|Year : 2015 | Volume
| Issue : 4 | Page : 974-976
Complete response of a recurrent-metastatic liposarcoma with dedifferentiated histological features following the administration of trabectedin and review of literature
Tulay Kus1, Gokmen Aktas1, Mehmet Emin Kalender1, Ediz Tutar2, Esra Ulker3, Celaletdin Camci1
1 Department of Internal Medicine, Division of Medical Oncology, Gaziantep Oncology Hospital, Gaziantep, Turkey
2 Department of Pathology, Gaziantep University, School of Medicine, Gaziantep, Turkey
3 Department of Internal Medicine, Gaziantep University, School of Medicine, Gaziantep, Turkey
|Date of Web Publication||15-Feb-2016|
Gaziantep University, School of Medicine, Department of Medical Oncology, Gaziantep Oncology Hospital, Gaziantep - 27310
Source of Support: None, Conflict of Interest: None
The present case report defines a rare case of a liposarcoma with bone metastasis resulting in a complete remission (CR) following trabectedin treatment. The patient was referred with abdominal swelling and pain. A retroperitoneal mass was detected and described as dedifferentiated liposarcoma (DDLS). The mass was surgically removed and consequently adjuvant chemotherapy was administered. Three months after the completion of chemotherapy, patient presented with bone metastasis in thoracic and lumbar vertebrae. Vertebroplasty and radiotherapy (RT) was performed. After these therapies, bone pain persisted and bone scintigraphy showed increased activity in L4, T11, and T12 vertebrae. Zoledronic acid was added to trabectedin treatment. CR has been detected on bone scintigraphy and positron emission tomography-computed tomography (PET-CT) after 18 weeks. Previous cases about liposarcoma treated with trabectedin were mostly about the myxoid/round cell type (former name, currently known as myxoid liposarcoma (MLS)) and mostly reported partial responses. In this study, trabectedin was used for the treatment of a metastatic retroperitoneal DDLS and a CR was achieved.
Keywords: Bone metastasis, complete response, dedifferentiated liposarcoma, trabectedin
|How to cite this article:|
Kus T, Aktas G, Kalender ME, Tutar E, Ulker E, Camci C. Complete response of a recurrent-metastatic liposarcoma with dedifferentiated histological features following the administration of trabectedin and review of literature. J Can Res Ther 2015;11:974-6
|How to cite this URL:|
Kus T, Aktas G, Kalender ME, Tutar E, Ulker E, Camci C. Complete response of a recurrent-metastatic liposarcoma with dedifferentiated histological features following the administration of trabectedin and review of literature. J Can Res Ther [serial online] 2015 [cited 2020 Sep 25];11:974-6. Available from: http://www.cancerjournal.net/text.asp?2015/11/4/974/158032
| > Introduction|| |
Soft tissue sarcomas (STSs) are a heterogeneous group of rare solid tumors of mesenchymal cell origin affecting approximately 1% of all adult malignancies.  Liposarcoma (LS) is the most frequent STS that occur in adults. In the World Health Organization (WHO) classification of adipocytic tumors published in 2013, LSs were classified as; intermediate (well differentiated LS (WDLS)) and malignant (dedifferentiated LS (DDLS), myxoid LS (MLS) including round cell LS, pleomorphic LS, and LS not otherwise specified). 
In general, LSs are known to be relatively chemoresistant subtypes of sarcomas, except the myxoid variant. DDLS primarily arises in the context of deep atypical lipomatous tumor. WDLS is intermediate malignancy due to lack of capacity to metastasize. DDLS has a rate of locoregional recurrence and distant metastasis about 10-15% and is mostly observed in the lungs. It has a more aggressive course than WDLS or MLS and has low response rate to current therapy.  Trabectedin is one of the novel systemic therapies being used for advanced LSs. Patients are treated with trabectedin as first-line treatment in the metastatic setting.
