Voprosy onkologii

On Victory Day and the 80th Anniversary of the Lifting of the Siege of Leningrad. Review of the Archives of the Pathological Anatomy Laboratory of the Oncology Institute

Alexey M. Belyaev — 2024-05-06

Eighty years ago, the 872-day Siege of Leningrad was lifted. Today it is impossible to find someone in modern St Petersburg who does not know about the horrors of war and the heroism of the people who lived through the siege of Leningrad and won after surviving starvation, bombing and the death of loved ones. The archive of the Laboratory of Pathological Anatomy now serves as a memorial to the past. Since its foundation in 1926, the N.N. Petrov Research Centre of Oncology of the Ministry of Health of the Russian Federation has preserved a unique record of the daily efforts of doctors and laboratory staff during the war and the siege. This publication presents that historical record.

Possibilities for Differential Diagnosis of Thyroid Follicular Neoplasia by Evaluation of Small Noncoding RNA

Ioannina A. Bandyk — 2024-05-06

Introduction. The preoperative differential diagnosis of follicular thyroid nodules is not a trivial issue due to the absence of objective signs of malignancy. This is stimulating efforts to find molecular markers of follicular cancer and to develop diagnostic test systems. Small regulatory RNAs are a large group of molecules that perform different biological functions, but have a similar biochemical structure. Quantitative analysis of different members of this group can be performed simultaneously using identical technology. This determines the possibility of a comprehensive assessment of the cellular biology of the samples analysed and the development of new diagnostic criteria. The purpose of the study was a comparative analysis of small RNAs expression profile in the samples of follicular thyroid cancer and follicular adenoma of the thyroid gland.

Materials and methods. The study included tissue samples of follicular carcinoma (FC, n = 12) and benign follicular adenoma (FA, n = 12) of the thyroid gland obtained after thyroidectomy and histological examination. Analysis of the expression profile of short RNAs was carried out using next generation sequencing.

Results. The expression (concentration) of transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), and a large group of unclassified molecules (miscRNA) is increased in FC compared to FA, but the diagnostic potential of individual molecules is relatively low. The total concentrations of microRNA molecules (miRNA) turned out to be comparable in the FC and FA groups; analysis of «reciprocal pairs» of miRNA markers allowed to differentiate FC and FA with a high degree of probability (AUC: 0.94-0.98). The total number of piwiRNA molecules was slightly higher in FC samples compared to FA; analysis of «reciprocal pairs» of piwiRNA marker allows us to reliably differentiate FC and FA (AUC: 1.00).

Conclusion. Analysis of the concentration of marker miRNA and piwiRNA in fine-needle aspiration biopsy material appears to be a promising method for additional diagnosis of thyroid nodules with a follicular structure.

Drug Therapy Strategy for Metastatic Breast Cancer in the Context of Expanding Anti-Tumor Drug Pallet

Larisa V. Bolotina — 2024-05-06

As the arsenal of drugs available to treat metastatic breast cancer (mBC) expands, there is a need to optimise existing approaches to create the most effective line of therapy. With the advent of novel monoclonal antibody-drug conjugates (ADCs) targeting a specific receptor combined with a cytostatic agent in clinical practice, this question has been raised in relation to the treatment of patients with triple negative (TN) and HER2 low breast cancer. This article reviews the key trials on the efficacy of sacituzumab govitecan and trastuzumab deruxtecan in the context of the latest version of clinical guidelines for the treatment of these types of mBC. The accumulation of practical experience and its generalisation in real-world clinical trials will eventually allow clinical oncologists to formulate a strategy for the consistent use of emerging conjugates.

Evaluation of Prognostic Factors in Men with Germ Cell Tumors: 10 Years of Experience of the Russian Reference Centre

Svetlana A. Protsenko — 2024-05-06

Introduction. Testicular germ cell tumors (TGCTs) are a group of malignant neoplasms that originate from germ cells. Despite the rarity of this pathology, TGCTs are the most common type of tumor in the young male population.

