Skip to main content

Advertisement

SpringerLink
Log in

Myxoid Liposarcomas: Systemic Treatment Options

  • Sarcoma (SH Okuno, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion Statement

Myxoid/round-cell liposarcoma (MRCL) account for 30% of liposarcomas and are the most chemo-sensitive subtype of liposarcoma. The 5-year local relapse and distant metastasis rates are 10% and 20%, respectively. In the advanced setting, the first-line median progression-free survival and overall survival is 9 and 30 months, respectively. The overall response rate (ORR) by RECIST with anthracycline-based chemotherapy is around 40% and with trabectedin is 20%, although response is higher when captured by CHOI criteria. Anthracycline-based combination chemotherapy regimens remain the standard of care first-line treatment option. However, trabectedin is also effective and may be considered in the first-line setting when anthracyclines cannot be prescribed. Beyond chemotherapy, new therapeutic classes are being developed, including autologous adoptive modified T cell receptor cellular therapies which have shown promising results thus far. These new therapies utilize the immunogenic potential of cancer testis antigens, NY-ESO-1 and MAGE-A4, which are expressed in the vast majority of MRCL. Early phase trials have shown encouraging results with up to 40% ORR and a median progression-free survival up to 8.7 months. Other innovative strategies are being developed, tailored to the molecular biology of MRCL. This review summarizes current evidence for the use of standard chemotherapy and the new biomarker-selected treatments under development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References and Recommended Readings

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Najbauer J, Ducimetière F, Lurkin A, Ranchère-Vince D, Decouvelaere A.-V, Péoc’h M, Istier L, Chalabreysse P, Muller C, Alberti L, 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. https://doi.org/10.1371/journal.pone.0020294.

  2. Lee ATJ, Thway K, Huang PH, Jones RL. Clinical and molecular spectrum of liposarcoma. J Clin Oncol. 2018;36:151–9. https://doi.org/10.1200/jco.2017.74.9598.

    Article  CAS  PubMed  Google Scholar 

  3. Pollack SM, Somaiah N, Araujo DM, Druta M, Van Tine BA, Burgess MA, Chawla SP, Seetharam M, Okuno SH, Bohac C, et al. Clinical outcomes of patients with advanced synovial sarcoma or myxoid/round cell liposarcoma treated at major cancer centers in the United States. Cancer Med. 2020;9:4593–602. https://doi.org/10.1002/cam4.3039. Retrospective multicenter study across nine cancer center in the USA demonstrating heterogeneity of first-line systemic treatment prescribed to patients with MRCL.

  4. WHO Classification of Tumours Editorial Board. Soft Tissue and Bone Tumours, International Agency for Research on Cancer: 2020.

  5. Smith TA, Easley KA, Goldblum JR. Myxoid/round cell liposarcoma of the extremities. Am J Surg Pathol. 1996;20:171–80. https://doi.org/10.1097/00000478-199602000-00005.

    Article  CAS  PubMed  Google Scholar 

  6. Haniball J, Sumathi VP, Kindblom LG, Abudu A, Carter SR, Tillman RM, Jeys L, Spooner D, Peake D, Grimer RJ. Prognostic factors and metastatic patterns in primary myxoid/round-cell liposarcoma. Sarcoma. 2011;2011:538085. https://doi.org/10.1155/2011/538085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Crozat A, Aman P, Mandahl N, Ron D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993;363:640–4. https://doi.org/10.1038/363640a0.

    Article  CAS  PubMed  Google Scholar 

  8. Paulien S, Turc-Carel C, Dal Cin P, Jani-Sait S, Sreekantaiah C, Leong SP, Vogelstein B, Kinzler KW, Sandberg AA, Gemmill RM. Myxoid liposarcoma with t(12;16) (q13;p11) contains site-specific differences in methylation patterns surrounding a zinc-finger gene mapped to the breakpoint region on chromosome 12. Cancer Res. 1990;50:7902–7.

    CAS  PubMed  Google Scholar 

  9. Knight JC, Renwick PJ, Dal Cin P, Van den Berghe H, Fletcher CD. Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis. Cancer Res. 1995;55:24–7.

    CAS  PubMed  Google Scholar 

  10. Panagopoulos I, Hoglund M, Mertens F, Mandahl N, Mitelman F, Aman P. Fusion of the EWS and CHOP genes in myxoid liposarcoma. Oncogene. 1996;12:489–94.

    CAS  PubMed  Google Scholar 

  11. Panagopoulos I, Lassen C, Isaksson M, Mitelman F, Mandahl N, Aman P. Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia. Oncogene. 1997;15:1357–62. https://doi.org/10.1038/sj.onc.1201281.

