Reviews

Soft Tissue Sarcoma: Diagnosis and Treatment

The Sarcoma Journal. 2017 December;1(1):7-19

References

2. National Comprehensive Cancer Network. NCCN clinical guidelines in oncology: soft tissue sarcoma. 2016

3. Coindre J, 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 2001;91:1914–26.

4. Dei Tos A. Liposarcoma: new entities and evolving concepts. Ann Diagn Pathol 2000;4: 252–66.

5. Wile AG, Evans HL, Romsdahl MM. Leiomyosarcoma of soft tissue: a clinicopathologic study. Cancer 1981;48:1022–32.

6. Hashimoto H, Daimaru Y, Tsuneyoshi M, Enjoji M. Leiomyosarcoma of the external soft tissues. A clinicopathologic, immunohistochemical, and electron microscopic study. Cancer 1986;57:2077–88

7. Fisher C. Synovial sarcoma. Ann Diagn Pathol 1998;2:401–21.

8. Newton WA Jr, Gehan EA, Webber BL, et al. Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification--an Intergroup Rhabdomyosarcoma Study. Cancer 1995;76:1073–85.

9. Furlong MA. Pleomorphic rhabdomyosarcoma in adults: a clinicopathologic study of 38 cases with emphasis on morphologic variants and recent skeletal muscle-specific markers. Mod Pathol. 2001;14:595–603.

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10. Anghileri M, Miceli R, Fiore M. Malignant peripheral nerve sheath tumors: prognostic factors and survival in a series of patients treated at a single institution. Cancer 2006;107:1065–74.

11. Miettinen M, Lasota J. Gastrointestinal stromal tumors–definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Archive 2001;438:1–12.

12. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 2006;23:70–83.

13. Young RJ, Brown NJ, Reed MW, et al. Angiosarcoma. Lancet Oncol 2010;11:983–91.

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

15. Penel N, Grosjean J, Robin YM, et al. Frequency of certain established risk factors in soft tissue sarcomas in adults: a prospective descriptive study of 658 cases. Sarcoma 2008;2008:459386.

17. Maki RG, Moraco N, Antonescu CR, et al. Toward better soft tissue sarcoma staging: building on American joint committee on cancer staging systems versions 6 and 7. Ann Surg Oncol 2013;20:3377–83.

18. Shiraki M, Enterline HT, Brooks JJ, et al. Pathologic analysis of advanced adult soft tissue sarcomas, bone sarcomas, and mesotheliomas. The Eastern Cooperative Oncology Group (ECOG) experience. Cancer 1989;64:484–90.

19. Presant CA, Russell WO, Alexander RW, Fu YS. Soft-tissue and bone sarcoma histopathology peer review: The frequency of disagreement in diagnosis and the need for second pathology opinions. The Southeastern Cancer Study Group experience. J Clin Oncol 1986; 4:1658–61.

20. Sundaram M, McLeod RA. MR imaging of tumor and tumorlike lesions of bone and soft tissue. AJR Am J Roentgenol 1990;155:817–24.

21. Ioannidis JP, Lau J. 18F-FDG PET for the diagnosis and grading of soft-tissue sarcoma: a meta-analysis. J Nucl Med 2003;44:717–24.

22. Tateishi U, Yamaguchi U, Seki K, et al. Bone and soft-tissue sarcoma: preoperative staging with fluorine 18 fluorodeoxyglucose PET/CT and conventional imaging. Radiology 2007;245:839–47.

23. Zagars GK, Ballo MT, Pisters PW, et al. Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients. Cancer 2003;97:2530–43

24. Rosenberg S, 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;196:305–14.

25. Lewis J, Leung D, Woodruff J, et al. Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single institution. Ann Surg 1998;288:355–65.

27. Stojadinovic A, Leung DH, Hoos A. Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tisusse sarcomas. Ann Surg 2002;235:424–34.

28. 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;359:2235–41.

29. Pervaiz N, Colterjohn N, Farrokhyar F, et al. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer 2008;113:573–81.

