Neural network analysis of some molecular parameters of the cervical epithelium for cervical cancer diagnostics

Background. A personalized approach is the basis for the specialized care for cancer patients. The relevance of cervical cancer (CC) is still high. The searches for diagnostic criteria of cervical epithelium malignancy are continuing. The application ohm technologies has led to a big number results, the analysis of which is often difficult. The neural network data analysis allows to solve these problems.Objective: to create a technology for diagnosing cervical intraepithelial neoplasia (CIN) and CC, based on a neural network analysis of some molecular parameters.Materials and methods. The research carried out among patients with CIN III (n = 15), patients with CC stages I–IV (n = 49). The control group consisted of female volunteers without cervical pathology (n = 15). Studied molecular parameters: the spectrum of fatty acids was determined in cervical biopsies, proteins OPN, ICAM-1 were studied in blood serum, proteins of the immune cycle sCD25, sCD27 – in the cervical epithelium. Research methods: gas-liquid chromatography, flow cytometry.Results. Significant differences of fatty acids spectrum, local level sCD27 were revealed in among the studied groups. The multilayer perceptron included C18:2ω6, OPN, ICAM-1, sCD25, sCD27. The performed neural network analysis of the molecular data allows to diagnose CIN III (Se = 0.92; Sp = 0.87; AUC = 0.94; p˂0.001) and CC (Se = 1.00; Sp = 1.00; AUC = 1.00; p˂0.001).Conclusion. The created model makes it possible to diagnose CIN III and CC with high accuracy. The configuration of the multilayer perceptron allows confirming the pathophysiological relationships between the studied molecular parameters, to expand the understanding of the mechanisms of cervical carcinogenesis.

10 years of success achieved by eribulin while treating HER2-negative mBC: from randomized studies to routine practice

The article reviews studies evaluating the efficacy and safety of eribulin chemotherapy in patients with HER2-negative advanced breast cancer. It analyzes the results derived from large randomized studies, highlights the main advantages peculiar to eribulin, and describes the key mechanisms of the antitumor activity displayed by the drug. Among those presented, there are significant retrospective studies evaluating the role of eribulin chemotherapy in late and early advanced breast cancer treatment lines, as well as an analysis of surveys aimed to evaluate the efficacy of the drug in various clinical settings (for visceral metastases, brain lesion, and in elderly patients). This article reflects the main results of Russian population analyses evaluating the efficacy and safety of eribulin chemotherapy in routine clinical practice.

Vulvar intraepithelial neoplasia. Literature review

Vulvar intraepithelial neoplasia (VIN) is the proliferation of atypical basal cells in the vulvar epithelium. The global VIN incidence has recently doubled; its incidence among white women under 35 years of age has almost tripled with a tendency for further growth. Such an increase in the number of usual-type VIN cases in young women is primarily attributed to infection with highly oncogenic human papillomavirus. The second type of dysplasia, namely differentiated VIN, is usually found in older women and is associated with chronic dystrophic diseases of the vulva, most frequently with lichen sclerosus of the vulva. VIN diagnosis is quite challenging; no screening programs for this disorder have been developed so far. Patients with VIN practice self-treatment for a long time, which aggravates their condition and might trigger the development of vulvar cancer. Several treatment options are currently available; however, their efficacy worldwide is not high.

Autologous dura mater grafts in reconstructive surgeries for breast cancer patients

Reconstructive surgeries have long been considered as an essential part of rehabilitation of breast cancer patients. The majority of patients tend to choose one-stage reconstruction, because this type of surgery ensures rapid emotional and physical recovery. Due to the lack of subcutaneous fat in a substantial proportion of cases, which leads to postoperative complications, the most common surgical tactics now is simultaneous reconstruction after subcutaneous mastectomy with subpectoral implant location and strengthening of the lower breast slope using different materials. So far, there has been no gold standard material for secure covering of the lower pole of the implant. Autologous acellular dura mater grafts are a promising material for breast reconstruction. Studies evaluating biointegration, compatibility, inertness, reactivity, and cost effectiveness of autologous acellular dura mater grafts have determined feasibility of using these grafts in reconstructive surgeries.