| > Case report|| |
A 40 year-old female patient was admitted to hospital with complaints of pelvic pain and a palpable abdominal mass in March 2013. Abdominal ultrasonography showed an 8 × 14 × 15 cm mass containing cystic and solid components extending from the left adnexal region to the middle abdomen. Patient was operated because of suspected gynecologic malignancy at initial diagnosis. A giant, 20 × 15 × 10 cm mass extending to the retroperitoneum and encovering the left ovary was observed at surgery. Left salphingooopherectomy and retroperitoneal mass excision was performed. Pathologic evaluation was reported as DDLS. CD68 and vimentin were positive, pancytokeratine, desmin, CD34, S100, Myo D1, myogenin, and CD117 were negative at the immunohistochemical stainings [Figure 1]. Ki67 proliferation index was 10%.
|Figure 1: Pathological presentation of the samples (hematoxylin and eosin staining; original magnification, (a) ×20, (b) ×40, (c) ×40) indicating a dedifferentiated liposarcoma|
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Abdomen computed tomography (CT) and bone scintigraphy were normal at diagnosis. Also hematologic and biochemical parameters were in normal range and viral tests for hepatitis were negative. Six cycles of adjuvant chemotherapy with ifosfamide 5,000 mg/m 2 intravenous (IV) 24 h 1 day (with mesna), doxorubicin 50 mg/m 2 IV 3-5 min IV 1 day was administered.
The patient experienced back pain 3 months after the completion of treatment. Vertebral magnetic resonance imaging (MRI) revealed metastatic lesions in T3 vertebra and a pathologic fracture with altitude loss in L2 and L5 vertebrae [Figure 2]a]. Thus, vertebroplasty was performed. Palliative radiotherapy (RT) was administered to vertebrae containing metastasis. Back pain of the patient persisted. Bone scintigraphy showed increased activity in L4, T11, and T12 vertebrae [Figure 3]a]. Trabectedin 1.5 mg/m 2 IV infusion per 3 weeks and zoledronic acid 4 mg per 4 weeks were initiated. Back pain resolved after the first administration of trabectedin. Elevation of alanine transaminase (ALT) to 245 mg/dl after third dose of trabectedin was detected and normalized after 2 weeks without any interpretation. After six cycles of chemotherapy, bone scintigraphy and positron emission tomography-CT (PET-CT) [Figure 3]b and [Figure 2]b-c] did not show any involvement . Complete remission (CR) was suggested.
|Figure 2: (a) Vertebral MR showing metastasis in T3 vertebrae and a pathologic fracture with altitude loss in L2 and L5 vertebraes. (b-c) Posttreatment PET-CT; showing just signs of vertebroplasty. MR = Magnetic resonance, PET-CT = positron emission tomography-computed tomography|
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|Figure 3: (a) Pretreatment bone scintigraphy showing increased activity in L4, T11, and T12 vertebraes. (b) Posttreatment bone scintigraphy without any involvement|
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| > Discussion|| |
Surgical resection of a localized tumor with grossly negative margins remains the standard and potentially curative treatment for patient with STSs, especially with retroperitoneal sarcomas.  However, complete surgical resection is achieved in less than 70% of these patients due to close proximity to vital organs.  Preoperative RT is often preferred, because it reduces the risk of tumor seeding and ensures resectability of the tumor. Postoperative treatment with RT or chemotherapy has been associated with improved progression-free survival (PFS) in retrospective nonrandomized studies with no improvement in overall survival (OS).
Conventional chemotherapy with doxorubicin and ifosfamide represents the mainstay of systemic treatment of STSs in the first line locally advanced and metastatic setting. Other commonly used agents are gemcitabine with docetaxel and the marine-derived compounds like trabectedin.
