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Siberian journal of oncology

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Vol 22, No 4 (2023)
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CLINICAL STUDIES

5-13 512
Abstract

Objective: The present study aimed to analyze the treatment outcomes and develop a predictive model of surgical treatment for gastric cancer, taking into account the comorbidity of patients.
Material and Methods. The treatment outcomes were studied in 477 (100 %) gastric cancer patients. Patients were stratifed into two groups according to the Age-Adjusted Charlson Comorbidity Index (ACCI) (0–4 points – 311 (65,2 %), more than 4 points – 166 (34,8 %) patients). Two hundred and seventy six patients (57.9 %) underwent distal or total gastrectomy, 178 (37.3 %) total gastrectomy, 19 (4 %) minimally invasive gastrectomy, and 4 (0.8 %) patients underwent extirpation of the gastric stump. The construction of models for the prognosis of surgical treatment was carried out using binary logistic regression, the comparison of models – by analyzing error curves (ROC-analysis).
Results. The incidence rate of postoperative complications (grade III-V) according to the Clavien-Dindo classifcation was signifcantly higher in group 2 (9.9 %, 47/477) compared to group 1 (2.1 %, 10/477) (χ2 =64.79, p<0.001; OR 11.9 [5.82–24.3]). Postoperative mortality rate was 0.2 % (1/477) in group 1 and 1.9 % (9/477) in group 2 (χ2 =13.7, p<0.001; OR 17.8 [2.23–142]). In a comparative analysis, the prognostic model, taking into account the ACCI of the patient, allowed prediction of the development of postoperative grade III–V complications according to the Clavien-Dindo with the greatest accuracy. The area under the curve (AUC) was 0.921 ± 0.01 (95 % CI: 0,96–0,998), sensitivity – 71.9 %, specifcity – 99.8 %, diagnostic accuracy – 96.4 %.
Conclusion. The inclusion of comorbidity in gastric cancer patients in the predictive concept makes it possible to improve the accuracy of prediction of postoperative complications of III–V grade according to Clavien-Dindo.

14-21 648
Abstract

Introduction. Sporadic cases of squamous cell carcinoma of the rectum (rSCC) do not allow a comparative characterization of tumor aggressiveness and its response to chemoradiotherapy in relation to more common squamous cell entities, in particular, anal squamous cell carcinoma (aSCC).
Objective: comparative evaluation of the short- and long-term results of chemoradiation therapy in patients with rSCC and aSCC.
Material and Methods. In this retrospective study we included patients with nonmetastatic squamous cell carcinoma of the rectum (rSCC) and anal canal squamous cell carcinoma (aSCC) who received chemoradiotherapy and compared them in a 1:1 ratio using propensity-score matching. The dynamics of tumor response to treatment were compared by Kaplan-Meier survival analysis (OS and RFS) followed by Log-Rank verifcation, rate of complete response after 6 months.
Results. A total of 15 pairs of matched patients were evaluated. Patients in both groups had reliably similar sex, age, histological grade, initial primary tumor size, differing only in tumor histological subtype. In the aSCC group, 60 % of patients had metastases to pelvic lymph nodes, while in the rSCC group metastases had 46.67 % (p=1). The median follow-up was 44 months. The 3-year OS in the aSCC group of patients was 76.9 %, and 71.4 % in the rSCC group (p=0.567). The 3-year DFS in the aSCC group was 66.7 %, and in the rSCC group 34.7 % (p=0.406). The rate of achieving complete clinical response to CRT after 6 months was 86.7 % for the aSCC group and only 46.7 % for the rSCC group (p=0.05). Organ-saving treatment was achieved in 93.3 % of aSCC patients and 73.3 % of rSCC patients (p=0.33).
Conclusion. Overall and recurrence-free survival rates were not signifcantly decreased for rSCC patients relative to aSCC patients. This indicates a similar course and prognosis in the two diseases, but rSCC is characterized by a signifcantly lower rate of complete response to treatment.