Impact of radiotherapy on long-term treatment outcomes in patients with breast cancer who have undergone simultaneous one-stage and two-stage reconstructive surgeries. Literature review

The evolution in reconstructive breast surgery in the form of widespread use of implants allows you to abandon the “simple” mastectomy in most patients, provide faster rehabilitation and minimize the psychological trauma due to the absence of a breast. However, in most cases, radiation therapy and/or drug treatment are necessary, as they reduce the risk of relapse, disease progression and mortality. The combined or complex treatment increases the frequency of postoperative complications, such as prolonged wound healing, infection, protrusion/extrusion of the endoprosthesis, the development of capsular contracture, seroma, hematoma, etc. The greatest negative impact on the aesthetic result, both in the early and in the long-term period, is provided by remote radiation therapy. On the other hand, performing reconstructive plastic surgery may complicate radiation therapy. The issues of how long it is necessary to conduct radiation therapy, what type of reconstruction and how to conduct radiation therapy, how to minimize the frequency of complications without compromising the oncological and aesthetic results of treatment of breast cancer patients remain controversial.

Descriptive characteristics of gynecological malignant neoplasms

Background. Gynecological malignant neoplasms (GMN) are the leading disease group among female cancers.Objective: to characterize GMN in females occupationally exposed to ionizing radiation over prolonged periods.Materials and methods. The cohort considered in the study included females (n = 5689) who had been hired at the Mayak Production Association in the period between 1948 and 1982. All these females were exposed to ionizing radiation over prolonged periods during their employment. They were followed up until 31.12.2018. Two groups of females were identified in the study cohort: the one with a verified GMN (the main group) and another one free of GMN (the control group). The occupational and reproductive characteristics were analyzed for the identified groups of females, and associations of GMN with various risk factors were assessed.Results. Among GMN the uterine corpus cancer had the top position. In 70 % of the females GMN were diagnosed during a menopausal period. The females of the main group demonstrated significantly higher frequency of underlying pre-malignant conditions (endometriosis, uterine myoma, endometrial hyperplastic processes, ovarian epidermoids, menopausal bleedings) compared to the control group.Conclusion. Studies of GMN in females occupationally exposed to ionizing radiation over prolonged periods for sure are of a certain scientific and practical interest. The findings can provide the basis for specialized cancer care for employees of the nuclear industry.

Results of organ-preserving treatment of breast cancer using intraoperative radial therapy

Objective: to compare the immediate and long-term outcomes of patients with early breast cancer treated with intraoperative radial therapy depending on the biological subtype of breast cancer.Materials and methods. We prospectively evaluated number of recurrences, cosmetic effect and early treatment results of 104 patients with early breast cancer aged 66.72 ± 0.68 years old. The mean follow-up period was 36 months. The mean dose on the surface of applicator was 17.8 Gy, on the depth 0.5 cm – 8.8 Gy, on the depth 1.0 cm – 5 Gy. The mean time of radiation was 22.15 min ± 28.09 sec.Results. The local recurrence was in 3 patients. The first patient had triple negative breast cancer subtype, the second patient had luminal B HER2+, and the third one had luminal B HER2– subtype. Relapses occurred in 7, 14 and 20 months after the end of treatment respectively. The recurrence rate in patients with luminal B biological subtype was 10.71 %; in patients with triple negative subtype was 20 %. All recurrences were found in the area of the postoperative scar.Conclusion. The obtained results question the rationale for the use of the demonstrated method in patients with luminal B and triple negative molecular subtypes of tumors.

