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Siberian journal of oncology

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Vol 23, No 6 (2024)
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CLINICAL STUDIES

7-21 1120
Abstract

Introduction. According to global data, gastric cancer (GC) is the 5-th most common malignancy with a high cancer-related mortality rate. However, in recent decades, there has been a tendency towards an increase in the incidence of GC among young patients (18 to 40 years old), which currently amounts to 4.4–9.8%. Aim: to evaluate the effectiveness of surgical, combined and palliative treatment options in early-onset GC. Material and Methods. the study included 129 patients aged 18–45 years, who underwent radical, cytoreductive and palliative surgery with or without combination with drug therapy for localized, locally-advanced and primary disseminated GC. the patients were divided into three clinical groups: 1) the surgical group (n=27) included patients with only surgical treatment; 2) the group of combined treatment (n= 58) included patients with PCI <7 who underwent surgery with the volume of CC0 in combination with CT (neoadjuvant, adjuvant, perioperative, simultaneously with or without hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and patients who underwent only HIPEC; 3) the additional (palliative) group (n=44) included patients with PCI>7 who underwent systemic CT in combination with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Results. the median overall survival (OS) in three groups was 58, 30 and 13 months, respectively. In patients with IV stage of disease who underwent HIPEC with CC0 surgery, OS in the 2nd group was 17 in comparison with 13 months in the third group (PIPEC). Conclusion. Aggressive multimodal treatment in the absence of comorbid status in young patients will allow for intensification of both the perioperative drug therapy component and the implementation of extended multivisceral resections that facilitate radical surgical treatment to improve both DFS and OS.

22-31 994
Abstract

Background. Evidence for the safety of using the hypofractionation (HF) regimen after immediate breast reconstruction (IBR) in patients with breast cancer is not well documented. the purpose of the study was a retrospective analysis of surgical treatment with IBR and postoperative radiation therapy (RT) in conventional fractionated (CF) and hypofractionated (HF) regimens in breast cancer patients. Material and Methods. a retrospective analysis of treatment outcomes was carried out in 219 breast cancer patients who underwent mastectomy with IBR using permanent implant or tissue expander. all patients received postoperative RT: 97 received CF RT (22–25 fractions of 2 Gy) and 122 HF RT (15–16 fractions of 2.66–2.7 Gy). Cosmetic complications were represented by reconstructive failure (RF). all patients underwent an analysis of the incidence of reconstructive failures (RF) or capsular contracture (CC) (Baker III–IV). Results. CF RT was performed in 97 women: 55 – after IBR using tissue expander and 42 using permanent implant. the median follow-up time was 61 months. Complications were observed in 37 women (35.1 %): RF in 22 cases (22.7 %) and CC in 12 (12.4 %) cases. the median time to RF was 8 months, CC – 48.5 months. after RT to the tissue expander, CC rate was 0 %, RF – 25.5 %. after RT to the implants, CC was revealed in 28.6 %, RF in 19 % cases. In patients who received HF RT, cosmetic complications were detected in 51 (41.8 %) of 122 patients. the median follow-up time was 34 months. RF was revealed in 22.1 % cases, the median time was 9 months. CC was observed in 24 women (19.7 %) with the median time of 27 months. after HF RT to the expander, CC was observed in 4.9 %, RF in 39 % of cases. After RT to the implant, CC was detected in 27.2 %, RF in 13.6 % of cases. no significant differences in the risk of complication between patients who received conventional or hypofractionated RT were found (р=0.19). after RT to the expander, no differences (р=0.18 and р=0.12). After RT to the implant, there were also no differences in the frequency of CC and RF (р=0.52 and р=0.42). Conclusion. There were no significant differences in the frequency of cosmetic complications after postoperative radiotherapy in conventional fractionation or moderate hypofractionation regimens.

