Note: Separate PDQ summaries on Childhood Soft Tissue Sarcoma Treatment and Uterine Sarcoma Treatment are also available.

Note: Estimated new cases and deaths from soft tissue sarcoma in the United States in 2008:[1]

• New cases: 10,390.
• Deaths: 3,680.

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Soft tissue sarcomas are malignant tumors that may arise in any of the mesodermal tissues of the extremities (50%), trunk and retroperitoneum (40%), or head and neck (10%). Rarely, these tumors arise in the gastrointestinal tract or gastrointestinal stroma, and a small percentage of these are called gastrointestinal stromal tumors (GISTs). Malignant GISTs can occur from the esophagus to the rectum but occur most commonly in the stomach and small intestine. Soft tissue sarcomas occur with greater frequency in patients with:[2]

• von Recklinghausen disease (neurofibromatosis).
• Gardner syndrome.
• Werner syndrome.
• Tuberous sclerosis.
• Basal cell nevus syndrome.
• Li-Fraumeni syndrome (p53 mutations).

Soft tissue sarcomas may be heterogeneous, so adequate tissue should be obtained via either core-needle or incisional biopsy for microscopic examination to determine histologic type and tumor grade. Careful planning of the initial biopsy is important to avoid compromising subsequent curative resection. Since the selection of treatment is determined by the grade of the tumor, it is essential to have a careful review of the biopsy tissue by a pathologist who is experienced in diagnosing sarcomas. Complete staging and treatment planning by a multidisciplinary team of cancer specialists is required to determine the optimal treatment for patients with this disease. In most cases, a combined modality approach of preoperative or postoperative radiation therapy is used, rather than the radical surgical procedures that were used in the past. The role of chemotherapy is less well defined. Because of the evolving nature of the state of the art in the treatment of this disease, all patients with such lesions should be included in a clinical trial whenever possible.

The prognosis for patients with adult soft tissue sarcomas depends on several factors, including the patient’s age and the size, histologic grade, and stage of the tumor.[3-5] Factors associated with a poorer prognosis include age older than 60 years, tumors larger than 5 cm, or high-grade histology.[6]

While low-grade tumors are usually curable by surgery alone, higher-grade sarcomas (as determined by the mitotic index and by the presence of hemorrhage and necrosis) are associated with higher local treatment failure rates and increased metastatic potential.[7] When feasible, wide margin function-sparing surgical excision is the cornerstone of effective treatment, with the goal of preservation of a functional extremity.[8,9] This may be facilitated by soft tissue reconstructive surgery.[10] Mohs surgical technique may be considered as an alternative to wide surgical excision for small, well-differentiated sarcomas when cosmetic results are considered to be very important, as margins can be assured with minimal normal tissue removal.[2,11] High-grade soft tissue sarcomas of the extremities can often be effectively treated while preserving the limb with combined-modality treatment consisting of preoperative or postoperative radiation therapy to reduce local recurrence. A phase II trial (SWOG-9119) was conducted of neoadjuvant therapy with DOX/DTIC/IFF for poor prognosis soft tissue sarcoma.[8,12-19] In adults, local control of high-grade soft tissue sarcomas of the trunk and the head and neck can be achieved with surgery, often in combination with radiation therapy with or without chemotherapy.[20]

Effective treatment of retroperitoneal sarcomas requires removal of all gross disease while sparing adjacent viscera not invaded by tumor. The prognosis for patients with high-grade retroperitoneal sarcomas is less favorable than for patients with tumors at other sites, partly because of the difficulty in completely resecting these tumors and the limitations placed on high-dose radiation therapy.[2,21] Surgical resection is the most effective treatment modality for GISTs.[22] Evidence indicates that imatinib mesylate, a tyrosine kinase inhibitor, induced sustained tumor response in patients with unresectable or metastatic GIST tumors.[23-25][Level of evidence: 3iiiDiv][26,27]

Several prospective randomized trials have been unable to confirm conclusively whether doxorubicin-based adjuvant chemotherapy benefits adults with resectable soft tissue sarcomas. The majority of these studies accrued small numbers of patients and did not demonstrate a metastasis-free survival or an overall survival (OS) benefit for adjuvant chemotherapy.[20] A small study of adjuvant chemotherapy showed a positive impact in disease-free survival and OS in patients treated with postoperative chemotherapy.[28] There was wide interstudy variability among the numerous trials, including differences in therapeutic regimens, drug doses, sample size, tumor site, and histologic grade. A quantitative meta-analysis of updated data from 1,568 individual patients from 14 trials of doxorubicin-based adjuvant therapy showed an absolute benefit from adjuvant therapy of 6% for local relapse-free interval (95% confidence interval [CI], 1–10), 10% for distant relapse-free interval (95% CI, 5–15), and 10% for recurrence-free survival (95% CI, 5–15); however, there was no OS benefit at 10 years.[29][Level of evidence: 1iiDii] Patients with high-grade tumors (grades 3 or 4) larger than 5 cm in diameter have the greatest tendency for disease to metastasize and are eligible for prospective clinical trials of adjuvant chemotherapy.

