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Siberian journal of oncology

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Vol 18, No 4 (2019)
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https://doi.org/10.21294/1814-4861-2019-18-4

EPIDEMIOGICAL STUDIES

5-12 1299
Abstract
Background. Cancer remains a difficult disease to prevent, detect, treat or manage it. The mortality rate is one of the most important criteria for assessing the health of the population. Nevertheless, the correct use of analytical indicators is important, especially when assessing time series. The crude cancer mortality rate is closely related to the proportion of elderly patients. All international publications (WHO, IARC, territorial cancer registries) assess the morbidity and mortality using the standardized indicators that eliminate the difference in the age structure of the compared population groups. The purpose of the study was to analyze cancer mortality in Russia and to calculate the medium-term mortality prognosis in crude and standardized rates up to 2025, as well as to highlight the main factors related to cancer mortality. Material and Methods. We used standard methods for estimating time series, including the moving average method. Results. We calculated the share of the elderly population in Russia (retirement age). It was found that from 1960 to 2017, the proportion of pensioners (men aged 60 and older and women aged 55 years and older) increased from 6.2 % to 15.8 % and from 16.2 % to 32.9 %, respectively, thus excluding the assessment of mortality by a crude mortality rate. From 2000 to 2017, the crude mortality rate of the population of Russia decreased by 2.7 %, while the standardized rate decreased by 20 % (19.6 %). The reduction in the mortality rate of the Russian population was significantly affected by a favorable change in the structure of mortality, the proportion of localizations of cancer with a high mortality rate decreased significantly. Conclusion. The calculations of the medium-term prognosis show that by 2025 the crude mortality rate will decrease to 195 ± 5.1 0/0000, and standardized rate to 100 ± 3.2 0/0000.

CLINICAL STUDIES

13-20 1651
Abstract
Special systems were developed for response assessment of immunooncology drugs. The role and benefits of particular system in assessing the efficacy of different immunotherapy methods are not clear yet. The objective of this study is to compare the responses on ipilimab (IPI) or dendritic cell vaccines (DCV) therapy by RECIST 1.1 and irRC criteria. Eighty two patients with unresectable disseminated or locally advanced stage III-IV melanoma were included. Fifty-five patients were treated with IPI and 27 – with DCV at the N.N. Petrov National Medical Research Center of Oncology from 2007 to 2016. Response by each system was compared to overall survival (OS). Response by both systems was a good marker for OS in IPI group (p=0,0001 for both systems) but not in DCV group (p=0,357 for RECIST and p=0,411 for irRC). Discrepancies in responses by different systems were detected in 5 patients in the IPI group and in 5 patients in the DCV group (p>0.05). The median of OS in IPI patients with PD by both systems was 8.8 mo. In case of mixed responses, (RECIST progression disease (PD) and irRC stable disease) OS in IPI group was 29.1+ mo, 16.7 mo. In the case of SD by RECIST and PD by irRC OS was 11.6+ mo. One patient with PD by RECIST and partial response by irRC lived 16.3 mo. OS in DCV group was 9.5+, 8.7, 15.3, 29.7 mo. in patients with mixed responses (PD+SD); 15,7 mo. in patient with SD by RECIST and PR by irRC. There was a trend to better overall survival of patients with PD according to the RECIST 1.1 and the absence of PD by irRC system in comparison with the PD by both systems in the treatment of IPI was revealed. In the DCV group the same pattern wasn’t found. Thus, both the RECIST 1.1 system and the irRC system are good surrogate markers for the overall survival. SD in patients receiving DCV cannot be considered a good response to therapy, since it does not improve the OS in comparison with patients who has PD by the same system. The irRC system allows to extract a subgroup of patients with better overall survival from patients with PD by RECIST among those who receive IPI but not DCV for systemic therapy of melanoma.
21-26 1037
Abstract

The purpose of the study was to compare the efficacy and toxicity of hypofractionated versus hyperfractionated radiotherapy in patients with inoperable lung cancer.

Material and Methods. Patients with inoperable lung cancer, who were treated between 2014 and 2017, were assigned to undergo radiotherapy in two arms: accelerated hypofractionated conformal radiotherapy arm with 70 patients (60 Gy in 25 fractions, with 2.4 Gy per fraction) and accelerated hyperfractionated radiotherapy with 49 patients (60–70 Gy with 1–1.5 Gy per fraction). At the same time, platinum-based chemotherapy was applied.

