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The Landmark Series: Multimodality Treatment of Extremity Sarcoma

  • Sarcoma
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Abstract

Multimodality treatment of primary soft tissue sarcoma has evolved over the last 50 years, including seminal studies in amputation versus limb-sparing surgery, incorporation of radiation therapy (XRT), and the continuing controversy over the utilization and efficacy of systemic chemotherapy. We review the landmark studies in the multimodality management of primary extremity and trunk soft tissue sarcoma.

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References

  1. IARC WHO Classification of Tumours-Soft Tissue and Bone Tumours. Vol 3. 5th ed. Lyon: IARC Press; 2020.

  2. von Mehren M, Kane JM, III, Benjamin RS, et al. NCCN Clinical Practice Guidelines in Oncology: Soft Tissue Sarcoma. In: 2019.

  3. Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg. 1982;196(3):305–315.

    Article  CAS  Google Scholar 

  4. Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol. 1996;14(3):859–868.

    Article  CAS  Google Scholar 

  5. 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(1):197–203.

    Article  CAS  Google Scholar 

  6. Beane JD, Yang JC, White D, Steinberg SM, Rosenberg SA, Rudloff U. Efficacy of adjuvant radiation therapy in the treatment of soft tissue sarcoma of the extremity: 20-year follow-up of a randomized prospective trial. Ann Surg Oncol. 2014;21(8):2484–2489.

    Article  Google Scholar 

  7. Pisters PW, Pollock RE, Lewis VO, et al. Long-term results of prospective trial of surgery alone with selective use of radiation for patients with T1 extremity and trunk soft tissue sarcomas. Ann Surg. 2007;246(4):675–681; discussion 681–672.

  8. Fiore M, Ford S, Callegaro D, et al. Adequate local control in high-risk soft tissue sarcoma of the extremity treated with surgery alone at a reference centre: should radiotherapy still be a standard? Ann Surg Oncol. 2018;25(6):1536–1543.

    Article  Google Scholar 

  9. Gundle KR, Kafchinski L, Gupta S, et al. Analysis of margin classification systems for assessing the risk of local recurrence after soft tissue sarcoma resection. J Clin Oncol. 2018;36(7):704–709.

    Article  Google Scholar 

  10. Blay J-Y, Honore C, Stoeckle E, et al. Surgery in reference centers improves survival of sarcoma patients: a nationwide study. Ann Oncol. 2019;30(7):1143–1153.

    Article  Google Scholar 

  11. O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002;359(9325):2235–2241.

    Article  Google Scholar 

  12. Davis AM, O’Sullivan B, Turcotte R, et al. Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiother Oncol. 2005;75(1):48–53.

    Article  Google Scholar 

  13. Dagan R, Indelicato DJ, McGee L, et al. The significance of a marginal excision after preoperative radiation therapy for soft tissue sarcoma of the extremity. Cancer. 2012;118(12):3199–3207.

    Article  Google Scholar 

  14. O’Donnell PW, Griffin AM, Eward WC, et al. The effect of the setting of a positive surgical margin in soft tissue sarcoma. Cancer. 2014;120(18):2866–2875.

    Article  Google Scholar 

  15. Kraybill WG, Harris J, Spiro IJ, et al. 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: Radiation Therapy Oncology Group Trial 9514. J Clin Oncol. 2006;24(4):619–625.

    Article  CAS  Google Scholar 

  16. Kraybill WG, Harris J, Spiro IJ, et al. Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514. Cancer. 2010;116(19):4613–4621.

    Article  CAS  Google Scholar 

  17. Palassini E, Ferrari S, Verderio P, et al. Feasibility of preoperative chemotherapy with or without radiation therapy in localized soft tissue sarcomas of limbs and superficial trunk in the Italian Sarcoma Group/Grupo Español de Investigación en Sarcomas randomized clinical trial: three versus five cycles of full-dose epirubicin plus ifosfamide. J Clin Oncol. 2015;33(31):3628–3634.

    Article  CAS  Google Scholar 

  18. Gronchi A, Verderio P, De Paoli A, et al. Quality of surgery and neoadjuvant combined therapy in the ISG-GEIS trial on soft tissue sarcomas of limbs and trunk wall. Ann Oncol. 2013;24(3):817–823.

