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The narrative review addresses the evidence that physical activity can improve the results of prevention and treatment and of the conditions that feature increased risks of their development with aging. The main attention is paid to cancer and problems arising because of physical activity limitations associated with COVID-19 pandemic. To promote physical activity, which is known to reduce the risks of COVID-19 complications and of cancer, it is important to help patients and physicians in understanding the reasons why physical activity can be beneficial, more than the pharmacological means thought to reproduce some of its effects, in cancer prevention and treatment upon all differences between the locations of tumors and the pathways of carcinogenesis. Therefore, the physiological and molecular mechanisms behind the usefulness of physical activity in oncology are discussed. Based on this discussion, data on quantitative relationships between oncological risks, physical activity, and the use of its alleged pharmacological mimetics are addressed. © 2021 Izdatel'stvo Meditsina. All rights reserved.

The article presents the results of a study of the biopsychosocial principle in the rehabilitation of patients with breast cancer. Aim. to assess the need for patients with operable breast cancer in rehabilitation measures at various stages of treatment. Results. when assessing the need for rehabilitation of patients with operable breast cancer, it was found that the need for rehabilitation measures in all patients increases in the postoperative period and persists for 12 months after the end of treatment. Special attention should be paid to the indicators of physical and social functioning in subgroups of patients who received neoadjuvant chemotherapy: increased fatigue, weight gain, unstable emotional background impose significant restrictions on the socio-role functioning of patients, reducing the quality of life and increasing the risks associated with the progression of the underlying disease, exacerbation of chronic diseases. Thus, patients who participated in the program of rehabilitation measures in the framework of the biopsychosocial approach showed the best performance after the end of treatment during the observation period: in the subgroup of patients receiving chemotherapy and rehabilitation in the framework of the biopsychosocial model, the dynamics of the recovery needs of the operation sought to average indicators by domain “b4552 Fatigue” – 21%, “b4551 Aerobic capacity “ – 18%, “d240 Handling stress and other psychological demands » – 39%, “b710 Mobility of joint functions “ – 29%, self-service (“d510 Washing”; “ d540 Dressing») – 21%, “b455 Exercise tolerance functions “ – 22%. In the subgroup of patients who received on-demand rehabilitation, there was an increase in the need for rehabilitation by domain: “d240 Handling stress and other psychological demands “ – 45%, “b4552 Fatigue” – 28%, self-service (“d510 Washing”; “ d540 Dressing») – 32%, b455 Exercise tolerance functions – 30%. Conclusion: The results of the study suggest a positive effect of rehabilitation measures on the functioning of patients with operable breast cancer.

The review presents the data on the specifics of mechanism of action, classification, and clinical manifestations of neurotoxicity effect. The most significant features of specific side effects when using taxanes in different treatment regimens, including cumulative doses, are considered. The proven methods of treatment and prevention of neuropathy caused by anticancer drugs are discussed.

Relevance: early breast cancer is detected in more than 60% of cases. Maintaining the quality of life of patients with early breast cancer at the highest possible level is a priority, along with the treatment of patients. Under a complex antitumor treatment as well as after its completion, more than 60% of patients with early breast cancer report the occurrence of functional disorders.An important aspect is to improve the effectiveness of the rehabilitation process of patients with early breast cancer taking into account scientifically-based and proven recommendations.Objective: to evaluate the event-free survival rate (EFS) of patients with EBC undergoing rehabilitation within a biopsychosocial approach.Materials and methods: 228 patients with breast cancer who received complex treatment from 2015 to 2019 were included in the study. The prospective part of the study included 114 patients with early breast cancer undergoing rehabilitation measures within the biopsychosocial approach. The control group which was selected retrospectively, using the method of "pairwise selection", included 114 patients with early breast cancer comparable in age, stage of the disease, volume of surgical treatment and menopausal status, undergoing physical and psychological rehabilitation prescribed by a doctor. Patients in both groups were stratified depending on preoperative chemotherapy. EFS was calculated over a 2-year follow-up period. Events that were censored were a disease progression, the appearance of metastases, the occurrence of another cancer, a new concomitant disease, an exacerbation of the concomitant pathology and death.Results: Rehabilitation measures within the biopsychosocial model improve the indicators of EFS in the group of patients with EBC: EFS was 18.3 months against 14.5 months in the control group (HR=0.91, 95% CI [0.83; 0.99]; p=0.0034). In a multi-factor analysis the key factors affecting EFS were neoadjuvant chemotherapy (HR=0.79, 95% CI [0.69; 0.94]; p=0.0025), age (HR=0.87, 95% CI [0.71;1.09]; p=0.0027) and menopausal status (HR=0.85, 95% CI [0.84; 0.95]; p=0.0022) (table 1). Conclusions: Rehabilitation measures within the biopsychosocial model improve the indicators of EFS in the group of patients with early breast cancer, the key factors affecting EFS were neoadjuvant chemotherapy, age and menopausal status. Table 1 Multi-factor analysis of event-free survival of patients with early breast cancer in the group of biopsychosocial model of rehabilitation versus control group.CharacteristicNumber of patientsHR (95% CI)Preoperative chemotherapyyes1520,84 (0,77; 1,1)no760,79 (0,69; 0,94)Menopauseyes1300,84 (0,77; 1,04)no980,85 (0,84; 0,95)Age group25-44610,87 (0,71; 1,09)45-601030,89 (0,74; 1,1)61-75641,01 (0,82; 1,24)EventDisease progression281,11 (0,86; 1,26)Exacerbation of the concomitant pathology160,83 (0,74; 0,96) Citation Format: Valeria Kluge, Tatiana Semiglazova, Petr Krivorotko, Elena Melnikova, Vladislav Semiglazov, Kristina Kondrateva, Svetlana Nazarova, Margarita Tynkasova, Bahtiyar Adhamov, Roman Pesotsky, Konstantin Zernov, Valentina Chulkova, Boris Kasparov, Denis Kovlen, Vladimir Semiglazov, Alexey Belyaev. Biopsychosocial approach in the rehabilitation of patients with early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-62.