Results. The rates of partial response, complete response, stable disease and progressive disease were 44.3, 7.2, 38.5 and 10.0 %, respectively in patients with hypofractionated conformal radiotherapy arm. The corresponding values were 71.4, 6.1, 16.4 and 6.1 %, respectively in patients with hyperfractionated radiotherapy arm. The 2-year overall survival rate was 62.8 % for the hypofractionated group and 58.1 % for the hyperfractionated group. Esophagitis III grade was observed in 4 (5.7 %) patients of the hypofractionated group and in 3 (6.5 %) patients of the hypofractionated group. Pneumonitis III grade was reported in 2 (2.9 %) patients in the hypofractionated radiotherapy arm and in 4 (8.7 %) patients in the hyperfractionated radiotherapy arm.

Conclusion. Results of the study showed that 3D-conformal hypofractionated radiotherapy combined with concurrent chemotherapy resulted no in severe radiation-induced complications, and demonstrated satisfactory short-and long-term treatment outcomes. 

27-33 1459
Abstract

Purpose of the study: to assess the efficacy and safety of morphine hydrochloride in the form of 10 mg filmcoated tablets and 1 % solution for injection in cancer patients with chronic pain syndrome of strong intensity.

Material and Methods. The study included 110 cancer patients with chronic pain syndrome of strong intensity. The study was conducted in compliance with the principles of the Helsinki Declaration, ICH GCP, GOST R 52379-2005, as well as other Russian laws regulating the conduct of clinical trials and work with opioid analgesics. Patients were randomized at a 1:1 ratio. Group I received 10 mg film-coated morphine tablets, 1 tablet orally every 4 hours for 7 days. Group II received 1 % morphine solution for injection, intramuscularly, 4 mg every 4 hours for 7 days. A Numeric Rating Scale for Pain (NRS, 0–100 mm) was used to assess the level of pain. The safety assessment was based on the collection of data on the registration of adverse events, including opioid-associated adverse effects.

Results. Enteral and parenteral morphine administration for 7 days demonstrated a statistically significant decrease in the intensity of pain syndrome in cancer patients. The use of morphine hydrochloride in tablets reduced the number of additional analgesics prescribed for cancer patients. Regarding opioid-associated adverse effects, a statistically significant difference in the incidence of constipation between two groups was observed.

Conclusion. The study showed that tablets and injectable dosage forms of morphine hydrochloride were comparable in efficacy and safety profile, thus predetermining the widespread clinical use of drugs produced by the domestic manufacturer in accordance with the “pain relief ladder”, proposed by WHO. 

LABORATORY AND EXPERIMENTAL STUDIES

34-42 1342
Abstract

Boron neutron capture therapy (BNCT) is a targeted therapy based on a selective damage to cancer cells due to the interaction between boron-10 isotope and neutron. Reactor-based BNCT has been found to be effective in the treatment of high-grade gliomas. It is believed that compact accelerator-based neutron sources will ensure widespread adoption of the technique in clinical practice. New accelerator-based neutron sources are being actively developed all over the world. At the Institute of Nuclear Physics (Russia), the accelerator-based neutron source was developed for pre-clinical studies of BNCT.

Purpose: to determine the cytopathic effects of accelerator-based BNCT on the human U87-glioblastoma cell line and to select a concentration of boron drugs that do not have a toxic effect on the cells before irradiation in vitro.

Material and Methods. To assess the cytopathic effects (MTT test and colony-forming assay) of various concentrations of boron-containing drugs, U87 cells were incubated with boronophenylalanine (BPA) and sodium borocaptate (BSH) for 1, 2 and 10 days. The effect of BNCT on the U87 cell line was determined using colony-forming assay.

Results. The MTT test showed a decrease in cell survival at a boron-10 isotope concentration of 160 μg/ml after 48 hours and 640 μg/ml after 24 hours of incubation for BPA. The cytopathic effects for sodium BSH appeared at a boron concentration of 80 µg / ml after 48 hours of incubation, and survival fraction of cells was reduced to 89 % compared to the control. According to the colonyforming assay, the cytotoxic effects of BSH and BPA at a boron concentration of 40 µg/ml in the medium were 79.6 and 84 %, respectively. The proportions of surviving cells were 18 ± 2 % and 13 ± 2 % after epithermal neutron irradiation in the presence of boronophenylalanine and in the presence of sodium borocaptate, respectively. Cell death without boron drugs occurred due to the neutron elastic scattering, nuclear reactions of thermal neutron capture by hydrogen and nitrogen, and accompanying gamma radiation.

