Липосаркомы: морфологические подтипы, факторы прогноза и терапевтические опции

1. Статистика злокачественных новообразований в России и странах СНГ в 2012 г. Под ред. М.И.Давыдова. М., 2014. / Statistika zlokachestvennyh novoobrazovanij v Rossii i stranah SNG v 2012 g. Pod red. M.I.Davydova. M., 2014. [in Russian]
2. Gadgeel SM, Harlan LC, Zeruto CA et al. Patterns of care in a population-based sample of soft tissue sarcoma patients in the United States. Cancer 2009; 115 (12): 2744–54.
3. Kindblom LG, Angervall L, Svendsen P. Liposarcoma: a clinicopathologic, radio-graphic and prognostic study. Acta Pathol Microbiol Scand (Suppl.) 1975; 253: 1–71.
4. Crago AM, Singer S. Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma. Curr Opin Oncol 2011; 23 (4): 373–8. http://dx.doi.org/10.1097/CCO.0b013e32834796e6
5. Evans HL. Liposarcoma: a study of 55 cases with reassessment of its classification. Am J Surg Pathol 1979; 3 (6): 507–23.
6. Fletcher CD. World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone. Lyon: IARC Press, 2002; p. 120–5.
7. Fletcher CD. WHO classification of tumours ofsoft tissue and bone. 4th ed. WHO Press, 2013.
8. Kilpatrick SE, Doyon J, Choong PF et al. The clinicopathologic spectrum of myxoid and round cell liposarcoma. A study of 95 cases. Cancer 1996; 77 (8): 1450–8.
9. Weiss SW, Rao VK. Well-differentiated liposarcoma (atypical lipoma) of deep soft tissue of the extremities, retroperitoneum, and miscellaneous sites. Am J Surg Pathol 1992; 16 (11): 1051–8.
10. Gebhard S, Coindre JM, Michels JJ et al. Pleomorphic liposarcoma: clinicopathologic, immunohistochemical, and follow-up analysis of 63 cases: a study from the French Federation of Cancer Centers Sarcoma Group. Am J Surg Pathol 2002; 26 (5): 601–16.
11. Henricks WH, Chu YC, Goldblum JR et al. Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation. Am J Surg Pathol 1997; 21 (3): 271–81.
12. Hornick JL, Bosenberg MW, Mentzel T et al. Pleomorphic liposarcoma. Am J Surg Pathol 2004; 28 (10): 1257–67. http://dx.doi.org/10. 1097/01.pas.0000135524.73447.4a
13. Canter RJ, Qin LX, Ferrone CR et al. Why do patients with low-grade soft tissuesarcoma die? Ann Surg Oncol 2008; 15 (12): 3550–60. http://dx.doi.org/10.1245/si 0434-008-0163-0
14. Binh M, Sastre-Garau X, Guillou L et al. MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms. Am J Surg Pathol 2005; 29 (10): 1340–7.
15. Fletcher CD, Akerman M, Dal Cin P et al. Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. Am J Pathol 1996; 148 (2): 623–30.
16. Pedeutour FA, Forus, Coindre JM et al. Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes. Cancer 1999; 24 (1): 30–41.
17. Antonescu CR, Tschernynvsky SJ, Docuseara R et al. Prognostic impact of P53 status, TLS-CHOP fusion transcript slructure, and histological grade in myxoidliposarcoma: a molecular and clinicopathologic study of 82 cases. Clin Cancer Res 2001; 7: 3977–87.
18. Aman PD, Ron, Mandahl N et al. Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12; 16)(q 13;p 11). Genes Chromosomes Cancer 1992; 5 (4): 278–85.
19. Knight JC, Renwick PJ, Cin PD et al. Translocation t(12; 16)(q 13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis. Cancer Res 1995; 55: 24–7.
20. Rabbitts TH, Forster A, Larson R et al. Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12; 16) in malignant liposarcoma. Nat Genet 1993; 4 (2): 175–80.
21. Ron D, Habener JF. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev 1992; 6 (3): 439–53.
22. Powers CA, Mathur M, Raaka BM et al. Is a high-affinity interactor for steroid, thyroid hormone, and retinoid receptors. Mol Endocrinol 1998; 12 (1): 4–18.