22-33 1285
Abstract

Introduction. The current standard of care is concurrent radiation therapy (RT) and chemotherapy with mitomycin or cisplatin in combination with fuoropyrimidine drugs. One possible option for effective chemotherapy regimens with a lower toxicity is the combination of oxaliplatin and capecitabine with RT.
The purpose of the study: a retrospective evaluation of the results of combined treatment of 74 patients with squamous cell carcinoma of the anus (SCCA) with the use of oxaliplatin and capecitabine.
Material and Methods. The study included 74 patients (men – 12.2 %, women – 87.8 %) with stage I–III SCCA. All patients underwent megavolt photon RT (2×25), a cumulative dose of 50 Gy and a boost of 10 Gy to the anal canal. From days 1 to 14 and from days 22 to 36 of RT, capecitabine was administered orally at a dose of 825 mg/m2  twice a day in combination with intravenous administration of oxaliplatin 50 mg/m2  on days 1, 8, 22, and 29 of RT. If a residual tumor 6 months after completion of chemoradiotherapy was found, patients underwent surgery.
Results. All 74 patients underwent RT with a cumulative dose of 60 Gy. Chemotherapy, according to the protocol, was completed in 58 (78.4 %) patients. Grade 3-4 toxicity was noted in 11 (14.9 %) patients. In 64 patients (86.5 %), a complete clinical response was registered. At least one late radiation side effects according to the RTOG (LENT SOMA) scale was noted in 48 (98.0 %) patients, including grade 3-4 complications in 12 (24.5 %) patients. With a median follow-up of 40 months (3-82) cumulative three-year local recurrence rate, overall and relapse-free survival were 15.3 ± 4.5 %, 73.7 ± 5.7 % and 53.5 ± 6.4 %, respectively.
Conclusion. Combined treatment of SCCA, based on the combination of RT with chemotherapy with oxaliplatin and capecitabine, is feasible and has acceptable acute toxicity. Additional clinical studies are needed using this chemotherapy regimen in combination with modern RT techniques.

34-43 628
Abstract

The objective of the study is to compare the effectiveness of various systemic therapies in the 3rd and subsequent lines of therapy of metastatic colon cancer.
Material and Methods. Retrospective multicenter study collected data from 2 clinics of the Russian Federation. We considered overall survival (OS) as the main criterion of effectiveness. Progression-free survival (PFS) was the additional criterion. We performed a single- and multifactorial analysis of the effect of various parameters on PFS. To evaluate the effectiveness of regorafenib and the reintroduction of previously effective drugs, we should prove the equivalence of reintroduction of the 3rd line chemotherapy (CT) and targeted therapy to regorafenib on the 6-month overall survival, provided that the equivalence boundaries would be between 0.8 and 1.25. To reach the 0.05 probability of type I error and the 80 % study power, 178 patients (89 in each group) should be included in the study.
Results. The database identifed 215 patients with morphologically confrmed metastatic colon cancer who received two or more lines of antitumor drug therapy from 2010 to 2021. We selected 132 patients with the history of regorafenib therapy and 83 patients with the reintroduction of a previously used chemotherapy regimen as 3rd line treatment. The median OS in the reintroduction and regorafenib groups did not differ (HR, 1.01; 95 % CI, 0.7–1.45; p=0.920); 6-month OS were 74 and 70 %, respectively. Progression-free survival was signifcantly higher in the reintroduction group (HR, 1.94; 95 % CI, 1.3–2.7; p<0.001). Multivariate analysis showed that the reintroduction of previous treatment regimens kept its independent positive effect on PFS (HR, 1.9; 95 % CI, 1.3–2.8; p<0.001). In our study, toxicity on the 3rd line of CT developed in 117 (54.4 %) of 215 patients and signifcantly more frequent in the regorafenib group: 67.4 % (89/132) vs 33.7 % (28/83) in the group with repeated administration of previously effective regimens (p<0.001).
Conclusion. Regorafenib and reintroduction of the previous treatment in the 3rd line did not differ in overall survival. Progression-free survival was signifcantly higher in the reintroduction group as the 3rd line of treatment, with signifcantly lower toxicity. 

