissue sarcoma: a survival study by the EORTC soft tissue and bone sarcoma group. Lancet Oncol. 2014;15(4):415–23.

    Article  CAS  PubMed  Google Scholar 

  3. Tap WD, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomized phase 2 trial. Lancet. 2016;388(10043):488–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lilly Reports Results of Phase 3 Soft Tissue Sarcoma Study of LARTRUVO®. Eli Lilly and Company. Published January 18, 2019. https://investor.lilly.com/news-releases/news-release-details/lilly-reports-results-phase-3-soft-tissue-sarcoma-study. Accessed 07 Feb 2019.

  5. Zhang L, et al. Vascular endothelial growth factor overexpression by soft tissue sarcoma cells: implications for tumor growth, metastasis, and chemoresistance. Cancer Res. 2006;66(17):8770–8.

    Article  CAS  PubMed  Google Scholar 

  6. Chao C, et al. Vascular endothelial growth factor and soft tissue sarcomas: tumor expression correlates with grade. Ann Surg Oncol. 2001;8(3):260–7.

    Article  CAS  PubMed  Google Scholar 

  7. van der Graaf WT, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379(9829):1879–86.

    Article  PubMed  CAS  Google Scholar 

  8. Hirota S, et al. Gain-of-function mutation of c-kit in human gastrointestinal stromal tumors. Science. 1998;219:577–80.

    Article  Google Scholar 

  9. Heinrich MC, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–10.

    Article  CAS  PubMed  Google Scholar 

  10. Joensuu H, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001;344(14):1052–6.

    Article  CAS  PubMed  Google Scholar 

  11. Demetri GD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347(7):472–80.

    Article  CAS  PubMed  Google Scholar 

  12. Blanke CD, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008;26(4):626–32.

    Article  CAS  PubMed  Google Scholar 

  13. Dematteo RP, et al. Adjuvant imatinib mesylate after resection of localized, primary gastrointestinal stromal tumor: a randomized, double-blind, placebo-controlled trial. Lancel. 2009;373:1097–104.

    Article  CAS  Google Scholar 

  14. Joesnsuu H, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor. JAMA. 2012;307:1265–72.

    Article  Google Scholar 

  15. Demetri GD, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:295–302.

    Article  CAS  PubMed  Google Scholar 

  16. Demetri GD, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006;368:1329–38.

    Article  CAS  PubMed  Google Scholar 

  17. Joensuu H, et al. KIT and PDGFRA mutations and the risk of GI stromal tumor recurrence. J Clin Oncol. 2015;33:634–42.

    Article  CAS  PubMed  Google Scholar 

  18. Ricci R. Syndromic gastrointestinal stromal tumors. Hered Cancer Clin Pract. 2016;14:15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Heinrich MC, et al. Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol. 2008;26(33):5360–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Garner AP, et al. Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients. Clin Cancer Res. 2014;20:5745–55. https://doi.org/10.1158/1078-0432.CCR-14-1397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Heinrich MC, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21:4342–9.

    Article  CAS  PubMed  Google Scholar 

  22. Heinrich MC, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol. 2008;26:5352–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Heinrich MC, et al. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res. 2012;18:4375–84.

    Article  CAS  PubMed  Google Scholar 

  24. NCT02847429; EudraCT: 2015–000287-34.

    Google Scholar 

  25. Rose S. BLU-285, DCC-2618 show activity against GST. Cancer Discov. 2017;7:121–2.

    Article  Google Scholar 

  26. Singer S, et al. Gene expression profiling of liposarcoma identifies distinct biological types/subtypes and potential therapeutic targets in well-differentiated and dedifferentiated liposarcoma. Cancer Res. 2007;67:6626–36.

    Article  CAS  PubMed  Google Scholar 

  27. Knight JC, et al. Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis. Cancer Res. 1995;55(1):24–7.

    CAS  PubMed  Google Scholar 

  28. Antonescu CR, et al. Monoclonality of multifocal myxoid liposarcoma: confirmation by analysis of TLS-CHOP or EWS-CHOP rearrangements. Clin Cancer Res. 2000;6(7):2788–93.

    CAS  PubMed  Google Scholar 

  29. D’Incalci M, Galmarini CM. A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther. 2010;9:2157–63.

    Article  PubMed  CAS  Google Scholar 

  30. Demetri GD, et al. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016;34:786–93.

    Article  CAS  PubMed  Google Scholar 

  31. Bai RL, et al. Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. J Biol Chem. 1991;266:15882–9.

    CAS  PubMed  Google Scholar 

  32. Schöffski P, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016;387:1629–37.

    Article  PubMed  CAS  Google Scholar 

  33. Gibault L, et al. New insights in sarcoma oncogenesis: a comprehensive analysis of large series of 160 soft tissue sarcomas with complex genomics. J Pathol. 2011;223:64–71.

