Trends in incidence, molecular diagnostics, and treatment of patients with breast cancer in Kazakhstan, 2014-2019

Relevance: Globocan reported 4,390 new breast cancer cases and 1,654 deaths from breast cancer in the Republic of Kazakhstan (RK) in 2020. Molecular diagnostics of breast cancer includes the determination of Hormone Receptor (HR), HER2, and Ki-67 status to detect patients with HR-positive tumors and administer effective treatment. Methods: This observational study included a retrospective analysis of incidence, molecular diagnostics, and treatment regimens in women with a confirmed breast cancer diagnosis aged 18 years old and older, registered in the RK Electronic Registry of Cancer Patients (ERCP) from 1 January 2014 till 31 December 2019. Results: In the study period (2014 to 2019), the number of breast cancer cases registered annually has doubled. The incidence increased by 46.9%. The share of locally advanced and advanced forms of breast cancer has decreased. The proportion of Luminal type A (HR+/HER2-) among newly diagnosed patients ranged from 17.9% to 30%. Chemotherapy and endocrine therapy with goserelin, buserelin, leuprorelin, and fulvestrant are standard first- and second-line treatments for HR+ breast cancer. Since fulvestrant indications have been expanded, more than 50% of patients with HR-positive advanced breast cancer receive fulvestrant as the first-line therapy. Conclusion: Breast cancer incidence growth and a decrease in the share of locally advanced and advanced breast cancer cases in the RK could be attributed to increased coverage of eligible women aged 40 to 70 with breast cancer mammographic screening. Although international guidelines support the administration of hormone therapy with or without targeted therapy in women with HR-positive, HER2-metastatic breast cancer, upfront use of chemotherapy remains common in the RK even in the absence of visceral crisis. The use of CDK4/6 inhibitor palbociclib in combination with hormone therapy has become routinely available since 2019.

Morphological characteristics of changes in the squamous epithelium of the upper part of the digestive tract in model organisms in the settings of provoked carcinogenesis

Relevance: Noticeable spreading of malignant neoplasms of upper section of digestive system and the worsening of these patients’ quality of life in case of late diagnostics stimulate the development of protocols for early detection of precancerous changes. The purpose of the study was to investigate the morphological characteristics of changes in the squamous epithelium of the upper part of the digestive tube in model organisms under provoked carcinogenesis when exposed to substances with proven carcinogenic activity. Methods: 40 female nonlinear white rats obtained from the Orekhovo-Zuevsky urban settlement veterinary station were used as model organisms. The rats were divided into 4 equal groups. The first control group was not exposed to any specific influences. In groups 2-4, the rats underwent sedation and mechanical scarification microtraumatization of the oral mucosa. Then, they were applied twice a week by 0.9% NaCl solution (control group 2), 1% aqueous solution of dimethyl sulfoxide (DMSO, Akrikhin, Russia) (control group 3), or 1% aqueous solution of DMSO containing 0.1 mg/ml 4-nitroquinoline-N-oxide (4- NQO, Acros Organics, USA) (experimental group 4). Results: The cytological picture associated with chronic trauma to the mucous membrane of the upper digestive tract was characterized by nonspecific reactions: inflammation, hyper- and parakeratosis, and atrophic changes. There were no statistically significant differences in the frequency of such changes between the experimental and control groups. Specific changes in squamous epithelium towards a precancerous state in the experimental group with chronic exposure to a substance with carcinogenic activity occurred significantly more often than in the control groups (p <0.05), as proven by the results of comparative histological verification. Conclusion: Cytological study can be offered for clinical study as a screening tool for precancerous oropharynx and upper esophagus conditions

