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Siberian journal of oncology

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Vol 19, No 5 (2020)
View or download the full issue PDF (Russian)
https://doi.org/10.21294/1814-4861-2020-19-5

EPIDEMIOGICAL STUDIES

5-14 1140
Abstract

Background. Over the past decades, there has been a steady increase in the incidence of childhood cancer. The most childhood cancers are detected at advanced stages. The incidence of childhood cancer increased by 12.8 % (from 11.7 per 100,000 in 2007 to 13.2 per 100,000 in 2017) and the prevalence increased by 37.9 % (from 63.9 in 2007 to 88.1 in 2017 per 100,000). The purpose of the study was to develop algorithms for early cancer detection in children.

Material and Methods. In the Arkhangelsk region, the algorithm for referring a patient to a consultation with a pediatric oncologist was introduced into pediatric clinical practice in 2016. To evaluate the effectiveness of the algorithm, we compared two groups of patients with histologically verified solid malignant neoplasms. Group I included 49 patients, who received treatment in 2011–15 (before performing the experiment), and group II consisted of 51 patients, who received treatment in the Department of Pediatric Oncology in 2016–18 (the control group).

Results. The use of the algorithm for referring a patient to a consultation with a pediatric oncologist led to the increase in the 3-year survival time from 25.04 ± 2.05 months to 30.3 ± 1.57 months (р=0,045). The time parameters of various stages preceding the start of specialized treatment were statistically significantly reduced: the time from the visit of a pediatric oncologist to verification of the diagnosis decreased from 9.0 (7.0; 14.0) to 7.0 (5.0; 9, 0) days (p˂0.001); the time from diagnosis verification to the beginning of specialized treatment – from 12.0 (8.0; 16.0) to 8.0 (6.0; 10.0) days (p˂0.001); the time from the visit of a pediatrician to referral to a pediatric oncologist – from 11.0 (6.0; 17.0) to 2.0 (1.0; 3.0) days (p˂0.001); the time from the visit of a pediatrician until the beginning of specialized treatment – from 23.0 (17.0; 32.0) to 9.0 (8.0; 12.0) days (p˂0.001).

Conclusion. The introduction of a structural and functional model for organizing medical care for children with cancer was shown to be effective. 

15-20 1060
Abstract

The purpose of the study was to assess thyroid cancer epidemiology in the Udmurt Republic during 2008–18 and to estimate thyroid cancer raetes until 2023.

Material and Methods. The incidence of thyroid cancer in the Udmurt Republic was studied over a 10-year period (2008–18) according to state statistical accounting and reporting documentation.

Results. The age-standardized incidence rate of thyroid cancer in the Udmurt Republic for both sexes increased from 2.57 ± 0.36 per 100,000 population in 2008 to 6.60 ± 0.61 per 100,000 population in 2018, with an average annual percentage change of 9.9 %. The mortality rate from thyroid cancer decreased from 0.39 ± 0.12 per 100,000 population in 2008 to 0.36 ± 0.14 per 100,000 population in 2018.The incidence of thyroid cancer in the Udmurt Republic in 2023 was estimated to be 10.24 per 100,000 population.

Conclusion. In the Udmurt Republic, the increase in the incidence of thyroid cancer is significantly higher than in the Volga Federal District and Russia. The obtained estimates of thyroid cancer incidence until 2023 can be used in developing programs for early detection and prevention of this disease. 

CLINICAL STUDIES

21-27 1115
Abstract

A multicenter randomized trial was conducted to assess histopathological response to neoadjuvant chemoradiotherapy in patients with locally advanced gastric cancer.

Material and Methods. Patients of the study group received conformal radiation therapy (total dose of 46 Gr/23 fractions) with concurrent chemotherapy consisted of capecitabine at a dose of 1850 mg/m2 twice daily during the whole course of radiotherapy, and oxaliplatin at a dose of 85 mg/m2 on days 1 and 21. After an interval of 4–6 weeks and a control examination, in the absence of disease progression, patients were scheduled for surgery (gastrectomy or D2 subtotal gastric resection) and 4 cycles of adjuvant chemotherapy according to the FOLFOX4 or CAPOX regimens.