30. Suit HD, Mankin HJ, Wood WC, Proppe KH. Preoperative, intraoperative, and postoperative radiation in the treatment of primary soft tissue sarcoma. Cancer 1985;55:2659–67

31. 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;359:2235–41.

32. Yang J, Chang A, Baker A, 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.

33. Pisters PW, Harrison LB, Leung DH, et al. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996;14:859–68.

34. Alektiar KM, Brennan MF, Healey JH, Singer S. Impact of intensity-modulated radiation therapy on local control in primary soft-tissue sarcoma of the extremity. J Clin Oncol 2008;26:3440–5.

35. 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.

36. Fakhari N, Ebm C, Kostler WJ, et al. Intensified adjuvant IFADIC chemotherapy in combination with radiotherapy versus radiotherapy alone for soft tissue sarcoma: long-term follow-up of a prospective randomized feasibility trial. Wein Klin Wochenschr 2010;122:614–9.

37. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Lancet 1997;350:1647–54.

38. Gronchi A, Frustaci S, Mercuri M, et al. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol 2012;30:850–56.

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39. Pisters PW, Leung DH, Woodruff J. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 1996;14:1679–89.

40. Whooley B, Gibbs J, Mooney M. Primary Extremity Sarcoma: What is the Appropriate Follow-up? Annals of Surg Oncol 2000; 7: 9-14.

41. Whooley BP, Mooney MN, Gibbs JF, Graybill WG. Effective follow-up strategies in soft tissue sarcoma. Sem Surg Oncol 1999;17:83–87.

42. Billingsley KG, Burt ME, Jara E, et al. Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg 1999;229:602–10.

43. Bramwell VH, Anderson D, Charette ML; Sarcoma Disease Site Group. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft tissue sarcoma. Cochrane Database Syst Rev 2003;(3):CD003293.

44. Edmonson J, Ryan L, Blum R. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol 1993;11:1269–75.

45. Santoro A, Tursz T, Mouridsen H. 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 1995;13:1537–45.

46. Tap WD, Jones RL, Van Tine B, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet 2016;388:488–97.

47. Borden EC, Amato DA, Rosenbaum C, et al. Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol 1987;5:840–50.

48. Omura GA, Major FJ, Blessing JA, et al. A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer 1983;52:626–32.

49. 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 1993;11:1276–85.

50. Maki R, Wathen K, Patel SR, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected]. J Clin Oncol 2007; 25: 2755–63.

51. Hensley ML, Maki R, Venkatraman E, et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol 2002;12:2824–31.

52. Garcia-del-Muro X, Lopez-Pousa A, Maurel J, et al. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol 2011;29:2528–33.

53. Grosso F, Jones RL, Demetri GD, et al. Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol 2007;7:595–602.

54. Italiano A, Cioffi A, Penel N, et al. Comparison of doxorubicin and weekly paclitaxel efficacy in metastatic angiosarcomas. Cancer 2012;118:3330–6.

55. Penel N, Italiano A, Ray-Coquard I, et al. Metastatic angiosarcomas: doxorubicin-based regimens, weekly paclitaxel and metastasectomy significantly improve outcome. Ann Oncol 2012;23:517–23.

56. Samuels BL, Chawla S, Patel S, et al. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol 2013;24:1703–9.

57. Schöffski P, Ray-Coquard IL, Cioffi A, et al. Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histolical subtypes. Lancet 2011;11:1045–52.

58. Van der Graaf W, Blay JY, Chawla S, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet 2012;379:1879–86.

59. Dileo P, Morgan JA, Zahrieh D, et al. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer 2007;109:1863–9.

• Which subtypes are most likely to metastasize?

Although the vast majority of sarcomas spread hematogenously, 3 have a propensity to spread lymphogenously: epithelioid sarcoma, rhabdomyosarcoma, and clear-cell sarcoma. Additionally, certain subtypes are more likely to metastasize: leiomyosarcomas, synovial sarcomas, neurogenic sarcomas, rhabdomyosarcomas, and epithelioid sarcomas.²³ Sarcomas metastasize to the lungs more frequently than to the liver. The metastatic pattern is defined primarily by sarcoma subtype and site of primary tumor. Sarcomas rarely metastasize to the brain (~1%).