    Article  CAS  PubMed  Google Scholar 

  12. Callegaro D, Miceli R, Bonvalot S, Ferguson P, Strauss DC, Levy A, Griffin A, Hayes AJ, Stacchiotti S, Le Pechoux C, et al. Impact of perioperative chemotherapy and radiotherapy in patients with primary extremity soft tissue sarcoma: retrospective analysis across major histological subtypes and major reference centres. Eur J Cancer. 2018;105:19–27. https://doi.org/10.1016/j.ejca.2018.09.028.

    Article  PubMed  Google Scholar 

  13. Tuzzato G, Laranga R, Ostetto F, Bubbico E, Vara G, Bianchi G Primary high-grade myxoid liposarcoma of the extremities: prognostic factors and metastatic pattern. Cancers Basel 2022, 14. https://doi.org/10.3390/cancers14112657.

  14. Fiore M, Grosso F, Lo Vullo S, Pennacchioli E, Stacchiotti S, Ferrari A, Collini P, Lozza L, Mariani L, Casali PG, et al. Myxoid/round cell and pleomorphic liposarcomas: prognostic factors and survival in a series of patients treated at a single institution. Cancer. 2007;109:2522–31. https://doi.org/10.1002/cncr.22720.

    Article  PubMed  Google Scholar 

  15. Hoffman A, Ghadimi MP, Demicco EG, Creighton CJ, Torres K, Colombo C, Peng T, Lusby K, Ingram D, Hornick JL, et al. Localized and metastatic myxoid/round cell liposarcoma: clinical and molecular observations. Cancer. 2013;119:1868–77. https://doi.org/10.1002/cncr.27847.

    Article  CAS  PubMed  Google Scholar 

  16. Muratori F, Bettini L, Frenos F, Mondanelli N, Greto D, Livi L, Franchi A, Roselli G, Scorianz M, Capanna R, et al. Myxoid liposarcoma: prognostic factors and metastatic pattern in a series of 148 patients treated at a single institution. Int J Surg Oncol. 2018;2018:8928706. https://doi.org/10.1155/2018/8928706.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Moreau LC, Turcotte R, Ferguson P, Wunder J, Clarkson P, Masri B, Isler M, Dion N, Werier J, Ghert M, et al. Myxoid\round cell liposarcoma (MRCLS) revisited: an analysis of 418 primarily managed cases. Ann Surg Oncol. 2012;19:1081–8. https://doi.org/10.1245/s10434-011-2127-z.

    Article  PubMed  Google Scholar 

  18. Chowdhry V, Goldberg S, DeLaney TF, Cote GM, Chebib I, Kim J, Lozano-Calderon SA, De Amorim Bernstein K. Myxoid liposarcoma: treatment outcomes from chemotherapy and radiation therapy. Sarcoma. 2018;2018:8029157. https://doi.org/10.1155/2018/8029157.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Abaricia S, Hirbe AC. Diagnosis and treatment of myxoid liposarcomas: histology matters. Current Treatment Options in Oncology. 2018;19(12):64. https://doi.org/10.1007/s11864-018-0590-5.

    Article  PubMed  Google Scholar 

  20. Lansu J, Braam PM, van Werkhoven E, Scholten AN, Schrage Y, van Houdt WJ, van Langevelde K, Haas RL. A moderate dose of preoperative radiotherapy may improve resectability in myxoid liposarcoma. Eur J Surg Oncol. 2021;47:2633–9. https://doi.org/10.1016/j.ejso.2021.06.020.

    Article  PubMed  Google Scholar 

  21. Lansu J, Bovee J, Braam P, van Boven H, Flucke U, Bonenkamp JJ, Miah AB, Zaidi SH, Thway K, Bruland OS, et al. Dose reduction of preoperative radiotherapy in myxoid liposarcoma: a nonrandomized controlled trial. JAMA Oncol. 2021;7:205865.

    Article  Google Scholar 

  22. Chung PW, Deheshi BM, Ferguson PC, Wunder JS, Griffin AM, Catton CN, Bell RS, White LM, Kandel RA, O’Sullivan B. Radiosensitivity translates into excellent local control in extremity myxoid liposarcoma: a comparison with other soft tissue sarcomas. Cancer. 2009;115:3254–61. https://doi.org/10.1002/cncr.24375.

    Article  PubMed  Google Scholar 

  23. Guadagnolo BA, Zagars GK, Ballo MT, Patel SR, Lewis VO, Benjamin RS, Pollock RE. Excellent local control rates and distinctive patterns of failure in myxoid liposarcoma treated with conservation surgery and radiotherapy. Int J Radiat Oncol Biol Phys. 2008;70:760–5. https://doi.org/10.1016/j.ijrobp.2007.07.2337.

    Article  PubMed  Google Scholar 

  24. von Mehren M, Kane JM, Agulnik M, Bui MM, Carr-Ascher J, Choy E, Connelly M, Dry S, Ganjoo KN, Gonzalez RJ, et al. Soft Tissue Sarcoma, NCCN Clinical Practice Guidelines in Oncology. J of the Nat Com Cancer Net. 2022;20:815–33. Updated NCCN guidelines include recommendation of anthracycline-based chemotherapy as first-line systemic therapy option, with trabectedin as an alternate therapeutic option.

  25. Jones RL, Fisher C, Al-Muderis O, Judson IR. Differential sensitivity of liposarcoma subtypes to chemotherapy. Eur J Cancer. 2005;41:2853–60. https://doi.org/10.1016/j.ejca.2005.07.023.

    Article  CAS  PubMed  Google Scholar 

  26. Benjamin RS, Wiernik PH, Bachur NR. Adriamycin chemotherapy—efficacy, safety, and pharmacologic basis of an intermittent single high-dosage schedule. Cancer. 1974;33:19–27. https://doi.org/10.1002/1097-0142(197401)33:1%3c19::aid-cncr2820330107%3e3.0.co;2-m.

    Article  CAS  PubMed  Google Scholar 

  27. Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay J-Y, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, et al. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15:415–23. https://doi.org/10.1016/s1470-2045(14)70063-4.

    Article  CAS  PubMed  Google Scholar 

  28. Le Cesne A, Judson I, Crowther D, Rodenhuis S, Keizer HJ, Van Hoesel Q, Blay JY, Frisch J, Van Glabbeke M, Hermans C, et al. Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: a trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 2000;18:2676–84. https://doi.org/10.1200/JCO.2000.18.14.2676.

    Article  PubMed  Google Scholar 

  29. Casali PG, Abecassis N, Aro HT, Bauer S, Biagini R, Bielack S, Bonvalot S, Boukovinas I, Bovee J, Brodowicz T, et al. Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29:268–9. https://doi.org/10.1093/annonc/mdy321.

    Article  Google Scholar 

  30. Tap WD, Wagner AJ, Schöffski P, Martin-Broto J, Krarup-Hansen A, Ganjoo KN, Yen C-C, Abdul Razak AR, Spira A, Kawai A, et al. Effect of doxorubicin plus olaratumab vs doxorubicin plus placebo on survival in patients with advanced soft tissue sarcomas. Jama 2020, 323, 1266. https://doi.org/10.1001/jama.2020.1707.

  31. Katz D, Boonsirikamchai P, Choi H, Lazar AJ, Wang WL, Xiao L, Park MS, Ravi V, Benjamin RS, Araujo DM. Efficacy of first-line doxorubicin and ifosfamide in myxoid liposarcoma. Clin Sarcoma Res. 2012;2:2. https://doi.org/10.1186/2045-3329-2-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Patel SR, Burgess MA, Plager C, Papadopoulos NE, Linke KA, Benjamin RS. Myxoid liposarcoma. Experience with chemotherapy. Cancer. 1994;74:1265–9. https://doi.org/10.1002/1097-0142(19940815)74:4%3c1265::aid-cncr2820740414%3e3.0.co;2-x. Neoadjuvant non-inferiority trial comparing trabectedin with anthracyline-ifosfamide combination in localized high-risk MRCL patients.

  33. Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay J-Y, Tendero O, Beveridge RD, et al. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017;18:812–22. https://doi.org/10.1016/s1470-2045(17)30334-0.

    Article  CAS  PubMed  Google Scholar 

  34. Gronchi A, Palmerini E, Quagliuolo V, Martin Broto J, Lopez Pousa A, Grignani G, Brunello A, Blay J-Y, Tendero O, Diaz Beveridge R, et al. Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: final results of a randomized trial from Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) sarcoma groups. J Clin Oncol. 2020;38:2178–86. https://doi.org/10.1200/jco.19.03289.

    Article  CAS  PubMed  Google Scholar 

  35. Gronchi A, Palmerini E, Quagliuolo V, Martin Broto J, Lopez-Pousa A, Grignani G, Brunello A, Blay J-Y, Diaz Beveridge R, Ferraresi V, et al. Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: results of the expanded cohort of myxoid liposarcoma of the randomized clinical trial from the Italian Sarcoma Group (ISG), the Spanish Sarcoma Group (GEIS), the French Sarcoma Group (FSG), and the Polish Sarcoma Group (PSG). J Clin Oncol. 2022;40:11508–11508. https://doi.org/10.1200/JCO.2022.40.16_suppl.11508.

    Article  Google Scholar 

  36. Assi T, Kattan J, El Rassy E, Honore C, Dumont S, Mir O, Le Cesne A. A comprehensive review of the current evidence for trabectedin in advanced myxoid liposarcoma. Cancer Treat Rev. 2019;72:37–44. https://doi.org/10.1016/j.ctrv.2018.11.003.

    Article  CAS  PubMed  Google Scholar 

  37. D’Incalci M, Galmarini CM. A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther. 2010;9:2157–63. https://doi.org/10.1158/1535-7163.MCT-10-0263.

    Article  CAS  PubMed  Google Scholar 

  38. Germano G, Frapolli R, Simone M, Tavecchio M, Erba E, Pesce S, Pasqualini F, Grosso F, Sanfilippo R, Casali PG, et al. Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Res. 2010;70:2235–44. https://doi.org/10.1158/0008-5472.CAN-09-2335.

    Article  CAS  PubMed  Google Scholar 

  39. Ryan DP, Supko JG, Eder JP, Seiden MV, Demetri G, Lynch TJ, Fischman AJ, Davis J, Jimeno J, Clark JW. Phase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies. Clin Cancer Res. 2001;7:231–42.

    CAS  PubMed  Google Scholar 

  40. Taamma A, Misset JL, Riofrio M, Guzman C, Brain E, Lopez Lazaro L, Rosing H, Jimeno JM, Cvitkovic E. Phase I and pharmacokinetic study of ecteinascidin-743, a new marine compound, administered as a 24-hour continuous infusion in patients with solid tumors. J Clin Oncol. 2001;19:1256–65. https://doi.org/10.1200/JCO.2001.19.5.1256.

    Article  CAS  PubMed  Google Scholar 

  41. Villalona-Calero MA, Eckhardt SG, Weiss G, Hidalgo M, Beijnen JH, van Kesteren C, Rosing H, Campbell E, Kraynak M, Lopez-Lazaro L, et al. A phase I and pharmacokinetic study of ecteinascidin-743 on a daily x 5 schedule in patients with solid malignancies. Clin Cancer Res. 2002;8:75–85.

    CAS  PubMed  Google Scholar 

  42. Twelves C, Hoekman K, Bowman A, Vermorken JB, Anthoney A, Smyth J, van Kesteren C, Beijnen JH, Uiters J, Wanders J, et al. Phase I and pharmacokinetic study of Yondelis (Ecteinascidin-743; ET-743) administered as an infusion over 1 h or 3 h every 21 days in patients with solid tumours. Eur J Cancer. 2003;39:1842–51. https://doi.org/10.1016/s0959-8049(03)00458-1.

    Article  CAS  PubMed  Google Scholar 

  43. Garcia-Carbonero R, Supko JG, Manola J, Seiden MV, Harmon D, Ryan DP, Quigley MT, Merriam P, Canniff J, Goss G, et al. Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol. 2004;22:1480–90. https://doi.org/10.1200/JCO.2004.02.098.

    Article  CAS  PubMed  Google Scholar 

  44. Yovine A, Riofrio M, Blay JY, Brain E, Alexandre J, Kahatt C, Taamma A, Jimeno J, Martin C, Salhi Y, et al. Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. J Clin Oncol. 2004;22:890–9. https://doi.org/10.1200/JCO.2004.05.210.

    Article  CAS  PubMed  Google Scholar 

  45. Le Cesne A, Blay JY, Judson I, Van Oosterom A, Verweij J, Radford J, Lorigan P, Rodenhuis S, Ray-Coquard I, Bonvalot S, 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;23:576–84. https://doi.org/10.1200/JCO.2005.01.180.

    Article  CAS  PubMed  Google Scholar 

  46. Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, 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;27:4188–96. https://doi.org/10.1200/JCO.2008.21.0088.

    Article  CAS  PubMed  Google Scholar 

  47. Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, et al. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015;16:406–16. https://doi.org/10.1016/s1470-2045(15)70098-7.

    Article  CAS  PubMed  Google Scholar 

  48. Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, 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. https://doi.org/10.1200/jco.2015.62.4734.

    Article  CAS  PubMed  Google Scholar 

  49. Grosso F, Jones RL, Demetri GD, Judson IR, Blay J-Y, Le Cesne A, Sanfilippo R, Casieri P, Collini P, Dileo P, et al. Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol. 2007;8:595–602. https://doi.org/10.1016/s1470-2045(07)70175-4.

    Article  CAS  PubMed  Google Scholar 

  50. Blay JY, Leahy MG, Nguyen BB, Patel SR, Hohenberger P, Santoro A, Staddon AP, Penel N, Piperno-Neumann S, Hendifar A, et al. Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas. Eur J Cancer. 2014;50:1137–47. https://doi.org/10.1016/j.ejca.2014.01.012.

    Article  CAS  PubMed  Google Scholar 

  51. Gronchi A, Bui BN, Bonvalot S, Pilotti S, Ferrari S, Hohenberger P, Hohl RJ, Demetri GD, Le Cesne A, Lardelli P, et al. Phase II clinical trial of neoadjuvant trabectedin in patients with advanced localized myxoid liposarcoma. Ann Oncol. 2012;23:771–6. https://doi.org/10.1093/annonc/mdr265.

    Article  CAS  PubMed  Google Scholar 

  52. Gronchi A, Hindi N, Cruz J, Blay JY, Lopez-Pousa A, Italiano A, Alvarez R, Gutierrez A, Rincon I, Sangalli C, et al. Trabectedin and radiotherapy in soft tissue sarcoma (TRASTS): results of a phase I study in myxoid liposarcoma from Spanish (GEIS), Italian (ISG), French (FSG) sarcoma groups. EClinicalMedicine. 2019;9:35–43. https://doi.org/10.1016/j.eclinm.2019.03.007.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Pautier P, Italiano A, Piperno-Neumann S, Chevreau C, Penel N, Firmin N, Boudou-Rouquette P, Bertucci F, Balleyguier C, Lebrun-Ly V, et al. Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2022;23:1044–54. https://doi.org/10.1016/s1470-2045(22)00380-1.

    Article  CAS  PubMed  Google Scholar 

  54. Blay J-Y, von Mehren M, Samuels BL, Fanucchi MP, Ray-Coquard I, Buckley B, Gilles L, Lebedinsky C, Elsayed YA, Le Cesne A. Phase I combination study of trabectedin and doxorubicin in patients with soft-tissue sarcoma. Clin Cancer Res. 2008;14:6656–62. https://doi.org/10.1158/1078-0432.Ccr-08-0336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Okuno S, Ryan LM, Edmonson JH, Priebat DA, Blum RH. Phase II trial of gemcitabine in patients with advanced sarcomas (E1797). Cancer. 2003;97:1969–73. https://doi.org/10.1002/cncr.11290.

    Article  CAS  PubMed  Google Scholar 

  56. Švancárová L, Blay JY, Judson I.R, van Hoesel QGCM, van Oosterom AT, le Cesne A, Keizer HJ, Hermans C, van Glabbeke M, Verweij J, et al. Gemcitabine in advanced adult soft-tissue sarcomas. a phase II study of the EORTC soft tissue and bone sarcoma group. European Journal of Cancer 2002;38:556–9. https://doi.org/10.1016/s0959-8049(01)00408-7.

  57. Leu KM, Ostruszka LJ, Shewach D, Zalupski M, Sondak V, Biermann JS, Lee JS, Couwlier C, Palazzolo K, Baker LH. Laboratory and clinical evidence of synergistic cytotoxicity of sequential treatment with gemcitabine followed by docetaxel in the treatment of sarcoma. J Clin Oncol. 2004;22:1706–12. https://doi.org/10.1200/JCO.2004.08.043.

    Article  CAS  PubMed  Google Scholar 

  58. Maki RG, Wathen JK, Patel SR, Priebat DA, Okuno SH, Samuels B, Fanucchi M, Harmon DC, Schuetze SM, Reinke D, 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. J Clin Oncol. 2007;25:2755–63. https://doi.org/10.1200/jco.2006.10.4117.

    Article  CAS  PubMed  Google Scholar 

  59. Schöffski P, Ray-Coquard IL, Cioffi A, Bui NB, Bauer S, Hartmann JT, Krarup-Hansen A, Grünwald V, Sciot R, Dumez H, 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. https://doi.org/10.1016/s1470-2045(11)70230-3.

    Article  PubMed  Google Scholar 

  60. Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. The Lancet. 2016;387:1629–37. https://doi.org/10.1016/s0140-6736(15)01283-0.

    Article  Google Scholar 

  61. Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D’Adamo DR, Guo M, et al. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017;35:3433–9. https://doi.org/10.1200/JCO.2016.71.6605.

    Article  CAS  PubMed  Google Scholar 

  62. Kim CG, Sim NS, Kim JE, Yun K-H, Lee YH, Kim SH, Baek W, Han YD, Kim SK, Kim JH, et al. Phase II clinical trial of eribulin–gemcitabine combination therapy in previously treated patients with advanced liposarcoma or leiomyosarcoma. Clin Cancer Res. 2022;28:3225–34. https://doi.org/10.1158/1078-0432.Ccr-22-0518.