    Article  CAS  PubMed  Google Scholar 

  34. Leitao MM Jr, et al. Immunohistochemical expression of estrogen and progesterone receptors and outcomes in patients with newly diagnosed uterine leiomyosarcoma. Gynecol Oncol. 2012;124:558–62.

    Article  CAS  PubMed  Google Scholar 

  35. George S, et al. Phase 2 trial of aromatase inhibitor with letrozole in patients with uterine leiomyosarcomas expressing estrogen and/or progesterone receptors. Cancer. 2014;120:738–43.

    Article  CAS  PubMed  Google Scholar 

  36. Portera CA, et al. Alveolar soft part sarcoma: clinical course and patterns of metastasis in 70 patients treated at a single institution. Cancer. 2001;91:585–91.

    Article  PubMed  Google Scholar 

  37. Ladanyi M, et al. The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene. 2001;20:48–57.

    Article  CAS  PubMed  Google Scholar 

  38. Tsuda M, et al. TFE3 fusions activate MET signaling by transcriptional up-regulation, defining another class of tumors as candidates for therapeutic MET inhibition. Cancer Res. 2007;67:919–29.

    Article  CAS  PubMed  Google Scholar 

  39. Kummar S, et al. Cediranib for metastatic alveolar soft part sarcoma. J Clin Oncol. 2013;31:2296–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Stacchiotti S, et al. Sunitinib in advanced alveolar soft part sarcoma: evidence of a direct antitumor effect. Ann Oncol. 2011;22:1682–90.

    Article  CAS  PubMed  Google Scholar 

  41. Eilber FC, et al. Chemotherapy is associated with improved survival in adult patients with primary extremity synovial sarcoma. Ann Surg. 2007;246(1):105–13.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sleijfer S, et al. Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: an exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) Eur. J Cancer. 2010;46(1):72–83.

    CAS  Google Scholar 

  43. Jungbluth AA, et al. Monophasic and biphasic synovial sarcomas abundantly express cancer/testis antigen NY-ESO-1 but not MAGE-A1 or CT7. Int J Cancer. 2001;94:252–6.

    Article  CAS  PubMed  Google Scholar 

  44. Lai JP, et al. NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY- ESO-1-based targeted therapy and differential diagnosis. Mod Pathol. 2012;25:854–8.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Robbins PJ, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011;29:917–24.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Shimizu A, et al. The dermatofibrosarcoma protuberans-associated collagen type lalpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res. 1999;59:3719–23.

    CAS  PubMed  Google Scholar 

  47. Rutkowski P, et al. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol. 2010;28:1772–179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Toro JR, et al. Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978-2001: an analysis of 26,758 cases. Int J Cancer. 2006;119:2922–30.

    Article  CAS  PubMed  Google Scholar 

  49. Penel N, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX study. J Clin Oncol. 2008;26:5269–74.

    Article  CAS  PubMed  Google Scholar 

  50. Maki RG, et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol. 2009;27(19):3133–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Agulnik M, et al. An open-label trial multicenter phase II study of bevacizumab for the treatment of angiosarcoma. J Clin Oncol 2009 ASCO Annual Meeting Proceedings. 2009;27(Suppl15):10522.

    Google Scholar 

  52. Tawbi HA, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017;18:1493–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ben-Ami E, Barysauskas CM, Solomon S, et al. Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the uterus: results of a phase 2 study. Cancer. 2017;123:3285–90.

    Article  CAS  PubMed  Google Scholar 

  54. Maki RG, Jungbluth AA, Gnjatic S, et al. A pilot study of anti-CTLA4 antibody ipilimumab in patients with synovial sarcoma. Sarcoma. 2013;2013:168145.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Harbor-UCLA Medical Center, Torrance, CA, USA

    An Ngoc Nhu Uche

  2. Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA, USA

    Warren A. Chow

Authors
  1. An Ngoc Nhu Uche
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Warren A. Chow
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Warren A. Chow .

Editor information

Editors and Affiliations

  1. Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA

    Ravi Salgia

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Uche, A.N.N., Chow, W.A. (2020). Sarcomas. In: Salgia, R. (eds) Oncology in the Precision Medicine Era. Springer, Cham. https://doi.org/10.1007/978-3-030-31471-2_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-31471-2_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-31470-5

  • Online ISBN: 978-3-030-31471-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation