Maligne Bindegewebstumore – Sarkome

Zusammenfassung

Malignome der Weichgewebe sind selten. Grundsätzlich können jedoch praktisch alle Malignome des Bindegewebes, auch diejenigen, die typischerweise die tieferen Weichteile betreffen, auch einmal dermal oder so oberflächlich auftreten, dass der Dermatologe involviert wird in die Diagnostik und Therapie. In der Natur unseres Faches liegt es aber auch, dass der Dermatologe involviert wird bei „unklaren Schwellungen“ der Weichteile. Grundzüge des Managements der Weichgewebetumoren im Allgemeinen sollten daher bekannt sein, da der Dermatologe unter Umständen wesentlich zur Verkürzung des oft zu langen prädiagnostischen Intervalls beitragen kann. Daneben gibt es für den Dermatologen auch zahlenmäßig relevante Entitäten (Dermatofibrosarkoma protuberans, Leiomyosarkom, atypisches Fibroxanthom), sowie solche, die aggressiv und klinisch-differenzialdiagnostisch wichtig sind, wenn auch selten (Angiosarkom, epitheloides Sarkom), und es gibt auch versteckte Restrisiken, an die gedacht werden sollte, z. B. ein Neurofibrosarkom auf dem Boden einer langjährigen Neurofibromatose oder Übertherapie einer nodulären Fasciitis, eines Pseudosarkoms. Diese Aspekte werden ihrer klinischen Bedeutung entsprechend in diesem Artikel behandelt.

Abstract

Malignant tumors of the soft tissues are rare. However, as a principle, all diverse kinds and entities of those tumors can – occasionally – also occur dermal or so superficial that the dermatologist may be involved in the diagnosis and even the treatment. Moreover, due to the nature of our subject, the dermatologist may become involved in patients’ management with “unclear swellings” of tissues. So, the basic principles of managing this situation should be well known, because the dermatologist may contribute to shortening of the pre-diagnostic interval, which is too long all too often.

Finally, there are entities, which are relevant to the dermatologist due to their frequency of occurrence (dermatofibrosarcoma protuberans, leimyosarcoma, atypical fibroxanthoma), or entities rare, but highly aggressive and easily mixed up with other clinical conditions (angiosarcoma, epithelioid sarcoma), and there are pitfalls to be aware of such as the occurrence of a neurofibrosarcoma in the background of a long-lasting neurofibromatosis or the risk of unreflected overtreatment, e. g. in the case of nodular fasciitis, a pseudosarcoma. These aspects will be considered in this article according to their clinical significance.

• Literatur

• 1 Ducimetiere F, Lurkin A, Ranchere-Vince D et al. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One 2011; 6 e20294
• 2 Weiss SW, Goldblum JR. Enzinger & Weiss’s Soft tissue tumors. 5th. edition. Philadelphia: Mosby; 2008
• 3 Taylor BS, Barretina J, Maki RG et al. Advances in sarcoma genomics and new therapeutic targets. Nature reviews Cancer 2011; 11: 541-557
• 4 Katenkamp D, Katenkamp K. Modern morphological diagnosis and current classification of soft tissue sarcomas. Moderne morphologische Diagnostik und aktuelle Klassifikation von Weichteilsarkomen. Chirurg 2009; 80: 186-193
• 5 Thway K, Fisher C. Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. Am J Surg Pathol 2012; (Epub ahead of print)
• 6 Patel KU, Szabo SS, Hernandez VS et al. Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberans cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assays. Human pathology 2008; 39: 184-193
• 7 Sirvent N, Maire G, Pedeutour F. Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment. Genes Chromosomes Cancer 2003; 37: 1-19
• 8 Gibault L, Ferreira C, Perot G et al. From PTEN loss of expression to RICTOR role in smooth muscle differentiation: complex involvement of the mTOR pathway in leiomyosarcomas and pleomorphic sarcomas. Mod Pathol 2012; 25: 197-211
• 9 Gibault L, Perot G, Chibon F et al. New insights in sarcoma oncogenesis: a comprehensive analysis of a large series of 160 soft tissue sarcomas with complex genomics. e J Pathol 2011; 223: 64-71