Management

› Case Continued

The patient undergoes an ultrasound to better visualize the mass. Given the heterogeneous character of the mass, he is referred for an MRI to evaluate the mass and a CT scan of the chest, abdomen, and pelvis to evaluate for distant metastases. MRI reveals a 5.1 cm × 4.6 cm heterogeneous mass invading the superficial fascia of the rectus femoris muscle. No suspicious lymph nodes or other masses are identified on imaging. The patient next undergoes an image-guided core needle biopsy. Pathology from that procedure is consistent with a stage III, T2bNxMx, grade 3, dedifferentiated liposarcoma.

• What is the best management approach for this patient?

Surgery

Surgery is the mainstay of treatment for STS. Patients with the best prognosis are those who undergo complete resection with negative surgical margins.^24,25 Goal tumor-free margin is 1 to 3 cm.²⁶ Complete resection confers the best long-term survival. Both local and metastatic recurrence is higher in patients with incomplete resection and positive margins.^24,25 In a study that analyzed 2084 localized primary STSs, patients with negative margins had a local recurrence rate of 15% versus a rate of 28% in patients with positive margins. This translated into higher 5-year local recurrence-free survival for patients with negative surgical margins (82%) compared to patients with positive margins (65%).²⁷ Another study similarly found that patients with negative margins at referral to their institution who underwent postoperative radiation had high local control rates of 93% (95% confidence interval [CI] 87% to 97%) at 5, 10, and 15 years.²⁶ Although radiation improves local control, neither preoperative or postoperative radiation has been shown to improve progression-free or overall survival.²⁸ Other factors that are associated with risk of recurrence are tumor location, history of previous recurrence, age of patient, histopathology, tumor grade, and tumor size. Approximately 40% to 50% of patients with high-grade tumors (defined as size > 5 cm, deep location, and high grade) will develop distant metastases.²⁹

Zagars et al found that positive or uncertain resection margin had a relative risk of local recurrence of 2.0 (95% CI 1.3 to 3.1; P = 0.002), and presentation with locally recurrent disease (vs new tumor) had a relative risk of local recurrence of 2.0 (95% CI 1.2 to 3.4; P = 0.013).²⁶ Patients with STS of head and neck and deep trunk have higher recurrence rates than those with superficial trunk and extremity STS. A single-institution retrospective review demonstrated that patients with completely resectable retroperitoneal sarcomas have longer median survival (103 months) compared to patients with incompletely resected abdominal sarcomas (18 months).²⁵Rosenberg and colleagues compared amputation to limb-sparing surgery and radiation.²⁴ Their prospective analysis of 65 patients found no difference in disease-free and overall survival between the 2 treatment groups.The limb-sparing treatment group had higher rates of local recurrence, which was highly correlated with positive surgical margins on pathology.²⁴Evidence from this and similar studies has resulted in radical amputations being replaced by conservative limb-sparing procedures and radiation therapy. In those found to have positive margins, re-resection is an option for some. Patients who undergo re-resection have higher local control rates than patients with positive margins who do not undergo re-resection. The 5-year control rate for patients who undergo re-resection is 85% (95% CI 80% to 89%) compared to 78% (95% CI 71% to 83%) for those who do not undergo re-resection. Similarly, patients who undergo re-resection have lower rates of metastases at 5, 10, and 15 years as well as higher 5-, 10-, and 15-year disease-free survival rates.²⁶

› Case Continued

The patient is referred for limb-sparing surgery after presentation at a multidisciplinary tumor board. Prior to undergoing resection of the tumor, he is also referred to radiation-oncology to discuss the risks and benefits of combination radiotherapy and surgery as opposed to surgical resection alone.

• What is the evidence for radiation therapy?

Radiation THERAPY

Radiation therapy is used in the preoperative, intraoperative, and postoperative settings to reduce the risk of local recurrence. There are several options for radiation, including external beam radiation therapy (EBRT), intraoperative radiation, and brachytherapy. A newer strategy, intensity-modulated radiation therapy (IMRT), utilizes 3-dimensional modeling to reduce radiation dosages. Overall there are no differences in overall survival or local recurrence rates between preoperative and postoperative radiation in STS.²⁸

References

1. American Cancer Society. Cancer facts and figures 2016. American Cancer Society Web site. www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Accessed December 20, 2016.