23. Kuroda M, Ishida T, Takanashi M et al. Oncogenic transformation and inhibition of adipocytic conversion of preadipocytes by TLS/FUS-CHOP type II chimeric protein. Am J Pathol 1997; 151 (3): 735–44.
24. Downes KA, Goldblum JR, Montgomery EA et al. Pleomorphic liposarcoma: a clinicopathologic analysis of 19 cases. Mod Pathol 2001; 14 (3): 179–84.
25. Mertens F, Fletcher CD, Dal Cin P et al. Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: a report of the CHAMP Study GrouP. Chromosomes and Morphology. Genes Chromosomes Cancer 1998; 22 (1): 16–25.
26. Schneider-Stock R, Walter H, Radig K et al. MDM2 amplification and loss of heterozygosity at Rb and p53 genes: no simultaneous alterations in the oncogenesis of liposarcomas. J Cancer Res Clin Oncol 1998; 124: 532–40.
27. Fayette J, Martin E, Piperno-Neumann S et al. Angiosarcoma: a heterogeneous group of sarcomas with specific behavior depending on primary site: a retrospective study of 161 cases. Ann Oncol 2007; 18: 2030–6.
28. Singer S, Antonescu CR, Riedel E et al. Histologic subtype and margin of resection predict pattern of recurrence and survival for retroperitoneal liposarcoma. Ann Surg 2003; 238 (3): 358–70. http://dx. doi.org/10.1097/01.sla.0000086542. 11899.38 [discussion: 370-1]
29. Schwab JH, Boland PJ, Antonescu C et al. Spinal metastases from myxoid liposarcoma warrant screening with magnetic resonance imaging. Cancer 2007; 110 (8): 1815–22. http://dx.doi.Org/10.1002/ cncr.22992
30. McCormick D, Mentzel T, Beham A et al. Dedifferentiated liposarcoma: clinicopathologic analysis of 32 cases suggesting a better prognostic subgroup among pleomorphic sarcomas. Am J Surg Pathol 1994; 18 (12): 1213–23.
31. Murphey MD, Arcara LK, Fanburg-Smith J. Imaging of musculoskeletal liposarcoma with radiologic-pathologic correlation. Radiographics 2005; 25 (5): 1371–95.
32. Engstrom K, Bergh P, Gustafson P et al. Liposarcoma: outcome based on the Scandinavian Sarcoma Group register. Cancer 2008; 113 (7): 1649–56. http://dx.doi.org/10.1002/cncr.23784
33. Kim HS, Lee J, Yi SY et al. Liposarcoma: exploration of clinical prognostic fan tors for risk based stratification of therapy. BMC Cancer 2009; 9: 205. http://dx, doi.org/10.1186/1471-2407-9-205
34. Linehan DC, Lewis JJ, Leung D et al. Influence of biologic factors and anatomic site in completely resected liposarcoma. J Clin Oncol 2000; 18 (8): 1637–43.
35. Lucas DR, Nascimento AG, Sanjay BK et al. Well-differentiated liposarcoma. The Mayo Clinic experience with 58 cases. Am J Clin Pathol 1994; 102 (5): 677–83.
36. Moreau LC, Turcotte R, Ferguson P et al. Myxoid/round cell liposarcoma (MRCLS) revisited: an analysis of 418 primarily managed cases. Ann Surg Oncol 2012; 19 (4): 1081–8. http://dx.doi.org/10.1245/ s10434-011-2127-z
37. Ghert MA, Abudu A, Driver N et al. The indications for and the prognostic significance of amputation as the primary surgical procedure for localized soft tissue sarcoma of the extremity. Ann Surg Oncol 2005; 12 (1): 10–7. http://dx.doi.org/10.1245/ASO.2005.03.097
38. Liu CY, Yen CC, Chen WM et al. Soft tissue sarcoma of extremities: the prognostic significance of adequate surgical margins in primary operation and reoperation after recurrence. Ann Surg Oncol 2010; 17 (8): 2102–11. http://dx.doi.org/ 10.1245/s 10434-010-0997-0
39. McKee MD, Liu DF, Brooks JJ et al. The prognostic significance of margin width for extremity and trunk sarcoma. J Surg Oncol 2004; 85 (2): 68–76. http://dx.doi. org/10.1002/jso.20009
40. Rosenberg SA, Tepper J, Glatstein E et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluation of (1) limb sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982; 196 (3): 305–14.