32-40 1099
Abstract

177Lu-PSMA-617 is a new therapy option for PSMA-positive metastatic castrate-resistant metastatic prostate cancer (mCRPC) with proven efficacy. 225Ac-PCMA-617 is an alpha emitter, making this drug potentially more powerful. Despite the active use of 225Ac-PSMA-617 worldwide, no randomized phase III studies have yet been conducted. The present prospective cohort study presents the experience of 225Ac-PSMA-617 use in the A.F. Tsyb MRRC. Material and Methods. the study included mCRPC patients with prostate-specific membrane antigen (PSMA) overexpression confirmed by PET-CT or SPECT-CT, who received the first course of therapy in 2023. Results. Forty three patients received 1 to 6 (median 2) administrations of 225Ac-PSMA-617, 26 (60 %) of these patients had a history of 177Lu-PSMA-617 therapy, 13 (30 %) had a history of radium chloride [223Ra] therapy, and 10 (23 %) patients had no history of chemotherapy. Five (12 %) had liver metastases at the time of inclusion in the study. PSA reduction of more than 50 % was recorded in 55 % of patients, with biochemical response significantly more frequent in the PSMA-naïve group, 63 % vs 35 %; the number of adverse events was also lower in this group. But no advantage in overall survival (OS) in PSMA-naïve patients was revealed at the present time. Favorable prognosis factors included a history of radium chloride [223Ra] therapy; in contrast, liver metastasis was a negative prognostic factor. the study found no differences in OS among taxane-naïve patients and patients with a history of 1–2 lines of chemotherapy. Continued therapy with androgen receptor targeted agents after initiation of 225Ac-PSMA-617 treatment also showed no effect on OS. Conclusions. 225Ac-PCMA-617 may be effective in 177Lu-PCMa resistance, but there are no data on the increase in overall patient survival when 225Ac-PCMA-617 is administered as first-line radioligand therapy.

41-50 878
Abstract

Several studies have shown that the increased expression of delta–like noncanonical Notch ligand 1 (DLK-1) is associated with more aggressive tumor characteristics in patients with glioblastoma. The aim of the study was to estimate the diagnostic and prognostic values of DLK-1 serum levels in glioblastoma patients. Material and Methods. The study included 39 patients with newly diagnosed glioblastoma. The DLK-1 level was evaluated in paired serum and cerebrospinal fluid samples in glioblastoma patients before starting chemoradiotherapy (CRT). All patients with glioblastoma received combined modality treatment. The DLK-1 level in blood serum was additionally assessed during follow-up visits. Results. The median levels of DLK-1 in paired CSF and serum samples before CRT were 1.17 ng/ml (95 % CI 0.78; 2.89) and 0.27 ng/ml (95 % CI 0.26; 0.29), respectively (p=0.006). The assessment of the DLK-1 serum level in glioblastoma patients didn’t show any significant differences related to the response to therapy. In patients with tumor progression after CRT, the median serum DLK-1 level before CRT was 0.43 ng/ml, and in patients with stable disease, the median serum level was 1.7 ng/ml (p=0.012). The DLK-1 serum levels were 1.60 ng/ml and 0.32 ng/ml in patients with favorable prognosis for progression–free survival and in patients with unfavorable prognosis, respectively (p=0.005). The median concentrations of DLK-1 in serum before starting CRT were 1.01 ng/ml and 0.32 ng/ml in patients with favorable prognosis of overall survival and in patients with unfavorable prognosis, respectively (p=0.04). The DLK-1 levels in 4 weeks after CRT were 1.53 ng/ml and 0.23 ng/ml in patients with favorable prognosis of overall survival and in patients with the unfavorable prognosis, respectively (p=0.04). Conclusion. The DLK-1 serum level in patients with glioblastoma cannot be used to diagnose disease progression. However, this marker is a prognostic factor for overall and progression-free survival, and allows identification of patients with favorable and unfavorable prognosis.