Aim. To evaluate unfavorable prognostic factors in men with TGCT.

Materials and Methods. The study included 273 patients with TGCT who were treated or repeated consultations at the N.N. Petrov NMRC of Oncology between 2011 and 2021. Survival was analysed using the Kaplan-Meier method and regression analysis using the Cox method.

Results. Factors significantly associated with inferior overall survival (OS) in non-seminomatous germ cell tumors (NSGCT) included presence of pulmonary metastases (HR 3.927, 95 % CI 1.051-11.111; p = 0.010), presence of non-pulmonary visceral metastases (HR 4.636, 95 % CI 1.710-12.570; p = 0.003), elevated lactate dehydrogenase (LDH) level ≥ 2.5 upper limit of normal (ULN) (HR 4.107, 95 % CI 1.614-10.451; p = 0.003), treatment in general hospitals (HR 2.37, 95 % CI 1.924-4.994; p = 0.003), and deviation from the standards of medical care (HR 3.731, 95 % CI 1.456-9.564; p = 0.006) were analyzed. The statistically significant factors associated with inferior OS for metastatic seminoma were the presence of pulmonary metastases (HR 2.15, 95 % CI 1.024-6.877; p = 0.035) and elevated LDH levels ≥ 2.5 × ULN (HR 2.419, 95 % CI 2.015-8.775; p = 0.027). In multivariate analysis performed for all patients, the absence of pulmonary metastases was associated with improved OS (HR 0.301, 95 % CI 0.100-0.910; p = 0.033).

Conclusion. Factors unfavourably affecting the prognosis with non-seminomatous and seminomatous germ cell tumors were identified. Comparable 3-year and 5-year OS data were obtained for patients treated at the N.N. Petrov NMRC of Oncology in comparison with international data.

Treatment Outcomes Evaluation in Breast Cancer Patients with a Pathological Complete Response after Neoadjuvant Systemic Therapy Depending on Different Types of Local Treatment

Petr V. Krivorotko — 2024-05-06

Introduction. Current opinion is that surgery is diagnostic rather than curative and does not affect long-term outcomes in breast cancer (BC) patients with complete pathomorphological response (pCR) after neoadjuvant systemic therapy (NST). As a minimally invasive method for diagnosing pCR in BC, vacuum-assisted biopsy (VAB) of the tumour bed has shown promising results. This paper presents a retrospective analysis of the outcomes of patients with triple-negative and HER2-positive BC who achieved pCR after NST according to different types of invasive breast surgery, including patients who underwent VAB alone without subsequent breast surgery.

Materials and methods. From 1 January 2021 to 1 July 2023, we analysed 3247 patients who underwent surgery at the Department of Breast Tumours at the N.N. Petrov NMRC of Oncology. Patients were included in the study if they had unifocal invasive HER2+ and TNBC (cT1-2N0-1M0) with histologically confirmed pathological complete response (ypT0N0) to NST. Exclusion criteria were an intraductal component detected by trephine bone marrow core biopsy and germline mutations in BRCA1/2. According to the planned analysis, all patients were divided into three groups: the breast-conserving surgery (BCS) group, the mastectomy (ME) group and the VAB group. Primary endpoint was 2-year ipsilateral breast tumour recurrence-free survival [IBTR-FS]. Secondary endpoints included 2-year disease-free survival (DFS) and complication rates.

Results. Of the 3 247 patients analyzed, 81 patients who met the inclusion criteria were included in the final analysis. There were 39 patients in the BCS group, 19 patients in the ME group, and 23 patients in the VAB group. The median follow-up was 24 months. The median survival was not reached for any of the endpoints. 2-year IBTR-FS was 100 % in the BCS group vs. 100 % in the ME group vs. 91.3 % in the VAB group [p = 0.159]. 2-year DFS was 97.4 % in the BCS group vs 94.7 % in the ME group vs 87.0 % in the VAB group [p = 0.396]. There was no difference in the hazard ratio (HR) for recurrence between the different types of surgery. When measuring HR adjusted for lymph node status (cN) and disease stage, there was a statistically significant higher risk in the VAB group [HR adjusted for cN: 12.236, (95 % CI, 1.163-128.773), p = 0.037; HR adjusted for stage: 17.071, (95 % CI, 1.255-232.173), p = 0.033].