41. 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 (9325): 2235–41. http://dx.doi.org/ 10.1016/S0140-6736(02)09292-9
42. Bonvalot S, Miceli R, Borselli M et al. Aggressive surgery in retroperitoneal soft tissue sarcoma carried out at high-volume centers is safe and is associated with Henze & Bauer improved local control. Ann Surg Oncol 2010; 17 (6): 1507–14. http://dx.doi.org/10.1245/s 10434-010-1057-5
43. Eilber FC, Eilber FR, Eckardt J et al. The impact of chemotherapy on the survival of patients with high-grade primary extremity liposarcoma. Ann Surg 2004; 240 (4): 686–97. http://dx.doi.org/10.1097/ 01.sla.0000141710.74073.0d
44. Gronchi A, Vullo S.Lo, Fiore M et al. Aggressive surgical policies in a retrospectively reviewed single-institution case series of retroperitoneal soft tissue sarcoma patients. J Clin Oncol 2009; 27 (1): 24–30. http://dx.doi.org/10.1200/JCO.2008.17.8871
45. 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 1998; 228 (3): 355–65.
46. 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 (3): 573–81. http://dx.doi.org/10.1002/ cncr.23592
47. 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: 1045–54.
48. 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 (4): 1117–27. http://dx.doi.org/10.1016/ S0360-3016(03)00186-X
49. Gortzak E, Azzarelli A, Buesa J et al. A randomized phase II study on neoadjuvant chemotherapy for "high-risk" adult soft-tissue sarcoma. Eur J Cancer 2001; 37 (9): 1096–103.
50. Gronchi A, Bui BN, Bonvalot S et al. Phase II clinical trial of neoadjuvant trabectedin in patients with advanced localized myxoid liposarcoma. Ann Oncol 2012; 23 (3): 771–6. doi: 10.1093/annonc/ mdr265. Epub 2011.
51. 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): 619–25. http://dx.doi.org/10.1200/JC0.2005.02.5577
52. 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): 4613–21. http://dx.doi.org/10.1002/ cncr.25350
53. Italiano A, Toulmonde M, Cioffi A et al. Advanced well-differentiated dedifferentiated liposarcomas: role of chemotherapy and survival. Ann Oncol 2012; 23 (6): 1601–7. http://dx.doi.org/10.1093/annonc/mdr485
54. Jennings TA, Peterson L, Axiotis CA et al. Angiosarcoma associated with foreign body material: a report of three cases. Cancer 1988; 62 (11): 2436–44.
55. Jones RL, Fisher C, Al-Muderis O et al. Differential sensitivity of liposarcoma subtypes to chemotherapy. Eur J Cancer 2005; 41 (18): 2853-60. http://dx.doi.org/10.1016/j.ejca.2005.07.023
56. Nielsen OS, Judson I, van Hoesel О et al. Effect of high-dose ifosfamide in advanced soft tissue sarcomas. A multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2000; 36 (1): 61–7.
57. Patel SR, Vadhan-Raj S, Papadopolous N et al. High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies-dose-response and schedule dependence. J Clin Oncol 1997; 15: 2378–84.
58. Феденко A.A. Модификация режимов химиотерапии сарком мягких тканей. Старые препараты и новые возможности. Саркомы костей, мягких тканей и опухоли кожи. 2015; 4: 3–20. / Fedenko A.A. Modifikatsiia rezhimov khimioterapii sarkom miagkikh tkanei. Starye preparaty i novye vozmozhnosti. Sarkomy kostei, miagkikh tkanei i opukholi kozhi. 2015; 4: 3–20. [in Russian]
59. Demetri GD, Chawla SP, von Mehren M et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol 2009; 27 (25): 4188–96; doi: 10.1200/JCO.2008. 21.0088. Epub 2009.
60. 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 (10): 3252–9.