    Article  CAS  PubMed  Google Scholar 

  63. Chen TW-W, Yen C-C, Hong R-L, Lee J-C, Chang K, Yu C-W, Chen S-C, Chen M-L, Hsu M-C, Kung T-F, et al. A phase Ib/II study of the combination of lenvatinib (L) and eribulin (E) in advanced liposarcoma (LPS) and leiomyosarcoma (LMS) (LEADER): Efficacy updates. J Clin Oncol. 2022;40:11506–11506. https://doi.org/10.1200/JCO.2022.40.16_suppl.11506.

    Article  Google Scholar 

  64. Sleijfer S, Ray-Coquard I, Papai Z, Le Cesne A, Scurr M, Schoffski P, Collin F, Pandite L, Marreaud S, De Brauwer A, 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;27:3126–32. https://doi.org/10.1200/JCO.2008.21.3223.

    Article  CAS  PubMed  Google Scholar 

  65. van der Graaf WTA, Blay J-Y, Chawla SP, Kim D-W, Bui-Nguyen B, Casali PG, Schöffski P, Aglietta M, Staddon AP, Beppu Y, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet. 2012;379:1879–86. https://doi.org/10.1016/s0140-6736(12)60651-5.

    Article  Google Scholar 

  66. Samuels BL, Chawla SP, Somaiah N, Staddon AP, Skubitz KM, Milhem MM, Kaiser PE, Portnoy DC, Priebat DA, Walker MS, et al. Results of a prospective phase 2 study of pazopanib in patients with advanced intermediate-grade or high-grade liposarcoma. Cancer. 2017;123:4640–7. https://doi.org/10.1002/cncr.30926.

    Article  CAS  PubMed  Google Scholar 

  67. Antonescu CR, Tschernyavsky SJ, Decuseara R, Leung DH, Woodruff JM, Brennan MF, Bridge JA, Neff JR, Goldblum JR, Ladanyi M. Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases. Clin Cancer Res. 2001;7:3977–87.

    CAS  PubMed  Google Scholar 

  68. Stahlberg A, Kabjorn Gustafsson C, Engtrom K, Thomsen C, Dolatabadi S, Jonasson E, Li CY, Ruff D, Chen SM, Aman P. Normal and functional TP53 in Genetically Stable Myxoid/Round Cell Liposarcoma. PLoS One. 2014;9:e113110. https://doi.org/10.1371/journal.pone.0113110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Nassif EF, Auclin E, Bahleda R, Honoré C, Mir O, Dumont S, Mery B, Hodroj K, Brahmi M, Trédan O, et al. TP53 Mutation as a prognostic and predictive marker in sarcoma: pooled analysis of MOSCATO and ProfiLER precision medicine trials. Cancers 2021, 13. https://doi.org/10.3390/cancers13133362.

  70. Demicco EG, Torres KE, Ghadimi MP, Colombo C, Bolshakov S, Hoffman A, Peng T, Bovee JV, Wang WL, Lev D, et al. Involvement of the PI3K/Akt pathway in myxoid/round cell liposarcoma. Mod Pathol. 2012;25:212–21. https://doi.org/10.1038/modpathol.2011.148.

    Article  CAS  PubMed  Google Scholar 

  71. Nabeshima A, Matsumoto Y, Fukushi J, Iura K, Matsunobu T, Endo M, Fujiwara T, Iida K, Fujiwara Y, Hatano M, et al. Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways. Br J Cancer. 2015;112:547–55. https://doi.org/10.1038/bjc.2014.637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cheng H, Dodge J, Mehl E, Liu S, Poulin N, van de Rijn M, Nielsen TO. Validation of immature adipogenic status and identification of prognostic biomarkers in myxoid liposarcoma using tissue microarrays. Hum Pathol. 2009;40:1244–51. https://doi.org/10.1016/j.humpath.2009.01.011.

    Article  CAS  PubMed  Google Scholar 

  73. Negri T, Virdis E, Brich S, Bozzi F, Tamborini E, Tarantino E, Jocolle G, Cassinelli G, Grosso F, Sanfilippo R, et al. Functional mapping of receptor tyrosine kinases in myxoid liposarcoma. Clin Cancer Res. 2010;16:3581–93. https://doi.org/10.1158/1078-0432.CCR-09-2912.

    Article  CAS  PubMed  Google Scholar 

  74. Roulleaux Dugage M, Nassif EF, Italiano A, Bahleda R. Improving immunotherapy efficacy in soft-tissue sarcomas: a biomarker driven and histotype tailored review. Front Immunol. 2021;12:775761. https://doi.org/10.3389/fimmu.2021.775761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Hemminger JA, Toland AE, Scharschmidt TJ, Mayerson JL, Guttridge DC, Iwenofu OH. Expression of cancer-testis antigens MAGEA1, MAGEA3, ACRBP, PRAME, SSX2, and CTAG2 in myxoid and round cell liposarcoma. Mod Pathol. 2014;27:1238–45. https://doi.org/10.1038/modpathol.2013.244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Pollack SM, Jungbluth AA, Hoch BL, Farrar EA, Bleakley M, Schneider DJ, Loggers ET, Rodler E, Eary JF, Conrad EU 3rd, et al. NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma. Cancer. 2012;118:4564–70. https://doi.org/10.1002/cncr.27446.

