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The purpose of the study was to evaluate anorectal function with high-resolution anorectal manometry in patients receiving combination treatment for rectal cancer. Material and methods. We analyzed literature data (PubMed, Scopus, eLIBRARY databases) and our treatment outcomes in 50 rectal cancer patients receiving combination or surgical treatment at Rostov Research Institute of Oncology. Results. The mean anal resting pressure was 1.8 times lower, and the maximal anal squeeze pressure was 1.5 times lower in patients after combination treatment, compared to surgical treatment (p

e19520 Background: The purpose of this study was to compare morphological and immunophenotypic characteristics of the tumor population of B-lymphocytes with varying restrictions of immunoglobulin light chains in patients with chronic lymphocytic leukemia (CLL). Methods: We examined 30 patients with CLL (median age 64.9±8.6 years). All patients underwent CBC+DIFF blood tests (Sysmex XE 2100, Japan), morphological examinations (BioVision; Micros, Austria), and immunophenotyping (IPT) by multicolor flow cytometry (Navios 10/3, Beckman Coulter, USA) of the bone marrow and venous blood. According to the IPT results, the patients were divided into: group 1 - 22 patients (73.3%) with tumor cells expressing kappa immunoglobulin light chains, and group 2 - 8 patients (26.7%) with lambda immunoglobulin light chains. Statistical processing of results was performed in the STATISTICA 13.0 program. Results: Morphological tests revealed differences between tumor populations of B lymphocytes. In group 1, the tumor population was represented by small cells of the same type with scanty, often unvisible cytoplasm and nuclei with a lumpy chromatin structure, without distinct nucleoli. In group 2, the sizes of cells varied from small to large, with abundant cytoplasm, round or folded nuclei, smoothed chromatin structure and 1-2 nucleoli. Prolymphocytes were observed among tumor cells (8.1±1.7% of WBC). IPT also revealed differences in tumor clones: morphological uniformity of tumor cells in group 1 was observed in the distribution of tumor cells reflected in low parameters of light scattering on the diagram: location to the left along the FSC axis - from 200 to 400 units and below along the SSC axis - from 10 to 160 units. In group 2, the lymphoid zone was heterogeneous and stretched on the plot: location to the right along the FSC axis - from 200 to 1000 units and higher along the SSC axis - from 10 to 400 units, closer to the monocyte zone, which indicated morphological polymorphism of tumor cells. The expression of CD45 also differed: in group 1, the expression was higher and tumor B lymphocytes were higher by fluorescence intensity on a dot plot on the CD45 / SSC scale in the second half of the third decade and in the fourth decade - to the right compared with group 2, where aberrant B lymphocytes were in the third decade and more to the left. The CD45 expression allowed defining differentiation of the tumor clone: the population in group 1 was represented by mature cells, and in group 2 by less mature and/or intermediate forms. There were no significant differences in the expression of other markers. The revealed differences were typical of both the peripheral blood and bone marrow. Conclusions: The study established morphological and immunophenotypic differences between tumor clones of B lymphocytes expressing either kappa or lambda immunoglobulin light chains in patients with CLL.

e17008 Background: Radiotherapy (RT) is one of the main treatments for prostate cancer (PC). The effectiveness of RT depends on the initial radioresistance of tumor cells provided by their certain molecular features - the transcriptional activity of genes, miRNAs and long non-coding RNAs (lncRNAs). Together, these indicators form a competing endogenous RNAs network (ceRNAs). The aim of this work was to study the ceRNA features in PC patients with different responses to RT. Methods: The study included 400 patients with PC, 90 of them developed biochemical recurrence after RT (Novalis TX, TFD = 75 Gy). Tumor tissue samples were obtained by biopsy. The RNA fraction was isolated and purified using the RNeasy Plus Universal Kits. Bioinformatic search for miRNAs was performed using a modified TarPmiR algorithm. The miRNA-lncRNA interactions were assessed by bioinformatics. Expression of AKT, ATM, BRIP, BRCA1/2, CDK1, CDKN1B, CCND1/3, EXO1, H2AX, KU70, PTEN, RAD50, RAP80, RIF1, RNF168, TOPB1, TP53, XRCC4, BAX, CASP-8, -3, -9, MDM2, BCL2, RBBP8, EP300 genes, miRNA and lncRNA were determined by RT-qPCR. Differences were assessed using the Mann-Whitney test (Bonferroni correction was used). Results: The expression of CDK1, CDKN1B, RBBP8, XRCC4, BRCA2, RAD50 genes in tumor tissues of patients with biochemical recurrence (group 1) was higher (p < 0.005) and the expression of TP53 and BCL2 was lower than the values in tumor tissues in patients without recurrence (group 2). Bioinformatic search for miRNAs targeting the CDK1, CDKN1B, RBBP8, XRCC4, BRCA2, RAD50, TP53 and BCL2 revealed 1725 miRNAs, 78 of which were validated (miRDB) and had a minimum free energy of miRNA-mRNA interaction. Patients in group 1 showed differential expression of miRNAs targeting genes BCL2 (increased miR-139-5p, miR-4446-5p, miR-211-5p); CDK1 (decreased miR-330-3p, miR-5580-3p, miR-429), CDKN1B (decreased miR-6841-3p); RAD50 (decreased miR-433-3p, miR-3691-5p); RBBP8 (decreased miR-130b-3p); TP53 (increased miR-6884-5p, miR-149-3p, miR-6860, miR-4728-5p, let-7b-5p); XRCC4 (decreased miR-4489) and BRCA2 (decreased miR-7151-3p). The interaction of these miRNAs with 160 lncRNAs was mathematically predicted. Patients in group 1 demonstrated increased expression of lncRNAs LINC00641, SCAMP1, MALAT1, MATN1-AS1 (miR-429) , LINC00657 and GAS5 (miR-433-3p), CCAT1 (miR-130b-3p) and reduced expression of S NHG3, DHRS4-AS1 (miR-139-5p) and MAL2 (let-7b-5p). Conclusions: Our study of the ceRNA network features and RT effectiveness for PC established the mechanisms of radioresistance development and its predictors.

e23556 Background: The system of insulin-like growth factors (IGF) is involved in the pathogenesis of many malignant tumors. At the same time, the specificity of this system in recurrent soft tissue sarcomas is unknown. The purpose of this study was to analyze the IGF system in tumors and their peritumoral areas in men with recurrent soft tissue sarcomas. Methods: The study included 26 men aged 57.8±6.2 years with primary (n = 12, group 1, controls) and recurrent (n = 14, group 2, main group) soft tissue sarcoma of the extremities, T2bN0M0. Grade 1 tumors were diagnosed in 6 patients of group 1 and in 7 patients of group 2, while the other patients had G3 or G4 tumors. 95% of tumors were liposarcomas. All patients of group 2 had previously underwent surgical and radiation treatment for primary sarcomas and their relapses (up to 2 episodes), with the last surgery more than 1 year ago. Levels of the IGF system components were determined in tumor (T) and peritumoral (PT) tissues by ELISA, and ratios of IGF(T)/IGF(PT) were calculated. Results: Levels of the IGF system components in patients of group 1 were similar in T and PT. In group 2, levels of IGF1 and IGFВР2 in T were respectively 2.2 and 1.6 times (p < 0.05) lower than in PT, but did not differ significantly from the levels in group 1. The IGF1(T)/IGF1(PT) ratio in patients of group 2 was 1.8 times (p < 0.05) lower than in group 1. PT levels of IGF2 in group 2 depended on the tumor grade: they were 1.5 times (p < 0.05) higher in G1 than in G3-G4, while no such dependence was observed in T. Conclusions: The levels of the IGF system components in recurrent soft tissue sarcomas in older men had some peculiarities. Unlike primary sarcomas with similar levels of the studied components of the IGF system in tumors and in peritumoral tissues, recurrent tumors contained less IGF1 and IGFBP2 than the corresponding peritumoral areas. The levels of IGF2 in the peritumoral tissues of recurrent tumors depended on the tumor grade.