Background Previous studies on neoadjuvant therapy for BRCA1-driven ovarian cancer (OC) demonstrated higher efficacy of mitomycin C plus cisplatin combination as compared to standard drug schemes. These data call for evaluation of the utility of this regimen for the treatment of recurrent BRCA1-associated OC. Methods The study included 12 BRCA1 germ-line mutation carriers, whose disease relapsed after one (n = 4) or two (n = 8) lines of chemotherapy. The patients received cisplatin 100 mg/m2 and mitomycin C 10 mg/m2, given every four weeks, for 6 (n = 10), 8 (n = 1) or 5 (n = 1) cycles. Retrospective data on conventional treatment of OC relapses in BRCA1 heterozygotes (n = 47) served as a control. Results Grade 3–4 toxicities were observed in 4/12 (33%) cases. There were 6 complete responses (CR), 4 partial responses (PR) and 2 instances of stable disease (SD). Comparison of patients receiving mitomycin C plus cisplatin (n = 4) or conventional therapy (n = 44) at first relapse demonstrated marginal improvement of the progression-free survival (PFS) (16.6 months vs. 10.2 months, P = .067). Use of mitomycin C plus cisplatin (n = 8) for the treatment of second relapse resulted in significant prolongation of PFS as compared to standard regimens (n = 31) (14.8 months vs. 4.8 months, P = .002). Conclusions Mitomycin C plus cisplatin shows promising activity in recurrent BRCA1-driven ovarian cancer.

Introduction: The effects of chemotherapy are known to depend on the time of administration. Circadian rhythms are disturbed in tumors and in tumor bearers. Agents involved in controlling the circadian rhythms (chronobiotics) potentially can modify the outcomes of chemotherapeutics administered at different times of the day. Pineal hormone melatonin (MT) is a prototypic chronobiotic. Objective: The aim of the study was to investigate if MT can affect efficacy or toxicity of chemotherapy drugs administered at the extreme time points of the working day of hospital personnel. Methods: Cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and adriamycin and docetaxel (AT) cytotoxic drug combinations were administered on day 0 at 11:00 a.m. or at 5:00 p.m. (UTC+03:00) to 6-month-old female HER2/neu transgenic FVB/N mice bearing mammary adenocarcinomas. Some mice were additionally provided with MT in drinking water (20 mg/L) at night 1 week before or 3 weeks after treatment or during both periods. Tumor node sizes, body weight, and blood cell counts were determined right before treatment and on days 2, 7, 14, and 21. Results: Significant decrease in the mean tumor node volume was found by days 14 and 21 upon all CAF and AT treatment schedules, except in animals treated with AT at 5:00 p.m. without supplementation with MT. In the latter case, mean tumor node volume on day 21 was the same as in the control. Supplementation of AT administered at 5:00 p.m. with MT improved the tumor response. CAF and AT regimens supplemented with MT also augmented the number of tumor nodes that did not increase by more than 20% by day 21 as compared to CAF or AT alone, respectively. This effect was significant in groups treated with AT at 5:00 p.m. and consistent upon other schedules. On day 7, leukopenia and anemia were registered in groups treated with CAF regimen; however, blood cell counts normalized by day 14. Both CAF and AT were associated with drop in the body weight registered on day 7. Supplementation with MT did not affect changes of the body weight and blood counts. Conclusions: MT supplementation to cytotoxic drugs can improve antitumor response, especially if it is blunted because of an inappropriate time of administration.