Results.The study included 70 patients, including of 35 patients in the study group. Men predominated (n=23), the age ranged from 22 to 76 years (median – 61 years). The middle third of the stomach was the most common tumor location (n=19); involvement of the entire stomach occurred in 5 cases. Ulcerative and diffuse infiltrative forms were the most common (n=29). Well-and moderately-differentiated adenocarcinoma was observed in 11 patients and poorly – differentiated adenocarcinoma in 24 patients, including signet ring-cell cancer (n=8). In accordance with the clinical T, N and M categories, patients were distributed as follows: T3 – 22 patients, T4a/b – 13; N0 – 13, N1 – 12, N2–3 – 10; M0 – 35; stage IIB – 12, and stage III–IVA – 23 patients. Gastrectomy was performed in 30 patients and subtotal resection of the stomach in 4 patients; D2 lymphodissection was performed in all cases. One patient was not operated on due to disease progression. Of the 47 patients achieving pathological response, 5 (14.7%) patients had a complete pathological response. Among patients achieving pathological response, a statistically significant predominance of less advanced tumors was found (in accordance with the ypT category and stage).

Conclusion. In general, a decrease in the pathological tumor stage compared to clinical stage was registered in 62 % of patients. Taking into account the data available in the world literature on high survival rates in patients with pathological complete regression, the optimization and implementation of neoadjuvant therapy techniques is of great importance. 

28-34 891
Abstract

Purpose: to study the effect of low-level laser therapy (LLLT) in correction of blood hemodynamic and rheological parameters after surgery for head and neck cancer.

Material and Methods. The study included 134 head and neck cancer patients with a median age of 54.24 ± 12.7 years (range: 23–78 years). There were 39 (29.1 %) men and 95 (70.9 %) women. To assess the effectiveness of LLLT, all patients were divided into 3 groups. Group I included 45 patients, who received conventional therapy without the use of LLLT. Group II consisted of 45 patients, who received conventional therapy in combination with LLLT. Group III included 44 patients, who received LLLT alone. Azor 2K-02 was used as a source of LLLT in the red to near infrared spectral range. Characteristics of blood flow in the vessels of the neck and the rheological properties of blood, as well as the parameters of spontaneous platelet aggregation and the content of soluble fibrinmonomer complexes in the blood plasma of patients were studied.

Results. The data obtained indicated that the use of LLLT promoted normalization of blood rheological properties in patients, who underwent surgery. Normalization of blood rheological properties occurred faster and lasted for a longer period. In patients, who received conventional therapy in combination with LLLT, the hemodynamic and rheological parameters of blood were improved 2–14 days after therapy, whereas in patients receiving conventional therapy alone, this improvement was seen 30 or more days after therapy.

Conclusion. LLLT in combination with conventional therapy was shown to have a positive effect on hemodynamic and rheological parameters after surgery for head and neck cancer. 

35-43 1353
Abstract

Oral cavity and oropharyngeal cancers usually require extensive surgeries accompanied by damages to anatomical structures and impaired speech function. The use of reconstructive-plastic techniques to replace defects after surgical resection allows the creation of a favorable functional basis for speech restoration.

The purpose of the study was to compare the effectiveness and terms of speech restoration in patients with oral cavity and oropharyngeal cancers after surgical treatment using various reconstructive surgery techniques to restore postoperative defects.

Material and Methods. Speech rehabilitation results were analyzed in 56 patients with stage II–IV oral cavity and oropharyngeal cancers. The age of the patients ranged from 26 to 70 years. The patients underwent either hemiglossectomy or glossectomy followed by reconstructive surgery. Postoperative speech rehabilitation was performed according to the technique developed in the Department of Head and Neck Tumors of the Cancer Research Institute. Speech function was assessed before starting treatment, at the beginning of treatment and after completion of speech rehabilitation.