Conclusion. The study clearly showed a decrease in the proportion of surviving U87 cells after accelerator-based BNCT in the presence of 10B-enriched BSH and BPA. 

ONCOLOGY PRACTICE

43-49 1088
Abstract

The purpose of the study was to analyze infectious complications caused by multi-drug-resistant organisms depending on anticancer therapy.

Material and Methods. A total of 229 cancer patients with infectious complications of cancer therapy were included into the study.

Results. Lung cancer was the most predominant cancer (26.6 %) followed by gastric cancer (25.3 %) and esophageal cancer (14.4 %). Infectious complications occurring after surgery were observed in 83.4 % of the patients. Infectious complications caused by Acinetobacter baumannii were the most common (40.6 %), followed by Klebsiella pneumoniae (28.5 %), Pseudomonas aeruginosa (19.5 %), Staphylococcus spp. (9.4 %), and Enterococcus spp. (1.8 %).

Conclusion. Infectious complications occurred more frequently in postoperative cancer patients (p<0.02), and the ESKAPE group pathogens were the leading cause of these infections. 

REVIEWS

50-58 1223
Abstract

The aim of the study was to summarize data on the role of tumor-associated dendritic cells (DC) in the formation of squamous cell carcinoma microenvironment, their participation in the development of immune inflammatory responses in the tumor stroma and relation to tumor progression.

Material and Methods. We analyzed 79 publications available from Pubmed, Google Scholar, Elibrary databases from January 2000 to December 2017.

Results. The characteristics of different types of DC, including Langerhans cells (CR), were presented. The different methods of DC identification were described. The information on the presence of DC in squamous cell carcinomas was analyzed. The influence of the tumor on DCs, as well as the relationship between the number and functional characteristics of DCs and invasive/metastatic tumor potentialities was described. The prognostic value of DCs and their effect on disease-free, metastasis-free and overall survival rates were analyzed. The data on the association between DCs and the response to chemoradiotherapy were presented. The analysis of the relationship between the DC characteristics and the development of immuno-inflammatory responses in the tumor microenvironment was carried out.

Conclusion. The methodological approaches to the detection of DCs are variable, but the sensitivity of each method, as well as the comparison of different methods for estimating the number and functional characteristics of DCs, have been little studied. There is no data on the relationship between the length of DC dendrites and the parameters of invasive/metastatic tumor potentialities, disease-free, metastasis-free and overall survival rates. Numerous studies indicate the association between the number of DCs and the tumor progression, however these data are contradictory. There is no data about the relationship between the number of DCs and hematogenous metastasis of squamous cell carcinomas. The association of tumor-associated DC with the types of immunoinflammatory responses in the tumor microenvironment has been insufficiently studied. 

59-66 1057
Abstract

Purpose of research: to identify the prospects of search for new antitumor non-camptothecin inhibitors of topoisomerase I/II among the various chemical compounds based on the analysis of side effects.

Material and Methods. The analysis included 65 relevant literature sources for 2002–2018 years, found in Systems such as Scopus, Web of Science, Pubmed, and eLIBRARY.

Results. The antitumor and side effect characteristics of the agents, associated with the selective suppression of the activity of type I and/or II topoisomerase (Top1, Top2) in tumor cells were emphasized. Examples of the relationship between side effects of inhibitors and their structure and catalytic mechanisms were given. The following factors were highlighted as significant: 1) blocking of cells in G2 and S phases with a delay of entry into mitosis; 2) inhibition of the reaction of re-ligation with DNA breaks without re-linking; 3) launching of cytotoxic events with the inhibition of DNA replication and generation of double-strand breaks. Incurable cancers, such as gastric cancer, colorectal cancer, non-small cell lung cancer, hepatocellular carcinoma, glioblastoma, etc. were determined as more sensitive to inhibitors. Side effects of treatment and their connection with the mechanism of activity were described.

Conclusion. Based on the comparative analysis of prognostically valuable data regarding the efficacy and safety of topoisomerase I/II inhibitors, multitargeted heterocyclic condensed nitrogen-containing compounds, in particular, anthrafurans, can be considered as new promising clinical candidates with higher selectivity of action.