44-54 355
Abstract

Platinum is the main component of the most chemotherapy (CT) regimens, but their use may be limited because of nephrotoxicity. Kidney injury molecule 1 (KIM-1) is considered as an early marker of cisplatininduced acute kidney injury (AKI).
The aim of our study was to evaluate the changes in the burinary levels of KIM-1 (uKIM-1) in cancer patients receiving nephrotoxic CT throughout the entire course of the treatment.
Material and Methods. The level of uKIM-1 was determined by enzyme immunoassay in untreated 19 patients with solid malignancies before each CT cycle (regimens with cisplatin or oxaliplatin) and every next day after cytostatic drugs administration. uKIM-1 values were normalized to urinary creatinine concentration (uKIM-1). The kidneys function was assessed by the serum creatinine (sCr) and glomerular fltration rate (GFR) value.
Results. According to laboratory parameters, renal function in patients before treatment corresponded to normal ranges. During CT, an increase in sCr by more than 50 % (decrease in GFR to 68 ml/min/1.73 m2 ), which corresponded to stage I AKI (KDIGO) was revealed in one patient (5.3 %) only. uKIM-1 levels before CT were above the upper limit of normal range (3.4 ng/mguCr) in 3 patients (15.8 %; median 2.1 ng/mguCr); at the beginning of the 2nd cycle of CT they were increased in 9 patients (47.4 %; median 3.2 ng/mguCr; p=0.0025, Mann-Whitney test); at the beginning of the 3rd cycle of CT uKIM-1 levels were increased in 12 patients (63.2 %; median 4.9 ng/mguCr; p=0.00007). During CT with cisplatin the average level of uKIM-1 increased with each subsequent cycle, in most cases it increased already the day after the administration of cytostatic drugs. No increase in uKIM-1 levels was observed during treatment with oxaliplatin-based regimens. The achievement of the threshold uKIM-1 level of 6.0 ng/mguCr at the beginning of the next cycle of CT was signifcantly associated with a high risk of its further increase (RR=18.8; p=0.0051).
Conclusion. An increase in the level of uKIM-1 after cisplatin administration can be regarded as a marker of subclinical kidney damage. In the future, the increase in uKIM-1 level at the beginning of the cycle of CT may be a reason for enhanced preventive measures or the appointment of less nephrotoxic treatment regimens.

LABORATORY AND EXPERIMENTAL STUDIES

55-64 426
Abstract

The mechanism of the relationship between pretumor changes in the bronchial respiratory epithelium and the risk of progression of non-small cell lung cancer (NSCLC) remains unclear. It has been suggested that the relationship between reactive changes in the bronchial mucosa and NSCLC progression may be caused by the functional status of monocytic-macrophage cells as important participants in infammation, which determines both the risk of premalignant changes in the epithelium and malignant progression.
The purpose of the study was to investigate the phenotypic profle of peripheral blood monocytes and macrophages induced from monocytes in vitro depending on the state of respiratory epithelium in NSCLC patients.
Material and Methods. The study included 39 patients with newly diagnosed NSCLC. Based on the morphological examination of small bronchi taken at the distance of 3–5 cm from the tumor, patients were divided into the following groups depending on the type of pretumor changes: no pretumor changes (n=6), isolated basal cell hyperplasia (BCH) (n=13), combination of BCH and squamous metaplasia (SM) (n=3), combination of unchanged epithelium and focal BCH (n=17). The phenotypic features of peripheral blood monocytes and in vitro-induced macrophages were assessed before treatment using fow cytometry.
Results. The state of the respiratory epithelium in NSCLC patients prior to the start of anticancer treatment was associated with the phenotypic features of peripheral blood monocytes, but not with the profle of macrophages induced from them. Distortion of the response of induced macrophages to the polarizing stimuli was observed in NSCLC patients: the cultured cells responded to both M1 and M2 inducers (LPS and IL-4, respectively) with a phenotype shift to M2, while the CD206 marker expression varied depending on the presence and type of pretumor changes.
Conclusion. The phenotypic profle of peripheral blood monocytes was associated with the state of the respiratory epithelium in NSCLC patients before anti-tumor treatment, but not with the phenotypic features of induced macrophages.