With distant metastases (stage IV), surgery with curative intent is possible for patients selected for optimal underlying biologic behavior (i.e., patients with a limited number of metastases, with a long disease-free interval, and with slow clinical growth) with pulmonary metastases who have undergone or are undergoing complete resection of the primary tumor.[30-32] Doxorubicin alone or with dacarbazine is considered the best chemotherapeutic regimen for advanced sarcoma.[33-35] A randomized trial of 340 patients with advanced sarcoma showed a higher response rate (32% vs. 17%, P < .002) and longer time-to-progression (6 vs. 4 months, P < .02) for doxorubicin, dacarbazine, ifosfamide, and mesna (MAID) versus doxorubicin and dacarbazine alone.[36][Level of evidence: 1iiDiii] The increased response rate of the MAID regimen may be justified in preoperative management of younger patients with borderline resectability, but the increased toxic effects argue against its use in older patients.[36]

Complete surgical resection is often difficult for sarcomas of the retroperitoneum because of their large size before detection and anatomic location.[37,38] Prospective randomized trials have not shown improved survival with preoperative or postoperative adjuvant chemotherapy for this subgroup.[29]

References

1. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed October 1, 2008. 
   
   
2. Brennan M, Singer S, Maki R, et al.: Sarcomas of the soft tissues and bone. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1581-1631. 
   
   
3. Le Doussal V, Coindre JM, Leroux A, et al.: Prognostic factors for patients with localized primary malignant fibrous histiocytoma: a multicenter study of 216 patients with multivariate analysis. Cancer 77 (9): 1823-30, 1996.  [PUBMED Abstract]
   
   
4. Le QT, Fu KK, Kroll S, et al.: Prognostic factors in adult soft-tissue sarcomas of the head and neck. Int J Radiat Oncol Biol Phys 37 (5): 975-84, 1997.  [PUBMED Abstract]
   
   
5. Coindre JM, Terrier P, Guillou L, et al.: Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer 91 (10): 1914-26, 2001.  [PUBMED Abstract]
   
   
6. Vraa S, Keller J, Nielsen OS, et al.: Prognostic factors in soft tissue sarcomas: the Aarhus experience. Eur J Cancer 34 (12): 1876-82, 1998.  [PUBMED Abstract]
   
   
7. Collin CF, Friedrich C, Godbold J, et al.: Prognostic factors for local recurrence and survival in patients with localized extremity soft-tissue sarcoma. Semin Surg Oncol 4 (1): 30-7, 1988.  [PUBMED Abstract]
   
   
8. Watson DI, Coventry BJ, Langlois SL, et al.: Soft-tissue sarcoma of the extremity. Experience with limb-sparing surgery. Med J Aust 160 (7): 412-6, 1994.  [PUBMED Abstract]
   
   
9. Geer RJ, Woodruff J, Casper ES, et al.: Management of small soft-tissue sarcoma of the extremity in adults. Arch Surg 127 (11): 1285-9, 1992.  [PUBMED Abstract]
   
   
10. Lohman RF, Nabawi AS, Reece GP, et al.: Soft tissue sarcoma of the upper extremity: a 5-year experience at two institutions emphasizing the role of soft tissue flap reconstruction. Cancer 94 (8): 2256-64, 2002.  [PUBMED Abstract]
    
    
11. Fish FS: Soft tissue sarcomas in dermatology. Dermatol Surg 22 (3): 268-73, 1996.  [PUBMED Abstract]
    
    
12. Marcove RC, Sheth DS, Healey J, et al.: Limb-sparing surgery for extremity sarcoma. Cancer Invest 12 (5): 497-504, 1994.  [PUBMED Abstract]
    
    
13. Williard WC, Collin C, Casper ES, et al.: The changing role of amputation for soft tissue sarcoma of the extremity in adults. Surg Gynecol Obstet 175 (5): 389-96, 1992.  [PUBMED Abstract]
    
    
14. 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 16 (1): 197-203, 1998.  [PUBMED Abstract]
    
    
15. Schmidt RA, Conrad EU 3rd, Collins C, et al.: Measurement and prediction of the short-term response of soft tissue sarcomas to chemotherapy. Cancer 72 (9): 2593-601, 1993.  [PUBMED Abstract]
    