61. Grosso F, Jones RL, Demetri GD et al. Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol 2007; 8 (7): 595–602. http://dx.doi.org/ 10.1016/S1470-2045(07)70175-4
62. Hoiczyk M, Grabellus F, Podleska L et al. Trabectedin in metastatic soft tissue sarcomas: role of pretreatment and age. Ann Oncol 2013; 43: 23–8. http://dx.doi. org/10.3892/ijo.2013.1928
63. 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 (6): 1703–9. http://dx.doi.org/10.1093/annonc/mds659
64. Demetri GD, von Mehren M 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.
65. Феденко А.А. Стратегия лекарственного лечения сарком мягких тканей. Дис. … д-ра мед. наук. М., 2016 / Fedenko A.A. Strategiia lekarstvennogo lecheniia sarkom miagkikh tkanei. Dis. … d-ra med. nauk. M., 2016 [in Russian]
66. Sleijfer S, Ray-Coquard I, Papai Z et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol 2009; 27 (19): 3126–32; doi: 10.1200/JCO.2008.21.3223. Epub 2009.
67. Cortes J et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 2011; 377 (9769): 914–23.
68. Kaufman PA et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2015; 33 (6): 594–601.
69. Инструкция по медицинскому применению препарата Халавен®: РУ ЛП-001782 от 24.07.2012, с изменениями от 15.06.2016. / Instruktsiia po meditsinskomu primeneniiu preparata Khalaven®: RU LP-001782 ot 24.07.2012, s izmeneniiami ot 15.06.2016. [in Russian]
70. Yoshida T, Ozawa Y, Kimura T et al. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states. Br J Cancer 2014; 110: 1497–505.
71. Kawano S, Asano M et al. Antimitotic and non-mitotic effects of eribulin mesilate in soft tissue sarcoma. Anticancer Res 2016; 36: 1553–61.
72. 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 histological subtypes. Lancet Oncol 2011; 12: 1045–52.
73. Schöffski P, Chawla S 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 (10028): 1629–37.
74. Driscoll JJ, Rixe O. Overall survival: still the gold standard: why overall survival remains the definitive end point in cancer clinical trials. Cancer J 2009; 15: 401–5.
75. Chawla S, Schöffski P, Grignani G et al. Subtype-specific Activity in Liposarcoma Patients From a Phase 3, Open-label, Randomized Study of Eribulin Versus Dacarbazine in Patients With Advanced Liposarcoma or Leiomyosarcoma. Poster No. 163. Presented at the ASCO, June 3–7, 2016; Chicago, Illinois.

________________________________________________

1. Statistika zlokachestvennyh novoobrazovanij v Rossii i stranah SNG v 2012 g. Pod red. M.I.Davydova. M., 2014. [in Russian]
2. Gadgeel SM, Harlan LC, Zeruto CA et al. Patterns of care in a population-based sample of soft tissue sarcoma patients in the United States. Cancer 2009; 115 (12): 2744–54.
3. Kindblom LG, Angervall L, Svendsen P. Liposarcoma: a clinicopathologic, radio-graphic and prognostic study. Acta Pathol Microbiol Scand (Suppl.) 1975; 253: 1–71.
4. Crago AM, Singer S. Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma. Curr Opin Oncol 2011; 23 (4): 373–8. http://dx.doi.org/10.1097/CCO.0b013e32834796e6
5. Evans HL. Liposarcoma: a study of 55 cases with reassessment of its classification. Am J Surg Pathol 1979; 3 (6): 507–23.
6. Fletcher CD. World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone. Lyon: IARC Press, 2002; p. 120–5.
7. Fletcher CD. WHO classification of tumours ofsoft tissue and bone. 4th ed. WHO Press, 2013.
8. Kilpatrick SE, Doyon J, Choong PF et al. The clinicopathologic spectrum of myxoid and round cell liposarcoma. A study of 95 cases. Cancer 1996; 77 (8): 1450–8.
9. Weiss SW, Rao VK. Well-differentiated liposarcoma (atypical lipoma) of deep soft tissue of the extremities, retroperitoneum, and miscellaneous sites. Am J Surg Pathol 1992; 16 (11): 1051–8.
10. Gebhard S, Coindre JM, Michels JJ et al. Pleomorphic liposarcoma: clinicopathologic, immunohistochemical, and follow-up analysis of 63 cases: a study from the French Federation of Cancer Centers Sarcoma Group. Am J Surg Pathol 2002; 26 (5): 601–16.