• 10 Darier JFM. Dermatofibromes progressifs et récidivants ou fibrosarcomes de la peau. Ann Dermatol Syphil 1924; 5: 545-562
• 11 Ugurel S, Kortmann RD, Mohr P et al. Short German guidelines: dermatofibrosarcoma protuberans. J Dtsch Dermatol Ges 2008; 6 (Suppl. 01) 17-S18
• 12 Lemm D, Mugge LO, Mentzel T et al. Current treatment options in dermatofibrosarcoma protuberans. J Cancer Res Clin Oncol 2009; 135: 653-665
• 13 Marcus JR, Few JW, Senger C et al. Dermatofibrosarcoma protuberans and the Bednar tumor: treatment in the pediatric population. J Pediatr Surg 1998; 33: 1811-1814
• 14 Pack GT, Tabah EJ. Dermato-fibrosarcoma protuberans. A report of 39 cases. AMA Arch Surg 1951; 62: 391-411
• 15 Parlette LE, Smith CK, Germain LM et al. Accelerated growth of dermatofibrosarcoma protuberans during pregnancy. J Am Acad Dermatol 1999; 41: 778-783
• 16 Fiore M, Miceli R, Mussi C et al. Dermatofibrosarcoma protuberans treated at a single institution: a surgical disease with a high cure rate. J Clin Oncol 2005; 23: 7669-7675
• 17 Mentzel T, Beham A, Katenkamp D et al. Fibrosarcomatous (“high-grade”) dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance. Am J Surg Pathol 1998; 22: 576-587
• 18 Mentzel T, Scharer L, Kazakov DV et al. Myxoid dermatofibrosarcoma protuberans: clinicopathologic, immunohistochemical, and molecular analysis of eight cases. Am J Dermatopathol 2007; 29: 443-448
• 19 Lal P, Sharma R, Mohan H et al. Dermatofibrosarcoma protuberans metastasizing to lymph nodes: a case report and review of literature. J Surg Oncol 1999; 72: 178-180
• 20 Mavili ME, Gursu KG, Gokoz A. Dermatofibrosarcoma with lymph node involvement. Ann Plast Surg 1994; 32: 438-440
• 21 Cai H, Wang Y, Wu J et al. Dermatofibrosarcoma protuberans: clinical diagnoses and treatment results of 260 cases in China. Journal of surgical oncology 2012; 105: 142-148
• 22 Valdivielso-Ramos M, Hernanz JM. Dermatofibrosarcoma Protuberans in Childhood. Actas Dermosifiliogr 2012; (Epub ahead of print)
• 23 Terrier-Lacombe MJ, Guillou L, Maire G et al. Dermatofibrosarcoma protuberans, giant cell fibroblastoma, and hybrid lesions in children: clinicopathologic comparative analysis of 28 cases with molecular data--a study from the French Federation of Cancer Centers Sarcoma Group. Am J Surg Pathol 2003; 27: 27-39
• 24 Fisher C, Mentzel T, Thway K et al. Diagnostic Pathology. Soft Tissue Tumors. Salt Lake City/USA: Amirsys; 2011
• 25 Jha P, Moosavi C, Fanburg-Smith JC. Giant cell fibroblastoma: an update and addition of 86 new cases from the Armed Forces Institute of Pathology, in honor of Dr. Franz M. Enzinger. Ann Diagn Pathol 2007; 11: 81-88
• 26 Lindner NJ, Scarborough MT, Powell GJ et al. Revision surgery in dermatofibrosarcoma protuberans of the trunk and extremities. Eur J Surg Oncol 1999; 25: 392-397
• 27 Reimann JD, Fletcher CD. Myxoid dermatofibrosarcoma protuberans: a rare variant analyzed in a series of 23 cases. Am J Surg Pathol 2007; 31: 1371-1377
• 28 Calonje E, Fletcher CD. Myoid differentiation in dermatofibrosarcoma protuberans and its fibrosarcomatous variant: clinicopathologic analysis of 5 cases. J Cutan Pathol 1996; 23: 30-36
• 29 Davis DA, Sanchez RL. Atrophic and plaquelike dermatofibrosarcoma protuberans. Am J Dermatopathol 1998; 20: 498-501
• 30 Szollosi Z, Nemes Z. Transformed dermatofibrosarcoma protuberans: a clinicopathological study of eight cases. J Clin Pathol 2005; 58: 751-756
• 31 Mendenhall WM, Zlotecki RA, Scarborough MT. Dermatofibrosarcoma protuberans. Cancer 2004; 101: 2503-2508
• 32 Thornton SL, Reid J, Papay FA et al. Childhood dermatofibrosarcoma protuberans: role of preoperative imaging. J Am Acad Dermatol 2005; 53: 76-83
• 33 Malhotra B, Schuetze SM. Dermatofibrosarcoma protuberans treatment with platelet-derived growth factor receptor inhibitor: a review of clinical trial results. Curr Opin Oncol 2012;
• 34 Chang CK, Jacobs IA, Salti GI. Outcomes of surgery for dermatofibrosarcoma protuberans. Eur J Surg Oncol 2004; 30: 341-345