65-73 395
Abstract

Targeted therapy and immunotherapy are considered promising novel therapies capable of increasing the effcacy of prostate cancer (PCa) treatment.
The purpose of the study was to obtain and characterize TRAMP-C2 subcutaneous and ascite-solid models of prostate cancer in C57Bl/6j mice to study specifc anti-tumor activity of the candidate molecules of targeted drugs and adjust immunotherapy strategies in an evidence-based manner.
Material and Methods. We used cultured TRAMP-C2 cells in subcutaneous and ascites mouse prostate cancer models. Histological and immunohistochemical methods were used to study the tumor tissues.
Results. The high in vivo growth ability of TRAMP-C2 cells was demonstrated in subcutaneous and intraperitoneal inoculation of C57Bl/6j mice. These tumors are characterized by a high reproducibility and level of PSMA expression. Histological study showed that subcutaneous and carcinomatous TRAMP-C2 tumor nodules had solid structure morphologically corresponding to low differentiated neoplasm, cytomorphological analysis of smears showed that peritoneal fuid containd a large number of rounded tumor cells, macrophages and erythrocytes.
Conclusion. The obtained subcutaneous and ascite-solid models of TRAMP-C2 can be useful for the development of new ways to effectively treat cancer, including targeted and immunotherapy, as well as for the experimental study of biotherapeutic effects using PSMA as a target, and photoinduced effects.

74-83 375
Abstract

Currently, cytostatic drugs are widely used not only in cancer treatment, but also in the treatment of autoimmune infammatory diseases. A favorable prognosis of the disease, ability to reproduce, young age and the absence of children serve as an incentive to decide on the need for childbearing. There is concern, that the mutagenic effects of chemotherapy in germ cells, the ability to induce epigenetic changes in them, may have phenotypic manifestations in offspring. Conception in the early stages after treatment (impact on mature and differentiating germ cells) has been proven to increase the risk of defective offspring. Data on the health of the offspring of patients conceived in the long term after treatment (impact on stem spermatogenic cells) are contradictory.
The aim of the study was to assess long-term toxic effects of cytostatic drugs in the male rat offspring copulated in terms corresponding to the effect on stem spermatogonial cells (SSCs).
Material and Methods. The experiments were carried out on autobred male Wistar rats (n=140), aged 2.5 months, 70 of which made up the group of intact animals. The effect of cytostatic drugs (etoposide, irinotecan, cisplatin, carboplatin, methotrexate, farmorubicin, and paclitaxel) injected 3 and 6 months before mating was assessed on the offspring of intact female and male rats.
Results. The male rat offspring treated with cytostatic drugs was found to be viable. Gross external developmental anomalies were detected in 2 cases. In several offspring, a slowdown in physical development, decrease in the rate of formation of sensory-motor refexes and learning ability were observed. The most toxic drugs were etoposide and paclitaxel.
Conclusion. The offspring of rats treated with cytostatic drugs in terms corresponding to the effect on the SSCs is at risk. The degree of severity of long-term effects varies signifcantly and depends on the type of the drugs used. A decrease in the ability to learn is the most frequently detected abnormalities in offspring. Judging by the timing of conception after cytostatic exposure, a signifcant increase in the period of time after the administration of the drug before mating is not always justifed.

ONCOLOGY PRACTICE

84-93 611
Abstract

Background. Depending on the stage or location of the tumor, kidney resection or nephrectomy is the gold standard of treatment for renal cell carcinoma Preservation of organ function is essential for patients with localized tumors, especially with one kidney, chronic kidney disease, proteinuria, or multiple/bilateral masses. An important goal of kidney resection is to preserve the functional activity of the organ; however, the surgery leads to its decrease because of the loss of vascularized nephrons and irreversible ischemic damage.
Description of the clinical case. A 24-year-old female was diagnosed with cT1bN0M0, Stage I right kidney cancer. An abdominal cavity and retroperitoneal MSCT with intravenous contrast showed a mass in the right kidney, extending into the renal sinus and causing pyelocalicoectasia. A laparoscopic resection of the right kidney was performed using the patented technique developed at the P.A. Herzen Moscow Oncology Research Institute and providing selective intra-arterial cold ischemia. This was prompted by the complex tumor anatomy, which indicated a prolonged kidney ischemia.
Conclusion. Cold arterial perfusion has several advantages. First, it quickly cools the renal parenchyma to 25 °C, enabling faster and more comfortable kidney resection and suturing. Second, it eliminates the reverse venous blood fow caused by the positive perfusion pressure in the collecting system. Third, it does not imply the additional objects (for example, ice or clamps) in the work area, therefore not affecting the intraoperative view. The literature suggests hypothermia as the method of choice in most diffcult cases (resection of a single kidney, a large-diameter tumor, a high R.E.N.A.L. index). 

