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Adjuvant therapy for extremity sarcomas

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Opinion statement

Extremity soft tissue sarcomas (STS) represent a rare, heterogeneous malignancy. Surgery is the primary treatment for patients with no evidence of metastatic disease, and for small low-grade superficial tumors in which adequate margins can be obtained, it may be the only therapy indicated. For large, deep tumors or tumors that are close to important neurovascular structures or bone, the addition of radiotherapy to resection has improved local control and increased limb salvage without affecting overall survival. Adjuvant chemotherapy has been an issue of considerable debate. Because 50% of patients with high-risk tumors will develop metastatic disease, effective systemic treatment with chemotherapy is needed. Unfortunately, studies have shown minimal improvement in overall survival when chemotherapy is added to the local treatment of high-risk extremity STS. More recently, a few trials of neoadjuvant chemotherapy consisting of mesna, doxorubicin, ifosfamide, and dacarbazine and high-dose doxorubicin and ifosfamide have shown some early promising results, but at the price of increased toxicity. Targeted therapy has shown some of its best results with gastrointestinal stromal tumors, but so far there has been little success in treating extremity STS. At this time, high-dose adjuvant or neoadjuvant chemotherapy should be given in the setting of a clinical trial to patients with high-risk tumors who can tolerate a potentially toxic chemotherapeutic regimen. The goal of these trials should be to assess new combination therapies, possibly including targeted therapies, for the management of large highgrade, high-risk soft tissue sarcomas.

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References and Recommended Reading

  1. Rosenberg SA, Tepper J, Glatstein E, et al.:The treatment of soft-tissue sarcomas of the extremities. Ann Surg 1982, 196:305–315.

    Article  PubMed  CAS  Google Scholar 

  2. Cormier JN, Pollock RE:Soft tissue sarcomas. CA Cancer J Clin 2004, 54:94–109.

    Article  PubMed  Google Scholar 

  3. Pisters PWT, Leung DHY, Woodruff J, et al.:Analysis of prognostic factors in 1041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 1996, 14:1679–1689. Retrospective analysis of 1041 patients with localized STS of extremities, demonstrating the importance of grade, depth, size, and histologic subtype on disease-specific survival.

    PubMed  CAS  Google Scholar 

  4. Coindre JM, Terrier P, Bui NB, et al.:Prognostic factors in adult patients with locally controlled soft tissue sarcoma:a study of 546 patients from the French Federation of Cancer Centers Sarcoma Group. J Clin Oncol 1996, 14:869–877.

    PubMed  CAS  Google Scholar 

  5. Wunder JS, Healey JH, Davis AM, et al.:A comparison of staging systems for localized extremity soft tissue sarcoma. Cancer 2000, 88:2721–2730.

    Article  PubMed  CAS  Google Scholar 

  6. Trovik CS, Bauer HCF, Alvegard TA, et al.:Surgical margins, local recurrence and metastasis in soft tissue sarcomas:559 surgically-treated patients from the Scandinavian Sarcoma Group register. Eur J Cancer 2000, 36:710–716.

    Article  PubMed  CAS  Google Scholar 

  7. Spiro IJ, Gebhardt MC, Jennings LC, et al.:Prognostic factors for local control of sarcomas of the soft tissues managed by radiation and surgery. Semin Oncol 1997, 24:5460–5466.

    Google Scholar 

  8. Wylie JP, O'Sullivan B, Catton C, et al.:Contemporary radiotherapy for soft tissue sarcoma. Semin Surg Oncol 1999, 17:33–46.

    Article  PubMed  CAS  Google Scholar 

  9. Bhangu AA, Beard JAS, Grimer RJ:Should soft tissue sarcoma be treated at a specialist center? Sarcoma 2004, 1:1–6.

    Article  Google Scholar 

  10. Kattan MW, Leung DHY, Brennan MF:Postoperative nomogram for 12-year sarcoma-specific death. J Clin Oncol 2002, 20:791–796.

    Article  PubMed  Google Scholar 

  11. Geer RJ, Woodruff J, Casper ES, et al.:Management of small soft-tissue sarcoma of the extremity in adults. Arch Surg 1992, 11:1285–1289.