• 35 DuBay D, Cimmino V, Lowe L et al. Low recurrence rate after surgery for dermatofibrosarcoma protuberans: a multidisciplinary approach from a single institution. Cancer 2004; 100: 1008-1016
• 36 Farma JM, Ammori JB, Zager JS et al. Dermatofibrosarcoma protuberans: how wide should we resect?. Ann Surg Oncol 2010; 17: 2112-2118
• 37 Fields RC, Hameed M, Qin LX et al. Dermatofibrosarcoma protuberans (DFSP): predictors of recurrence and the use of systemic therapy. Ann Surg Oncol 2011; 18: 328-336
• 38 Breuninger H, Schaumburg-Lever G. Control of excisional margins by conventional histopathological techniques in the treatment of skin tumours. An alternative to Mohs' technique. J Pathol 1988; 154: 167-171
• 39 Galimberti G, Montano AP, Kowalczuk A et al. Outcomes in 11 patients with dermatofibrosarcoma protuberans treated with Mohs micrographic surgery. Int J Dermatol 2012; 51: 89-93
• 40 Ballo MT, Zagars GK, Pisters P et al. The role of radiation therapy in the management of dermatofibrosarcoma protuberans. Int J Radiat Oncol Biol Phys 1998; 40: 823-827
• 41 Haas RL, Keus RB, Loftus BM. Soft Tissue Tumours Working Group et al. The role of radiotherapy in the local management of dermatofibrosarcoma protuberans. Eur J Cancer 1997; 33: 1055-1060
• 42 Greco A, Roccato E, Miranda C et al. Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement. Int J Cancer 2001; 92: 354-360
• 43 Sjoblom T, Shimizu A, O’Brien KP et al. Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. Cancer Res 2001; 61: 5778-5783
• 44 Price VE, Fletcher JA, Zielenska M et al. Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans. Pediatr Blood Cancer 2005; 44: 511-515
• 45 Stacchiotti S, Pedeutour F, Negri T et al. Dermatofibrosarcoma protuberans-derived fibrosarcoma: clinical history, biological profile and sensitivity to imatinib. Int J Cancer 2011; 129: 1761-1772
• 46 Gupta P, Tewari M, Shukla HS. Gastrointestinal stromal tumor. Surg Oncol 2008; 17: 129-138
• 47 Macapinlac M, Elrafei T, Cunningham I. Dermatofibrosarcoma protuberans: neoadjuvant therapy with imatinib mesylate and use of plasma PDGF-B levels to monitor clinical response. J Clin Oncol annual meeting proceedings 2004; 22: 9094
• 48 Wang WL, Bones-Valentin RA, Prieto VG et al. Sarcoma metastases to the skin: A clinicopathologic study of 65 patients. Cancer 2011;
• 49 Leiomyosarcoma. In: Weiss SW, Goldblum JR, eds. Enzinger and Weiss's soft tissue tumors. 5th. ed. St. Louis, London, Philadelphia, Sydney, Toronto: Mosby; 2008: 545-561
• 50 Svarvar C, Bohling T, Berlin O et al. Clinical course of nonvisceral soft tissue leiomyosarcoma in 225 patients from the Scandinavian Sarcoma Group. Cancer 2007; 109: 282-291
• 51 Annest NM, Grekin SJ, Stone MS et al. Cutaneous leiomyosarcoma: a tumor of the head and neck. Dermatol Surg 2007; 33: 628-633
• 52 Massi D, Franchi A, Alos L et al. Primary cutaneous leiomyosarcoma: clinicopathological analysis of 36 cases. Histopathology 2010; 56: 251-262
• 53 Kraft S, Fletcher CD. Atypical intradermal smooth muscle neoplasms: clinicopathologic analysis of 84 cases and a reappraisal of cutaneous “leiomyosarcoma”. The American journal of surgical pathology 2011; 35: 599-607
• 54 Starling 3rd J, Coldiron BM. Mohs micrographic surgery for the treatment of cutaneous leiomyosarcoma. Journal of the American Academy of Dermatology 2011; 64: 1119-1122
• 55 Huether MJ, Zitelli JA, Brodland DG. Mohs micrographic surgery for the treatment of spindle cell tumors of the skin. Journal of the American Academy of Dermatology 2001; 44: 656-659
• 56 Lee J, McGuire C. Clinical efficacy of vorinostat in a patient with leiomyosarcoma. Clin Med Insights Oncol 2012; 6: 101-105
• 57 Iorizzo 3rd LJ, Brown MD. Atypical fibroxanthoma: a review of the literature. Dermatol Surg 2011; 37: 146-157
• 58 Sakamoto A, Oda Y, Itakura E et al. Immunoexpression of ultraviolet photoproducts and p53 mutation analysis in atypical fibroxanthoma and superficial malignant fibrous histiocytoma. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 2001; 14: 581-588