94-100 314
Abstract

The purpose of the study was to assess the risk of developing local recurrence in patients with locally advanced breast cancer, taking into account unfavorable prognostic factors, and to determine the indications for adjuvant neutron therapy.
Material and Methods. The treatment outcomes in 155 patients with stage T2–4N0–3M0 locally advanced breast cancer were analyzed. The patients received adjuvant radiation therapy delivered to soft tissues of the anterior chest wall (the area of the postoperative scar). The study group (n=89) received neutron therapy, and the control group received photon therapy. The main clinical and morphological prognostic factors: age, menstrual function, size of the primary tumor, invasion of the lymphatic vessels, tumor invasion into the dermis, multicentric tumor growth, tumor grade, presence of absence of edematous-infltrative form of the tumor, receptor status (RP, RE, Her2-neu), and Ki67 were studied in all patients with locally advanced breast cancer.
Results. A probabilistic mathematical model that made it possible to predict the development of local recurrence in the postoperative period was created. The model was highly informative (χ2 =43.7; p<0.001). The sensitivity of the model was 87.1 %, the specifcity was 85.7 %, and the diagnostic accuracy was 86.4 %. We present a clinical case with an estimated risk of developing local recurrence of breast cancer of 99 %. A patient received adjuvant neutron therapy, which made it possible to avoid the development of recurrence. At 5 years of follow-up after combined treatment modality including neutron therapy to the postoperative scar area, no evidence of local recurrence was found.
Conclusion. Based on the data obtained, the approach to indications for adjuvant neutron therapy, namely: stage III B-C breast cancer, tumor invasion into the dermis, angiolymphatic invasion, grade 3 tumor, triple-negative tumor subtype and overexpression Her2-neu subtype. 

REVIEWS

101-108 591
Abstract

Objectives. Up to date managing a cervical esophageal carcinoma (CEC) has remained a controversial challenge. The choice of treatment is still uncertain. In the present review we attempted to assess eligibility of surgery in treatment of CEC.
Material and Methods. We have enquired particular publication databases and the enquiries yielded 24 contributions matching study selection criteria such as (1) original articles published from 2000 to 2022, (2) primary tumor localization in the cervical esophagus, (3) squamous cell carcinoma, (4) available characteristics of studied groups (age, sex, T, N, M, stage), (5) detailed description of curative procedures (radiation therapy, chemotherapy, surgery), (6) information about overall survival. These publications represented two arms of 14 surgical and 17 non-surgical subgroups to analyze. Individual patient data and parameter estimates have been renewed on the basis of original Kaplan‒Meier curves plotted.
Results. The analysis revealed a highly heterogeneous (I2 =83.76 %; 95 % CI, 71.40–92.16) random effects model. Including a surgical option into treatment of CEC did not affect 3-year overall survival (р=0.665); 46.4 % (95 % CI, 37.4–55.6) vs 43.7 % (95 % CI, 35.3–51.6), respectively. Possibilities of surgical and non-surgical modalities employment were discussed.
Conclusion. In treatment of CEC CRT and surgery are non-inferior to each other. These modalities are evenly associated with posterior side effects and complications, which adversely affect functional outcomes and survival. The choice of a treatment mode may depend on tumor response to induction therapy. The latter demands further investigations.

109-117 467
Abstract

Over the past 5 years, checkpoint inhibitors including anti-CTLA-4 and anti-PD-1/PD-L1 blockers have changed approaches to therapy of metastatic renal cell cancer. However, more than 55 % of patients with advanced kidney cancer remain resistant to immunotherapy. This paper refects the causes that lead to primary and acquired resistance to immune checkpoint inhibitors during the treatment of metastatic renal cell cancer.
The purpose of the study was to elucidate the mechanisms underlying resistance to checkpoint inhibitors during the treatment of metastatic kidney cancer.
Material and Methods. A literature search was conducted using Pubmed database in the time interval between 2010 and 2023. We identifed 286 publications of which 59 were relevant for our review.
Results. There are many factors that contribute to primary or acquired resistance to immunotherapy, including factors associated with the tumor cell as well as tumor microenvironment factors.
Conclusion. Many innovative approaches to overcoming resistance to monoclonal antibodies are being investigated in clinical trials. In connection with the advent of new methods, the cellular composition of the tumor microenvironment and its role in the emergence of tumor resistance to immunotherapy are becoming increasingly clear. New biomarkers are emerging to help identify the best candidates for immunotherapy in metastatic kidney cancer. However, they require further study. 