e17554 Background: Thrombosis in patients with gynecologic cancers worsens the outcome of antitumor treatment and is one of the leading causes of their death. The kallikrein-kinin system (KKS) is involved in both the regulation of thrombus formation and the development of cancer. The purpose of this study was to analyze characteristics of the KKS components in the blood in patients with endometrial cancer (EM) and ovarian cancer (OC) with and without secondary thrombosis (VTEC). Methods: The study included 39 patients, mean age 58.0±4.2 years: main groups – patients with OC T1c-3cN0M0 (n = 10) or EC T1a-2N0M0 (n = 9) with VTEC; comparison groups - patients with OC (n = 10) or EC (n = 10) without VTEC. EC was represented by adenocarcinomas (G1-G3), OC by serous carcinomas (90%) and clear cell adenocarcinomas (10%). The control group included healthy women of the corresponding age (n = 10). Blood levels of kallikrein 1 (K1), kallikrein 14 (K14), and kininogen (KG) were measured by ELISA after the surgery. Results: EC patients with VTEC showed 1.5 times (p < 0.05) higher blood levels of K1, compared to donors, while other indices were unchanged. EC patients without VTEC had 4 times lower KG levels, compared to donors and EC+VTEC. In OC, regardless of the presence or absence of VTEC, levels of K1 in the blood increased, as well as in women with EC+VTEC, by 1.5 times (p < 0.05) compared with donors, which was combined with a twofold increase in KG in OC+VTEC and a decrease in KG by 1.4 times in OC patients without VTEC. Blood levels of K14 increased only in OC patients without VTEC by an average of 1.9 times (p < 0.05) compared with donors and OC+VTEC. Conclusions: The revealed changes in some KKS components in the blood demonstrate the similarity (K1 increase) and differences (KG increase only in OC) in the pathogenesis of thrombosis associated with gynecologic cancers. The mechanisms of protection against VTEC in the early postoperative period also showed common (KG decrease) and specific features associated with the characteristics of cancer (K14increase only in OC). The development of therapy aimed at correcting the identified disorders will allow an antitumor treatment program for this category of patients with maximum efficiency improving their quality of life and survival.

e17512 Background: Cervical cancer (CC) is one of the most common cancers in women worldwide (4th in frequency). Traditionally, radical hysterectomy or radiation therapy (RT) is used as the standard treatment for early-stage CC, and locally advanced cancers are treated with RT alone. RT results in complete clinical response only in a part of patients due to formation of malignant cell radioresistance. To date, a significant marker list has been identified to predict the response to RT, but none of them has yet entered clinical practice. Therefore, the aim of this study was bioinformation and laboratory screening of molecular markers for low invasive determination of the CC sensitivity to RT. Methods: The study was performed on 300 CC patients (IB1, IB2, IIA1, tumor < 4 cm) and 30 donors without cancer. The Cancer Genome Atlas database was analyzed to identify potential markers. To obtain data from the Genomic Data Commons Data Portal, we used the TCGABiolinks package of the R language in the Rstudio shell. The GISTIC, MutSig and RAE algorithms were used to identify genome regions whose sizes varied (copy number variation, CNV) significantly in a number of tumor samples. The identified markers (CNV) were validated by RT-PCR in extracellular DNA (cfDNA). Blood was collected before the RT. The remote RT was performed on the Varian TrueBeam linear accelerator in VMAT/IMRT mode (TFD 50Gr). Differences were assessed using the Mann-Whitney test (Bonferroni correction was used). Results: RT result analysis allowed to divide patients into 2 groups - sensitive to RT (n = 170, group 1) and resistant (n = 130, group 2). Bioinformation analysis allowed to isolate a number of genes that altered copying and were associated with sensitivity to RT - ERBB2, BIRC2, TRPC6, YAP1, MIR569, LRRC31, SPRED3, MIR4456, CYP1A, CYP1A, FOXO1, ENOX1, EPSTI1, NEK5, KCTD4, SERP2, MIR621, PTEN, SOD2, MIR3939, ATM, CASP1, CASP4, CASP5, CHEK1 and H2AFX. The CNV of these genes was analyzed in cfDNA. In group 1, a decrease (p < 0.05) in the CNV of H2AFX, ATM, CHEK1, LINC00558, LINC00400 and an increase (p < 0.05) in the CNV of CASP1, CASP4, CASP5, CYP1A1, CYP1A2 and GPX4 were found. In group 2, a decrease (p < 0.05) in the CNV of CASP4, CASP5, CYP1A1, YAP1 and MIR569 and an increase in the CNV (p < 0.05) of H2AFX, ATM, CHEK1, ERBB2 and BIRC2 were found in relation to these indicators in donors without cancer. CNV of H2AFX, ATM, CHEK1, ERBB2, BIRC2, MIR569, LINC00400, CASP4, CASP5 and CYP1A1 genes differed statistically significantly (p < 0.005) in 2 groups of CC patients. Conclusions: The markers identified with a combination of bioinformatics and molecular genetic approaches - the CNV of H2AFX, ATM, CHEK1, ERBB2, BIRC2, MIR569, LINC00400, CASP4, CASP5 and CYP1A1 genes in cfDNA - can become the basis for a low invasive determination of the CC sensitivity to RT.

e15536 Background: Radiotherapy (RT) is a key component of rectal cancer (RC) treatment, however, cases of non-response to preoperative RT in patients are very common, which is associated with radioresistance of tumor cells, mediated by their molecular characteristics, including the expression level of long non-coding RNA (lncRNA). lncRNAs are longer than 200 bp, show specific expression to various incentives, regulate transcription by acting as molecular traps, and can serve as biomarkers. The number of genes encoding lncRNA is 2 times greater than the number of protein coding genes. However, the rapid degradation of lncRNA molecules in the extracellular environment makes this indicator unsuitable for low invasive diagnostics. The problem can be solved by switching to a more stable marker - gene copy number variation (CNV) of lncRNA, which can be determined in extracellular DNA (cfDNA) of blood plasma. Therefore, the aim of this study was to identify the relationship between CNV of lncRNA genes in cfDNA of blood plasma and the RT effectiveness for rectal tumors. Methods: We used cfDNA from blood plasma obtained before RT from 200 RC patients and from the blood plasma of 50 apparently healthy donors (without cancer, AHD). RT was carried out on Novalis TX linear accelerator (TFD = 54 Gy). Blood samples were separated into plasma and cell fraction by centrifugation. Isolation of cfDNA from plasma was carried out by the phenol-chloroform extraction method. Determination of lncRNA genes CNV ( XIST, HELLPAR, NEAT1, AC008124.1, AC016717.2, AC093297.2, AC097634.1, BX890604.1, CASC9, IQCH-AS1, LINC00662, LINC00707, LINC01089, LINC01468, LINC0154, MALAT0154, MUC20-OT1, PVT1, VASH1-AS1) was performed by Real-Time qPCR. Differences were assessed using the Mann-Whitney test (Bonferroni correction was used). Results: An analysis of RT results in 200 patients allowed dividing them into 2 groups: complete tumor regression (group 1, n = 120) and minor or no tumor regression (group 2, n = 80). In cfDNA of patients in group 1, a decrease (p < 0.05) in the CNV of lncRNA XIST, HELLPAR, NEAT1, AC008124.1 and AC016717.2 genes was found by 2.5, 3.3, 2.0, 2.0, and 5.0 times, respectively, relative to the AHD. In cfDNA of patients in group 2, an increase (p < 0.05) in the CNV of lncRNA XIST, HELLPAR, NEAT1, AC008124.1, LINC01089, LINC01547 and VASH1-AS1 genes by 1.9, 2.9, 3.5, 3.7, 2.6, 4.7 and 1.9 times was found respectively relative to the AHD. Differences (p < 0.05) by 4.8, 9.7, 7.0, 7.4, 5.0, 3.1, 4.8 and 2.2 times were observed between 2 groups of patients in terms of CNV of XIST, HELLPAR, NEAT1, AC008124.1, AC016717.2, LINC01089, LINC01547 and VASH1-AS1 genes, respectively. Conclusions: Increased CNV of XIST, HELLPAR, NEAT1, AC008124.1, LINC01089, LINC01547 and VASH1-AS1 genes in blood plasma cfDNA is associated with low RT efficiency.

