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Introduction. Giant cell tumor of bone is a relatively rare, locally aggressive osteolytic skeletal neoplasm with uncertain behavior: recurrence rates up to 70 % and distant metastases occur 2–6 % of cases. Nowadays denosumab is the choice of therapy for patients  with unresectable  or advanced disease. However,  the efficiency,  duration or administration and most of all safety of continuous denosumab are not established.Materials and methods.  Fourty advanced or unresectable giant cell tumor cases were observed from 2005 till 2020 in N.N. Blokhin National Medical Research Center of Oncology. The average age of pts was 33,6 ± 13,1 years (18–64), and the women and men ratio was about 2,1 : 1. The most commonly affected sites were long bones of the lower extremities (22,5 %), sacrum (22,5 %), long bones of the upper extremities (17,5 %), spine (17,5 %), pelvis (10 %) and others. 70 % of cases were anatomically compounded due to tumor localization and 27,5 % of cases were primary disease. 37,5 % of cases were with pulmonary metastases. Patients underwent computed tomography / magnetic resonance imaging every 3 months during the first three years and then once every six months. Patient received subcutaneous denosumab 120 mg every 4 weeks with a loading dose of 120 mg subcutaneous on study days 8 and 15. After 2 years monthly therapy and confirmed stabilization  effect patient  then  received maintenance  therapy: once in three  months injection. All patients received daily calcium and vitamin D supplement.Results. Median follow-up was 52,8 ± 41,3 months (3–219 months). The average denosumab injections were 25 ± 16 (4–85). Clinical and radiographically stabilization of the effect occurred on average at 12 ± 8 (4–32) injections. Hypocalcemia was registered in one case (2.5 %). There was significant improvement of Karnofsky scale, Visual analogue scale (VAS) and Watkins scale (p <0.001). 5-year progression-free survival for was 70.1 % (95 % confidence interval 55.7–88.0), the median was not reached. Progression of disease was observed only in subgroup with violations in denosumab administration or its cancellation (32,5 %). 3-year progression-free survival in subgroup with violations in denosumab administration or its cancellation was 10 % (95 % confidence interval 15.5–64.1). In subgroup with continuous denosumab and once in three months injection after 2 years monthly therapy there was no signs of progression.Conclusions. In this study we showed evidence of safety and effectiveness of continuous denosumab for unresectable or advanced giant cell tumor even with once in three months injection therapy. Denosumab for advanced giant cell tumor of bone became a choice of treatment, but we need further investigation for observation long term denosumab effectiveness and complications.

Relevance. Giant cell tumor of the bone is most common in people of working age, which determines the high social significance of successful treatment of this category of patients. The main method of treatment is surgical. Currently, the targeted drug denosumab has appeared, the criteria for evaluating the effectiveness of therapy for which, according to the data of radiation methods, are not clearly defined.Target. To analyze and compare the possibilities of CT and MRI in evaluating the effectiveness of denosumab therapy for giant cell tumors.Materials and methods. The data of CT and MRI of 19 patients with giant cell tumor of tubular bones on the background of denosumab therapy were analyzed.Results. Before treatment, the extraosseous component was determined in 57.9 % (n = 11), after – 31.6 % (n = 6). The decrease occurred in 100 %, the disappearance – in 45 % (n = 11) of cases. The thickness of the extraosseous component before treatment ranged from 4 to 43 mm (Me = 15 mm), after treatment it ranged from 0 to 30 mm (Me = 8 mm). The decrease occurred in the range from 4 to 14 mm (M ± SD = 7 ± 4 mm). In 100 % of cases, a sclerotic rim appeared, the thickness of which after treatment ranged from 1 to 5 mm (Me = 3 mm). In the structure of the tumor, fibrosis occurred in 95 % (n = 18), a decrease in the cystic component occurred in 82 % (n = 9) of cases. Perifocal changes decreased in 100 % of cases. In 100 %, the average tumor density increased. The mean tumor density before treatment ranged from 27 to 65 HU (M ± SD = 42 ± 11 HU), after treatment it ranged from 69 to 500 HU (Me = 150 HU). The increase in density occurred in the range from 41 to 454 HU (Me = 101 HU). All differences are statistically significant (p < 0.05).Conclusions. Evaluation of effectiveness with the definition of quantitative and qualitative indicators is possible according to the data of both CT and MRI; with CT, changes are recorded longer, and more indicators available for quantitative measurement are determined.