p53 and EGFR gene mutations in malignant tumors of the lung

Relevance: Increased incidence of lung cancer globally and in Kazakhstan, lack of screening in hereditary cases, high mortality, and low survival of patients necessitate the study of the molecular genetic causes of the disease. At present, gene mutation studies for lung cancer diagnostics are expanding. However, many gene mutations revealed remain undercovered in the scientific literature, and there is not enough data on their prognostic and diagnostic value. The purpose of the study was to discover the specifics of the р53 gene mutations and reveal the EGFR exon 19 deletions and exon 21 L858R mutations in malignant tumors of the lung of various histogenesis. Methods: The mutations were studied in tumors (200 samples) and adjacent tissue (200 samples) of patients with lung cancer (squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lung) by polymerase chain reaction (PCR), electrophoresis, and EcoR1- and Pst1-restriction of samples after p53 gene fragments and cDNA amplification and mRNA revertase treatment. Another 263 lung cancer samples were evaluated by real-time PCR for EGFR exon 19 deletions and EGFR exon 21 L858R mutations. Results: The p53 gene was not expressed in 50% of SCC and adenocarcinoma of the lung samples. Restriction revealed p53 mRNA mutations in 100% of SCC and 75% of ADC samples. p53 exon-intron 5-6 was mutated in 50% of ADC and 70% of SCC samples, exon-intron 7-9 – in 60% of SCC cases. EGFR exons 19 and 21 mutations found in 65 of 263 lung tumor samples were associated with increased sensitivity to EGFR tyrosine kinase inhibitors. Conclusion: The p53 gene mutations revealed in most samples of SCC and ADC of the lung could be used to diagnose lung cancer and predict its severity. The identified EGFR mutations allow predicting the effectiveness of targeted therapy

Analysis of main statistical indicators of oral and pharyngeal cancer in the Republic of Uzbekistan

Relevance: According to GLOBOCAN data for 2020, oral and pharyngeal cancer ranked 25th in mortality (98 412 cases, 0.5% of all cancer deaths) and 26th in the number of diagnosed new cases (48 143 cases, 0.5% of all new cancer cases) in the world. Oral and pharyngeal cancer incidence is growing steadily globally and in the Republic of Uzbekistan. Oral and pharyngeal cancer ranks 16th in the structure of cancer incidence in the Republic of Uzbekistan, with a rate of 1.8 per 100 000 people. The purpose of the study was to analyze the main statistical indicators for tumors of the oral cavity and pharynx in the Republic of Uzbekistan in 2015-2021. Methods: We analyzed the main statistical indicators for tumors of the oral cavity and pharynx in the Republic of Uzbekistan for 2015- 2020 obtained from the Reporting Form #7 “Information about malignant neoplasms cases.” Results: Over the past six years, the incidence rate per 100,000 people has increased from 1.4 in 2015 to 1.8 in 2020. In 2015-2020, in the Republic of Uzbekistan, 2,240 patients died from malignant neoplasms of the oral cavity and pharynx. The mortality rate per 100,000 people decreased from 1.4 in 2015 to 1.2 in 2020. Conclusions: Tumors of the oral cavity and pharynx rank 16th in the structure of cancer incidence in the Republic of Uzbekistan and tend to grow. A recent increase in oral and pharyngeal cancer incidence and its late detection could be explained by worsening detection and diagnostics. The stabilization of oral and pharyngeal cancer mortality results in socio-economic losses for the Republic. The provided statistical data is the basis for improving the indicators of incidence and mortality related to oral and pharyngeal cancer in the Republic of Uzbekistan

Intensification of radiation therapy for localized breast cancer in the settings of the COVID-19 pandemic: A literature review