Phyllodes breast tumor. From diagnostic to pathomorphological examination

Background. Phylloid tumors are a fairly rare pathology (about 0.3–0.5 % of all breast tumors), which is why there is no single protocol for the treatment of this pathology. Also, due to the lack of data and the rare occurrence, it is difficult to diagnose and choose the final management tactics of the patient. Phylloid tumors can be benign, borderline, and malignant neoplasms, which also complicates the treatment process. The final decision on the choice of patient management tactics can be made only after receiving the results of a planned pathomorphological examination.Materials and methods. In this article, we will discuss the results of major retrospective studies, including data on epidemiology, etiology, diagnostic approach, strategies and results of treatment of phylloid breast tumors, as well as present data on patients treated at the Russian Scientific Center of Radiology of the Ministry of Health of the Russian Federation for the period from January 2010 to February 2021.Results. The main methods of instrumental diagnosis of phylloid tumors are mammography, ultrasound and MRI. Morphological examination is important in making a diagnosis. Fine-needle biopsy often does not allow establishing an accurate diagnosis, and therefore the main method of diagnosis remains pathohistological examination. The main method of treatment of phylloid tumors remains surgical, where, depending on the trepan biopsy, the question of the feasibility of performing an organ-preserving operation is decided.Conclusion. Phylloid tumors are a rare type of breast neoplasm, which is the reason for the relatively small amount of scientific research that addresses this particular problem.

Estimating long-term overall survival with olaparib as maintenance therapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations

Background. According to randomized clinical trial SOLO1 olaparib statistically significantly improves progression-free survival versus placebo as a maintenance monotherapy in patients aged 18 and over with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response to first-line chemotherapy. As the data on overall survival (OS) in this trial remains interim it is still uncertain whether treatment with olaparib can provide any benefits in terms of OS.Objective: to evaluate a long-term OS for olaparib versus placebo as a maintenance monotherapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response to first-line chemotherapy.Materials and methods. A 10-year mathematic model of disease progression and survival on olaparib versus placebo was developed. Modelling was based on data on progression-free survival from SOLO1 trial and data on OS after platinum-sensitive and platinum-resistant relapses from OCEANS and AURELIA trials. Additionally, patients who haven’t been treated with olaparib after first-line therapy in base-case scenario were assumed to get olaparib as a second-line treatment after platinum-sensitive relapse; mortality modelling for these patients was based on data from SOLO2 trial.Results. Median OS for olaparib was 107 months versus 66 months for placebo. 46 % of patients treated with olaparib were alive by the end of 10-year modelling period, but only 28 % patients from the placebo group. Hazard ratio of death for olaparib versus placebo was 0.64 (95 % confidence interval 0.49–0.84). Probabilistic sensitivity analysis showed robustness of these results.Conclusion. Using olaparib as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response on first line chemotherapy, statistically significantly reduces risk of death by 36 %, compared to placebo.

Molecular genetic predictors of metastatic lesions of regional lymph nodes in patients with breast cancer

Objective: to identify molecular genetic predictors of metastatic spread to regional lymph nodes in patients with breast cancer (BC) based on the analysis of gene expression profile of the primary tumor.Materials and methods. The study included 358 patients with BC who underwent surgical treatment in breast cancer department of Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. Among all included into the study patients, 132 (36.9 %) had metastases in at least one axillary lymph node. Molecular genetic examination of the tumor tissue was carried out using reverse transcription polymerase chain reaction; the diagnostic panel consisted of 45 functional and 3 reference genes. Results. Patients with metastases to regional lymph nodes were generally younger (p = 0.006), had larger primary tumor (p<0.001) and higher total malignancy score (p<0.001). The groups were also significantly different in tumor location (p = 0.005). Comparative analysis of transcriptome tumor profiling revealed statistically significant differences between groups in the level of expression of three genes: TMEM45A (p = 0.016), CCND1 (p = 0.019), and MIA (p = 0.046). Based on the data obtained we used mathematical modeling and created a predictive model, which with a high degree of probability (AUC = 0.791) allowed to predict the presence of regional lymph nodes metastases in patients with BC.Conclusion. TMEM45A, CCND1 and MIA gene expression in the primary tumor were the markers of lymph node involvement in BC. The developed predictive genetic signature can become an additional diagnostic tool to predict the risk of lymph node metastases at the point of planning the volume of axillary surgery in patients with BC.