51-61 947
Abstract

Objective: to evaluate and compare the qualitative and quantitative composition of the intestinal microbiota in patients with malignant neoplasms of various localizations. Material and Methods. The study included patients who received different types of treatment in N.N. Blokhin Oncology Research Center, Moscow, Russia in 2023 for gastric cancer, including cardioesophageal adenocarcinoma (group 1), esophageal squamous cell carcinoma (group 2) and metastatic or locally advanced melanoma of the skin (group 3). All patients had to have morphologic verification of the diagnosis at the time of inclusion, be over 18 years old, have an ECOG performance status of ≤1, and have no evidence of intestinal infection, as well as not take antibiotics within 28 days prior to entry into the study. Stool samples were collected during patients’ hospitalization. The quantitative and qualitative composition of microorganisms of 17 taxonomic groups was evaluated. Microorganisms were cultured according to standard microbiological methods, taking into account the growth conditions of a particular group of microorganisms. Species identification of microbial isolates was obtained by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF) and MALDI Biotyper v.3.0 software (Bruker daltonics, Germany). Descriptive statistics methods from the SPSS Statistics, v.27 software package were used. To quantitatively describe the species diversity of the gut microbiota, calculations were performed using the Margalef species richness index (d) and Shannon’s (H) diversity index. The criterion of uniformity of microbial species distribution according to their abundance in the population community was evaluated using the Pielow index (E). The Hutcheson’s T-criterion was used to test the significance of differences between sample sets of Shannon index values and to obtain statistically correct estimates of differences (p≤0.05). Results. A total of 63 samples of biological material (feces) were investigated. A change in the quantitative composition of intestinal microbiota in all study groups was found, which may have a negative impact on the general condition of the patient and the effectiveness of antitumor treatment. The increase in the proportion of Proteobacteria (Enterobacterales) can be considered as a risk factor for the development of infectious complications caused by Gram-negative microorganisms. The analysis of factors influencing the taxonomic diversity of intestinal microbiota revealed no significant differences in the composition of intestinal microbiota between the groups of patients with malignant tumors of different nosological forms (p>0.05). 

LABORATORY AND EXPERIMENTAL STUDIES

62-69 917
Abstract

Introduction. In the development of new methods of radiotherapy, studies of the biological effects of sparsely (photons, electrons) and densely (protons, ions) ionizing radiation are relevant. Reproducibility is a challenge in preclinical studies. Dosimetric phantoms of laboratory animals are an effective tool for dose assessment, facilitating standardization of tests conducted under different conditions. existing phantoms often fail to address radiobiological issues like placing of biological samples or dosimetry detectors. A method for manufacturing dosimetric phantoms must be developed to accurately manufacturing products and modify their design in accordance with the task. Aim. This study develops a numerical model to simulate the interaction of photon, electron and proton therapeutic beams with 3D-printed PLA plastic samples and to determine the optimal 3D printing parameters for imitating soft tissues. Material and Methods. Fused filament fabrication proposed as effective means of creating such devices, given that the majority of polymers exhibit properties closely aligned with those of biological tissues, are employed in the manufacture of standard phantoms. A major advantage of 3D printing is the ability to make items with different specifications. Numerical simulation was employed to investigate the interaction of PLA plastic with an ionizing radiation used in radiotherapy. Results. the calculated depth dose distributions of different types of radiation in soft tissues and PLA plastic of varying densities were obtained. It was demonstrated that for adipose imitation using photons and electrons, it is necessary to utilise PLA plastic 3D-printed samples with a density of 0.91 g/cm³ (fill factor of 75 %); for muscle – 1.06 g/ cm³ (fill factor of 88 %). For proton and carbon ion, the density of PLA plastic samples for adipose imitation was determined to be 0.97 g/cm³ (fill factor of 80 %); for muscle – 1.11 g/cm³ (fill factor of 93 %). Conclusion. The study demonstrates that the interaction of PLA plastic with rarely and densely ionizing radiation may be differed. This is a crucial consideration when planning experiments using solid-state dosimetric phantoms.