11. Henricks WH, Chu YC, Goldblum JR et al. Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation. Am J Surg Pathol 1997; 21 (3): 271–81.
12. Hornick JL, Bosenberg MW, Mentzel T et al. Pleomorphic liposarcoma. Am J Surg Pathol 2004; 28 (10): 1257–67. http://dx.doi.org/10. 1097/01.pas.0000135524.73447.4a
13. Canter RJ, Qin LX, Ferrone CR et al. Why do patients with low-grade soft tissuesarcoma die? Ann Surg Oncol 2008; 15 (12): 3550–60. http://dx.doi.org/10.1245/si 0434-008-0163-0
14. Binh M, Sastre-Garau X, Guillou L et al. MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms. Am J Surg Pathol 2005; 29 (10): 1340–7.
15. Fletcher CD, Akerman M, Dal Cin P et al. Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. Am J Pathol 1996; 148 (2): 623–30.
16. Pedeutour FA, Forus, Coindre JM et al. Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes. Cancer 1999; 24 (1): 30–41.
17. Antonescu CR, Tschernynvsky SJ, Docuseara R et al. Prognostic impact of P53 status, TLS-CHOP fusion transcript slructure, and histological grade in myxoidliposarcoma: a molecular and clinicopathologic study of 82 cases. Clin Cancer Res 2001; 7: 3977–87.
18. Aman PD, Ron, Mandahl N et al. Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12; 16)(q 13;p 11). Genes Chromosomes Cancer 1992; 5 (4): 278–85.
19. Knight JC, Renwick PJ, Cin PD et al. Translocation t(12; 16)(q 13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis. Cancer Res 1995; 55: 24–7.
20. Rabbitts TH, Forster A, Larson R et al. Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12; 16) in malignant liposarcoma. Nat Genet 1993; 4 (2): 175–80.
21. Ron D, Habener JF. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev 1992; 6 (3): 439–53.
22. Powers CA, Mathur M, Raaka BM et al. Is a high-affinity interactor for steroid, thyroid hormone, and retinoid receptors. Mol Endocrinol 1998; 12 (1): 4–18.
23. Kuroda M, Ishida T, Takanashi M et al. Oncogenic transformation and inhibition of adipocytic conversion of preadipocytes by TLS/FUS-CHOP type II chimeric protein. Am J Pathol 1997; 151 (3): 735–44.
24. Downes KA, Goldblum JR, Montgomery EA et al. Pleomorphic liposarcoma: a clinicopathologic analysis of 19 cases. Mod Pathol 2001; 14 (3): 179–84.
25. Mertens F, Fletcher CD, Dal Cin P et al. Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: a report of the CHAMP Study GrouP. Chromosomes and Morphology. Genes Chromosomes Cancer 1998; 22 (1): 16–25.
26. Schneider-Stock R, Walter H, Radig K et al. MDM2 amplification and loss of heterozygosity at Rb and p53 genes: no simultaneous alterations in the oncogenesis of liposarcomas. J Cancer Res Clin Oncol 1998; 124: 532–40.
27. Fayette J, Martin E, Piperno-Neumann S et al. Angiosarcoma: a heterogeneous group of sarcomas with specific behavior depending on primary site: a retrospective study of 161 cases. Ann Oncol 2007; 18: 2030–6.
28. Singer S, Antonescu CR, Riedel E et al. Histologic subtype and margin of resection predict pattern of recurrence and survival for retroperitoneal liposarcoma. Ann Surg 2003; 238 (3): 358–70. http://dx. doi.org/10.1097/01.sla.0000086542. 11899.38 [discussion: 370-1]
29. Schwab JH, Boland PJ, Antonescu C et al. Spinal metastases from myxoid liposarcoma warrant screening with magnetic resonance imaging. Cancer 2007; 110 (8): 1815–22. http://dx.doi.Org/10.1002/ cncr.22992
30. McCormick D, Mentzel T, Beham A et al. Dedifferentiated liposarcoma: clinicopathologic analysis of 32 cases suggesting a better prognostic subgroup among pleomorphic sarcomas. Am J Surg Pathol 1994; 18 (12): 1213–23.