• 59 Sakamoto A, Oda Y, Tsuneyoshi M et al. Expression of the UV-induced molecule, Gadd45, in atypical fibroxanthoma. Histopathology 2007; 50: 939-941
• 60 Beer TW, Drury P, Heenan PJ. Atypical fibroxanthoma: a histological and immunohistochemical review of 171 cases. Am J Dermatopathol 2010; 32: 533-540
• 61 Rosenberg AE. Pseudosarcomas of soft tissue. Arch Pathol Lab Med 2008; 132: 579-586
• 62 Erickson-Johnson MR, Chou MM, Evers BR et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest 2011; 91: 1427-1433
• 63 de Feraudy S, Fletcher CD. Intradermal nodular fasciitis: a rare lesion analyzed in a series of 24 cases. The American journal of surgical pathology 2010; 34: 1377-1381
• 64 Vogt T. [Angiosarcoma]. Hautarzt 2008; 59: 237-248 quiz 249 – 250
• 65 Vogt T, Brockmeyer N, Kutzner H et al. Short German guidelines: angiosarcoma and Kaposi sarcoma. J Dtsch Dermatol Ges 2008; 6: 19-24
• 66 Mentzel T, Schildhaus HU, Palmedo G et al. Postradiation cutaneous angiosarcoma after treatment of breast carcinoma is characterized by MYC amplification in contrast to atypical vascular lesions after radiotherapy and control cases: clinicopathological, immunohistochemical and molecular analysis of 66 cases. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 2012; 25: 75-85
• 67 Young RJ, Brown NJ, Reed MW et al. Angiosarcoma. Lancet Oncol 2010; 11: 983-991
• 68 Asgari MM, Cockerell CJ, Weitzul S. The head-tilt maneuver: a clinical aid in recognizing head and neck angiosarcomas. Arch Dermatol 2007; 143: 75-77
• 69 Santi R, Cetica V, Franchi A et al. Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy. Histopathology 2011; 58: 455-466
• 70 Mendenhall WM, Mendenhall CM, Werning JW et al. Cutaneous angiosarcoma. Am J Clin Oncol 2006; 29: 524-528
• 71 Donghi D, Kerl K, Dummer R et al. Cutaneous angiosarcoma: own experience over 13 years. Clinical features, disease course and immunohistochemical profile. J Eur Acad Dermatol Venereol 2010; 24: 1230-1234
• 72 Guo T, Zhang L, Chang NE et al. Consistent MYC and FLT4 gene amplification in radiation-induced angiosarcoma but not in other radiation-associated atypical vascular lesions. Genes, chromosomes & cancer 2011; 50: 25-33
• 73 Bundscherer A, Vogt T, Kohl G et al. Antiproliferative effects of rapamycin and celecoxib in angiosarcoma cell lines. Anticancer research 2010; 30: 4017-4023
• 74 Palta M, Morris CG, Grobmyer SR et al. Angiosarcoma after breast-conserving therapy: long-term outcomes with hyperfractionated radiotherapy. Cancer 2010; 116: 1872-1878
• 75 Koontz BF, Miles EF, Rubio MA et al. Preoperative radiotherapy and bevacizumab for angiosarcoma of the head and neck: two case studies. Head Neck 2008; 30: 262-266
• 76 Fury MG, Antonescu CR, Van Zee KJ et al. A 14-year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy. Cancer J 2005; 11: 241-247
• 77 Penel N, Bui BN, Bay JO et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study. J Clin Oncol 2008; 26: 5269-5274
• 78 Schlemmer M, Reichardt P, Verweij J et al. Paclitaxel in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma group. Eur J Cancer 2008; 44: 2433-2436
• 79 Stacchiotti S, Palassini E, Sanfilippo R et al. Gemcitabine in advanced angiosarcoma: a retrospective case series analysis from the Italian Rare Cancer Network. Ann Oncol 2012; 23: 501-508
• 80 Vogt T, Hafner C, Bross K et al. Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors. Cancer 2003; 98: 2251-2256
• 81 Maki RG, D’Adamo DR, Keohan ML et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol 2009; 27: 3133-3140
• 82 Chase DR, Enzinger FM. Epithelioid sarcoma. Diagnosis, prognostic indicators, and treatment. The American journal of surgical pathology 1985; 9: 241-263
• 83 Evans HL, Baer SC. Epithelioid sarcoma: a clinicopathologic and prognostic study of 26 cases. Semin Diagn Pathol 1993; 10: 286-291
• 84 Halling AC, Wollan PC, Pritchard DJ et al. Epithelioid sarcoma: a clinicopathologic review of 55 cases. Mayo Clin Proc 1996; 71: 636-642
