12 lat walki z tłuszczakomięsakiem: opis przypadku
Mykola Kononenko, Ihor Vynnychenko, Yuliia Moskalenko, Oleksandr Vynnychenko
Department of Surgery and Oncology, Sumy State University, Sumy, Ukraine
The proportion of liposarcoma in the structure of cancer incidence is from 10 to 35% of all mesenchymal tumors. This clinical observation describes an 12-year struggle with myxoid liposarcoma of the left upper arm, during which 17 surgeries were performed due to local recurrences, 17 radiation therapy courses and 5 chemotherapy courses were conducted. Clinical observation shows the whole complexity of myxoid liposarcoma treatment. The effectiveness of therapeutic management is determined by persistent surgery, and also by the lack of expression of Pgp, glutathione-S-transferase, metallothionein and mutant p53 in tumor structure.
Wiad Lek 2017, 70, 5, 995-997
The proportion of liposarcoma in the structure of cancer incidence is from 10 to 35% of all soft tissue sarcomas [1, 13]. Most often they are located on the extremities (60%) and retroperitoneal space (10-20%) [7, 11]. Slightly more common they are in men (57%), the average age of patients at the time of diagnosis – 51 years old .
In 2005, a 67-year-old man was operated due to presence of a neoplasm of the outer surface of middle third of the left arm. The result of histopathological study revealed a myxoid variant of liposarcoma. In total, for the period from July 2005 to September 2016, 17 operations measures were performed due to local recurrences of the tumor. After 6 local recurrences, 6 courses of postoperative radiation and 1 chemotherapy were condacted, in March 2011 multiple metastases in the lungs and skeleton bones were revealed in the patient. Because of the extension to the upper limb girdle and invasion to scapula, in December 2012 an operation was performed on removal of the left upper limb girdle – the arm with scapula (amputatio interscapulothoracica) (Fig. 1).
A non-relapsive period lasted 1.5 years. The first relapse was in the area of the 1st rib. The tumor was removed by resection. Later local recurrences occurred in soft tissues of the left half of the neck. Each operation was followed by postoperative radiotherapy (30 Gy).
Immunohistochemistry of the expression of Ki-67, p53 and HSP 90 showed high proliferative potential of the patient’s malignant tumor (Ki-67 – 45%), the lack of mutant p53 and moderate expression of protein HSP-90, which are characteristic for liposarcoma, confirmed the earlier established histological diagnosis (Fig. 2).
In addition, immunohistochemistry of surgical material was performed. It was found out that malignant liposarcoma cells do not express proteins connected with drug resistance, the expressions of Pgp, glutathione-S-transferase and metallothionein were not found, indicating the sensitivity of liposarcoma to cytostatic therapy of a wide range of anticancer drugs. Different chemotherapy courses were used for the treatment, but only the scheme of chemotherapy №3 showed clinical effect (stabilization of multiple metastases in lungs and skeletal bones).
Chemotherapy №1 (the 1st day: doxorubicin 60 mg/m² intravenously (i/v); cisplatin 100 mg/m² i/v);
Chemotherapy №2 (the 1st day: vincristine 1.4 mg/m², doxorubicin 50 mg/m², dacarbazine 400 mg/m², cyclophosphamide 500 mg/m² i/v; the 2nd day: dacarbazine 400 mg/m² i/v; the 3d day: dacarbazine 400 mg/m² i/v);
Chemotherapy №3 (the 1st day: methotrexate 40 mg/m², cyclophosphamide 500 mg/m², doxorubicin 50 mg/m² i/v);
Chemotherapy №4 (the 1st day: ifosfamide – 5000 mg/m² i/v 24 h. infusion; mesna – 6000 mg/m² i/v 24 h. infusion; doxorubicin 50 mg/m² i/v; the 2nd day: mesna – 3000 mg/m² i/v);
Chemotherapy №5 (ifosfamide 800 mg/m² from the 1st till the 5th day i/v; etoposide 100 mg/m² from the 1st till the 5th day i/v).
The last surgery was conducted in June 2016. Unfortunately, it turned out to be palliative due to the growing of tumor into the larynx. The patient is currently running a course of radiotherapy.
Clinical observation shows the complexity of myxoid liposarcoma treatment. Regular local recurrences of the disease, low sensitivity to radiotherapy and chemotherapy initiate the search for other methods of treatment.
Highly differentiated and myxoid liposarcomas are the most common (50% of all liposarcomas). Their clinical course, compared to other histological types, is more favorable. A unique synchronous or metachronous metastasis into axillary cavity and retroperitoneal space is characteristic for myxoid liposarcoma, even in the absence of pulmonary metastasis [4, 9].
The basic treatment of patients with liposarcoma is surgery. As a preferred method it is used in the presence of resectable primary highly differentiated tumors (T1a) with negative margins. Combined and complex treatments are also used .
In addition to surgical method, radiotherapy plays an important role in the treatment of patients with liposarcoma. In Massachusettss General Hospital (MGH) wide fields of total focal dose 50 Gy (single focal dose 1,8–2,0 Gy) are given after removal of large tumors, and then narrow fields of 10–16 Gy are given to the tumor bed . In M.D. Andersen Cancer Center (M.D.ACC) total focal dose 60 Gy (single focal dose 2 Gy) is used in the presence of negative resection margins, 64–66 Gy is used with positive ones. In addition, it is appropriate to use neoadjuvant radiotherapy for liposarcoma treatment . However, there is still no generally accepted point of view in which cases it is appropriate to use adjuvant treatment, and which cases demand neoadjuvant treatment. Postoperative radiation is used much more frequently. In the case of our patient wide fields of total focal dose 30 Gy (single focal dose 2,0 Gy) were given.
Sensitivity of liposarcoma to chemotherapy is proved, although, according to some sources, the use of combined schemes of the 1st-line chemotherapy with concurrent use of ifosfamide and doxorubicin is justified in the muscular type sarcomas and is not appropriate in other histological variants . The structure of the second and third lines of chemotherapy includes gemcitabine, docetaxel, and also trabectedin [6, 14]. Overall, the researchers have concluded that only myxoid type of liposarcoma is sensitive to chemotherapy, and all the other subtypes are chemoresistant.
The use of a considerable number of chemotherapy schemes for the patient is determined by the lack of expression of Pgp, glutathione-S-transferase and metallothionein, indicating the sensitivity of this liposarcoma to the cytostatic action of a wide range of anticancer drugs. This clinical observation demonstrates that, despite some clinical effect, it is difficult to achieve a long-term recurrence-free period with the help of cytostatic agents.
In the last decade the understanding of various genetic and molecular aberrations in liposarcoma has increased, which has led to the development of alternative therapeutic strategies: the inhibition of heat shock proteins 90 (Hsp90) ; the use of inhibitors of cyclin-dependent kinase 4 (CDK4), CDK4/6 and insulin-like growth factor (anti-IGF-1R antibodies) [3, 15], and also antigen-specific vaccine based on carcinoembryonic antigen (NY-ESO-1) .
This patient has been living with myxoid liposarcoma for 12 years. The effectiveness of therapeutic management is determined by persistent surgery, and also by the lack of expression of Pgp, glutathione-S-transferase, metallothionein and mutant p53 in tumor structure. This clinical observation shows the low sensitivity of liposarcoma to radiation and chemotherapy, but proves that using these methods in the presence of metastasis can stabilize the process. Alternative therapy methods could improve the general treatment outcome.
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Address for correspondence
Department of Surgery and Oncology,
Sumy State University, 2, Rymskogo-Korsakova St.,
40007, Sumy, Ukraine,
Fig. 1. Computerized tomography before and after removal of the left upper limb girdle.