e13042 Background: The purpose of this study was to analyze the prognostic value of blood levels of fibrinogen (F) in bone metastases from breast cancer (BC). Methods: The study included 160 patients with nodular BC pT2-3N0-1M0-1, including 48 patients in a prospective group (PG) and 112 patients in a retrospective group (RG). All patients underwent initial clinical and laboratory examinations, including determination of alkaline phosphatase (AP) activity (Cobas Integra 4000 plus, Switzerland) and parameters of coagulation hemostasis (STA Compact, France). Bone scintigraphy was performed for complaints of bone pain and/or in cases of elevated AP activity, regardless of SXCT data. Results were considered statistically significant at p < 0.05. Results: Patients in PG were divided into two subgroups depending on F levels: in 31 (64.6%) patients F = 3.67±0.5 g/L, insignificantly exceeding the norm (2.8±0.3 g/L); in 17 (35.4%) patients F = 6.9±0.3 g/L, being 1.9 and 2.5 times (p < 0.05) higher than in subgroup 1 and the norm, respectively. AP activity exceeded the norm by 26% and 40%, respectively (p < 0.1). Bone metastases were detected before treatment in 24 (21.4%) women of RG with pain syndrome; all these patients showed increased blood levels of F, on average up to 7.86±0.8 g/L, similarly to patients in subgroup 2 of PG. F levels in other 88 (78.6%) patients in RG were 3.4±0.6 g/L. The nature and severity of AP changes in RG patients and in both PG subgroups were similar. Initially elevated F levels in 17 PG patients remained unchanged after antitumor treatment (6.2±0.6 g/L). AP activity values were stable after treatment being only 36% and 28% (p < 0.1) higher than the norm, respectively. None of the patients with high F levels complained about bone pain. Unscheduled bone scintigraphy was appointed to 17 patients of PG without clinical symptoms or x-ray (SXCT) signs of pathology but with initially high F which did not decline after treatment. Bone scintigraphy showed metastases to the spine and pelvic bones in 12 of 17 (70.5%) patients 1 month after treatment, subsequently confirmed by MRI results. Conclusions: Initial levels of F within 6.9±0.6 g/L which do not decline after the special treatment allow predicting unfavorable BC course and the presence of metastases to the spine and/or pelvic bones without clinical signs of progression. The proposed method allows diagnosis of advanced tumor process in the absence of clinical signs of the disease with an accuracy of 87.8%, and allows timely corrections to the treatment plan.

Results of preoperative radiation therapy for 119 patients with resectable rectal T3-4N0-1M0 cancer were analyzed. 52 patients received a short-term course of the large-fraction radiation therapy and 67 patients received a prolonged course of chemoradiation therapy. The results demonstrated that the prolonged course reduced clinical signs of the disease twice as much as the short course, it reduced the tumor size and increased the distance to the anorectal line (p

We analyzed literature data and our results of preoperative radiotherapy for 179 patients with resectable rectal cancer T2-4N0-2M0. The purpose of the study was to analyze the complete clinical response to chemoradiotherapy for rectal cancer. The results showed the advantages of monitoring patients with complete clinical response before total mesorectumectomy: no complications and deaths after surgery; absence of a syndrome of low anterior resection of the rectum and dysfunction of the pelvic organs; low intestinal stoma rates; similar overall survival of patients. The problems associated with the “Watch and Wait” tactics were: absence of standardized criteria for including patients in the protocol and absence of the standard protocol of treatment; no reliable criteria for the complete clinical response; high recurrence rates. Thus the “Watch and Wait” approach could be applied during a clinical study at a reference center with a multidisciplinary medical team; otherwise, total mesorectumectomy should be used as the standard treatment for rectal cancer.

e14027 Background: The existing modern standards of combination treatment of HGG patients do not provide recovery and a long-term favorable prognosis, and the increasong incidence of HGG determines the need for additional effective technologies for anticancer and decongestant therapy. One of such methods involves TMS, and we have reported its preliminary assessment earlier (DOI: 10.1200/JCO.2020.38.15_suppl.2545). In this study, we continued the observation to examine the survival of patients. Methods: Patients with HGG received combination treatment: stage 1 – surgical removal of tumors within visible unaltered tissues; stage 2 – radiation therapy (the Varian Novalis linear accelerator) to the bed of the removed tumor, single boost dose 2 Gy, total boost dose 60 Gy; stage 3 – multi-course chemotherapy: temozolomide 150 mg/m² on days 1-5 with a 23-day interval. Starting from the second day after surgery, patients of group 1 (n = 25) received 10 TMS sessions, and during radiotherapy – 15 TMS sessions. Patients of group 2 (n = 25) received combination treatment without TMS. 6 and 12 months after the surgery, survival of patients was assessed with the Kaplan-Meier method and the Log-Rank test. Results: After 6 months of the follow-up, the survival of patients in group 1 remained at 100%, while in the control group it decreased to 88.8±8.7%. The difference in the 1-year overall survival was even more pronounced: in group 1, it was 68.5±10.4%, exceeding the value in group 2 (52.0±7.5%.) The differences were statistically significant (Log-Rank test p = 0.001). Conclusions: The results confirm the effectiveness of accompanying TMS in the early postoperative period, as well as at the stage of radiation therapy. The undoubted effectiveness of the considered techniques makes it expedient to include this type of treatment in the combination therapy for HGG patients. The reported study was funded by RFBR, project number № 19-315-90082\19.

e14025 Background: The effectiveness of radiation therapy in the classical and stereotactic treatment regimens of the primary glioblastoma multiforme was analyzed and compared. Methods: 87 patients with primary glioblastoma multiforme were hospitalized during the study period. 17 patients of them were in the treatment group (stereotactic radiotherapy, dose per fraction 2 Gy, 60 Gy total dose, CTV 2.0 cm, PTV 0.1 cm - group 1), and 70 patients were in the control group (conventionally fractionated radiotherapy, dose per fraction 2 Gy, 60 Gy total dose, CTV 2.0 cm, PTV 0.5 cm - group 2). Patients of both groups were treated with alkylating agents as the third stage of complex treatment. MGMT methylation was evaluated by pyrosequencing. Results: The use of stereotactic radiation therapy allowed to conduct a full course of treatment without interruption, whereas in the second group, due to the development of adverse reactions, the course was interrupted for 7 patients (10%). The advantage of stereotactic radiation therapy was a less pronounced increase and rapid regression of neurological deficits during treatment, manifested by better local control for 6 months. Hypermethylation of MGMT was detected in 39% of glioblastoma cases and was not detected in non-tumor tissue. The presence of promoter methylation disrupts DNA repair and is associated with longer survival in glioblastoma patients receiving alkylating agents. Note that the median survival of patients with MGMT hypermethylation in the group 1 was 285 days (IQR = 323.75), and in the group without hypermethylation was significantly more than 338.5 days (IQR = 476) (p = 0.045). A similar trend was observed in the second group: in patients with hypermethylated MGMT, the median survival was 271 days (IQR = 337), the result is different from patients without hypermethylated MGMT – 342 days (IQR = 493) (p = 0.039). Conclusions: As a result, the application of the stereotactic approach of radiation therapy in the complex treatment of patients with glioblastoma and their classification by the MGMT methylation status with a cut-off point of 10% has the basis for improving the effectiveness and tolerability of radiation therapy and contributes to the overall survival of patients.