118-127 1005
Abstract

Purpose of the study: to analyze published data on the mechanisms of action of interferon gamma (IFN-γ) in tumor growth and to evaluate the possibility of its use in the treatment of solid tumors.
Material and Methods. More than 200 publications were found in the Scopus, Pubmed, eLibrary and other databases, the search keywords were: interferon gamma, tumor growth, cancer therapy. This review includes 54 papers.
Results. IFN-γ is a pleiotropic cytokine with antiviral, antitumor, and immunomodulatory functions and plays an important role in coordinating the innate and adaptive immune response. The success of immuno-oncology drugs and chemotherapy in the treatment of malignant tumors depends on the stimulation of the production and adequate signaling of IFN-γ. Suppression and loss of IFN-γ receptor and downstream signaling mediators, and amplifcation of molecules that inhibit the IFN-γ signaling pathway are common mechanisms for tumor cells to escape from the immune system. The development of malignant processes is accompanied by a change, more often a decrease, in the secretion of IFN-γ, which attracts the attention of researchers to its exogenous administration. Determination of the IFN-γ signature may be a predictive marker of clinical response to anticancer drug therapy. The antitumor properties of IFN-γ are largely dose-dependent, which has been clearly shown in clinical and experimental studies. Low doses of the drug often promote tumor growth. On the contrary, the use of high doses is usually accompanied by an antitumor effect. IFN-γ or its inducers remain promising agents for cancer therapy. Combinatorial strategies involving IFN-γ may be a rational option to overcome tumor resistance to blockade of immune checkpoints.
Conclusion. It is necessary to continue fundamental and applied research to study the feasibility of using interferon gamma as a therapeutic agent in tumor growth.

128-134 346
Abstract

Background. Imbalance of aminothiol metabolism is a potential risk factor for malignant transformation of cells and caner development, including breast cancer, which is the most commonly diagnosed cancer in the world.
The purpose of the study was to summarize the available data on the characteristics of thiol metabolism as one of the factors contributing to the progression of breast cancer.
Material and Methods. Data were searched from 1999 to 2022 using the Web of Science, Scopus, MedLine, The Cochrane Library, PubMed databases, which made it possible to assess the role of thiol-dependent metabolic disturbances in the regulation of tissue redox balance in breast cancer genesis.
Results. The review considers the results of both our own data and international studies on breast cancer, which suggest that an imbalance of thiol compounds necessary to maintain a moderately reducing cellular environment that counteracts oxidative stress during cellular metabolism and detoxifcation under conditions of tumor progression can provoke reprogramming of the leading links of antiblastoma resistance, contributing to cancer progression.
Conclusion. A more detailed study of the mechanisms of aminothiol metabolism in breast cancer emphasizes their particular importance for stabilizing the cellular genome and providing antitoxic protection of the cell, as well as understanding the important role of thiols as a coordination center in redox signaling. Disturbances at any stage of thiol metabolism can play an etiological role in oncogenetic pathologies, while the role of thiols as signaling molecules and the regulation of their metabolism should not be generalized for the entire group of diseases. Determination of serum markers of the redox state in patients with breast cancer, especially during antitumor therapy, can serve for an objective assessment of the effectiveness of treatment and the adaptive capabilities of the body, as well as predicting tumor growth and optimizing the program for screening and preventing cancer.