Trabectedin is a novel chemotherapeutic drug that is a tritetrahydroisoquinoline alkaloid initially isolated from the marine ascidian, ecteinascidia turbinata. This agent binds to the minor groove of deoxyribonucleic acid (DNA) and interacts with proteins of the DNA repair machinery, causes cell cycle arrest in S and G2 phases and inhibits cell proliferation.  Trabectedin has been approved by the European Union in 2007 for treatment of patients with advanced STS after failure of therapy with an anthracycline and ifosfamide.
Prospective phase II studies established therapeutic potential of trabectedin. Garcia-Carbonero et al., reported 10 patients with LS.  One of the patients with myxoid/round cell had a CR. Yovine et al., and Le Cesne et al.,'s study did not report CR. , The treatment efficacy of trabectedin was evaluated specifically for myxoid/round cell LS in a multicenter, retrospective study reported by Grosso et al. Progression-free survival was 92% at 3 months and 88% at 6 months. Rate of CR was 2%.  Samuels et al., reported 233 patients with LS. Two (1%) patients with LS exhibited CR. However, the subtype of LS was not described in these studies. 
According to these studies, complete response rates are very low and partial or complete responses are observed mostly in the subtype of myxoid/round cell LSs. DDLS is a subtype of LPS which has a very low response rate. Tsoukalas et al., reported a case with local recurrent mixed-type, high-grade mesenteric LS with wide areas of necrosis, areas of dedifferentiation, and features of a LS where CR was observed following treatment with trabectedin. 
This case report describes a very rare case of dedifferentiated LS with bone metastasis that showed a complete response following treatment with trabectedin. It is possible that using trabectedin as the first-line treatment in metastatic setting could be associated with CR achieved in our case and trabectedin might be a better option in DDLS which is known to respond poorly to conventional chemotherapy. Randomized studies are difficult to design because of the rarity of DDLS subtype. We aim to contribute to the literature with our anecdotal case report.
| > References|| |
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29.
Doyle LA. Sarcoma classification: An update based on the 2013 World Health Organization Classification of Tumors of Soft Tissue and Bone. Cancer 2014;120:1763-74.
Cho J, Lee SE, Choi YL. Diagnostic Value of MDM2 and DDIT3 Fluorescence in situ
hybridization in liposarcoma classification: A single-institution experience. Korean J Pathol 2012;46:115-22.
Anaya DA, Lev DC, Pollock RE. The role of surgical magrin status in retroperitonela sarcoma. J Surg Oncol 2008;98:607-10.
Ballo MT, Zagars GK, Pollock RE, Benjamin RS, Feig BW, Cormier JN, et al
. Retroperitoneal soft tissue sarcoma: An analysis of radiation and surgical treatment. Int J Radiat Oncol Biol Phys 2007;67:158-63.
Hoiczyk M, Grabellus F, Podleska L, Ahrens M, Schwindenhammer B, Taeger G, et al
. Trabectedin in metastatic soft tissue sarcomas: Role of pretreatment and age. Int J Oncol 2013;43:23-8.
Garcia-Carbonero R, Supko JG, Manola J, Seiden MV, Harmon D, Ryan DP, 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.
Yovine A, Riofrio M, Blay JY, Brain E, Alexandre J, Kahatt C, et al
. Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. J Clin Oncol 2004;22:890-9.
Le Cesne A, Blay JY, Judson I, Van Oosterom A, Verweij J, Radford J, 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.
Grosso F, Jones RL, Demetri GD, Judson IR, Blay JY, Le Cesne A, et al
. Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: A retrospective study. Lancet Oncol 2007;8:595-602.
Samuels BL, Chawla S, Patel S, von Mehren M, Hamm J, Kaiser PE, et al
. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: Results of a worldwide expanded access program study. Ann Oncol 2013;24:1703-9.
Tsoukalas N, Tolia M, Lypas G, Panopoulos C, Barbounis V, Koumakis G, et al
. Complete remission of a reccurrent mesenteric liposarcoma with rare histological features following the administration of trabectedin. Oncol Lett 2014;7:47-9.
[Figure 1], [Figure 2], [Figure 3]