e15014 Background: Radiotherapy (RT) is one of the main treatments for prostate cancer (PC). The effectiveness of such therapy depends on the initial radioresistance of tumor cells, which is ensured by their certain molecular features, which include the genes copy number variation (CNV). Model experiments on cell cultures (obtained from surgical material) have shown that CNVs have high potential as predictors of RT sensitivity. However, this potential is limited by the high level of invasiveness in obtaining biomaterials. A possible solution to this problem lies in the transition to CNV study in the extracellular DNA (cfDNA) of blood plasma. The aim of the study was to screen predictors of radioresistant PC based on the genes CNV in cfDNA. Methods: The study included 400 patients with diagnosed PC (T2a-3bN0M0, st. II-III), 40 of them after RT had a state of biochemical relapse (RT was performed on a Novalis TX linear accelerator (Varian, USA) (TFDisoeff = 75 Gr), mean time to biochemical relapse 7.5 months). Blood samples were separated into plasma and cell fraction by centrifugation. Isolation of cfDNA from blood plasma was performed using a set of reagents “DNA-Plasma-M” (Russia). Determination of the relative CNV of 13 genes (CDK1, CCND3, CDKN1B, TP53, PTEN, BCL2, XRCC4, BAX, RBBP8, H2AX, BRCA2, RAD50, EP300) was performed using the Real-Time qPCR method. Differences were assessed using the Mann-Whitney test; the Benjamin-Hochberg correction was used to correct multiple comparisons. Results: In the group with biochemical relapse (n = 40), the CNV of genes CDK1, CDKN1B, RBBP8, XRCC4, BRCA2 and RAD50 was statistically significantly (p < 0.05) higher by 2.0 times, 2.3 times, 2.1 times, 1.4 times, 2.4 times and 2.8 times, respectively, relative to the CNV of these genes in the cfDNA of the group without relapse (n = 360). Conclusions: Thus, it was found that the CNV of 6 genes (CDK1, CDKN1B, RBBP8, XRCC4, BRCA2 and RAD50) may be a potential molecular marker of radiosensitivity of prostate tumors. Based on the obtained data, a low invasive method for determining the prostate tumors sensitivity to RT has been developed.

3025 Background: Radiotherapy (RT) is a key component of rectal cancer (RC) treatment, however, nonresponsiveness in patients to preoperative RT is very common, usually due to the tumor cells radioresistance, mediated by their molecular characteristics, such as gene expression. The features of mRNA rapid degradation in extracellular environment make this indicator unsuitable for low invasive diagnostics. The solution to this problem is possible by switching to a more stable marker - the copy number variation (CNV), which can be determined in the extracellular DNA (cfDNA) circulating in the blood plasma. Therefore, the aim of the study was to identify the relationship between the level of genes CNV in the cfDNA of blood plasma with the effectiveness of rectal tumors RT. Methods: We used cfDNA preparations from blood plasma obtained before RT from 200 patients with RC, as well as from blood plasma of 50 apparently healthy donors (AHD, without cancer). RT was carried out on a linear accelerator Novalis TX (SFD = 2.4 Gy, TFD = 54.0 Gy). Blood samples were separated into plasma and cell fraction by centrifugation. Isolation of cfDNA from blood plasma was performed using the phenol-chloroform method. Determination CNV of 5 genes (BRCA2, H2AX, CASP9, RBBP8 and BCL2) was performed using Real-Time qPCR method. Differences were assessed using Mann-Whitney test; the Bonferroni correction was used to correct multiple comparisons. Results: RT results for 200 patients allowed them to be divided into 2 groups. After RT, 120 patients showed complete tumor regression (group 1), 50 patients showed insignificant tumor regression and 30 patients did not regress (group 2). In cfDNA of group 1 patients was found CNV decrease (p < 0.05) of H2AX and RBBP8 genes by 2.5 and 2.0 times, respectively, relative to AHD group. In the cfDNA of group 2patients an increase (p < 0.05) of BRCA2, H2AX, RBBP8 and BCL2 genes CNV was found by 2.0, 2.2, 2.0 and 2.0 times, respectively, relative to AHD group. Only 2 genes CNV differed in group 1 from group 2: the CNV of H2AX and RBBP8 was 5.4 and 4.0 times less respectively (p < 0.005). Conclusions: Thus, it has been found that increased CNV of genes BRCA2, H2AX, BCL2, RBBP8 in blood plasma cfDNA is associated with low efficiency of RT. At the same time, the CNV of H2AX and RBBP8 genes in cfDNA of patients with RC has the greatest potential as a marker of the RT effectiveness.

e17515 Background: The purpose of the study was to evaluate advantages of combination ozone therapy as an effective factor of radiomodification and radioprotection in the treatment of patients with cervical cancer. Methods: The study included 20 patients with stage IIIb cervical cancer T3бNхM0, the mean age 52 years. Controls (n = 10) received standard chemoradiation therapy; the main group (n = 10) received combination ozone therapy in addition to chemoradiation therapy. Systemic ozone therapy involved intravenous administration of 250 ml ozonized solution of 0.9% sodium chloride, 15 sessions during external beam radiotherapy. Local ozone therapy involved 15-minute instillations into the vagina during brachytherapy. All patients received standard chemoradiation therapy, total irradiation dose to the primary focus 80 Gy, plus weekly cisplatin 40 mg/m2. Results: In the main group, pain and discomfort in the lower abdomen were managed in 20% patients by the 5th session of ozone therapy; 30% - on the 10th day; in 50% - on the 14th day. In the control group, such symptoms in 40% of patients were reduced after 20 days. The main group showed a more rapid regression of tumor infiltration, disappearance of purulent discharge, relief of intoxication syndrome. Manifestations of gastrointestinal toxicity were observed in 10% of the main group and in 100% controls; leukopenia developed in 7 patients in the control group and was not registered in the main group. MRI showed complete clinical regression in 90% in the main group and in 65% in the control group. The treatment was completed within 7 weeks in the main group and 8.5 weeks in the control group. Conclusions: Combination ozone therapy causes a more pronounced antitumor effect, and its radioprotective effects significantly reduce the severity of chemotherapy-induced disorders. It does not aggravate concomitant pathology and shortens the treatment period.

e17514 Background: Malignant pelvic tumors account for more than 25% of cancer incidence in Russia. Radiation therapy is the most common treatment for such patients; however, 10-15% of patients develop radiation-induced complications of the pelvic organs, and more effective treatments are required to manage these complications. Methods: The study included 30 patients with cervical cancer T3NхM0 after combination treatment. 7-10 months after combined radiation treatment (total radiation dose to the primary focus 80 Gy), patients developed erosive ulcerative radiation rectitis (RTOG grade 1 and 2). Patients were divided into 2 groups: main group (n = 15) – conservative treatment combined with LILEDR. Each course included 10 LILEDR sessions, the red spectrum λ = 640 nm on the cubital vein projection (exposure time 5 minutes, dose 6.86 J/cm2) and locally on the ulcerated zones (exposure time 3 minutes, dose 3.96 J/cm2). Patients received 2 LILEDR courses with a 1-month interval. The control group received only conservative therapy. Results: Main clinical manifestations of rectitis (tenesmus, bloody mucous discharge) disappeared in the main group already on the 3-4th day of the first course, epithelialization of ulcerative defects occurred in a shorter period of 7-10 days. Soft superficial scars not causing rectal stenosis formed at the site of the ulcer by the end of LILEDR courses. The control group showed long periods of the ulcer epithelialization up to 30 days, late remission and a lingering recurrent character of the disease. Conclusions: LILEDR in combination with the main conservative therapy allows rapid managing with the clinical symptoms of radiation rectitis and regression of disorders developed after the complex treatment, which improves the quality of life of patients and shortens the rehabilitation period.