67-77 1261
Abstract

The purpose of the study was to provide up-to-date data on the efficacy of positron emission computed tomography (PET) for the diagnosis, assessment of tumor extension and monitoring of colorectal cancer.

Material and Methods. The Medline and Pubmed databases were used for searching for publications devoted to clinical trials of diagnostic value of PET with 18F-Ftordesoxyglucose (PET with 18F-FDG).

Results. Data on the value of PET with 18F-FDG in visualization of the primary tumor, detection of lymph node and distant metastases and assessment of the treatment response in patients with colorectal cancer were presented.

Conclusion. PET with 18F-FDG was shown to be a promising imaging method for colorectal cancer. It is the most sensitive method in the detection of liver metastases. 18F-FDG PET is particularly superior to CT and MET in the ability to assess tumor response to treatment and predict early tumor response to therapy. The development of new radiopharmaceuticals for the diagnosis, staging, monitoring and prediction of colorectal cancer is of great importance. 

78-84 3088
Abstract

The purpose of the study was to provide current data about various methods of treatment of early and locally advanced esophageal cancer.

Material and Methods. A search was made on available literature sources published in the Pubmed, Medline, Elibrary, Cochrane Library, CyberLeninka, Global Health and other databases. 123 articles published from 2001 to 2018 were found and analyzed to write this review.

Results. Esophageal cancer is the 7-th most common cancer worldwide. Esophageal cancer has a favorable prognosis only in patients with early stage cancer. The use of endoscopic technology provides a minimally invasive approach to the treatment of esophageal cancer and significantly increases survival of patients. Surgical resection remains the mainstay of treatment for esophageal cancer. For patients with locally advanced esophageal cancer, a multimodal approach is required, including a rational combination of radical surgery with chemo and/or radiation therapy. In many countries, preoperative chemotherapy has entered the standard of treatment for II–III stages of esophagus cancer. However, the development of novel approaches to the treatment of esophageal cancer is of great importance. For advanced cancer patients, palliative chemo- or chemoradiotherapy remains the main treatment modality.

Conclusion. The choice of the treatment option for esophageal cancer remains a challenging clinical problem and depends on the particular type of cancer, tumor stage, functional status of patients. 

85-91 932
Abstract

Background. Psychiatrists providing consultation in cancer centers need to understand the patient’s mental health without possibility of collecting data on the objective case history and follow-up.

Purpose: to analyze the modern methods of assessment of psychopathological disorders in cancer patients.

Material and Methods. Publications indexed in PubMed and devoted to the analysis of defense mechanisms, strategies for overcoming challenges, responses to acute and chronic stress, and support for family members of cancer patients were analyzed.

Results. Modified psychosomatic interviews used for cancer patients, attachment styles, coping strategies, and defense mechanisms were described. The taxonomic system of the most common mental disorders in modern psycho-oncology was presented.

Conclusion. The modified psychiatric interview, during which the defense mechanisms, coping styles, coping reactions with acute and chronic stress, methods of functioning of cancer patient’s family are assessed, allows a psychiatrist to obtain essential information about psychopathological status of a patient within the first (and often the only) appointment. A multidimensional diagnostic approach helps to assess the involvement of various damaging factors in a patient’s current mental status. Conclusion made by a psychiatrist in terms of the taxonomic systems of the International Statistical Classification of Diseases and Health Related Problems (ICD) or the Diagnostic and Statistical Manual of Mental Disorders (DSM) allows him to provide information to an oncologist in a uniquely interpretable (standardized) form. 

CASE REPORTS

92-101 1189
Abstract
Breast cancer (BC) is one of the most common malignancies and the leading cause of cancer-related death in women worldwide. Currently, mammography and ultrasound are the methods most commonly used for the detection of BC, but these methods have significant limitations in the absence of “classic” visual symptoms of cancer in the breast tissue. In the complicated clinical situations, such methods as magnetic resonance imaging and positron emission tomography are used for the differential diagnosis of breast cancer. Over the past 20 years, the BC imaging capabilities have expanded due to the introduction of optical methods into clinical practice. These methods are based on differences in the optical properties between normal and pathological breast tissues. Optical imaging provides the ability to obtain indirect information about oxygenation, blood supply, delivery and consumption of oxygen in the breast tissue, as well as changes in its scattering properties. We present a clinical case of a woman with enlarged axillary lymph nodes. After the core biopsy of the lymph node, histological examination reveled breast cancer metastasis. The standard imaging modalities, such as digital mammography and ultrasound, did not show the evidence of breast cancer. However, the use of diffuse optical spectroscopy (DOS) allowed the detection of changes in the absorption and scattering coefficients in a small part of the breast tissue characteristic of a malignant tumor. Ultrasound and mammography images of this site of the breast demonstrated the features of benign lesion. After ultrasound-guided biopsy, cytological examination revealed cancer cells. Thus, the method of DOS allowed identification of changes characteristic to malignant tumor that was not detected by routine imaging modalities.
102-105 1908
Abstract