Results. After surgery, all patients demonstrated impaired speech function, ranging from distorted pronunciation to the complete absence of verbal communication for 5 (71.4%) and 4 (80%) patients from Ib and IIb respectively. Speech rehabilitation started 16 to 32 days after surgery. Restoration of the activity and coordination of the articulatory apparatus muscles, speech exhalation and reconstructed tongue was followed by a sound pronunciation. Postoperative speech rehabilitation allowed improvement of speech function in 100 % of cases (56 patients). A complete speech restoration was achieved for 7 patients (12.5%). The majority of these patients were from the group with hemiglossectomy. In the group of patients with glossectomy, the amplitude and coordination of movements, which could be achieved by performing articulation exercises for the reconstructed tongue, depended on the size of the remaining part of their own tissues.

Conclusion. Good values of all studied parameters were observed in patients, who underwent hemiglossectomy followed by reconstruction with a free revascularized flap. No statistically significant differences between the studied parameters were found in patients, who underwent glossectomy. Speech restoration parameters were significantly better in the group of patients with hemiglossectomy and reconstruction with a free revascularized flap than in the group of patients with glossectomy). 

44-50 875
Abstract

The development of laboratory criteria for predicting esophageal cancer (EC) prognosis is of great importance due to the need to achieve personalized approach to cancer treatment. Since the role of lymphocytic infiltration in EC remains controversial, our goal was to develop a prognostic algorithm for estimating the risk of esophageal squamous cell carcinoma progression, considering its lymphocytic microenvironment.

Material and Methods. Tumor tissues were obtained from 40 EC patients during surgery; the tissues were homogenized, and lymphocyte subsets (Т-В-NK, T-reg) were determined by flow cytometry. A prognostic algorithm for calculating the risk of EC progression within 3 years was developed using discriminant analysis with the calculation of the three F functions: F0 , F6–12, F12–24, corresponding to the absence of the risk of EC progression during 3 years (F0 ); a high risk of EC progression during 6–12 months (F6–12); a high risk of EC progression during 12–24 months (F12–24) after surgery.

Results. Only two factors showed the highest discriminant power, allowing us to consider the differences as statistically significant – CD3+CD4+ and T-reg cells in tumors. When dividing EC patients into groups based on the prediction of time to disease progression, coefficients were calculated and mathematical functions were determined for three discriminant functions (F0 , F6–12, F12–24) organized into a model. The F coefficient calculated for each patient allowed us to predict the risk of EC progression 6–12 and 12–24 months after surgery or the absence of disease progression within 3 years after surgery.

Conclusions. The development of EC progression after surgery is apparently influenced by the lymphocytic microenvironment, predominantly by CD3+CD4+ and T-regs; their determination and inclusion in the prognostic algorithm can be important for personalized approach to the treatment of EC patients. 

LABORATORY AND EXPERIMENTAL STUDIES

51-60 871
Abstract

Introduction. Proteins associated with cellular motility are known to play an important role in invasion and metastasis of cancer, however there is no evidence of their association with the development of malignant tumors including endometrial cancer (EC).

The aim of the present study was to investigate the levels of actin-binding proteins, p45-Ser-β-catenin, and calpain activity in endometrial hyperplasia and in EC.

Material and Methods. Total calpain activity, p45-Ser β-catenin, Arp3, gelsolin, cofillin and thymosin β-4 levels were evaluated in 43 postmenopausal patients with stage I–II endometrioid EC and 40 endometrial hyperplasia patients. Flow cytometry and Western blotting were used for expression determination of p45 Ser β-catenin and actin-biding proteins. Total calpain activity was estimated by fluorimetric method.

Results. Levels of cofilin-1, thymosin β-4 and calpain activity were higher in cancer tissues than in endometrial hyperplasia. Cofilin-1 and thymosin β-4 levels were associated with the depth of myometrial invasion. The thymosin β-4 expression was correlated with the presence of tumor cervical invasion. Revealed correlations between the actin-binding proteins, p45-Ser-β-catenin and total calpain activity in endometrial hyperplasia tissue, but not in the tissue of cancer, is evidence of the involvement of these proteases in regulation of cell migration in endometrial hyperplasia. Levels of thymosin β-4, cofilin and total calpain activity are independent cancer risk factors in patients with endometrial hyperplasia.

Conclusion. The level of actin-binding proteins as well as the total calpain activity were enhanced in endometrium carcinoma tissues compared to endometrial hyperplasia. The levels of thymosinβ-4, cofilin and total calpain activity in endometrial hyperplasia tissues are associated with a hyperplasia transition to cancer and may be considered as predictive biomarkers. 