e13531 Background: Preoperative radiation therapy (RT) followed by surgery is the main effective treatment for colorectal cancer. However, some patients do not respond to preoperative RT due to the radioresistance of tumor cells, depending on their molecular characteristics, in particular on the expression of a certain group of genes. The aim of this work was to study the effect of expression of BRCA2, H2AX, RBBP8, CASP9 and BCL2 genes on the effectiveness of preoperative RT for rectal tumors. Methods: In the study, paired biopsy preparations (obtained by VCS before irradiation) of normal and tumor tissues of the rectum (adenocarcinoma G1-2) in 30 patients were used. RT was carried out on a Novalis TX linear accelerator (Varian, USA) (SFD = 2.4 Gy to TFD = 54 Gy). RNA isolation was performed by Chomczynski&Sacchi method. Reverta-L kits were used to synthesize cDNA libraries. Using the RT-qPCR method, the relative expression of 5 genes was determined: BRCA2, H2AX, CASP9, RBBP8 and BCL2 (reference GAPDH, ACTB and B2M). Statistical analysis was performed using the Shapiro–Wilk and Mann–Whitney criteria. Results: 2 clusters of patients were identified that differed in the expression of the BRCA2, H2AX, CASP9, RBBP8 and BCL2 genes. In cluster 1, 81% of patients had increased expression of the CASP9 gene and 100% decreased expression of the BRCA2, H2AX, RBBP8, and BCL2 genes. In cluster 2, the expression of the CASP9 gene was reduced in 100% of patients and the expression of the BRCA2, H2AX, RBBP8 and BCL2 genes was increased in 93%. A subsequent analysis of the results of RT showed that 16 patients had complete tumor regression after RT, while expression of the H2AX and RBBP8 genes was reduced by a factor of 2 (p < 0.05), and the expression of the CASP9 gene was increased by a factor of 4 (p < 0.005) relative to normal tissues. 8 patients showed slight tumor regression, and 6 patients had no regression at all, while their expression of the BRCA2, H2AX, RBBP8 and BCL2 genes was statistically significantly (p < 0.005) 2, 4, 6 and 3 times higher, respectively, and that of CASP9 gene was 4 times lower than in patients with complete tumor regression. Conclusions: The study found that the expression of BRCA2, H2AX, CASP9, RBBP8 and BCL2 genes affects the effectiveness of RT, enhancing it in patients with increased expression of CASP9 and reduced expression of H2AX and RBBP8, and vice versa, the effectiveness of therapy decreases with increased expression of H2AX, RBBP8, BRCA2 and BCL2.

e18030 Background: Chemoradiation therapy (CRT) radiomodified with platinum-based drugs is recommended for patients with inoperable cervical cancer. However, the introduction of chemotherapy medicines increases the number of hematological and non-hematological complications. Prolonged RT significantly decreases survival of patients. This requires more effective methods helping to prevent chemoradiotherapy complications. The purpose of the study was to evaluate the effectiveness of ozone therapy as an accompanying treatment for chemoradiotherapy for cervical cancer (CC). Methods: The study included 20 patients diagnosed with cT3NхM0 CC. The control group (n = 10) received standard CRT with weekly cisplatin radiomodification (40 mg/m2). The main group (n = 10) received CRT with weekly cisplatin radiomodification (40 mg/m2) and additional infusions of 250 ml ozonized solution of 0.9% sodium chloride (a total of 15 infusions). Results: In the main group, CRT did not cause a significant aggravation of gastrointestinal and general symptoms, compared with the initial state. The rate of dyspeptic disorders (nausea, diarrhea, bloating) was 10% in the main group and 100% in controls. In the control group, clinical pain decreased only by the 25th day; 100% of patients developed gastrointestinal toxicity grade 1 (80%) and 2 (20%); 100% of patients complained of weakness during treatment. 7 patients developed leukopenia. Anemia in 5 patients remained at the level of 95g/L, in 3 patients - aggravation up to 80g/L. In the main group, treatment was completed within 7 weeks. In the control group, the duration of CRT was 8 weeks due to toxicity. Conclusions: Ozone therapy in addition to the conventional conservative treatment significantly decreases the severity of CRT-induced complications which allows complete treatment planned, while maintaining optimal treatment duration.

e15618 Background: Lung cancer is a challenging cancer problem, despite significant progress in its therapy. The search of drugs for the treatment of lung cancer is an urgent task. The creation of animal models of lung cancer plays a key role in preclinical trials and in understanding the mechanisms of tumor pathogenesis. The purpose of the study was to create a subcutaneous cell line-derived xenograft (CDX) model of lung cancer using the human lung cancer cells A459 and to compare results of subcutaneous injections of a cell suspension with different numbers of cells in two groups of animals. Methods: A CDX model of lung cancer was created using the human lung cancer cells A459 and male BALB/c Nude mice divided into two groups (n = 4 and n = 6) with subcutaneous injections of a mix of a cell suspension with Matrigel (200 μl). The injection mix contained 5*106 cells in 100 μl of serum-free RPMI-1640 medium and 100 μl of Matrigel (n = 4) and 10*106 cells in 100 μl of serum-free RPMI-1640 medium and 100 μl of Matrigel (n = 6). Results: Animal models receiving a suspension of 10*106 cells in 100 μl of serum-free RPMI-1640 medium and 100 μl of Matrigel were characterized by a higher tumor growth index compared to animals receiving 5*106 cells in 100 μl of serum-free RPMI-1640 medium and 100 μl of Matrigel. Models created with the injections of 10*106 cells showed a larger volume of tumor nodes: 65.33±1, 39.2±1, 41.79±1, 36.64±1, 75.87±1 and 43.13±1 mm3. CDX models created with the injections of 5*106 cells were characterized by a division of the single tumor node by the 30th day of the experiment which complicated the measurement. Conclusions: The creation of a CDX model with injections of 5*106 cells is undesirable due to the nonlinear growth of the xenograft and its division into several tumor nodes. Subcutaneous CDX models of lung cancer created with injections of 10*106 cells showed the linear growth and the formation of the single tumor node.