    Article  CAS  PubMed  Google Scholar 

  77. Mahalingam P, Julve M, Huang P, Furness AJS, Pollack SM, Jones RL. Immunotherapy of sarcomas with modified T cells. Curr Opin Oncol. 2022;34:362–70. https://doi.org/10.1097/cco.0000000000000843.

    Article  CAS  PubMed  Google Scholar 

  78. D’Angelo SP, Druta M, Van Tine BA, Liebner DA, Schuetze S, Nathenson M, Holmes AP, D’Souza J, Kapoor GS, Zajic S, et al. Primary efficacy and safety of letetresgene autoleucel (lete-cel; GSK3377794) pilot study in patients with advanced and metastatic myxoid/round cell liposarcoma (MRCLS). J Clin Oncol. 2022;40:11500–11500. https://doi.org/10.1200/JCO.2022.40.16_suppl.11500. Primary results of a pilot study of adoptive modified TCR cell therapy against NY-ESO-1.

  79. Zhang X, Weng D, Pan Q, Liu J, Han Z, Peng R, Xu B, Wen X, Cen H, Yan C, et al. Phase I clinical trial to assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of NY-ESO-1–specific TCR T-cells (TAEST16001) in HLA-A*02:01 patients with advanced soft tissue sarcoma. J Clin Oncol. 2022;40:11502–11502. https://doi.org/10.1200/JCO.2022.40.16_suppl.11502.

    Article  Google Scholar 

  80. D’Angelo SP, Van Tine BA, Attia S, Blay J-Y, Strauss SJ, Valverde Morales CM, Abdul Razak AR, Van Winkle E, Trivedi T, Biswas S, et al. SPEARHEAD-1: A phase 2 trial of afamitresgene autoleucel (formerly ADP-A2M4) in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma. J Clin Oncol. 2021;39:11504–11504. https://doi.org/10.1200/JCO.2021.39.15_suppl.11504. Primary results of a pilot study of adoptive modified TCR cell therapy against MAGE-A3.

  81. Somaiah N, Chawla SP, Block MS, Morris JC, Do K, Kim JW, Druta M, Sankhala KK, Hwu P, Jones RL, et al. A Phase 1b study evaluating the safety, tolerability, and immunogenicity of CMB305, a lentiviral-based prime-boost vaccine regimen, in patients with locally advanced, relapsed, or metastatic cancer expressing NY-ESO-1. OncoImmunology 2020, 9. https://doi.org/10.1080/2162402x.2020.1847846.

  82. Somaiah N, Block MS, Kim JW, Shapiro GI, Do KT, Hwu P, Eder JP, Jones RL, Lu H, ter Meulen JH, et al. First-in-class, first-in-human study evaluating LV305, a dendritic-cell tropic lentiviral vector, in sarcoma and other solid tumors expressing NY-ESO-1. Clin Cancer Res. 2019;25:5808–17. https://doi.org/10.1158/1078-0432.Ccr-19-1025.

    Article  CAS  PubMed  Google Scholar 

  83. Pollack SM. The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients. Expert Rev Vaccines. 2018;17:107–14. https://doi.org/10.1080/14760584.2018.1419068.

    Article  CAS  PubMed  Google Scholar 

  84. Pishvaian MJ, Marshall JL, Wagner AJ, Hwang JJ, Malik S, Cotarla I, Deeken JF, He AR, Daniel H, Halim A-B, et al. A phase 1 study of efatutazone, an oral peroxisome proliferator-activated receptor gamma agonist, administered to patients with advanced malignancies. Cancer. 2012;118:5403–13. https://doi.org/10.1002/cncr.27526.

    Article  CAS  PubMed  Google Scholar 

  85. Sanfilippo R, Dei Tos AP, Casali PG. Myxoid liposarcoma and the mammalian target of rapamycin pathway. Curr Opin Oncol. 2013;25:379–83. https://doi.org/10.1097/CCO.0b013e32836227ac.

    Article  CAS  PubMed  Google Scholar 

  86. Trautmann M, Cyra M, Isfort I, Jeiler B, Kruger A, Grunewald I, Steinestel K, Altvater B, Rossig C, Hafner S, et al. Phosphatidylinositol-3-kinase (PI3K)/Akt signaling is functionally essential in myxoid liposarcoma. Mol Cancer Ther. 2019;18:834–44. https://doi.org/10.1158/1535-7163.MCT-18-0763.