e23528 Background: Sarcoma is a heterogeneous group of tumors that arise from connective tissue. The most frequent localizations of primary tumors are soft tissues and bones of the extremities, and the lungs is the most common localization of metastases. Pazopanib is an antineoplastic agent, multi-kinase inhibitor that retards angiogenesis in tumor tissues and has been shown to be effective in the treatment of patients with advanced sarcoma. Median progression-free survival was 4,6 months (95% CI 3,7–4,8) for pazopanib compared with 1,6 months (0,9–1,8) for placebo in the PALETTE clinical trial. This study designed to detect epidemiology data as well as the pazopanib efficiency for rare sarcoma subtypes. Methods: We collected data from 109 cases with 20 different sarcoma histotypes and 15 localizations, at N.N. Blokhin National Medical Research Center of Oncology from 2018 till 2020. Disease was histologically confirmed by a sarcoma pathologist. The average age of patients was 47.8 years and the women and men ratio was about 2:1. Patients received pazopanib 800 mg once daily and passed control examinations every 2 or 3 months (CT/MRI). Treatment response was assessed by RECIST criteria. Results: The most frequent localizations of primary tumors were the soft tissues of the extremities (39.6%), the uterus (16.9%) and the retroperitoneum (13.2%). The main histological subtypes were leiomyosarcoma (33.6%) and synovial sarcoma (14.9%). There were also included such types like a embryonal rhabdomyosarcoma, chondrosarcoma, Ewing tumors, EHE, alveolar soft part sarcoma, PEComa, clear cell sarcoma, adamantinoma, solitary fibrous tumor, epithelioid sarcoma and myxoid liposarcoma. The majority of patients (61%) received more than 2 of therapy. The average duration of therapy was 7.5 months. Best tumor response by RECIST was as follows: complete response 0 (0%), partial response 2 (2%), stable disease 81 (88,3%), progression disease 25 (27,3%) cases. Median progression-free survival was 8 months (95% CI 6,7-9,2) for pazopanib. Median overall survival was not reached. Overall pazopanib was well tolerated, except one case with SAE. Conclusions: In this study we observed pazopanib efficiency in a rare for pazopanib sarcoma subtypes such as myxoid liposarcoma (1 PR), PEComa, adamantinoma, embryonal rhabdomyosarcoma, malignant peripheral nerve sheath tumor and Ewing tumors. Also our study confirms pazopanib long-term disease control in alveolar soft part sarcoma, clear cell sarcoma, leiomyosarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma which explains median PFS 8 months.

Introduction. Primary malignant tumors of the skeletal system mostly develop in young and middle-aged people. Morbidity in this age group amounts to between 75 and 80 % of overall morbidity. Due to low survival caused by patient death in the first 5 years mostly because of metastases of primary malignant tumors, the main focus of treatment was on prolongation of life, study and development of new methods of conservative therapy. Therefore, until the early 1970 amputation surgery was the generally accepted standard of surgical intervention. Positive oncological results required revision of the surgical concept of treatment in this patient group. This problem was solved through active development of oncological endoprosthesis started in the second half of the 1970s and led to shaping of orthopedic oncology into a separate oncological specialty. The study objective is to study long-term oncological results of treatment of patients with primary and metastatic tumors of the locomotor system after oncological endoprosthesis.Materials and methods. The study included 1292 patients with primary sarcomas of the bones, soft tissues and patients with metastatic and benign bone tumors who underwent 1200 bone resections/extirpations of varying scale with endoprosthetic replacement between January of 1992 and January of 2020. In the total group of patients who underwent endoprosthesis, the number of men and women was approximately the same: 677 (52.4 %) and 615 (47.6 %), respectively. At the time of surgery, age of the patients in the total group varied between 10 and 81 years. Mean patient age was 34.7 years. Most commonly, endoprosthetic replacement was performed in patients between the ages of 21 and 30 years (in 29 % of cases). Oncological endoprosthesic replacement was performed in 814 (67.8 %) patients with primary malignant tumors, 143 (11.9 %) patients with metastatic lesions in long bones, and 243 (20.3 %) patients with benign neoplasms. Mean follow-up period after endoprosthesis of different bone segments was 82.8 months (between 0 and 335.7 months).Results. In 27 years of observations, total frequency of recurrences after endoprosthesis for various tumor locations (type V complication per the International Society of Limb Salvage system (2013) (ISOLS 2013)) was 8.8 % (86/979); among them recurrence in the bone (type VA complication) was observed in 1.7 % (17/979) of cases, recurrence in the soft tissues (type VB complication) in 7.0 % (69/979) of cases. Primary endoprosthetic replacement due to recurrence after previous surgical treatment leads to 2.2-time increase in the risk of development of this complication. The obtained results show that repeat recurrence significantly increases the risk of recurrence in soft tissues and does not affect the risk of recurrence in the bone. The most recurrences developed in patients with non-differentiated pleomorphic sarcoma (15.4 % of cases), chondrosarcoma (15.0 % of cases) and parosteal osteosarcoma (14.3 % of cases). Frequency of recurrences in patients with giant cell bone tumors and aneurysmal bone cysts was 4.0 and 3.8 %, respectively. In cases of tumor recurrence after endoprosthesis, limb amputation was the most common treatment: 33.7 % (28/83) of cases. In this study, recurrence mostly developed after femur resection with knee joint endoprosthesis: in 45.8 % (38/83) of cases. Frequency of oncological complications in patients with bone sarcomas who underwent endoprosthetic replacement was 31.9 % (283/886). In the total patient group in 27 years of observations, in 25.3 % (224/886) of patients disease progression in the form of metastases was observed. Local tumor recurrence was accompanied by metastases in 6.7 % (59/886) of cases.Conclusion. Decreased risk of development of local recurrences depends on the effectiveness of complex approach to therapy in this disease group. Changes in surgical endoprosthesis techniques in tumors of varying differentiation levels allowed to achieve significant radicalness of treatment. Progression risk for bone sarcomas, level of response to specialized therapy and, as a result, patient’s prognosis depend on the presence of epigenetic, genetic, molecular and chromosomal abnormalities.