e15590 Background: The initial radioresistance of tumor cells associated with certain molecular genetic features has a great influence on the effectiveness of radiation therapy (RD). These features include the transcriptional activity of genes that regulate DNA repair, cell cycle and apoptosis, and their copy number variation (CNV). The aim of the study was to analyze the expression and CNV of genes that regulate DNA repair, cell cycle and apoptosis in HT-29 cells subjected to RD. Methods: HT-29 cell culture was used in the study. For the model experiment, doses of 5 and 7 Gy were used (irradiation was performed 5 times every 24 hours on a Novalis TX linear accelerator). Cell counting was carried out in Goryaev chamber (0.4% trypan blue solution). On the 5th day of irradiation, HT-29 was removed from the substrate with Trypsin / Versen solution. RNA was isolated according to the method of Chomczynski&Sacchi. For cDNA synthesis was used a "REVERTA-L". reagent. The phenol-chloroform method was used to DNA isolate. The RT-qPCR method was used to determine the CNV and expression of 32 genes: AKT, ATM, BRIP, BRCA1, BRCA2, CDK1, CDKN1B, CCND1, CCND3, EXO1, FGFR2, HIST1, H2AX, KU70, PTEN, RAD50, RAP80, RIF1, RNF8 TOPB1, TP53, XRCC4, BAX, CASP8, CASP3, CASP9, MDM2, BCL2, RBBP8, EP300, LIG4, C-FLIP. Statistical analysis was performed using ANOVA and Spearman's rank correlation coefficient (r). Results: After irradiation, only a specific pool of HT-29 cells remained viable: 32% for 5 Gy and 20% for 7 Gy of the initial number of cells. In HT-29 cells irradiated with 7 Gy, the CNV of the BRCA2, H2AX, CASP9 and RBBP8 genes was increased (p < 0.05) and the CNV of BCL2 gene was reduced (p < 0.05) relative to intact cells. In cells irradiated with 5 Gy only CASP9 and RBBP8 CNV was statistically significantly (p < 0.05) increased. In cells irradiated with 5 and 7 Gy, expression of BRCA2, H2AX, CASP9 and RBBP8 genes was statistically significantly (p < 0.05) increased and the expression of the BCL2 gene was reduced relative to intact cells. A strong positive correlation was observed between CNV and expression of the studied genes: r = 0.998 for control, r = 0.989 for cells irradiated at 5 Gy, and r = 0.993 for cells irradiated at 7 Gy. Conclusions: The study showed that 5 day RD at 5 and 7 Gy leads to selective survival of 32% and 20% of cells, respectively, with increased CNV and expression of BRCA2, H2AX, RBBP8 CASP9 genes and reduced CNV and expression of BCL2 gene.

e15218 Background: Cancer-testis antigens (CTAs) are used as targets in immunotherapeutic approaches based on gene-cell vaccines (GCV). In some cases, it is possible to use experimental combinatorial therapy regimens that combine radiation and GCV. Despite numerous studies of the expression of CTA in tumors of various locations, including colon tumors, the transcriptional activity of CT-genes in tumor tissue of the colon after radiation therapy remains poorly studied. The aim of the study was to analyze changes in the expression of CT-genes in HT-29 cells after irradiation with a linear accelerator. Methods: The study used human cell culture HT-29. For the model experiment, 7 Gy fractionation option was used (irradiation was carried out 5 times every 24 hours). Irradiation was performed on a Novalis TX linear accelerator (Varian, USA). The ratio of living and dead cells was calculated in a Goryaev chamber using a 0.4% trypan blue dye solution. After microscopy on the 5th day of irradiation, the cell line was removed from the vial substrate by Trypsin/Versen solution. RNA was isolated by the Chomczynski&Sacchi method. For cDNA synthesis a set of "REVERTA-L" reagents used. Expression of 16 CT genes (MAGE-A1, -A2, -A3, -A4, MAGE-B1, -B2, GAGE-1, -3, -4, MAGEC1, BAGE, XAGE3, NYESO1, SSX2, SCP1, PRAME1) was determined using the Real-Time qPCR method (reference genes — GAPDH and B2M). Statistical analysis was performed using univariate analysis of variance (ANOVA) with repeated measurements. Results: After 5 days of exposure at a dose of 7 Gy, only 20% of the initial number of HT-29 cells remained viable. It was found that irradiation was statistically significantly (p < 0.05) influenced the increase in the expression of genes MAGEA1 by 1.8 times, MAGEB1 by 6.8 times, BAGE by 1.6 times, CTAGE1 by 3.3 times and SSX2 by 5.8 times relative to intact cells. Conclusions: Thus, tumor cells exposed to radiation at a dose of 7 Gy show an increase in the expression of 5 CT-genes, which, in turn, can increase their immunogenic potential.

Aim The aim hereof is a comprehensive study of the mental, adaptive and hormonal status in patients with lung cancer with varying prevalence of the malignant process. The obtained results are compared with data on the psychosomatic state and subclinical disorders in the thyroid system in patients with cardiovascular diseases. Materials and methods The characteristics of general non-specific adaptation reactions by the organism (AR), the level of personal and situational anxiety, the severity of depression, and the reactions to the disease are studied in 28 lung cancer patients with resectable and unresectable tumors. The “Antistress” expert software is used for the qualitative and quantitative evaluation of AR. The level of the adrenocortical and thyroid axis hormones in blood serum is studied in patients with resectable tumors. Results The relationship between the AR characteristics and the malignant process prevalence, a decrease in the ACTH concentration, an elevated level of cortisol and thyroxine are noted. The mental status has been characterized by non-depressiveness and dominance of the euphoric reaction to the disease. In patients with resectable tumors without detected metastases, who have shown the euphoric reaction, the maximum scores of AR are observed with a higher thyroxine concentration as compared with those in patients with metastases and low adaptation status, who have demonstrated the hypochondriacal type of the response. Conclusion The relationship between the characteristics of AR in patients with lung cancer and the cancer process prevalence is shown herein. It is assumed that thyroxine is involved in the formation of the positive psychoemotional states in the studied patients. The combination of the euphoric reaction with the maximum AR scores in patients with resectable lung cancer without detected metastases indicates that there is a psychophysiological mechanism of restraining tumor development; at the same time, it demonstrates that there is the need to refine the concept of the euphoric type of the response. The obtained results indirectly count in favor of the cardiovascular diseases therapy approaches, which involve the use of thyroxin drugs in accordance with the algorithms of activation therapy.

The new high-tech era begins not with supply of an innovative product to the market, but rather with an intellectual leap in the field of open issues in fundamental engineering, healthcare and education. In the present essay, an example of the successful translation of mathematical, physics- and engineering-related philosophy into the digital platform of Cardiometry is discussed. The theory of hemodynamics, the laws of axiomatics, logic and adaptation can be expressed in terms of mathematics. The original analytical software used in PC-assisted device Cardiocode allows carrying out a phase analysis of the hemodynamics within an extended range. Pilot studies conducted by us in cancer patients at the stages of multi-course chemotherapy have revealed abnormalities and disorders in hemodynamics, energy exchange and adaptation expectancy of the heart at early stages of cancer treatment that is of prognostic significance. Pronounced processes of destabilization in hemodynamics, a suppressed energy exchange and a degradation of adaptation capabilities by the end of the chemotherapy courses involves the appearance of cardiotoxic effects. Based on records covering the specific frequencies discovered in ECG & Rheogram, the R-R interval scatter plots, the metabolic parameters and the Baevsky stress index, we have demonstrated cardioprotective influence made by xenon as a possible solution of the indicated problem. Thus, the Cardiocode technology supports diagnostics by offering an original cardiometric approach, significantly broadening the notion of cardio-oncology from the perspective of the cardiotoxicity pathogenesis under the cancer development conditions and in treatment thereof.

e13511 Background: Development of alternative methods of non-invasive therapy in neurooncology is determined by the need to prevent the continued growth of glioblastoma and radiation-induced complications. Usage of electromagnetic influence for these reasons is determined by the oscillatory nature of intracellular processes and results of previous studies on the effect of weak electromagnetic radiation in tumor growth. The purpose of the study was to reveal the effect of a pulsed magnetic field (PMF) and ionizing radiation (IR) on human T98G glioblastoma cells. Methods: Human T98G glioblastoma cells were cultured in the RPMI-1640 medium (Biolot, Russia) supplemented with 10% fetal bovine serum (Thermo Scientific HyClone, USA). The culture was seeded in the Biofil plates (at least 8x105 cells per 3 mL of the medium), incubated (CB 150 Binder, Germany) and exposed to IR 10 Gy (TheratronEquinox-BestTheratronics) for 11.7 min. and/or PMF 15 mT or 300 mT with a sequence of frequencies 0.3-3.0-9.0 Hz for 7 min. (Neiro-MS/D by Neirosoft, Russia). The efficiency criteria were lethality and the mitotic activity of human T98G glioblastoma cells. Results: The highest cellular lethality was registered 3 hours (18.7 vs. 5.2% in controls, p≤0.05) and a day after IR exposure. PMF 15 or 300 mT alone increased lethality by 2.5-2.8 times compared to controls (p < 0.05). IR plus PMF (15 mT) did not caused increased lethality. At the same time, the most pronounced decrease in the mitotic activity a day after exposure (by 4.7 times, p < 0.05) was registered in PMF alone (15 mT). Conclusions: The inhibitory effect of PMF on the viability of human glioblastoma cells indicates the prospects for its use as an accompanying treatment in neurooncology.