• 85 Modena P, Lualdi E, Facchinetti F et al. SMARCB1/INI1 tumor suppressor gene is frequently inactivated in epithelioid sarcomas. Cancer Res 2005; 65: 4012-4019
• 86 Mentzel T. [Epithelioid sarcoma: morphologic variants and differential diagnosis]. Der Pathologe 2010; 31: 135-141
• 87 Leroy K, Dumas V, Martin-Garcia N et al. Malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1: a clinicopathologic and molecular study of 17 patients. Arch Dermatol 2001; 137: 908-913
• 88 Ducatman BS, Scheithauer BW. Postirradiation neurofibrosarcoma. Cancer 1983; 51: 1028-1033
• 89 Ducatman BS, Scheithauer BW, Piepgras DG et al. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer 1986; 57: 2006-2021
• 90 King AA, Debaun MR, Riccardi VM et al. Malignant peripheral nerve sheath tumors in neurofibromatosis 1. Am J Med Genet 2000; 93: 388-392
• 91 Bridge Jr RS, Bridge JA, Neft JR et al. Recurrent chromosomal imbalances and structurally abnormal breakpoints within complex karyotypes of malignant peripheral nerve sheath tumour and malignant triton tumour: a cytogenetic and molecular cytogenetic study. Journal of clinical pathology 2004; 57: 1172-1178
• 92 Sabah M, Cummins R, Leader M et al. Loss of p16 (INK4A) expression is associated with allelic imbalance/loss of heterozygosity of chromosome 9p21 in microdissected malignant peripheral nerve sheath tumors. Appl Immunohistochem Mol Morphol 2006; 14: 97-102
• 93 Brekke HR, Ribeiro FR, Kolberg M et al. Genomic changes in chromosomes 10, 16, and X in malignant peripheral nerve sheath tumors identify a high-risk patient group. J Clin Oncol 2010; 28: 1573-1582
• 94 Kaddu S, McMenamin ME, Fletcher CD. Atypical fibrous histiocytoma of the skin: clinicopathologic analysis of 59 cases with evidence of infrequent metastasis. The American journal of surgical pathology 2002; 26: 35-46
• 95 Guillou L, Gebhard S, Salmeron M et al. Metastasizing fibrous histiocytoma of the skin: a clinicopathologic and immunohistochemical analysis of three cases. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 2000; 13: 654-660
• 96 Colome-Grimmer MI, Evans HL. Metastasizing cellular dermatofibroma. A report of two cases. The American journal of surgical pathology 1996; 20: 1361-1367
• 97 Colby TV. Metastasizing dermatofibroma. The American journal of surgical pathology 1997; 21: 976
• 98 De Hertogh G, Bergmans G, Molderez C et al. Cutaneous cellular fibrous histiocytoma metastasizing to the lungs. Histopathology 2002; 41: 85-86
• 99 Simons A, Schepens M, Jeuken J et al. Frequent loss of 9p21 (p16(INK4A)) and other genomic imbalances in human malignant fibrous histiocytoma. Cancer Genet Cytogenet 2000; 118: 89-98
• 100 Grimer R, Judson I, Peake D et al. Guidelines for the management of soft tissue sarcomas. Sarcoma 2010; 506182
• 101 Kattan MW, Leung DH, Brennan MF. Postoperative nomogram for 12-year sarcoma-specific death. J Clin Oncol 2002; 20: 791-796
• 102 Van Glabbeke M, van Oosterom AT, Oosterhuis JW et al. Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens -- a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol 1999; 17: 150-157
• 103 Sleijfer S. Phase II studies in soft tissue sarcoma: time for reappraisal. Oncologist 2012; 17: 154-156
• 104 Sleijfer S, Ouali M, van Glabbeke M et al. Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: an exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG). Eur J Cancer 2010; 46: 72-83
• 105 Van Glabbeke M, Verweij J, Judson I et al. Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas. Eur J Cancer 2002; 38: 543-549
• 106 Skubitz KM, Haddad PA. Paclitaxel and pegylated-liposomal doxorubicin are both active in angiosarcoma. Cancer 2005; 104: 361-366
• 107 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; 20: 2824-2831
• 108 Le CesneA, Blay JY, Judson I et al. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol 2005; 23: 576-584
• 109 Maki RG, Wathen JK, 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: 2755-2763