Relevance: Since 2004, breast cancer steadily ranks first in the structure of the incidence of malignant neoplasms in the Republic of Kazakhstan in both sexes. In 2020, its share was 14.5% (vs. 15.2% in 2019). Breast cancer also constantly ranks first in the structure of female cancer incidence, with 44.3‰ in 2020 (vs. 51.6‰in 2019). In the early 1980s, radiation therapy was a standard specialized treatment for breast cancer. The current realities of the COVID-19 pandemic require a reorganization of healthcare facilities to determine the priorities. It is also important to balance the economic and clinical efficacy of radiotherapy methods applied. The study aimed to analyze the results of large randomized trials and compare breast cancer outcomes after hypofractionated and standard fractionation radiation treatment. Methods: We reviewed the results of large randomized trials of hypofractionated radiation therapy, emphasizing adequate patient selection according to the American Society of Therapeutic Radiology and Oncology (ASTRO) guidelines. Radiobiological aspects of hypofractionation were considered due to its implementation in clinical practice. The research materials were obtained from the “PubMed” database of evidence-based medicine by the keywords “radiotherapy,” “breast cancer,” “hypofractionation dose” for the period 2000-2021. Large randomized trials involving patients of any age diagnosed with stages T1-3, N0-1 breast cancer, who underwent beam therapy in standard or hypofractionated mode, met the criteria for inclusion in this study. Results: According to the results of large randomized trials, the hypofractionated regimen is similar to the standard regimen in terms of late effects on normal tissues and ensures good control over the oncological process. Conclusions: Hypofractionation has proven effectiveness and safety and has lower late and/or acute radiation toxicity when treating early breast cancer. Hypofractionation can become a new standard of radiation therapy at early stages after breast-conserving surgery.

Ways to improve the diagnostics and detection of cervical cancer development and recurrence risk

th and the third most common female cancer worldwide. The purpose of the study was to determine risk factors and time to progression and recurrence in patients with cervical cancer after complex treatment (neoadjuvant chemotherapy + radical hysterectomy + combined radiation therapy). Methods: This retrospective study involved female patients with stage IB-IIA cervical cancer registered at Shymkent city oncological dispensary in 2011- 2021 (n=883). All patients underwent (n=883) radical hysterectomy with pelvic lymph node dissection. The patients were selected who underwent radiation therapy of the lower pelvis at a dose of ≥40 g. The age-, stage-, and tumor morphological structure-dependent survival factors and recurrence risk were analyzed during the research decade. Results: Direct correlation of the disease stage and the recurrence period was established. The progression was most often 5 to 6 months after treatment. 68.7% of progression and 63.1% of recurrences occurred in the first year and a half after the end of treatment, so this period is considered the most “dangerous” regarding the recurrence risk. 5.3% of patients had a recurrence 19 to 24 months after treatment, 31.5% – after more than two years. Conclusions: In this research, cervical cancer progressed in 74 (10.6%) out of 883 women and recurred in 19 (3.0%). The recurrence was most frequent in women aged 45-50 years (28.4%) and 50-60 years (26.3%).

Lung cancer incidence and mortality trends in the Republic of Belarus (1990-2019)

favorable malignant diseases globally. In the Republic of Belarus, it ranks third (8.2%) in the cancer incidence structure and first (21.5%) in the cancer mortality structure. The object of the study were the lung cancer incidence and mortality trends in the Republic of Kazakhstan in 1990-2019. Methods: The present study included all patients - residents of Belarus, registered in the national cancer registry from 1990 to 2019 with a diagnosis of lung cancer (ICD-10 code: C33-C34). Demographic variables included gender, age, and area of residence (urban or rural). The number of PD cases is presented as absolute values and rough intensity indicators per 100,000 population. Standardized morbidity and mortality rates are calculated using the world standard (World) and are indicated per 100,000 population. Results: In the study period, the standardized incidence rate decreased from 27.5 to 25.6 per 100 000 population (– 7.1%, p<0.01). In males, it decreased from 62.1 to 54.6 per 100 000 males (– 12.1%, p<0.001); in females, it increased from 5.3 to 6.4 per 100 000 females (+20.7%, p<0.05). The standardized lung cancer mortality rate has decreased over the study period from 23.0 to 18.3 per 100 000 population (– 20.4%, p<0.001). In males, it went down from 53.6 to 40.7 (– 24.1%, p<0.001), and in women it changed slightly from 3.6 to 3.7 (+2.8%, p>0.05) per 100 000 of the relevant sex. The average annual increase in standardized mortality decreased eight times faster than the growth in standardized incidence. Conclusion: In the Republic of Belarus, lung cancer incidence is increasing in males and decreasing in females. At that, lung cancer mortality is decreasing. Quality specialized cancer care creates conditions for quicker negative growth of lung cancer standardized mortality vs. incidence