61-67 1625
Abstract

Purpose: to evaluate the effect of somatic mutations of the KRAS, NRAS, BRAF genes and the status of microsatellite instability on the overall and disease-free survival of patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Material and Methods. From 2012 to 2018, the study included 45 patients who underwent surgery for synchronous peritoneal carcinomatosis with colorectal cancer. In all patients, mutations of the KRAS, NRAS, BRAF genes and MSI status of the tumor and peritoneum metastases were determined using Sanger sequencing, fragment analysis and digital droplet polymerase chain reaction. The effect of mutations on patient survival was evaluated.

Results. The prevalence of somatic mutations was 69 % of patients. The discordance between the tumor and peritoneum metastases was 9 %. All tumors and peritoneum metastases were microsatellite stable. KRAS, NRAS, BRAF mutations did not affect the overall and disease-free survival (p=0.87 and p=0.85, respectively).

Conclusion. Somatic mutations in the KRAS, NRAS, or BRAF genes are not a prognostic factor affecting the overall and relapse-free survival of colorectal cancer patients with peritoneal carcinomatosis. The molecular status of primary tumor may differ from the status of peritoneal metastasis. It should be taken into account when prescribing targeted drugs. 

68-75 1124
Abstract

Introduction. The influence of chronic neurogenic pain on local levels of growth factors in the lung and the risk of lung cancer development has been little studied.

The purpose of the study was to analyze the levels of VEGF, TGF-β, IGF-I, IGF-II, FGF-21 and receptors of VEGFR2, TGF-βR2 in the lungs of white outbred rats with chronic neurogenic pain after intravenous injection of M1 sarcoma.

Material and Methods. A total of 28 white outbred male rats weighing 200–250 g were divided into 4 groups: 1 – sham-operated animals (control group) (n=7); 2 – animals with chronic neurogenic pain (n=7); 3 – sham-operated animals with intravenous injection of M1 sarcoma (n=7); 4 – rats with intravenous injection of M1 sarcoma in presence of chronic neurogenic pain (n=7). Animals were decapitated, the lungs were harvested on ice; 10 % cytosolic fractions were prepared in 0.1 M potassium phosphate buffer pH 7.4 containing 0.1 % Tween-20 and 1 % BSA. Levels of VEGFR2, TGF-β and receptors of TGF-βR2, IGF-I, IGF-II (CUSABIO BIOTECH Co., Ltd., China) and FGF21 (BioVender, Czech Republic) were determined by ELISA. The data were statistically processed using Statistica 10.0 software.

Results. Multifocal tumors of sarcoma in the lungs were determined only in the group of rats with chronic neurogenic pain after intravenous transplantation of M1 sarcoma. In the lungs of sham-operated animals, tumor foci were not detected after M1 sarcoma transplantation. Lung tissues with M1 growth and presence of chronic neurogenic pain demonstrated decreased VEGF-А levels with increased concentrations of TGFβ, IGF-I, IGF-II and FGF-21. Chronic neurogenic pain directly or indirectly influenced levels of some growth factors in the lung, and altered cell homeostasis making possible transplantation of M1 sarcoma into the lung. 

ONCOLOGY PRACTICE

76-81 1009
Abstract

Introduction. Cervical lymph node metastases can occur not only in patients when they are first diagnosed with papillary thyroid cancer but also in patients who have undergone thyroidectomy. 

Objective. The aim of this study was to assess the potential utility of neck ultrasound in diagnosing cervical lymph node metastases (levels I–VII) in patients who underwent surgical treatment for papillary thyroid cancer.

Material and Methods. B-mode sonography of all nodal levels in the neck was performed using a linear array transducer in the frequency range of 7.5–13 MHz, power mapping and panoramic scan to locate regional lymph node metastases. All lymph nodes removed during reoperations were submitted for histological evaluation. Sonographic examinations of cervical lymph nodes of the levels I–VII were performed in 2875 patients who had undergone thyroidectomy in different regions of the Russian Federation. The patients were admitted to our clinic to receive radioactive iodine therapy. All neck levels were assessed by ultrasound.