    Article  CAS  PubMed  Google Scholar 

  87. Juric D, Rodon J, Tabernero J, Janku F, Burris HA, Schellens JHM, Middleton MR, Berlin J, Schuler M, Gil-Martin M, et al. Phosphatidylinositol 3-kinase α–selective inhibition with alpelisib (BYL719) in PIK3CA-altered solid tumors: results from the first-in-human study. J Clin Oncol. 2018;36:1291–9. https://doi.org/10.1200/jco.2017.72.7107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. O’Reilly T, McSheehy PMJ, Wartmann M, Lassota P, Brandt R, Lane HA. Evaluation of the mTOR inhibitor, everolimus, in combination with cytotoxic antitumor agents using human tumor models in vitro and in vivo. Anticancer Drugs. 2011;22:58–78. https://doi.org/10.1097/CAD.0b013e3283400a20.

    Article  CAS  PubMed  Google Scholar 

  89. Pinto-Leite R, Arantes-Rodrigues R, Ferreira R, Palmeira C, Colaço A, Moreira da Silva V, Oliveira P, Lara Santos L. Temsirolimus improves cytotoxic efficacy of cisplatin and gemcitabine against urinary bladder cancer cell lines. Urologic Oncology: Seminars and Original Investigations 2014, 32, 41.e11–41.e22. https://doi.org/10.1016/j.urolonc.2013.04.012.

  90. Guo S, Lopez-Marquez H, Fan KC, Choy E, Cote G, Harmon D, Nielsen GP, Yang C, Zhang C, Mankin H, et al. Synergistic effects of targeted PI3K signaling inhibition and chemotherapy in liposarcoma. PLOS ONE. 2014;9:93996. https://doi.org/10.1371/journal.pone.0093996.

    Article  CAS  Google Scholar 

  91. Patwardhan PP, Ivy KS, Musi E, de Stanchina E, Schwartz GK. Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget. 2015;7:4093–109. https://doi.org/10.18632/oncotarget.6547.

    Article  PubMed Central  Google Scholar 

  92. Bauer T, Cho BC, Heist R, Bazhenova L, Werner T, Goel S, Kim D-W, Adkins D, Carvajal RD, Alva A, et al. First-in-human phase 1/1b study to evaluate sitravatinib in patients with advanced solid tumors. Invest New Drugs. 2022;40:990–1000. https://doi.org/10.1007/s10637-022-01274-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Tarantino P, Carmagnani Pestana R, Corti C, Modi S, Bardia A, Tolaney SM, Cortes J, Soria JC, Curigliano G. Antibody–drug conjugates: Smart chemotherapy delivery across tumor histologiesCA: A. Cancer Journal for Clinicians. 2021;72(165):182. https://doi.org/10.3322/caac.21705.

    Article  Google Scholar 

  94. Dolatabadi S, Jonasson E, Andersson L, Luna Santamaria M, Linden M, Osterlund T, Aman P, Stahlberg A. FUS-DDIT3 fusion oncoprotein expression affects jAK-STAT signaling in myxoid liposarcoma. Front Oncol. 2022;12:816894. https://doi.org/10.3389/fonc.2022.816894.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Dolatabadi S, Jonasson E, Linden M, Fereydouni B, Backsten K, Nilsson M, Martner A, Forootan A, Fagman H, Landberg G, et al. JAK-STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma. Int J Cancer. 2019;145:435–49. https://doi.org/10.1002/ijc.32123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

EFN received research support from Fondation Nuovo-Soldati and Fondation pour la Recherche Medicale.

Author information

Authors and Affiliations

  1. Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd, Houston, TX, USA

    Elise F. Nassif MD, MS, Prapassorn Thirasastr MD & Neeta Somaiah MD

  2. Department of Medical Oncology, Centre Léon Bérard Cancer Center, Lyon, France

    Elise F. Nassif MD, MS

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

    Elise F. Nassif MD, MS & Emily Z. Keung MD, AM

Authors
  1. Elise F. Nassif MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emily Z. Keung MD, AM
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prapassorn Thirasastr MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Neeta Somaiah MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neeta Somaiah MD.

Ethics declarations

Competing Interests

Dr. Somaiah is principal investigator on a trial from GSK (NCT03450122).

Conflict of Interest

The authors have no conflict of interest to disclose.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Sarcoma

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nassif, E.F., Keung, E.Z., Thirasastr, P. et al. Myxoid Liposarcomas: Systemic Treatment Options. Curr. Treat. Options in Oncol. 24, 274–291 (2023). https://doi.org/10.1007/s11864-023-01057-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-023-01057-4

Keywords

Search

Navigation