e17505Background: The purpose of the study was to determine the VEGF-A expression in patients with cervical cancer to assess its prognostic value. Methods: The study included 82 patients (23-70 yea...

e24327Background: The purpose of the study was to analyze the phenotypic profile of erythrocytes in Rhesus and Kell systems in patients with malignant and benign tumors. Methods: Phenotyping of ery...

e14508Background: We monitored the level of methotrexate and some laboratory parameters in patients with osteosarcoma to evaluate the toxicity of high-dosage EURAMOS chemotherapy. Methods: The stud...

e22007 Background: The purpose of the study was to analyze phenotypic characteristics of red blood cells by the AVBO, Rh and Kell systems in children with cancer. Methods: ABO and Rh blood groups were determined and erythrocyte antigens (D, С, с, Сw, Е, е, К, k) were typed (AutoVue Innova, USA) in blood samples of 114 children with solid tumors. Results: ABO blood groups distribution was as follows: A(II) > O(I) > B(III) > AB(IV) with A(II) prevalence. Rh(D)-positive phenotype was observed in 82 (71.9%) patients of 114: 47 (57.3%) boys and 35 (42.6%) girls. 32 (28.1%) patients of 114 were Rh(D)-negative: 15 (46.8%) boys and 17 (53.1%) girls. Only 8 (7%) children were Kell-positive, which was similar to the antigen prevalence in European population. 4 erythrocyte phenotypes were the most frequent in Rh(D)-positive patients: СсDееK− (34.1%), ССDееK− (22.0%), ccDEeK− (13.4%) and СсDЕеK− (11.0%). I.e., more than a half of children with oncopathologies (56.1%) had Kell-negative phenotypes, СсDееK− and ССDееK−. 86.4% of Rh(D)-positive patients had homozygous combinations of Rhesus antigens causing transfusion reactions - СС, сc, ЕЕ and ее. 18 (22.0%) of Rh(D)-positive patients were homozygous for the C antigen and 64 (78.0%), i.e. every third patient, had the c antigen. Children with the C antigen may be sensitized to the c antigen through blood transfusion with subsequent development of hemolytic complications. The K (Cellano) antigen was found in all children, and 93% of them had kk phenotype and 7% - Kk. The Сw (Willis) antigen was revealed only in 5 (6.0%) Rh(D)-positive patients with rare phenotypes - CwCceeK-, CwccEeK-, CwCcEEK-, CwCcEeK-. Matching a donor for patients with one of these phenotypes could pose a problem. Conclusions: Studying phenotypic characteristics of red blood cells is necessary for providing a successful blood transfusion, especially in children Kell-positive for the K antigen, in children homozygous for the C antigen with ССDееК- phenotype and in children with the Сw antigen and СwСсееК-, СwссЕеК-, СwСсЕЕК- and СwСсЕеК- phenotypes.

e19511 Background: Our purpose was to analyze levels and types of paraprotein in polychemotherapy combined with selective plasma exchange in patients with multiple myeloma. Methods: Blood levels of paraprotein (PP) were studied by capillary electrophoresis (Helena Bioscience V8), and content of plasma cells was determined in the bone marrow of 16 patients (main group) with multiple myeloma (MM) during polychemotherapy (PCT) plus selective plasma exchange (SPE). 14 patients receiving standard PCT were the controls. Results: MM patients in both groups were characterized with the presence of PP in the blood serum with the M-peak in the gamma-globulin zone. Only heavy IgG chains were found, bound to lambda (λ) light chains in 48% and to cappa (κ) light chains in 57.15%. The initial PP level in MM-IgGλ was 91.01±0.79 g/L and was 2.4 times higher than in MM-IgGκ (38.3±0.34 g/L). Significant differences in were found in PP reduction rate and intensity depending on the treatment. PP in the main group reduced by 42.4% after course1, by 41.4% after course 2, by 52.2% after course 3 and by 24% after course 4; in the control group – by 17.2%, 19.3%, 27.9% and 47.3%, respectively. PP levels decreased by 87.4% and 74.6% by the end of the treatment, respectively. The data were confirmed by a decrease in plasma cell content in the bone marrow of patients: up to 1.2% in the main group and 6.2% in the controls. Response to treatment in the main group was registered at the early stages of therapy, and at the late stages in the control group. Treatment effect was associated with the type of secreted PP. In MM-IgGκ, PP levels in the main group decreased by 59.7% after course 1, by 40.6% more after course 2 and by 51.9% after course 3; in MM-IgGλ – by 25.1%, 42.1% and 52.5%, respectively. Treatment effect was noted earlier and PP reduction was more intensive in MM-IgGκ than in MM-IgGλ. PP levels decreased by the end of the treatment by 85.4% in MM-IgGκ and by 73% in MM-IgGλ. Similar changes were observed in the control group. Conclusions: Increased rates and intensiveness of paraprotein reduction reflect effectiveness of polychemotherapy plus selective plasma exchange for multiple myeloma. Patients with MM-IgGκ are more sensitive to the therapy.

e17579 Background: Our purpose was to evaluate changes in blood parameters in patients with laryngeal squamous cell carcinoma (LSCC) during polychemotherapy (PCT) with cetuximab. Methods: Levels of white blood cells (WBC), immature granulocytes (IG) and neutrophils (Ne), as well as levels of C-reactive protein (CRP), lactate dehydrogenase (LDH) and creatinine were studied in the blood of 20 patients with stage I-III LSCC before therapy with cetuximab/cisplatin+5-fluorouracil and on days 2, 9 and 16 of the therapy. The control group (21 patients) received similar PCT without cetuximab. Treatment was assessed using the RECIST criteria. Results: Partial response was observed in 16 (80%) patients of the main group and in 5 (23.8%) controls, stabilization - 4 (20%) and 12 (57.4%), respectively, progression – in 4 (19%) patients of the control group. Patients of the main group with treatment effect showed WBC increase by 2 times after every cetuximab injection (days 2, 9, 16) compared with the initial levels due to Ne and IG increase by 2.7 and 4 times, respectively. WBC and IG levels measured on days 2, 9 and 16 were 13.40±2.86×109/L, 13.52±1.88×109/L, 12.25±2.08×109/L and 0.044±0.021×109/L, 0.056±0.015×109/L, 0.060±0.008×109/L, respectively (p < 0.001). A transient increase in the indexes was replaced by their decrease to the initial values, with the values similar to the reference ones by the end of the treatment. At the same time, we observed decrease in CRP and creatinine levels up to the reference levels (7.69±3.28 mg/L and 74.75±6.54 umol/L, respectively); LDH did not increase. Stabilization was characterized by unchanged WBC levels, positive dynamics of IG and slow decline of CRP level exceeding the reference one (10.0 mg/L) by the treatment end. Reduction of WBC and increase in IG and CRP levels were noted in the controls regardless of the PCT results which could be explained by severity of intoxication syndrome, partially due to the disease and partially due to PCT toxicity. Conclusions: A dual transient increase in WBC and IG levels, reduction of CRP and creatinine during the treatment and unchanged LDH indicate minimization of myelotoxic and general toxic effects of PCT in combination with cetuximab.