Conclusion. To determine the safety of VAB use, further observational studies and large randomised prospective trials are needed. There was no significant difference in the incidence of complications between the different types of invasive procedures in this cohort of patients.

Relevance and Legal Basis for Fertility Preservation of Cancer Patients: Institutional Experience and Literature Review

Olga E. Lavrinovich — 2024-05-06

Introduction. Malignant neoplasms (MN) are an important medical and social problem of modern public healthcare system. More and more patients of reproductive age face oncologic diseases and subsequent gonadotoxic therapy. Improvement of treatment methods, creation of new drugs leads to an increase in survival rates. With the development of new technologies, rehabilitation measures to restore impaired or lost functions and ensure a satisfactory quality of life are taking on a new meaning and reaching a new level of possible assistance. Nowadays rehabilitation measures for cancer patients should undoubtedly include measures to preserve, restore fertility and reproductive function.

Aim. To analyze the relevance and the legal framework regulating fertility preservation in cancer patients. To evaluate relevance demand for fertility preservation in cancer patients of reproductive age receiving treatment in N.N. Petrov NMRC of Oncology.

Results. Due to the lack of large prospective cohort and randomized trials on oncofertility, the level of evidence does not exceed "Class (level) III (C): controlled trials without randomization on a limited number of patients". Despite the great interest in this field of medicine, the practical implementation of measures and methods remains at a low level due to the lack of reliable statistical data and clinical recommendations based on them. Today, fertility preservation for cancer patients in the Russian Federation is only possible at the patient's own expense. The analysis of mandatory counselling of oncological patients at fertile age and the possibility of implementation of fertility preservation methods in N.N. Petrov NMRC of Oncology was performed. Over 2 years Oncofertility Laboratory conducted 594 primary consultations for patients from 18 to 45 years old, which made up 10.4 % of the whole reproductive group of patients with high risk of fertility loss. 24.9 % (n = 148) of all consulted patients used assisted reproductive technologies (ARTs) to preserve their reproductive potential. Given the importance of the development of this approach and the progress of modern technologies in oncological medical institutions at the federal level, it is necessary to organise specialised care for fertility preservation.

Message Editor-in-Chief of the journal «Voprosy Onkologii»

Aleksey M. Belyaev — 2023-12-29

The appeal of the Editor-in-Chief of the journal "Issues of Oncology" to the authors, readers and subscribers of the journal.

The original article Results of Using Intraoperative Sentinel Lymph Node Identification in the Surgical Management of Stage IA-IIA Non-Small Cell Lung Cancer

Kirill D. Badaev — 2024-05-06

Introduction. To evaluate the applicability, sensitivity and accuracy of the method of intraoperative determination of lymph flow pathways from the affected lobe and identification of sentinel lymph nodes in the surgical management of stage IA-IIA non-small cell lung cancer.

Materials and Methods. This prospective study has been conducted since November 2021 at the Department of Thoracic Oncology of the N.N. Petrov National Medical Research Centre of Oncology of the Ministry of Health of Russia. The study was approved by the local ethics committee № 1035 dated 08.10.2021. The analysis included 35 people.

Results. The SNLs were determined ex vivo in 34 of the 35 patients included in the study. In one case, it was not possible to reliably determine the radiopharmaceutical accumulation ex vivo and in the second and third points. According to the calculations, SLNs were identified in 97.14 % of cases. The number of patients with lymph node involvement was 5 out of 35. In five patients, metastatic lymph nodes were identified as sentinel lymph nodes. The accuracy of the method was 100 % (5 out of 5). The true negative rate was 30 out of 30 (100 %).