70-80 949
Abstract

The purpose of this study was to establish a model of uterine carcinoma in female laboratory rats by transplanting Guerin carcinoma directly into the uterine horn. Material and Methods. Fifteen nonlinear white laboratory rats weighing 250 ± 25 g served as the subjects of surgical intervention. all operative interventions were performed under xylazine-zoletil anesthesia. Female white laboratory rats were laparotomized under aseptic conditions using anesthesia. the incision length was 2 cm, and a tumor suspension containing 2.5-3.5×106 cells was injected into the lumen of the right uterine horn using an intravenous catheter with a 22G injection port (0.9 × 25 mm). tumor cells were counted using the ADAMIILS cell analyzer (Nano Entek, Korea). the tumor progression was monitored for 21 days. after euthanizing the animals under ether anesthesia, median longitudinal histological sections, 5–7 μm thick, were made from the tumor node and stained with hematoxylin-eosin and Van-Gizon using standard techniques. Results. Following the transplantation of Guerin’s carcinoma cell suspension, a tumor node of approximately 25 mm in diameter was identified macroscopically in the region of the inferior aspect of the right uterine horn. additionally, the presence of haemorrhagic effusion was documented in the abdominal cavity and tumor screenings. at light microscopy, areas of neutrophilic infiltration, significant narrowing of the lumen of the uterine horn with signs of involution, and prismatic epithelium of papillary structures were observed. the tumor cell features characteristic of Guerin’s carcinoma are preserved in the tumor node induced in the uterus, with a cytoplasmic-nuclear ratio that remains close to 1:1. the shapes of the nuclei vary, but the irregular ovoid shape remains dominant, and pathological mitotic figures are observed. the tumor stroma includes cytoplasmic branched connections connecting the tumor conglomeration. Conclusion. therefore, according to the morphological description, the presented experimental model demonstrates the possibility of intrauterine growth of Guerin’s carcinoma in animals and is most similar to the localization of the tumor focus in patients with gynecological cancer.

81-88 879
Abstract

Introduction. Ovarian cancer is one of the most common gynecological cancers worldwide, which is difficult to diagnose and treat. the high mortality rate from ovarian cancer makes the development of new therapeutic drugs relevant. Ribavirin (RBV), commonly used antiviral agent, revealed the anticancer potential, however, it led to the development of severe side effects as well. RBV derivatives were previously synthesized and tested as putative anticancer drugs in the models of hematological malignancies. The aim of this study was to estimate the anticancer effects of and RBV derivatives (MGs) in ovarian cancer cells in vitro. Material and Methods. Cytotoxic and cytostatic effects of the MGs on ovarian cancer cells (OVCAR3 and OVCAR4) were assessed using the MTT assay and cell counting with trypan blue staining. distribution of cell cycle phases and induction of apoptosis was evaluated using flow cytometry with propidium iodide and annexin V-FITC staining. Results. 1,2,4-triazole-3-carboxamides inhibited the proliferation and induced cell cycle arrest of ovarian cancer cells in vitro. Conclusion. these results provide the rationale for further studies of 1,2,4-triazole-3-carboxamides as anticancer drugs.

89-96 1004
Abstract

Introduction. Low-temperature plasma is currently used in medicine, including cancer therapy. Plasma-activated biological solutions have already been proposed as potential reagents for cancer treatment. However, the biological effects in cells induced by exposure to cold plasma still remain unexplored. Investigation of the molecular mechanisms of the effects of cold plasma on cells is of great clinical importance for its clinical application. the aim of the present study was to evaluate the effect of cold plasma exposure on apoptosis, catalase activity, and malonic dialdehyde content in MCF-7 breast cancer cell cultures compared to 3T3 normal fibroblast cells. Material and Methods. MCF-7 mammary epithelial cells were used as research objects, and NIH/3T3 mouse embryonic fibroblast cells were used as controls. Cell suspensions were treated using low-temperature atmospheric discharge plasma with escaping electrons. Annexin V and propidium iodide were used to quantify cell line apoptosis. The content of malonic dialdehyde was determined by the developing coloration of its solution with 2-thiobarbituric acid at high temperature in acidic medium. The activity of catalase was estimated by the rate of decomposition of hydrogen peroxide for a certain time of incubation of the mixture. Results. It was found that irradiation of MCF-7 cell culture with plasma led to an increase in the content of malondialdehyde, the main product of lipid peroxidation. the increase in this parameter is an indicator of cell membrane damage and oxidative stress induced by irradiation. In addition, under the same irradiation regime, cold plasma showed a stimulating effect on the culture of 3T3 cells, while on the MCF-7 culture, on the contrary, it stimulated the activation of apoptosis and cell death. Conclusion. In the present study, we found that exposure of tumor and normal cells to cold plasma promotes apoptosis activation. Catalase and MDA activity have been shown to be significant markers capable of assessing the intensity of oxidative stress. 