e19510 Background: The purpose of the study was to analyze changes in reticulocytic indices and their role in assessing the effectiveness of erythropoiesis in patients with multiple myeloma. Methods: Thestudy included 10 patients with primary multiple myeloma (MM) and 16 patients with recurrent MM, stage II-III. Parameters of the peripheral blood were studied: Hb, RBC, MCV, MCH, RBC-He (red cell hemoglobin content), RET (number and percentage), IRF (immature reticulocyte fraction), high (HFR), median (MFR) and low (LFR) fluorescence reticulocytes, RET-He (reticulocyte hemoglobin content), RPI (reticulocyte production index). Results: Anemia was found in21 (80.8%) patients before treatment: grade I in 30.8%, II in 46.1%, III in 3.8%; normocytic hypochromic anemia – 6, normocytic normochromic – 15. Anemia detection rate in primary MM was 60.0%, recurrent – 93.7%. RET levels in grade I-II anemia were close to the norm, but IRF was increased due to MFR increase by 3.7 times and HFR – by 4.7 times. Grade III anemia: RET number decreased by 1.6 times due to IRF reduction by 2 times, in particular MFR and HFR fractions. As a result, RET-He was decreased to varying degrees in all cases. Patients with complete or partial remission showed no significant changes in erythrocyte parameters, but had RET level increased by 2.5 times, IRF – by 9 times due to MFR increase by 6.5 times and HFR by 30.8 times, RPI - by 2.0 times. The data showed the effectiveness of erythropoiesis during anticancer therapy. We did not observe signs of increasing anemia syndrome in patients with stabilization or patients resistant to treatment, as well as in patients with initial grade III anemia. Hb, RBC, RET and RPI were unchanged, but the ratio of fractions changed: the number of mature ones - LFR increased by 1.4 times and young ones - HFR decreased by 2.5 times, RBC-He were increased and RET-He doubled compared to the levels before treatment, which indicated the activation of processes of erythrokaryocyte hemoglobinization. Conclusions: RET, IRF, RET-He and RPI indices adequately reflect the process of recovery of erythropoiesis and its effectiveness in real time which is extremely important in tumor therapy monitoring.

e22085 Background: The plasminogen regulation system is critical in triggering proteolysis to cleave the extracellular matrix and basement membrane. The “uPA-uPAR” system is involved in extravascular fibrinolysis and is responsible for the formation of plasmin associated with invasion and metastasis. The purpose of the study was to analyze levels of factors of the plasminogen regulation system in the blood of patients with cutaneous melanoma (M) and chronic neurogenic pain (CNP). Methods: Blood levels of PAP, uPA, uPAR and PAI-1 were measured by ELISA in patients with Т3-4NxM0 melanoma: 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: Blood levels of PAP in women with M+CNP were twice higher than in patients with M without CNP, the levels in men with M+CNP did not change; uPA content increased in both women and men with M without CNP by 1.4 and 1.5 times, uPA activity was elevated only in women by 2.4 times, in men it was reduced by 2 times; uPAR was increased by 1.5 times in women and men compared to the values in both female and male patients with M without CNP. PAI-1 content in women and men with M+CNP was similar to control values, and its activity was increased in women by 1.5 times and decreased in men by 2.5 times. Conclusions: The study gives significant additional information on the effect of CNP on relationships in the plasminogen activation system in a combination of cutaneous melanoma and CNB showing marked gender differences. The results should be taken into account in the special treatment of patients with melanoma.

2545 Background: The standard treatment of malignant brain gliomas, including surgical and radiation therapies, does not provide recovery and a long-time favorable prognosis. The development of technologies and international guidelines on the introduction of electric (TTF) and electromagnetic (TMS) fields in combination treatment for glioblastomas aims to improve immediate results, as shown in experiments on human glioblastoma cell culture. The TMS protocol requires further refinement in parameters of frequency, intensity, and exposure with an assessment of the immediate results of combined treatment. Methods: The study included 60 patients diagnosed with MBG receiving osteoplastic craniotomy with radical (within visible unchanged tissues) tumor removal. Starting from the second day after the surgery, patients of group 1 (n = 30) received 10 sessions of magnetotherapy in the double exposure mode. For the first morning exposure, we used an ultra-low-frequency magnetic field (ULFMF) (0.03 to 9.0 Hz) on the hypothalamus projection area to induce a general antistress reaction. After 2.5-3 hours, local (on the surgical site) TMS exposure with the Neuro-MSD system (Russia) was applied in the pulse algorithm, up to 1 GHz and 5 Hz, 15 mT, 3 min. The induction was reduced exponentially (C = 0.8). The control group 2 (n = 30) did not receive ULFMF or TMS. Magnetic resonance imaging (MRI) was used to determine the volume of tumors (Vt, cm3) and perifocal edema (Ve, cm3) calculated according to the Shrek’s formula for an ellipsoid (V = a×b×c×π/6). Results: Before surgery, Vt = 54.7±5.7cm3 in group 1, in group 2 - Vt = 60.9±8.5cm3 (no statistical differences). After surgery and the subsequent course of ULFMF and TMS, residual tumor volumes in group 1 were 2.5 times lower than in controls (p < 0.05). The difference between Ve values before and after treatment was on average 80.7 cm3 in group 1 and 41.8 cm3 in group 2 (p < 0.05). Conclusions: The inclusion of sequential ULFMF and TMS exposures into postoperative therapy for gliomas, taking into account various vectors of the influence on the projection of centers of homeostasis regulation and the surgical field, as well as the development of programmed modes of biotropic exposure parameters, improves antitumor and anti-edematous effects.

11556 Background: Tumor necrosis factor alpha (TNFa) and its receptor (TNFa-R) play an important role in tumor genesis. However, their involvement in the recurrence of sarcomas is poorly studied. The purpose of this study was to analyze levels of TNFa and TNFa-R in the blood of patients with recurrent soft tissue sarcomas. Methods: The study included 64 male and female patients, mean age 63.4±5.2 years. Main groups included patients with recurrent G1 and G3 soft tissue sarcomas T2bN0M0; comparison groups included patients with primary G1 and G3 soft tissue sarcomas T2bN0M0. 95% of tumors were liposarcomas, with solitary rhabdamyosarcomas, myxofibrosarcomas, epithelioid and undifferentiated sarcomas. All recurrent patients had previously underwent surgical and radiation treatment for primary sarcomas and their relapses (up to 2 episodes), with the last surgery more than 1 year ago. Control groups (n = 10 each) included healthy donors of similar age. Levels of TNFa and TNFa-R were measured in the blood serum by ELISA before the treatment. Results: No significant differences were found between TNFa levels in patients with primary and recurrent soft tissue sarcomas and in donors. Levels of TNFa-R in men with primary G3 sarcomas were 1.5 times (p < 0.05) higher compared with donors, 1.7 times (p < 0.05) higher than in men with primary G1 sarcomas, and 1.3 times (p < 0.05) higher than in women with primary G3 sarcomas. TNFa-R increased by 1.7 times (p < 0.05) in all men with recurrent sarcomas regardless of the tumor grade, compared with the levels in healthy men; however, in G1 it was 1.9 times (p < 0.05) higher than in men with primary G1 sarcomas, while in G3 it did not differ significantly from the levels in men with primary G3 sarcomas. TNFa-R in women increased only in recurrent G3 sarcomas by 2.5 times compared to healthy women. No differences were observed in TNFa-R levels between men and women with recurrent G3 sarcomas. Conclusions: An excess of TNFa-R in the blood is characteristic for the recurrent soft tissue sarcomas G1 in older men and G3 in older women. At the same time, high grade tumors in men are accompanied by an increase in TNFa-R in the blood in both primary and recurrent sarcomas.