Results. Sonography revealed cervical lymph node metastases in 267 (9.2 %) of 2875 patients with papillary thyroid cancer who had undergone thyroidectomy. Nodal metastasis in level VI only occurred in 70 (2.4 %) patients, in levels II–III–IV only in 150 (5.21 %), in level VB only in 32 (1.11 %), and at the same time in level VI and in levels II–III–IV in 15 (0.52 %) patients. There were no metastases in levels I, VA, VII of the neck. Solitary metastases to all levels were found in 7.5 %, multiple metastases in 1.2 %, and conglomerates in 0.6 % of cases. Solitary metastases in level VI were noted in 56 (1.9 %), in levels II–III–IV in 125 (4.3 %), and in level VB in 29 (1.0 %) patients. Multiple metastases in level VI were detected in 11 (0.38 %), in levels II–III–IV in 21 (0.73 %), and in level VB in 3 (0.1 %) patients. Median metastasis size was 2.1 ± 1.6 cm.

Conclusion. Post-thyroidectomy patients were found to have cervical lymph node metastases. Ultrasound scanning of the neck should be considered a key examination if there are cicatricial changes as it enables to identify metastasis and to determine its location. The maximal number of metastases was noted in levels II–III–IV. Cervical lymph node metastases occurred less frequently in the central level and level VB. The predominant metastatic pattern was solitary. There was an essential difference in metastatic spread to cervical lymph nodes between postthyroidectomy patients and patients who were first diagnosed with papillary thyroid cancer. 

82-87 1017
Abstract

Pancreaticoduodenal resection (PDR) with vascular reconstruction is performed in approximately 20 % of pancreatic cancer patients. The superior mesenteric vein resection and reconstruction has become a standard routine surgery, whereas arterial resection during pancreatic surgery is still an issue of controversial debate.

The purpose of the study was to evaluate short-and long-term outcomes of PDR with reconstruction of various arteries.

Material and Methods. Outcomes of 89 PDRs and pancreaticoduodenectomies performed in patients with stage II–IV periampullary carcinoma were assessed. The average age of the patients was 63.1 ± 8.2. There were 18 (20.2 %) PDRs with vascular reconstruction, of them 7 (7.8 %) were arterial resections.

Results. In patients who underwent artery resection (n=7), complications were observed in 5 (71.4 %) cases. Out of 71 patients who underwent PDR without arterial and/or venous resection, 29 (40.8 %) had complications (p=0.229). The postoperative mortality rates were 1 (14.3 %) and 3 (4.2 %), respectively (p=0.319). The median disease-free survival was 5.0 months (95 % CI 2.4–7.6 months) in the arterial resection group and 12.3 months (95 % CI 9.2–15.4 months) in the standard surgery group (log-rank test, p=0,011). The median overall survival was 8.0 months (95 % CI 3.7–12.3 months) in the in the arterial resection group and 21.8 months (95 % CI 15.9–27.7 months) in the standard surgery group (log-rank test, p=0.011).

Conclusion. The disease-free and overall survival rates were significantly worse in the arterial resection group than in the standard surgery group. This is most likely due to a small sample of patients. Further studies are needed to analyze the immediate and long-term treatment outcomes of PDR with arterial resection for pancreatic cancer. 

REVIEWS

88-96 1204
Abstract

Objective: to provide various methods for sentinel lymph node detection considering their advantages and disadvantages.

Material and Methods. The search of the relevant articles published in Pubmed, MedLine, RINTs, etc. database was conducted. 49 publications from 1970 to 2018 were analyzed.

Results. Currently, sentinel lymph node biopsy (SLN biopsy) has become a worthy alternative to traditional lymphatic surgery for early breast cancer. SLN biopsy significantly decreases the number of postoperative complications caused by lymphadenectomy and improves the quality of life of cancer patients. So far, a large number of SLN detection techniques have accumulated. Each of these techniques has its own advantages and disadvantages.

Conclusion. Despite a large number of SLN detection methods, the question of the optimal technique is currently debatable. 

97-107 2234
Abstract

The purpose of the study was to summarize the available data on etiology, diagnosis, clinical symptoms and signs as well as on various approaches to the treatment of neuroendocrine cervical tumors.