97-106 850
Abstract

The study objective. This paper reviews the express of C/D box snoRNAs (small nucleolar RNAs) and possibility of their use as biomarkers of radioresistance in chromosomal abnormalities. Material and Methods. The study compared the values of log2FC express of snoRNA C/Dbox in radiosensitive (HL-60) and radioresistant (K562) cell lines with different levels of chromosomal abnormalities. The cells were irradiated with X-ray radiation once at a dose of 4 Gy. The expression of snoRNA C/D was evaluated 1, 4 and 24 hours after irradiation, using new generation sequencing (NGS) MiSeq. Results. Different log2FC values were obtained in HL-60 and K562 cell lines 1 hour, 4 and 24 hours after irradiation. Positive expression of C/D snoRNA prevails in HL-60 throughout the experiment. In K562, the predominance of positive values of C/D snoRNA expression was observed 4 hours after irradiation, and negative values of log2FC were observed 24 hours later. the more anomalies there were in the chromosome, the greater the difference in expression we observed. at the same time, the number of C/D snoRNA changed maximally 24 hours after irradiation in the studied cell lines. We noted a greater number of C/D snoRNAs in the HL-60 cell line, and only 3 expressed C/D snoRNAs in the 15th marker chromosome in K562 out of 16 in HL-60 in the same chromosome. Conclusion. Our study showed a low informative value of using C/D snoRNAs family as markers of radiosensitivity in the presence of chromosomal abnormalities in cancer cells.

ONCOLOGY PRACTICE

107-117 999
Abstract

Background. Hyperglycemia (HG) is an on-target effect of ALP, and prophylactic with metformin was shown to decrease the rate and severity of HG. Here we present efficacy and safety of ALP in a large cohort of patients with rational approach to metformin usage based on risk factors of HG. Material and Methods. Patients (pts) with HR+/HeR2- PIK3CAmut ABC were treated with ALP 300 mg orally and FUL 500 mg IM until disease progression or intolerance. the primary endpoints were progression free survival (PFS) and rate of grade 3/4 HG in different risk groups. Pts were stratified to risk groups of HG based on the algorithm before starting ALP and received MET for prevention of HG. Results. a cohort comprised 139 pts. the median PFs (mPFS) on ALP – was 7.0 (CI 95 %: 5.0–8.9). the risk of HG was assessed in 138 pts: low (47), moderate (46), and high (42) risk, and 3 pts with type 2 diabetes mellitus. any grade HG was reported in 62 % pts, no cases HG G4 were detected. HG G3 was reported in 13 % pts; 10 % pts required ALP dose reduction to 250 mg due to HG G3; 3 pts (2 %) discontinued ALP due to HG. the mPFS in our analysis was longer than in BYlieve trial in cohort C: 7.0 vs 5.6 mo. We suggest that prophylactic of HG allowed maintenance of full dose of ALP in most patients and thus increased the efficacy of ALP. Furthermore, in contrast to the METALLICA trial we distinguished a low risk group (33 %) of pts who do not need the prophylactic use of MET. Conclusion. Rational use of MET in pts with moderate and high risk of HG reduces the frequency and severity of HG, decreases the rate of ALP dose reductions and as a result may increase the efficacy of ALP. Pts with low risk of HG don’t need MET for HG prevention.