2. National Comprehensive Cancer Network. NCCN clinical guidelines in oncology: soft tissue sarcoma. 2016

4. Dei Tos A. Liposarcoma: new entities and evolving concepts. Ann Diagn Pathol 2000;4: 252–66.

5. Wile AG, Evans HL, Romsdahl MM. Leiomyosarcoma of soft tissue: a clinicopathologic study. Cancer 1981;48:1022–32.

6. Hashimoto H, Daimaru Y, Tsuneyoshi M, Enjoji M. Leiomyosarcoma of the external soft tissues. A clinicopathologic, immunohistochemical, and electron microscopic study. Cancer 1986;57:2077–88

7. Fisher C. Synovial sarcoma. Ann Diagn Pathol 1998;2:401–21.

8. Newton WA Jr, Gehan EA, Webber BL, et al. Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification--an Intergroup Rhabdomyosarcoma Study. Cancer 1995;76:1073–85.

9. Furlong MA. Pleomorphic rhabdomyosarcoma in adults: a clinicopathologic study of 38 cases with emphasis on morphologic variants and recent skeletal muscle-specific markers. Mod Pathol. 2001;14:595–603.

10. Anghileri M, Miceli R, Fiore M. Malignant peripheral nerve sheath tumors: prognostic factors and survival in a series of patients treated at a single institution. Cancer 2006;107:1065–74.

11. Miettinen M, Lasota J. Gastrointestinal stromal tumors–definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Archive 2001;438:1–12.

12. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 2006;23:70–83.

13. Young RJ, Brown NJ, Reed MW, et al. Angiosarcoma. Lancet Oncol 2010;11:983–91.

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

15. Penel N, Grosjean J, Robin YM, et al. Frequency of certain established risk factors in soft tissue sarcomas in adults: a prospective descriptive study of 658 cases. Sarcoma 2008;2008:459386.

16. Guillou L, Coindre JM, Bonichon F, et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 1997;15:350–62.

17. Maki RG, Moraco N, Antonescu CR, et al. Toward better soft tissue sarcoma staging: building on American joint committee on cancer staging systems versions 6 and 7. Ann Surg Oncol 2013;20:3377–83.

18. Shiraki M, Enterline HT, Brooks JJ, et al. Pathologic analysis of advanced adult soft tissue sarcomas, bone sarcomas, and mesotheliomas. The Eastern Cooperative Oncology Group (ECOG) experience. Cancer 1989;64:484–90.

19. Presant CA, Russell WO, Alexander RW, Fu YS. Soft-tissue and bone sarcoma histopathology peer review: The frequency of disagreement in diagnosis and the need for second pathology opinions. The Southeastern Cancer Study Group experience. J Clin Oncol 1986; 4:1658–61.

20. Sundaram M, McLeod RA. MR imaging of tumor and tumorlike lesions of bone and soft tissue. AJR Am J Roentgenol 1990;155:817–24.

21. Ioannidis JP, Lau J. 18F-FDG PET for the diagnosis and grading of soft-tissue sarcoma: a meta-analysis. J Nucl Med 2003;44:717–24.

22. Tateishi U, Yamaguchi U, Seki K, et al. Bone and soft-tissue sarcoma: preoperative staging with fluorine 18 fluorodeoxyglucose PET/CT and conventional imaging. Radiology 2007;245:839–47.

23. Zagars GK, Ballo MT, Pisters PW, et al. Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients. Cancer 2003;97:2530–43

24. Rosenberg S, 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;196:305–14.

25. Lewis J, Leung D, Woodruff J, et al. Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single institution. Ann Surg 1998;288:355–65.

26. Zagars GK, Ballo MT, Pisters PW, et al. Surgical margins and reresection in the management of patients with soft tissue sarcoma using conservative surgery and radiation therapy. Cancer 2003;97:2544–53.