31. Murphey MD, Arcara LK, Fanburg-Smith J. Imaging of musculoskeletal liposarcoma with radiologic-pathologic correlation. Radiographics 2005; 25 (5): 1371–95.
32. Engstrom K, Bergh P, Gustafson P et al. Liposarcoma: outcome based on the Scandinavian Sarcoma Group register. Cancer 2008; 113 (7): 1649–56. http://dx.doi.org/10.1002/cncr.23784
33. Kim HS, Lee J, Yi SY et al. Liposarcoma: exploration of clinical prognostic fan tors for risk based stratification of therapy. BMC Cancer 2009; 9: 205. http://dx, doi.org/10.1186/1471-2407-9-205
34. Linehan DC, Lewis JJ, Leung D et al. Influence of biologic factors and anatomic site in completely resected liposarcoma. J Clin Oncol 2000; 18 (8): 1637–43.
35. Lucas DR, Nascimento AG, Sanjay BK et al. Well-differentiated liposarcoma. The Mayo Clinic experience with 58 cases. Am J Clin Pathol 1994; 102 (5): 677–83.
36. Moreau LC, Turcotte R, Ferguson P et al. Myxoid/round cell liposarcoma (MRCLS) revisited: an analysis of 418 primarily managed cases. Ann Surg Oncol 2012; 19 (4): 1081–8. http://dx.doi.org/10.1245/ s10434-011-2127-z
37. Ghert MA, Abudu A, Driver N et al. The indications for and the prognostic significance of amputation as the primary surgical procedure for localized soft tissue sarcoma of the extremity. Ann Surg Oncol 2005; 12 (1): 10–7. http://dx.doi.org/10.1245/ASO.2005.03.097
38. Liu CY, Yen CC, Chen WM et al. Soft tissue sarcoma of extremities: the prognostic significance of adequate surgical margins in primary operation and reoperation after recurrence. Ann Surg Oncol 2010; 17 (8): 2102–11. http://dx.doi.org/ 10.1245/s 10434-010-0997-0
39. McKee MD, Liu DF, Brooks JJ et al. The prognostic significance of margin width for extremity and trunk sarcoma. J Surg Oncol 2004; 85 (2): 68–76. http://dx.doi. org/10.1002/jso.20009
40. Rosenberg SA, Tepper J, Glatstein E et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluation of (1) limb sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982; 196 (3): 305–14.
41. 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 (9325): 2235–41. http://dx.doi.org/ 10.1016/S0140-6736(02)09292-9
42. Bonvalot S, Miceli R, Borselli M et al. Aggressive surgery in retroperitoneal soft tissue sarcoma carried out at high-volume centers is safe and is associated with Henze & Bauer improved local control. Ann Surg Oncol 2010; 17 (6): 1507–14. http://dx.doi.org/10.1245/s 10434-010-1057-5
43. Eilber FC, Eilber FR, Eckardt J et al. The impact of chemotherapy on the survival of patients with high-grade primary extremity liposarcoma. Ann Surg 2004; 240 (4): 686–97. http://dx.doi.org/10.1097/ 01.sla.0000141710.74073.0d
44. Gronchi A, Vullo S.Lo, Fiore M et al. Aggressive surgical policies in a retrospectively reviewed single-institution case series of retroperitoneal soft tissue sarcoma patients. J Clin Oncol 2009; 27 (1): 24–30. http://dx.doi.org/10.1200/JCO.2008.17.8871
45. 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 1998; 228 (3): 355–65.
46. 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 (3): 573–81. http://dx.doi.org/10.1002/ cncr.23592
47. 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: 1045–54.
48. 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 (4): 1117–27. http://dx.doi.org/10.1016/ S0360-3016(03)00186-X
49. Gortzak E, Azzarelli A, Buesa J et al. A randomized phase II study on neoadjuvant chemotherapy for "high-risk" adult soft-tissue sarcoma. Eur J Cancer 2001; 37 (9): 1096–103.
50. Gronchi A, Bui BN, Bonvalot S et al. Phase II clinical trial of neoadjuvant trabectedin in patients with advanced localized myxoid liposarcoma. Ann Oncol 2012; 23 (3): 771–6. doi: 10.1093/annonc/ mdr265. Epub 2011.