    
16. Temple WJ, Temple CL, Arthur K, et al.: Prospective cohort study of neoadjuvant treatment in conservative surgery of soft tissue sarcomas. Ann Surg Oncol 4 (7): 586-90, 1997 Oct-Nov.  [PUBMED Abstract]
    
    
17. Valle AA, Kraybill WG: Management of soft tissue sarcomas of the extremity in adults. J Surg Oncol 63 (4): 271-9, 1996.  [PUBMED Abstract]
    
    
18. Pollack A, Zagars GK, Goswitz MS, et al.: Preoperative vs. postoperative radiotherapy in the treatment of soft tissue sarcomas: a matter of presentation. Int J Radiat Oncol Biol Phys 42 (3): 563-72, 1998.  [PUBMED Abstract]
    
    
19. Schoenfeld GS, Morris CG, Scarborough MT, et al.: Adjuvant radiotherapy in the management of soft tissue sarcoma involving the distal extremities. Am J Clin Oncol 29 (1): 62-5, 2006.  [PUBMED Abstract]
    
    
20. O'Byrne K, Steward WP: The role of adjuvant chemotherapy in the treatment of adult soft tissue sarcomas. Crit Rev Oncol Hematol 27 (3): 221-7, 1998.  [PUBMED Abstract]
    
    
21. Lewis JJ, Leung D, Woodruff JM, et al.: Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single institution. Ann Surg 228 (3): 355-65, 1998.  [PUBMED Abstract]
    
    
22. Pidhorecky I, Cheney RT, Kraybill WG, et al.: Gastrointestinal stromal tumors: current diagnosis, biologic behavior, and management. Ann Surg Oncol 7 (9): 705-12, 2000.  [PUBMED Abstract]
    
    
23. Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al.: Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344 (14): 1052-6, 2001.  [PUBMED Abstract]
    
    
24. Blanke CD, von Mehren M, Joensuu H, et al.: Evaluation of the safety and efficacy of an oral molecularly-targeted therapy, STI157, in patients (pts) with unresectable or metastatic gastrointestinal stromal tumors (GISTs) expressing c-kit (CD117). [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1, 1a, 2001. 
    
    
25. Van Oosterom AT, Judson I, Verweij J, et al.: STI 571, an active drug in metastatic gastro intestinal stromal tumors (GIST), an EORTC phase I study. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-2, 1a, 2001. 
    
    
26. Demetri GD, von Mehren M, Blanke CD, et al.: Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347 (7): 472-80, 2002.  [PUBMED Abstract]
    
    
27. Bümming P, Andersson J, Meis-Kindblom JM, et al.: Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients. Br J Cancer 89 (3): 460-4, 2003.  [PUBMED Abstract]
    
    
28. 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 19 (5): 1238-47, 2001.  [PUBMED Abstract]
    
    
29. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 350 (9092): 1647-54, 1997.  [PUBMED Abstract]
    
    
30. van Geel AN, Pastorino U, Jauch KW, et al.: Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients. Cancer 77 (4): 675-82, 1996.  [PUBMED Abstract]
    
    
31. Casson AG, Putnam JB, Natarajan G, et al.: Five-year survival after pulmonary metastasectomy for adult soft tissue sarcoma. Cancer 69 (3): 662-8, 1992.  [PUBMED Abstract]
    
    
32. Putnam JB Jr, Roth JA: Surgical treatment for pulmonary metastases from sarcoma. Hematol Oncol Clin North Am 9 (4): 869-87, 1995.  [PUBMED Abstract]
    
    
33. Santoro A, Tursz T, Mouridsen H, et al.: Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 13 (7): 1537-45, 1995.  [PUBMED Abstract]
    
    
34. Zalupski M, Metch B, Balcerzak S, et al.: Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst 83 (13): 926-32, 1991.  [PUBMED Abstract]
    
    
35. Borden EC, Amato DA, Rosenbaum C, et al.: Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol 5 (6): 840-50, 1987.  [PUBMED Abstract]
    
    
36. Antman K, Crowley J, Balcerzak SP, et al.: An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol 11 (7): 1276-85, 1993.  [PUBMED Abstract]
    
    
37. Heslin MJ, Lewis JJ, Nadler E, et al.: Prognostic factors associated with long-term survival for retroperitoneal sarcoma: implications for management. J Clin Oncol 15 (8): 2832-9, 1997.  [PUBMED Abstract]
    
    
38. Jaques DP, Coit DG, Hajdu SI, et al.: Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum. Ann Surg 212 (1): 51-9, 1990.  [PUBMED Abstract]
    
    

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