27. Stojadinovic A, Leung DH, Hoos A. Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tisusse sarcomas. Ann Surg 2002;235:424–34.

28. 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;359:2235–41.

29. Pervaiz N, Colterjohn N, Farrokhyar F, et al. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer 2008;113:573–81.

30. Suit HD, Mankin HJ, Wood WC, Proppe KH. Preoperative, intraoperative, and postoperative radiation in the treatment of primary soft tissue sarcoma. Cancer 1985;55:2659–67

31. 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;359:2235–41.

32. Yang J, Chang A, Baker A, 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.

33. Pisters PW, Harrison LB, Leung DH, et al. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996;14:859–68.

34. Alektiar KM, Brennan MF, Healey JH, Singer S. Impact of intensity-modulated radiation therapy on local control in primary soft-tissue sarcoma of the extremity. J Clin Oncol 2008;26:3440–5.

35. 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.

36. Fakhari N, Ebm C, Kostler WJ, et al. Intensified adjuvant IFADIC chemotherapy in combination with radiotherapy versus radiotherapy alone for soft tissue sarcoma: long-term follow-up of a prospective randomized feasibility trial. Wein Klin Wochenschr 2010;122:614–9.

37. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Lancet 1997;350:1647–54.

38. Gronchi A, Frustaci S, Mercuri M, et al. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol 2012;30:850–56.

39. Pisters PW, Leung DH, Woodruff J. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 1996;14:1679–89.

40. Whooley B, Gibbs J, Mooney M. Primary Extremity Sarcoma: What is the Appropriate Follow-up? Annals of Surg Oncol 2000; 7: 9-14.

41. Whooley BP, Mooney MN, Gibbs JF, Graybill WG. Effective follow-up strategies in soft tissue sarcoma. Sem Surg Oncol 1999;17:83–87.

42. Billingsley KG, Burt ME, Jara E, et al. Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg 1999;229:602–10.

43. Bramwell VH, Anderson D, Charette ML; Sarcoma Disease Site Group. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft tissue sarcoma. Cochrane Database Syst Rev 2003;(3):CD003293.

44. Edmonson J, Ryan L, Blum R. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol 1993;11:1269–75.

45. Santoro A, Tursz T, Mouridsen H. 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 1995;13:1537–45.

46. Tap WD, Jones RL, Van Tine B, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet 2016;388:488–97.

47. Borden EC, Amato DA, Rosenbaum C, et al. Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol 1987;5:840–50.

48. Omura GA, Major FJ, Blessing JA, et al. A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer 1983;52:626–32.

49. 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 1993;11:1276–85.

50. Maki R, Wathen K, Patel SR, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected]. J Clin Oncol 2007; 25: 2755–63.

51. Hensley ML, Maki R, Venkatraman E, et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol 2002;12:2824–31.

52. Garcia-del-Muro X, Lopez-Pousa A, Maurel J, et al. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol 2011;29:2528–33.

53. Grosso F, Jones RL, Demetri GD, et al. Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol 2007;7:595–602.

54. Italiano A, Cioffi A, Penel N, et al. Comparison of doxorubicin and weekly paclitaxel efficacy in metastatic angiosarcomas. Cancer 2012;118:3330–6.

55. Penel N, Italiano A, Ray-Coquard I, et al. Metastatic angiosarcomas: doxorubicin-based regimens, weekly paclitaxel and metastasectomy significantly improve outcome. Ann Oncol 2012;23:517–23.

56. Samuels BL, Chawla S, Patel S, et al. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol 2013;24:1703–9.

57. Schöffski P, Ray-Coquard IL, Cioffi A, et al. Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histolical subtypes. Lancet 2011;11:1045–52.

58. Van der Graaf W, Blay JY, Chawla S, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet 2012;379:1879–86.

59. Dileo P, Morgan JA, Zahrieh D, et al. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer 2007;109:1863–9.

Soft Tissue Sarcoma: Diagnosis and Treatment

References

• Which subtypes are most likely to metastasize?

› Case Continued

• What is the best management approach for this patient?

Surgery

› Case Continued

• What is the evidence for radiation therapy?

Radiation THERAPY

Pages

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