Soft tissue sarcomas (STS) are heterogeneous cancers with more than 100 histological subtypes, different in molecular alterations, which make its personalized therapy very complex. Gold standard of chemotherapy for advanced STS includes combinations of Doxorubicin and Ifosfamide or Gemcitabine and Docetaxel. Chemotherapy is efficient for less than 50% of patients and it is followed by a fast development of drug resistance. Our study was directed to the search of genetic alterations in cancer cells associated with chemoresistance of undifferentiated pleomorphic and synovial sarcomas to the abovementioned genotoxic drugs. We analyzed chemoresistance of cancer cells in vitro using primary STS cultures and performed genetic analysis for the components of apoptotic signaling. In 27% of tumors, we revealed alterations in TP53, ATM, PIK3CB, PIK3R1, NTRK1, and CSF2RB. Cells from STS specimens with found genetic alterations were resistant to Dox, excluding the only one case when TP53 mutation resulted in the substitution Leu344Arg associated with partial oligomerization loss and did not cause total loss of TP53 function. Significant association between alterations in the components of apoptosis signaling and chemoresistance to Dox was found. Our data are important to elaborate further the therapeutic strategy for STS patients with alterations in apoptotic signaling.

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It perdormed the literature data analysis on the criteria and methods for assessing the clinical efficacy of the isolated limb perfusion method in the treatment of soft tissue sarcoma. It is noted that the use of isolated limb perfusion is a rather effective method providing local control of the tumor process in locally advanced forms of soft tissue sarcoma. It has been demonstrated that the use of such a neoadjuvant treatment regimen allows administration of the drug with the achievement of high local concentrations of chemotherapeutic drugs with a relatively low incidence of systemic side effects. Criteria for tumor response to therapy, in particular RECIST (Response Evaluation Criteria In Solid Tumors), Choi criteria, adapted for magnetic resonance imaging, are presented. It is noted that a number of studies have studied the possibility of using positron emission tomography with fluorodeoxyglucose labeled with 18F (18F-FDG) to assess the response to treatment in sarcomas. At the same time, it was shown that the results of studying the metabolic response are superior in accuracy to the method of assessment using the RECIST criteria and the assessment performed by the dynamics of the tumor tissue volume has significant potential in assessing the response to isolated limb perfusion in patients with soft tissue sarcoma. The importance of a one-time assessment of positron emission tomography with 18F-FDG parameters and Magnetic Resonance Imaging for soft tissue sarcoma is confirmed by the results of a combined analysis that takes into account both morphological characteristics and quantitative metabolic parameters of the tumor. The high potential of the combined assessment of metabolic and volume-morphological parameters obtained using these methods was demonstrated; it was noted that the combination of positron emission tomography data with 18F-FDG and Magnetic Resonance Imaging enhances the reliability and efficiency of planning and monitoring of soft tissue sarcoma treatment using the isolated limb perfusion method.