51. 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): 619–25. http://dx.doi.org/10.1200/JC0.2005.02.5577
52. 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): 4613–21. http://dx.doi.org/10.1002/ cncr.25350
53. Italiano A, Toulmonde M, Cioffi A et al. Advanced well-differentiated dedifferentiated liposarcomas: role of chemotherapy and survival. Ann Oncol 2012; 23 (6): 1601–7. http://dx.doi.org/10.1093/annonc/mdr485
54. Jennings TA, Peterson L, Axiotis CA et al. Angiosarcoma associated with foreign body material: a report of three cases. Cancer 1988; 62 (11): 2436–44.
55. Jones RL, Fisher C, Al-Muderis O et al. Differential sensitivity of liposarcoma subtypes to chemotherapy. Eur J Cancer 2005; 41 (18): 2853–60. http://dx.doi.org/10.1016/j.ejca.2005.07.023
56. Nielsen OS, Judson I, van Hoesel О et al. Effect of high-dose ifosfamide in advanced soft tissue sarcomas. A multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2000; 36 (1): 61–7.
57. Patel SR, Vadhan-Raj S, Papadopolous N et al. High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies-dose-response and schedule dependence. J Clin Oncol 1997; 15: 2378–84.
58. Fedenko A.A. Modifikatsiia rezhimov khimioterapii sarkom miagkikh tkanei. Starye preparaty i novye vozmozhnosti. Sarkomy kostei, miagkikh tkanei i opukholi kozhi. 2015; 4: 3–20. [in Russian]
59. Demetri GD, Chawla SP, von Mehren M et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol 2009; 27 (25): 4188–96; doi: 10.1200/JCO.2008. 21.0088. Epub 2009.
60. 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 (10): 3252–9.
61. Grosso F, Jones RL, Demetri GD et al. Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol 2007; 8 (7): 595–602. http://dx.doi.org/ 10.1016/S1470-2045(07)70175-4
62. Hoiczyk M, Grabellus F, Podleska L et al. Trabectedin in metastatic soft tissue sarcomas: role of pretreatment and age. Ann Oncol 2013; 43: 23–8. http://dx.doi. org/10.3892/ijo.2013.1928
63. 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 (6): 1703–9. http://dx.doi.org/10.1093/annonc/mds659
64. Demetri GD, von Mehren M 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.
65. Fedenko A.A. Strategiia lekarstvennogo lecheniia sarkom miagkikh tkanei. Dis. … d-ra med. nauk. M., 2016 [in Russian]
66. Sleijfer S, Ray-Coquard I, Papai Z et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol 2009; 27 (19): 3126–32; doi: 10.1200/JCO.2008.21.3223. Epub 2009.
67. Cortes J et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 2011; 377 (9769): 914–23.
68. Kaufman PA et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2015; 33 (6): 594–601.
69. Instruktsiia po meditsinskomu primeneniiu preparata Khalaven®: RU LP-001782 ot 24.07.2012, s izmeneniiami ot 15.06.2016. [in Russian]
70. Yoshida T, Ozawa Y, Kimura T et al. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states. Br J Cancer 2014; 110: 1497–505.
71. Kawano S, Asano M et al. Antimitotic and non-mitotic effects of eribulin mesilate in soft tissue sarcoma. Anticancer Res 2016; 36: 1553–61.
72. 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 histological subtypes. Lancet Oncol 2011; 12: 1045–52.
73. Schöffski P, Chawla S 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 (10028): 1629–37.
74. Driscoll JJ, Rixe O. Overall survival: still the gold standard: why overall survival remains the definitive end point in cancer clinical trials. Cancer J 2009; 15: 401–5.
75. Chawla S, Schöffski P, Grignani G et al. Subtype-specific Activity in Liposarcoma Patients From a Phase 3, Open-label, Randomized Study of Eribulin Versus Dacarbazine in Patients With Advanced Liposarcoma or Leiomyosarcoma. Poster No. 163. Presented at the ASCO, June 3–7, 2016; Chicago, Illinois.

А.А.Феденко*

ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*fedenko@eesg.ru

________________________________________________

A.A.Fedenko*

N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*fedenko@eesg.ru