Il-2 in combination with immune checkpoints inhibitors as a promising approach for cancer immunotherapy: A literature review

Relevance: Interleukin-2 (IL-2) alone has been shown to induce tumor regression and approved to treat metastatic renal cancer and melanoma. Checkpoint inhibitors realize their therapeutic effect through stimulation of immune system effectors; one of such mechanisms is the enhancement of IL-2 production by T-helpers. The purpose of the study was to determine the effectiveness of IL-2 administration as a component of combined immunotherapy with immune checkpoint inhibitors and to suggest the mechanisms by which IL-2 can reduce the frequency and severity of side effects during checkpoint inhibitor therapy without reducing their effectiveness. Methods: The literature search was performed in the PubMed, SCOPUS, and Web of Science databases by the keywords in article titles: “immunotherapy,” “checkpoint inhibitors,” “interleukin-2,” and “combination therapy” for the period 2011-2021. A total of 248 relevant articles were found. The review’s inclusion criteria were: clinical cases; data of clinical research methods; data on humans/body fluids from humans; literature reviews and meta-analyses. The selected 24 articles met the search criteria and were included in the review. Results: The combined action of IL-2 and сheckpoint inhibitors increases the proliferative and killer activity of the antitumor immunity effectors compared to the action of the same drugs in mono-mode at a level exceeding the summation effect. Conclusion: The combination of IL-2 and сheckpoint inhibitors can increase the effectiveness of anticancer treatment and is a promising area of immunotherapy

Surgical management of pancreatoduodenal tumors: the experience of using the developed operation technique

Relevance: The results of surgery in patients with pancreaticoduodenal cancer remain unsatisfactory. This complicates the choice of an optimal surgical technique in modern oncology. Surgery in the pancreaticoduodenal zone is associated with complications due to anatomical and physiological features of the pancreas and technical challenges of this surgical intervention. Despite preventive actions and innovative technologies, such a traumatic operation as pancreatoduodenal resection often produces complications, though recently fewer. This article describes a pancreaticoduodenal resection technique that reduces postoperative complication frequency and lethality in operable pancreaticoduodenal cancer. The purpose of the study was to assess the efficiency of an authorial pancreaticoduodenal resection technique (pancreaticojejunal invagination anastomosis) in pancreaticoduodenal cancer. The proposed pancreaticojejunal anastomosis-forming technique allowed reducing the postoperative complication frequency from 54.2% to 38,0% and postoperative lethality from 22.8% to 9,5%. Conclusion: This highly traumatic surgery is associated with postoperative complications (up to 50-70% of cases), which are quite severe and difficult to resolve and result in high fatality. The proposed pancreaticojejunal anastomosis forming technique has efficiently reduced postoperative complications and fatality to a significant extent.

Epidemiology of colorectal cancer in the Republic of Kazakhstan

Relevance: Today, colorectal cancer is one of the most important health issues in Kazakhstan and worldwide. Colorectal cancer leading positions in the general structure of oncopathologies force clinicians to develop ways to improve its statistical indicators. The purpose of the study was to investigate the epidemiological aspects of colorectal cancer in the Republic of Kazakhstan in 2010-2019. Results: The article presents and analyzes the epidemiological indicators of colorectal cancer in the Republic of Kazakhstan over the past decade. The incidence trends were studied considering the territorial characteristics, early detection, and neglect indicators for this type of malignant neoplasms in this country. We also analyzed the 5-year survival, one-year fatality, and mortality rates for the studied period. Comprehensive comparative analysis of these epidemiological indicators made it possible to visualize the results of many years of work to improve oncological indicators and formulate further improvement directions. Conclusions: An analytical assessment of colorectal cancer statistical indicators of over a decade showed an increase in incidence, with some regions leading year to year. However, such indicators as early detection, one-year fatality, and mortality from colorectal cancer have improved.