118-128 961
Abstract

Background. The main goal of treating patients with recurrent ovarian cancer is to prolong life and improve its quality. Approaches to the treatment of recurrent ovarian cancer have changed over the past decade. The choice of antitumor drug therapy is determined by the duration of platinum-free interval and the use of targeted therapy with bevacizumab or olaparib. Treatment regimens for relapses are not unified and treatment outcomes are contradictory. Aim: to analyze treatment outcomes of different chemotherapy regimens in patients with the first recurrence of ovarian cancer, depending on the duration of platinum-free interval. Material and Methods. A retrospective analysis of the first recurrence of ovarian cancer in 446 patients treated at the Primorsky Regional Oncology Center in the period 2004–2021 was carried out. All patients were divided into two groups depending on the treatment option for relapse: repeated cytoreduction followed by chemotherapy or only second-line chemotherapy, and into four groups depending on the chemotherapy regimens: 1 – platinum and taxane agents; 2 – platinum and taxane agents with bevacizumab; 3 – platinum agents and non-taxane agents with bevacizumab; 4 – monotherapy with non-platinum agents with bevacizumab. Results. Significant advantages in progression-free survival after second-line chemotherapy (PFS-2) were observed in patients with platinum-resistant relapse after the 4th chemotherapy regimen. Patients with platinum-sensitive relapse had the best treatment outcomes after the 3rd chemotherapy regimen and repeated cytoreduction followed by chemotherapy with a platinum-free interval of 6–12 months and 12–24 months with any platinum-containing chemotherapy regimen. In the platinum-free interval of more than 24 months, significant benefits were observed with a combination of platinum and taxane agents + bevacizumab. In the group of patients without surgery, there were significant benefits in all three intervals when prescribing a combination of platinum and non-oxane agents ± bevacizumab. There was a tendency to increase PFS-2 in patients with low-grade serous ovarian carcinoma compared with patients with high-grade serous carcinoma. The best rates of relapse-free survival were noted with maintenance therapy with olaparib. Conclusion. In patients with localized recurrence of ovarian cancer and a platinum-free interval of more than 6 months, it is advisable to perform repeated cytoreduction followed by chemotherapy, taking into account the duration of the platinum-free interval. The administration of PARP inhibitors in the maintenance therapy of platinum-sensitive recurrence of ovarian cancer improves treatment results.

129-137 885
Abstract

Background. Treatment of patients with locally advanced pelvic cancer remains challenging. The use of modern surgical techniques has expanded the feasibilities of performing multivisceral resections (MVR) in this category of patients. However, the postoperative period in patients who have undergone MVR is associated with a high risk of developing postoperative complications. The purpose of the study was to assess the short-term and long-term treatment outcomes in patients with locally advanced and multiple-primary pelvic cancer. Material and Methods. From 2009 to 2021, 114 patients treated in the clinics of Cancer Research Institute of Tomsk National Research Medical Center underwent MVR for primary or recurrent rectal cancer (n=40, 35.1 % and n=4, 3.5 %, respectively), female reproductive cancer (endometrial cancer: n=18, 17.1 % and recurrent ovarian cancer: n=18, 17.1 %), primary and recurrent bladder cancer (n=15, 13.2 % and n=2, 1.8 %, respectively), synchronous multiple primary pelvic tumors (n=8, 7.0 %) and extraorgan mesenchymal tumors of the pelvis (n=4, 3.5 %). Paraneoplastic complications were observed in 31 (27.2 %) patients. Invasion to more than 2 adjacent pelvic organs was diagnosed in 52 (45.4 %) cases. Total pelvic evisceration (TPE) was performed in 9 (7.9 %) patients, including 5 (4.4 %) patients who underwent TPE for primary rectal cancer with extensive local spread and 4 (3.5 %) patients who underwent TPE for multiple primary cancer: 2 (1.75 %) for synchronous primary rectal cancer and bladder cancer and 2 (1.75 %) for primary rectal cancer and recurrent bladder cancer. MVR for rectal cancer was the most common (n=101, 88.6 %). Resections with the formation of colorectal anastomosis were performed in 75 (65.8 %) cases and obstructive resections of the rectum were performed in 14 (12.5 %) cases. Urinary tract surgeries were performed in 66 (57.5 %) cases. One-stage plastic surgery of the resected segment as a transposition of one or both ureters into the bottom of the bladder was performed in 22 (19.3 %) cases. Heterotopic and orthotopic plastic surgery of the bladder was performed in 19 (16.6 %) and 5 (4.4 %) cases, respectively. Combined uterine extirpations, including vaginal resection, were performed in 52 (45.4 %) cases. Grade III postoperative complications according to the Clavien–Dindo classification occurred in 18.4 % of cases. Urological complications were the most common (8.7 %). Postoperative mortality rate was 0.8 %. The assessment of the long-term outcomes was carried out using the example of patients with rectal cancer (n=45), as the most homogeneous and largest subgroup. The overall 3-year survival rate was 71.1 % and the relapse-free 3-year survival rate was 60.0 %. Conclusion. Treatment of locally advanced pelvic cancer requires extensive surgeries performed by a multidisciplinary team of surgeons. The immediate results can be assessed as satisfactory. In case of resection of the urinary tract as a component of MVR, regardless of the primary localization of the tumor, primary plastic surgery of the bladder and/or ureters is preferable. Long-term outcomes allow us to consider MVR as a method of choice in the treatment of this group of patients.