    Google Scholar 

  12. Rydholm A, Gustafson P, Rooser B, et al.:Limb-sparing surgery without radiotherapy based on anatomic location of soft tissue sarcoma. J Clin Oncol 1991, 9:1757–1765.

    PubMed  CAS  Google Scholar 

  13. Baldini EH, Goldberg J, Jenner C, et al.:Long-term outcomes after function-sparing surgery without radiotherapy for soft tissue sarcoma of the extremities and trunk. J Clin Oncol 1999, 17:3252–3259.

    PubMed  CAS  Google Scholar 

  14. Stojadinovic A, Leung DHY, Allen P, et al.:Primary adult soft tissue sarcoma:time-dependent influence of prognostic variables. J Clin Oncol 2002, 20:4344–4352.

    Article  PubMed  Google Scholar 

  15. Karakousis CP, Emrich LJ, Rao U, et al.:Limb salvage in soft tissue sarcomas with selective combination of modalities. Eur J Surg Oncol 1991, 17:71–80.

    PubMed  CAS  Google Scholar 

  16. Spiro IJ, Rosenberg AE, Springfield D, et al.:Combined surgery and radiation for limb preservation in soft tissue sarcoma of the extremity:the Massachusetts General Hospital experience. Cancer Invest 1995, 13:86–95.

    PubMed  CAS  Google Scholar 

  17. Yang JC, Chang AE, Baker AR, et al.:Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998, 16:197–203. Randomized, controlled trial showing improvement in local control and no change in overall survival with the addition of adjuvant radiation for extremity STS.

    Google Scholar 

  18. Pisters PWT, Harrison LB, Leung DHY, et al.:Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996, 14:859–868. Randomized, controlled trial of surgery alone versus surgery and brachytherapy for extremity STS, demonstrating improved local control for high-grade tumors, with no improvement in disease-specific survival.

    Google Scholar 

  19. O'Sullivan B, Davis AM, Turcotte R, et al.:Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs:a randomized trial. Lancet 2002, 359:2235–2241.

    Article  PubMed  Google Scholar 

  20. Nielsen OS, Cummings B, O'Sullivan B, et al.:Preoperative and postoperative irradiation of soft tissue sarcomas:effect of radiation field size. Int J Radiat Oncol Biol Phys 1991, 21:1595–1599.

    PubMed  CAS  Google Scholar 

  21. Davis AM, O'Sullivan B, Turcotte R, et al.:Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiat Oncol 2005, 75:48–53.

    Article  Google Scholar 

  22. Fleming JB, Berman RS, Cheng SC, et al.:Long-term outcome of patients with American Joint Committee on Cancer stage IIB extremity soft tissue sarcomas. J Clin Oncol 1999, 17:2772–2780.

    PubMed  CAS  Google Scholar 

  23. Alektiar KM, Leung D, Zelefsky MJ, et al.:Adjuvant radiation for stage IIB soft tissue sarcoma of the extremity. J Clin Oncol 2002, 20:1643–1650.

    Article  PubMed  Google Scholar 

  24. Khanfir K, Alzieu L, Terrier P, et al.:Does adjuvant radiation therapy increase loco-regional control after optimal resection of soft-tissue sarcoma of the extremities? Eur J Cancer 2003, 39:1872–1880.

    Article  PubMed  CAS  Google Scholar 

  25. Lindberg RD, Martin RG, Romsdahl MM, et al.:Conservative surgery and postoperative radiotherapy in 300 adults with soft-tissue sarcomas. Cancer 1981, 47:2391–2397.

    Article  PubMed  CAS  Google Scholar 

  26. Karakousis CP, Zografos GC:Radiation therapy for high grade soft tissue sarcomas of the extremities treated with limb-preserving surgery. Eur J Surg Oncol 2002, 28:431–436.

    Article  PubMed  CAS  Google Scholar 

  27. Weitz J, Antonescu CR, Brennan MF, et al.:Localized extremity soft tissue sarcoma:improved knowledge with unchanged survival over time. J Clin Oncol 2003, 21:2719–2725.

    Article  PubMed  Google Scholar 

  28. Tierney JF:Adjuvant chemotherapy for localized resectable soft-tissue sarcoma of adults:meta-analysis of individual data. Lancet 1997, 350:1647–1654. Meta-analysis of 1586 patients, 886 with extremity STS, from randomized, controlled trials evaluating adjuvant chemotherapy showing 7% absolute benefit in survival at 10 years for extremity STS.