    Article  CAS  Google Scholar 

  19. Gronchi A, Hindi N, Cruz J, et al. Trabectedin and RAdiotherapy in Soft Tissue Sarcoma (TRASTS): Results of a phase I study in myxoid liposarcoma from Spanish (GEIS), Italian (ISG), French (FSG) Sarcoma Groups. EClinicalMedicine. 2019;9:35–43.

    Article  Google Scholar 

  20. Jakob J, Simeonova A, Kasper B, et al. Combined sunitinib and radiation therapy for preoperative treatment of soft tissue sarcoma: results of a phase I trial of the German interdisciplinary sarcoma group (GISG-03). Radiat Oncol. 2016;11:77.

    Article  Google Scholar 

  21. Haas RL, Gelderblom H, Sleijfer S, et al. A phase I study on the combination of neoadjuvant radiotherapy plus pazopanib in patients with locally advanced soft tissue sarcoma of the extremities. Acta Oncol. 2015;54(8):1195–1201.

    Article  CAS  Google Scholar 

  22. Canter RJ, Borys D, Olusanya A, et al. Phase I trial of neoadjuvant conformal radiotherapy plus sorafenib for patients with locally advanced soft tissue sarcoma of the extremity. Ann Surg Oncol. 2014;21(5):1616–1623.

    Article  Google Scholar 

  23. Keung EZ, Lazar AJ, Torres KE, et al. Phase II study of neoadjuvant checkpoint blockade in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. BMC Cancer. 2018;18(1):913.

    Article  CAS  Google Scholar 

  24. Bonvalot S, Rutkowski PL, Thariat J, et al. NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2–3, randomised, controlled trial. Lancet Oncol. 2019;20(8):1148–1159.

  25. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Lancet. 1997;350(9092):1647–1654.

  26. Pervaiz N, Colterjohn N, Farrokhyar F, Tozer R, Figueredo A, Ghert M. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer. 2008;113(3):573–581.

    Article  Google Scholar 

  27. Bramwell V, Rouesse J, Steward W, et al. Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma–reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1994;12(6):1137–1149.

    Article  CAS  Google Scholar 

  28. Woll PJ, Reichardt P, Le Cesne A, et al. Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol. 2012;13(10):1045–1054.

    Article  CAS  Google Scholar 

  29. Callegaro D, Miceli R, Bonvalot S, et al. Impact of perioperative chemotherapy and radiotherapy in patients with primary extremity soft tissue sarcoma: retrospective analysis across major histological subtypes and major reference centres. Eur J Cancer (Oxford, England: 1990). 2018;105:19–27.

  30. Callegaro D, Miceli R, Bonvalot S, et al. Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis. Lancet Oncol. 2016;17(5):671–680.

    Article  Google Scholar 

  31. Pasquali S, Pizzamiglio S, Touati N, et al. The impact of chemotherapy on survival of patients with extremity and trunk wall soft tissue sarcoma: revisiting the results of the EORTC-STBSG 62931 randomised trial. Eur J Cancer (Oxford, England: 1990). 2019;109:51–60.

  32. 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(5):1238–1247.

    Article  CAS  Google Scholar 

  33. Gronchi A, Stacchiotti S, Verderio P, et al. Short, full-dose adjuvant chemotherapy (CT) in high-risk adult soft tissue sarcomas (STS): long-term follow-up of a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. Ann Oncol. 2016;27(12):2283–2288.

    Article  CAS  Google Scholar 

  34. Gronchi A, Ferrari S, Quagliuolo V, et al. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017;18(6):812–822.

    Article  CAS  Google Scholar 

  35. Gronchi A, Palmerini E, Quagliuolo V, et al. Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: final results of a randomized trial from Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups. J Clin Oncol. 2020; 38(19):2178–2186.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Christina L. Roland MD, MS

  2. Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Winan van Houdt MD

  3. Sarcoma Service, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Alessandro Gronchi MD

Authors
  1. Christina L. Roland MD, MS
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  2. Winan van Houdt MD
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  3. Alessandro Gronchi MD
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Correspondence to Alessandro Gronchi MD.

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C. L. Roland, W. van Houdt and A. Gronchi have nothing to disclose.

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Roland, C.L., van Houdt, W. & Gronchi, A. The Landmark Series: Multimodality Treatment of Extremity Sarcoma. Ann Surg Oncol 27, 3672–3682 (2020). https://doi.org/10.1245/s10434-020-08872-1

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  • DOI: https://doi.org/10.1245/s10434-020-08872-1

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