The formation of esophagogastric anastomosis has a long history due to the search for the most reliable and safe fistula. The use of invagination anastomosis, proposed in the early 90s by Professor M.I. Davydov, fully met all the requirements, allowing significantly improve the quality of life of patients and significantly reducing the frequency of failure of the anastomoses to 0.5%.

Case description. We present the case of proximal gastric cancer invading the lower thoracic esophagus. The patient underwent proximal subtotal gastric and lower thoracic esophageal resection using the combination of a laparotomy and right thoracotomy. Contrast radiography performed on day 11 after surgery revealed esophagogastric anastomotic leak. The patient underwent urgent surgery.

Conclusion. This article presents a new treatment option for esophagogastric anastomotic leak by using endoscopic transesophageal clipping of the defect in combination with sanitation and drainage of the pleural/mediastinsl cavity. The proposed technique can be considered as a minimally invasive treatment method and can be used in any surgical clinic. 

106-111 19096
Abstract

Background. Esophageal cancer is among the ten most common cancers and causes-related mortality worldwide. Most patients present with an advanced stage tumor at diagnosis. To treat patients with esophageal cancer, radiation therapy in combination with chemotherapy is usually used. In the clinic of A.F. Tsyb Medical Radiological Scientific Center, patients with advanced esophageal cancer are treated with split-course radiotherapy delivered in two fractions (1–1.5 Gy) with a 4-hour interval. The positive effect is observed significantly earlier than in conventional radiotherapy.

Case description. A 50-year-old male patient presented with complaints of hoarseness of voice and difficulty swallowing in February 2015. The patient was diagnosed with stage cТ4N2M1 cervical esophageal cancer (tumor length 3.5 cm) with metastases in cervical lymph nodes and the thyroid and esophageal stenosis (stage IV). Cytological examination revealed keratinizing squamous cell esophageal carcinoma. The tumor was considered inoperable. The patient underwent gastrostomy. Radiation therapy delivered to the tumor and metastases was performed 5 times a week using two lateral fields and one anterior field. The total radiation dose was 60 Gy. A complete response was achieved. Three courses of chemotherapy with carboplatin (AUC 6), paclitaxel (75 mg/m2 ) with a 21-day interval were administered 2 months after radiotherapy. In January 2016, new metastases in the thyroid were detected. Thyroidectomy with microsurgical neurolysis of the laryngeal nerves was performed. The patient is alive 3 years and 7 months after diagnosis.

Conclusion. The use of nonconventional fractionated radiotherapy schedules in combination with chemotherapy allows satisfactory treatment outcomes in patients with advanced esophageal cancer to be obtained. 

112-115 967
Abstract

Background. Hepatocellular carcinoma is the most common liver cancer and is a leading cause of cancerrelated death worldwide. Its aggressiveness and extensive dissemination lead to a poor patient prognosis. The 5-year survival rate does not exceed 15 %. Despite advances in imaging techniques, its curable rate remains low, because signs and symptoms of liver cancer do not usually appear until the late stages. There is no standard curative treatment for advanced liver cancer.

Description. We present the case of a 56- year-old female patient with stage T3N0M0 hepatocellular carcinoma. The patient had a tumor of 20 cm in diameter and 2400 g in weight. The patient underwent right hemihepatectomy and cryodestruction of the liver stump along the resection margin. No evidence of tumor recurrence was found with a follow-up of 12 years.

Conclusion. Cryodestruction of the liver stump along the resection margin increases the potential for a higher cure rate in patients with hepatocellular carcinoma, even in cases of extensive organ damage in the absence of metastasis and tumor ingrowth into surrounding organs. 



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