Conclusion. The results obtained using intraoperative peritumoral administration of radiopharmaceuticals to diagnose lymphatic flow and determine SLNs demonstrate the high accuracy of the method and warrant further study.

Brachytherapy in the Treatment of Non-Small Cell Lung Cancer

Andrey Ivanovich Arseniev — 2024-05-06

The literature review is dedicated to analysing the feasibility, efficacy and safety of using brachytherapy in non-small cell lung cancer. A small number of publications highlighting this issue attract attention. It is shown that the method can be implemented with different isotopes and radiation dose rate options from ultra-low to high. There are three main approaches to brachytherapy in thoracic oncology: intraoperative, interstitial and intraluminal. A number of clinical trials, prospective randomised trials and meta-analyses have shown that brachytherapy significantly increases objective response, local control and survival rates in both localised and widespread disease, with acceptable side effects. The focus is on the possibilities of using intraluminal endobronchial brachytherapy in central lung cancer with lesions of the large bronchi and trachea as part of radical, palliative and symptomatic treatment. It has been shown that it is preferable to use equipment with a high dose rate source in order to shorten the duration of the sessions and reduce patient pain. It is a reasonable method when the options of radiotherapy and chemotherapy have been exhausted. It is recommended that the appropriateness of endobronchial brachytherapy be determined on an individual basis. The own data show that median survival in the endobronchial brachytherapy group was 19 months versus 8 months in the no brachytherapy group, 1-year overall survival was 68 % versus 33 %, and 2-year survival was 37 % versus 8 %. One of the indications for palliative use of the method is endobronchial obstruction, especially recurrent. It is recommended that new randomized controlled trials (RCTs) be conducted to evaluate the efficacy and safety of the method. Improvements in brachytherapy outcomes can be achieved through the use of modern high-tech equipment, improved planning systems, radiation dose calculation methods, fractionation mode and optimization of combination with systemic treatment.

Comparative Activity of Chlonisol and Lomustinе in Mice with Intraorbital Transplant of Ehrlich Carcinoma

Valery Anatolyevich Alexandrov — 2024-05-06

Aim. To model the orbital tumor by intraorbital transplantation of Ehrlich carcinoma (EC) in mice and to evaluate the activity of the domestic compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1,3-propanediol (chlonisol) in this model in comparison with its structural analogous drug lomustine.

Materials and methods. To model intraorbital tumors in 40 BALB/c mice, tumor cells of the standard EC strain (1 × 10⁶ cells in 0.05 ml of sterile 0.9 % sodium chloride solution) were used, which were injected using a thin needle transconjunctivally into the cavity of the right orbit above its lower wall. When testing the method (on 10 mice), it was shown that the tumor grows rapidly, destroys the structures, and spreads beyond the orbit. Other mice were divided into three groups (10 animals each) with a single dose of lomustine (50 mg/kg, per os), chlonisol (20 mg/kg, i.p.) or vehicle (control). The antitumor activity of the drugs was assessed by the inhibition of the transplanted tumor growth and the survival rate of the animals.

Results. Both the drugs inhibited tumor growth: lomustine — by 59-72 %, and chlonisol — by 95-100 % compared with the control (р < 0,01-0,0001). The inhibitory activity of chlorinisol was statistically significantly higher than that of lomustine. Median lifespan was increased by 28 % (p = 0.006) with lomustine treatment compared to control, and 212 % (p < 0.0001) with chlorinisol treatment. Median lifespan was increased by 28 % (p = 0.006) with lomustine treatment, and 212 % (p < 0.0001) with chlorinisol treatment compared to control. When the efficacy of the drugs was compared, chlorinisol showed a 144 % higher rate of efficacy than lomustine (p = 0.0005). Half of the mice in the chlorinisol group lived more than 90 days without recurrence, which can be considered as cure.

Conclusion. In mice with EC transplanted into the orbit, the antitumor activity of the compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1,3-propanediol (chlonisol) was statistically significantly higher than that of its structural analogue, the drug lomustine.