REVIEWS

138-148 937
Abstract

Background. Anaplastic thyroid cancer is a rare but aggressive disease with an extremely low survival rate. Improved diagnostic and therapeutic options have enabled the development of a multidisciplinary approach (surgery + radiation therapy + systemic antitumor therapy options) that has improved overall survival, highlighting the importance of a multidisciplinary approach. However, despite the widespread use of chemotherapy, targeted therapy and immunotherapy, patient outcomes remain disappointing. Objective. To analyze literature data on approaches to systemic therapy for anaplastic thyroid cancer, highlight the key disadvantages of existing treatment methods and identify promising areas of research in this area. Material and Methods. The literature search for the review was performed using the following databases: Web of Science, Scopus, Medline, the Cochrane library, and RSCI. During the literature search, 395 sources were analyzed, 59 scientific publications were selected. the review included studies covering the period from 1985 to 2024. Results. This review analyzes the current state of systemic therapy for anaplastic thyroid cancer. Chemotherapy remains one of the main methods of treatment, but its effectiveness is limited, and toxicity limits its use in weakened patients. lack of sensitivity in patients with a target mutation and acquired resistance limit the effectiveness of targeted therapy, and insufficient efficiency and the need for waiting time for the effect to be realized limit the benefits of immunotherapy. Based on the results obtained, the most optimal treatment modality appears to be combination therapy (targeted therapy + immunotherapy). Conclusion. Despite advances in therapy modalities, prognosis for patients remains unfavorable. Further research is necessary to develop more effective and safe treatments. Particular attention should be paid to the study of the molecular mechanisms of the development of anaplastic thyroid cancer and resistance to systemic therapy, the search for new targets for targeted therapy and the improvement of approaches combined with immunotherapy.

149-158 2103
Abstract

Objective: to summarize the available data on clinical trials of vaccines based on mRNA encoding neoantigens. Material and Methods. Data were searched on https://classic.clinicaltrials.gov and https://pubmed.ncbi.nlm.nih.gov/, from January 2013 to May 2024 using the keywords “neoantigen” and “vaccine”, and the information on mRNA-based drugs was then selected. Of the 148 studies retrieved, 54 were selected to write a systematic review. Results. A bibliometric analysis of data in the field of therapeutic cancer vaccines from 2013 to 2024 showed that the majority of studies focused on mRNA vaccines encoding neoantigens. this paper presents a brief description of the mRNA platform and provides an overview of clinical trials of anticancer mRNA vaccines from 2013 to 2024. Preparations of leading biotech firms in Europe and the USA involved in the development of anticancer mRNA vaccines, such as Cevumeran (BioNTech), mRNA-4157/V940 (Moderna), as well as vaccines from companies in the PRC - Stemirna Therapeutics, NeoCura, Hangzhou Neoantigen Therapeutics, etc. - are reviewed. Conclusion. The use of vaccine technology based on mRNAs encoding tumor neoantigens can significantly increase the potential of antitumor immunotherapy.