    Article  Google Scholar 

  29. Brodowicz T, Schwameis E, Widder J, et al.:Intensified adjuvant IFADIC chemotherapy for adult soft tissue sarcoma:a prospective randomized feasibility trial. Sarcoma 2000, 4:151–160.

    CAS  PubMed  Google Scholar 

  30. Gortzak E, Azzarelli A, Buesa J, et al.:A randomized phase II study on neo-adjuvant chemotherapy for ‘high-risk’ adult soft-tissue sarcoma. Eur J Cancer 2001, 37:1096–1103.

    Article  PubMed  CAS  Google Scholar 

  31. Frustaci S, Gherlinzoni F, De Paoli A, et al.:Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles:results of the Italian Randomized Cooperative Trial. J Clin Oncol 2001, 19:1238–1247. Randomized, controlled trial of surgery and radiation alone versus surgery, radiation, and chemotherapy for extremity STS. Initial analysis showed improved overall survival at 59 months, but at 89 months, the survival benefit was no longer statistically significant.

    PubMed  CAS  Google Scholar 

  32. Frustaci S, De Paoli A, Bidoli E, et al.:Ifosfamide in the adjuvant therapy of soft tissue sarcomas. Oncology 2003, 65(Suppl 2):80–84.

    Article  PubMed  CAS  Google Scholar 

  33. Petrioli R, Coratti A, Correale P, et al.:Adjuvant epirubicin with or without ifosfamide for adult soft-tissue sarcoma. Am J Clin Oncol 2002, 25:468–473.

    Article  PubMed  Google Scholar 

  34. Cormier JN, Huang X, Xing Y, et al.:Cohort analysis of patients with localized, high-risk, extremity soft tissue sarcoma treated at two cancer centers:chemotherapyassociated outcomes. J Clin Oncol 2004, 22:4567–4574.

    Article  PubMed  Google Scholar 

  35. Grobmyer SR, Maki RG, Demetri GD, et al.:Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol 2004, 15:1667–1672.

    Article  PubMed  CAS  Google Scholar 

  36. Ferrari A, Gronchi A, Casanova M, et al.:Synovial sarcoma:a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 2004, 101:627–634.

    Article  PubMed  Google Scholar 

  37. Eilber FC, Eilber FR, Eckardt J, et al.:The impact of chemotherapy on the survival of patients with highgrade primary extremity liposarcoma. Ann Surg 2004, 4:284–295.

    Google Scholar 

  38. Delaney TF, Spiro IJ, Suit HD, et al.:Neoadjuvant chemotherapy and radiotherapy for large extremity soft-tissue sarcomas. Int J Radiat Oncol Biol Phys 2003, 56:1117–1127. Cohort study treating large high-grade extremity STS with MAID interdigitated with radiation and surgery compared with historical controls demonstrated an 87% 5-year actuarial survival for patients treated with MAID protocol.

    Article  Google Scholar 

  39. Kraybill WG, Harris J, Spiro IJ, et al.:A phase II study of neoadjuvant chemotherapy and radiation therapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall. J Clin Oncol 2006, 24:619–625. Phase II trial evaluating neoadjuvant MAID interdigitated with radiation and surgery for treatment of extremity STS. The study demonstrated a good pathologic response but with increased toxicity.

    Article  PubMed  CAS  Google Scholar 

  40. Borden EC, Baker LH, Bell RS, et al.:Soft tissue sarcomas of adults:state of the translational science. Clin Cancer Res 2003, 9:1941–1956.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Roswell Park Cancer Institute, Elm and Carlton Streets, Carlton Building Room #252, 14263, Buffalo, NY, USA

    William G. Kraybill MD

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  1. Michael Schlieman MD
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  2. Richard Smith MD
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  3. William G. Kraybill MD
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Schlieman, M., Smith, R. & Kraybill, W.G. Adjuvant therapy for extremity sarcomas. Curr. Treat. Options in Oncol. 7, 456–463 (2006). https://doi.org/10.1007/s11864-006-0021-x

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