Material and Methods. The relevant sources were searched in the PubMed and cochrane Library systems, and publications from 1980 to 2019 were analyzed, 53 of which were used to write this review. We also included 6 case reports from N.N. Petrov National Research Center of Oncology.

Results. Neuroendocrine tumors (NETs) are extremely rare and aggressive malignancies of the female genital tract, among which NETs of the cervix are the most common. Due to the rarity of these tumors, there are currently no treatment standards based on prospective, well-planned clinical trials. For these reasons, NETs present a significant therapeutic challenge for clinicians. Case reports. Six patients ranged in age from 32 to 71 years, with a median age of 46 years, were diagnosed with large-cell neuroendocrine carcinoma (4 patients) and small-cell neuroendocrine carcinoma (2 patients). One patient with stage IIIA dropped out of the follow-up schedule. Out of 5 followed up patients, 2 patients with stage IIIA and IIB died of disease progression after 6 and 11 months, respectively. One patient with stage IB1 is in remission for 16 months. Two patients with stage IIB continue to receive primary treatment.

Conclusion. Neuroendocrine carcinoma of the cervix is a rare variant of cervical cancer. The choice of treatment options is decided only by a multidisciplinary team of doctors, and further research is required. 

108-113 1193
Abstract

The purpose of the study was to conduct a systematic analysis of the data available in the modern literature on the systemic (abscopal) effects in radiation therapy, which are mediated by immunological phenomena.

Material and Methods.A structured search for articles published in peer-reviewed journals between January 2000 and February 2019 was conducted using MEDLINE database. The review included data from registered clinical trials at Clinicaltrials.gov, showing the results of the combined use of immunotherapy and radiation therapy.

Results. There is an opinion that the systemic effect of radiotherapy is mediated by immunological phenomena. In connection with the recent data, there is a growing interest in the combined use of immunotherapy with radiation therapy in order to increase the efficacy of systemic therapy. However, the incidence of abscopal effects after standard radiation treatment is very low. In this regard, stereotactic ablative radiotherapy, due to its high immunogenic potential, low toxicity and short duration of the treatment, is apparently an attractive partner for immunotherapy in patients with metastatic disease.

Conclusion. In view of the variety of the immunological effects of radiotherapy, further studies of the effect of radiation therapy on the immune system of cancer patients are needed, and the use of various combinations of immunotherapy and radiation therapy should be continued. All this, ultimately, will help improve the survival rates of cancer patients. 

114-120 1049
Abstract

The purpose of the study was to analyze literature data on the use of extracorporal hemocorrection as a pathogenetically significant component of rehabilitation for cancer patients.

Material and Methods. Literature search was carried out using keywords: rehabilitation of cancer patients, plasmapheresis, extracorporeal hemocorrection, hemodialysis. Out of 250 selected articles, 42 were used to write a review.

Results. Methods of extracorporeal hemocorrection are successfully used in the treatment of a wide range of diseases; therefore, the feasibility of applying these methods for rehabilitation of cancer patients is being studied. The review presents literature data on the feasibility of using the methods of extracorporal hemocorrection methods to compensate for the pathophysiological processes related to cancer development.

Conclusion. The analysis shows that a positive experience of using the methods of extracorporal hemocorrection for rehabilitation of cancer patients has been gained. However, no clear criteria for the application of these methods and for the assessment of their effectiveness have been developed. 

121-130 1126
Abstract

Several studies have shown that the use of inhibitors of vascular endothelial growth factor (Vascular Endothelial Gowth Factor, VEGF) in the treatment of glioblastoma results in a significant increase in the rate of progression-free survival. However, administration of anti-VEGF agents is associated with the development of a wide range of adverse drug reactions (ADR), among which, hematotoxic ADR is the most common.

The purpose of this study was to conduct a systematic review based on the results of randomized controlled clinical studies on the type and frequency of hematotoxic ADRs associated with anti-VEGF and chemotherapeutic agents in the treatment of glioblastoma.