159-167 952
Abstract

Purpose of the study: to assess the problem of psychological assistance to cancer patients and ways to resolve this problem. Material and Methods. The search for relevant sources was carried out in Scopus, Web of Science, PubMed, elibrary, including publications from February 2005 to December 2023. Of the 534 scientific articles found, 53 were used to write the systematic review. Results. Cancer patients are characterized by a high incidence of anxiety, depressive disorders and suicidal thoughts. Research in recent decades has shown that although more than a third of cancer patients experience stress and more than half experience depression and anxiety due to a cancer diagnosis, many do not seek psychological help to address their problems. Stress leads to an increased risk of comorbid psychological disorders and suboptimal compliance with anticancer therapy, potentially leading to decreased health and chance of recovery. In addition, psychological well-being is a necessary component for the recovery of the patient’s body after therapy, especially with a favorable prognosis. Research has shown that relatives caring for terminal cancer patients also need psychological help. active use of the work of a psychologist in the treatment of cancer patients will improve treatment results, improve the quality of care provided and comply with the principles of personalized medicine. to optimize the provision of psychological assistance, it is necessary to take measures to expand and make it accessible, for which the optimal methods are to regulate it in the treatment plan for cancer patients. Conclusion. In the current healthcare system, it is necessary to widely introduce consultations with psychologists in the treatment of cancer patients, which will increase the effectiveness of therapy and patient survival. the task of the oncologist is to identify patients with psychological disorders, especially those prone to suicidal behavior, anxiety and depression, and to correctly explain to them the need to receive psychological help, thanks to which the patient will not only be able to get rid of his emotional problems, but will also make sure that he needs to continue the treatment prescribed by the doctor.

CASE REPORTS

168-175 908
Abstract

Background. Currently, low-dose computed tomography (LDCT) is the only screening test that reduces the risk of death from lung cancer. However, there are a number of disadvantages, such as lack of widespread use, high cost, high false-positive rate and the need to conduct studies only in high-risk groups, which significantly limit mass screening. exhaled breath analysis, which uses sensitive breath sensors, is a promising method to improve early diagnosis of lung cancer. Cancer Research Institute of Tomsk National Research Medical Center together with Tomsk State University and Tomsk Polytechnic Research Institute has developed a gas analysis complex capable of analyzing the gas composition of exhaled air with remote sampling from bags. during the study, data obtained by digitizing signals from gas analysis system sensors and patient metadata are recorded in a database for subsequent automated processing and analysis using a neural network. Case description. A 48-year-old female patient with a long history of smoking came to the clinic of the Cancer Research Institute for consultation with suspected pathological infiltration around the celiac trunk detected by abdominal CT. As a clinical trial of the developed gas analytical complex for cancer detection, a sample of exhaled air was taken, and the comparison of the composition of volatile organic compounds (VOCs) with that in the control group (healthy individuals) revealed abnormalities characteristic of lung cancer. the patient underwent a chest CT scan, which revealed stage IIB peripheral cancer of the lower lobe of the left lung. the original sensor gas analysis complex, which has no analogues in Russia, was used for the first time in the detection of lung cancer. the data obtained allowed us to suspect the presence of lung tumor in the patient and perform radical surgical treatment. the composition of VOCs in exhaled air was assessed on day 10 after surgery, and no significant changes in the composition of exhaled air were observed. Conclusion. Machine learning algorithms are actively used to diagnose socially significant diseases. the platforms being developed based on arrays of chemical sensors with data analysis using a neural network are promising candidates for implementation in screening activities.

176-184 945
Abstract

Background. Lung cancer is one of the most common cancers worldwide. Most cases of newly diagnosed lung cancer are associated with distant metastasis. High incidence and mortality rates as well as high rates of recurrence in patients with stage I–III non-small cell lung cancer (NSCLC), even after radical surgical treatment, determine the relevance of developing new approaches to drug therapy. The aim of the study was to demonstrate a successful clinical case showing a long-term, more than 8-year overall and relapse-free survival in a patient with metastatic NSCLC treated with an immune checkpoint inhibitor. Case presentation. An 80-year-old patient with stage IB lung adenocarcinoma underwent radical surgery in august 2014. A follow-up examination in April 2016 revealed disease progression (liver metastases and mediastinal lymph node metastases, and solitary metastasis to the chest wall on the right). Taking into account the absence of driver mutations, 102 cycles of durvalumab monotherapy were administered as a phase III multicenter open randomized trial. At a follow-up period of 96 months, no signs of disease progression and treatment-related serious adverse events were observed. Conclusion. Drug therapy of metastatic NSCLC remains challenging and should take into account the clinical, molecular, genetic, and immunohistochemical characteristics of the tumor. Further in-depth studies of new approaches and treatment options for NSCLC patients are required.



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ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)