CASE REPORTS

135-141 672
Abstract

Background. Ovarian cancer is the third most common cancer of the female reproductive system after cervical and uterine cancer and is diagnosed at stage III–IV in 2 out of 3 cases. Maintenance therapy with PARP inhibitors signifcantly prolongs disease-free and overall survival.
The purpose of the study was to demonstrate long-term remission in a patient with advanced ovarian cancer using maintenance therapy with PARP inhibitors (olaparib).
Description of the clinical case. A 54-year-old female patient with verifed stage IV ovarian cancer, peritoneal carcinomatosis and left-sided pleurisy received combined modality treatment, including 2 courses of neoadjuvant chemotherapy with paclitaxel/carboplatin, cytoreductive surgery and 6 courses of postoperative chemotherapy with docetaxel/cisplatin. The patient was diagnosed with a somatic BRCA2 gene mutation (c.3708delA), which was detected by tumor DNA sequencing. The patient received maintenance therapy with olaparib for 38 months, resulting in no evidence of disease progression.
Conclusion. This clinical case demonstrates the feasibility of using maintenance therapy with PARP inhibitors in a patient with initially disseminated platinum-sensitive ovarian cancer. Olaparib maintenance therapy provides stable long-term remission with no signs of adverse events and determined effect on quality of life of the patient.

142-148 445
Abstract

Background. According to literature data, errors in the diagnosis of gastrointestinal tumors (GIST) are uncommon, accounting for approximately 6% of cases that results in treatment failure.
Case report. Here, we describe a rare case of a 58-year-old female patient with extragastrointestinal stromal tumor (EGIST) in the evidence of testicular feminisation syndrome (TFS) – Morris syndrome. This hereditary pathology is associated with complete insensitivity of target organs to androgens and was described in 1953 by the American gynaecologist John Morris. The patient was referred to the cancer clinic, where she was wrongly diagnosed with uterine leiomyoma. Interdisciplinary approach, cancer alarm, active surgical tactics, additional immunohistochemical (IHC) and molecular genetic studies (MGI) allowed verifcation of the true diagnosis. There are reported cases of EGIST of the bladder, prostate, retroperitoneum, mesentery, omentum, and posterior mediastinum. However, we were not able to fnd publications regarding the cases of EGIST originating from the vaginal wall. Combination of TFS and EGIST is a unique case in our clinical practice.
Conclusion. The study of rare cases expands the understanding of the molecular pathogenesis of malignancies. Patients with rare types of malignant tumors should be obligatorily examined and treated in specialized cancer clinics with involvement of certifed oncologists, surgeons, chemotherapists, geneticists.

149-153 346
Abstract

Background. Nasopharyngeal cancer is a rare head and neck cancer with a relatively high risk of locoregional recurrence and distant metastases. The most common sites of metastases are bones (70–80 %) followed by liver (30 %), lung (18 %), and lymph node (axillary, mediastinal, pelvic, and inguinal). Thyroid gland is an uncommon site of metastasis with an incidence ranging from 0.5% to 24 %. Thyroid metastasis from nasopharyngeal cancer has been reported in only 9 cases in the world literature and no one in Russia.
Case report. We report a case of thyroid metastasis from nasopharyngeal cancer found incidentally in a 53-year-old female patient.
Conclusion. Metastases to the thyroid gland are rare, and patients with metastatic thyroid disease rarely present with organ-specifc symptoms, thus raising diagnostic diffculties for both clinicians and the pathologists. This clinical report demonstrates the diffculties of differential diagnosis,as well as the importance of a thorough collection of complaints, anamnesis, and clinical examination.

154-158 316
Abstract

Background. Sclerosing mucoepidermoid thyroid carcinoma (SMTC) is a recently recognized malignant neoplasm of the thyroid. SMTC was frst reported in 1991. It arises in a background of Hashimoto thyroiditis (HT). There are two variants of mucoepidermoid carcinoma of thyroid gland: the conventional and sclerosing variants. SMTC has recently been recognized as a separate disease entity by World Health Organization (WHO).
Description of the clinical case. We present the case of a 51-year-old woman with a 2-year history of autoimmune thyroiditis with a thyroid nodule. The patient had no symptoms or signs of compression. The level of thyroid–stimulating hormone (TSH) was 15.8 (range 0.4-4.0), antibodies to peroxidase: 150 Iu/ml. Scintigraphy of the thyroid gland revealed a dominant cold nodule (1.5×2 cm) in the right lobe of the gland. The control ultrasound examination showed negative fndings. Fine needle aspiration cytology of the nodule revealed follicular lesion in a background of TH. Extrafascial thyroidectomy was performed. The patient was followed up for 10 months.

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