Material and Methods. Pubmed, EMBASE, Cohrane Library and eLibrary databases were used to identify reports from randomized controlled clinical studies on the safety of anti-VEGF drugs as the main/auxiliary treatment for patients with glioblastoma, and published from January 2008 to August 2019. The main criteria for inclusion of studies in the systematic review were determined.

Results. The combined data analysis included 13 randomized controlled clinical trials. The average incidence of hematotoxic ADRs associated with anti-VEGF agents in monotherapy for glioblastoma was 27.7 %. Neutropenia and thrombocytopenia were the most common types of ADR. The average incidence of hematotoxic ADRs associated with cytotoxic drugs in monotherapy for glioblastoma was 48.1 %, and lymphopenia and thrombocytopenia were the main types of hematotoxic ADRs. The average incidence of hematotoxic ADRs associated with the combined use of anti-VEGF and chemotherapeutic drugs was 46.2 %. In this case, the most common ADRs were thrombocytopenia, neutropenia, and anemia. The use of a combination of anti-VEGF, chemotherapeutic drugs and radiation therapy was associated with the development of hematotoxic ADRs with an average incidence of 12.3 %. The most common ADR was severe thrombocytopenia.

Conclusion. The use of anti-VEGF drugs as monotherapy for glioblastoma was associated with a lower incidence of hematotoxic ADRs. In this case, bevacizumab was the safest anti-VEGF agent in relation to hematotoxicity. The highest incidence of hematotoxic ADRs is observed for a combination of antiVEGF and cytotoxic drugs, such as cediranib with lomustine and bevacizumab with carboplatin. 

CASE REPORTS

131-144 2417
Abstract
Anaplastic thyroid cancer is one of the most aggressive and fatal human carcinomas. A significant experience in using various kinase inhibitors for anaplastic thyroid cancer therapy has been accumulated worldwide. The most encouraging results were obtained after using a combination of b-Raf and MEK kinase inhibitors (vemurafenib/dabrafenib and trametinib/cobimetinib, respectively) for the treatment of the unresectable BRAFV600E-positive anaplastic thyroid cancer. This drug combination makes it possible to perform surgery followed by chemoradiotherapy and other targeted therapies. Here we report a clinical case of anaplastic thyroid cancer in a 69-year-old woman, who was treated with neoadjuvant targeted therapy. The treatment was carried out on the basis of three medical institutions: the National Medical Research Radiological Centre (Moscow), the N.I. Pirogov Clinic of Advanced Medical Technologies (St. Petersburg) and the Endocrinology Research Center (Moscow). Since there is still no universal protocol for treating ATC patients, and only palliative therapy is used in most cases, we emphasized on diagnostic and treatment errors of this disease. Special attention was paid to the importance of using molecular diagnostics and modern medical imaging technologies.
145-153 1018
Abstract

The article shows the feasibility of detecting and monitoring primary breast diffuse large B-cell lymphoma using single-photon emission computed tomography (SPECT) with 99mTc-1-thio-D-glucose (99mТс-TG), a new radiopharmaceutical. The innovative radiopharmaceutical makes it possible to evaluate the metabolism of tumor tissue without using positron emission tomography. The findings of 99mTc-TG SPECT obtained during diagnosis and monitoring of the patient were confirmed by the results of computed tomography. A comprehensive examination of the patient, including 99mTc-TG SPECT, made it possible to diagnose a rare case of primary breast lymphoma. Primary breast lymphoma accounts for 1.7–2.2 % of all extranodal nonHodgkin lymphomas. Diffuse large B-cell lymphoma is the most common histological type occurring usually as a unilateral palpable tumor in middle-aged women. Extranodal lymphomas account for less than 0.5 % of all malignant neoplasms of the breast. After 6 courses of immunochemotherapy, the patient underwent 99mTc-TG SPECT, which demonstrated persistent hypermetabolic activity in the breast. The patient received radiation therapy to the remaining tumor of the left breast. The patient is in remission and followed up at the Cancer Research Institute of Tomsk National Research Medical Center. Thus, 99mTc-TG SPECT is believed to be a promising method for visualizing primary breast lymphomas and assessing their treatment outcomes. It is an alternative to the standard approach using 18F-FDG positron emission tomography. The method compares favorably with positron emission tomography with its wide availability and low cost of study. 



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