Relevance: The strategy of finding evidence on the use of rehabilitation technologies in patients with lung cancer is based on scientometric analysis. Methods: For the period from 1991 to 2018. Using PICO (T) technology in electronic databases (PEDro, PubMed, Elibrary, Cochrane Library), full-text analysis of 249682 studies was performed. MeSH bibliographic descriptors: «lung cancer», «rehabilitation», «physical therapy». Studies were evaluated on a PEDro scale, which includes 10 parameters of the level of evidence: randomization, endpoint evaluation, blinding, etc. Results: The verified distribution profile of research on the quality of evidence showed that 55.9% of studies had a quality level of 4 to 8 on the PEDro scale. One study had a quality level of 9 points (0.8%). The bulk of research (69%) is devoted to the study of the effectiveness of exercise. Evaluation of the effectiveness of respiratory gymnastics, traditional health practices (Tai Chi, gypsy, yoga, etc.) are devoted to 7.5% of the studies. 6.5% of works are devoted to studying the effectiveness of acupuncture. Analysis of the effectiveness of non-invasive ventilation technology (mainly CPAP), the effects of artificially modified air (aerosol therapy, aerophytotherapy), and therapeutic physical factors of mechanical nature (massage, vibrotherapy) is devoted to 10.8% of studies. The use of technologies of physical rehabilitation measures using electromagnetic factors is devoted to 3.2%. In 2% of the studies, an assessment of the effectiveness of respiratory gymnastics was presented, and in a number of works, such technologies of physical rehabilitation, which are gaining popularity in the rehabilitation of patients with lung cancer, have been studied as kinesio-taping and audio-visual relaxation (1% each). Conclusion: Clinical recommendations developed on the basis of the obtained results will form the basis of a new, evidence-based stage in the development of the rehabilitation of patients with lung cancer in Russia.

Aim: to analyze the dynamics of morbidity and mortality from digestive diseases, as well as their causes, in the RF Northwestern Federal District (NWFD).Materials and methods. A statistical analysis was carried out on the basis of the 2007–2017 annual reports of the Medical Information and Analytical Center (MIAC) in St. Petersburg and the reports of the chief gastroenterologists of the Northwestern Federal District subjects.Results. In the RF Northwestern Federal District, an increase in both morbidity and mortality from digestive diseases is observed. The main non-oncological reasons for the development of these disorders include alcoholic liver disease, chronic alcoholic pancreatitis, peptic ulcer complications and NSAID-associated gastropathies. Along with a decrease in the incidence of gastric cancer, an increase in the incidence of colorectal cancer, as well as pancreatic cancer, is observed. A decrease in mortality from all the aforementioned cancer localizations is revealed.Conclusions. The main reasons for the increase in morbidity and mortality due to gastroenterological diseases in the RF Northwestern Federal District include alcohol abuse among the population, inadequate prevention of gastric helicobacteriosis, insufficient expertise of physicians in terms of Helicobacter pylorieradication and cancer prevention.

The first part of the study includes a brief historical outline on the creation of an objective system for assessing the activities of the oncological service in Russia and the Northwestern Federal District of the Russian Federation.Dynamic series of all types of indicators of the populations morbidity and mortality have been presented, an increasing process of reliability and improvement of the quality of registration of primary patients with malignant tumors has been shown.In Russia, aswell as in the Northwestern Federal District of the Russian Federation, standardized indicators of the malignant tumorsincidence remain at a relatively low level. In the world ranking of Cancer Registries, the Russian Federation is on 300th place among 450 others.The mortality rate of the population in most localizations isrecorded above the average European indicators.

The spectrum of BRCA1 and BRCA2 mutations in Slavic countries is characterized by a high prevalence of founder alleles. We analyzed a large data set of Russian breast cancer (BC) and ovarian cancer (OC) patients, who were subjected to founder mutation tests or full-length BRCA1 and BRCA2 analysis. The most commonly applied test, which included four founder mutations (BRCA1: 5382insC, 4153delA, 185delAG; BRCA2: 6174delT), identified BRCA1 or BRCA2 heterozygosity in 399/8533 (4.7%) consecutive BC patients, 230/2317 (9.9%) OC patients, and 30/118 (25.4%) women with a combination of BC and OC. The addition of another four recurrent BRCA1 mutations to the test (BRCA1 C61G, 2080delA, 3819del5, 3875del4) resulted in evident increase in the number of identified mutation carriers (BC: 16/993 (1.6%); OC: 34/1289 (2.6%); BC + OC: 2/39 (5.1%)). Full-length sequencing of the entire BRCA1 and BRCA2 coding region was applied to 785 women, very most of whom demonstrated clinical signs of BRCA-driven disease, but turned out negative for all described above founder alleles. This analysis revealed additional BRCA1 or BRCA2 mutation carriers in 54/282 (19.1%) BC, 50/472 (10.6%) OC, and 13/31 (42%) BC + OC patients. The analysis of frequencies of founder and “rare” BRCA1 and BRCA2 pathogenic alleles across various clinical subgroups (BC vs. OC vs. BC + OC; family history positive vs. negative; young vs. late-onset; none vs. single vs. multiple clinical indicators of BRCA1- or BRCA2-associated disease) revealed that comprehensive BRCA1 and BRCA2 analysis increased more than twice the number of identified mutation carriers in all categories of the examined women. Full-length BRCA1 and BRCA2 sequencing is strongly advised to Slavic subjects, who have medical indications for BRCA1 and BRCA2 testing but are negative for recurrent BRCA1 and BRCA2 mutations.

ObjectivesCisplatin and mitomycin C exert high activity towards BRCA1-deficient cells. This study aimed to evaluate the efficacy of a combination of these drugs in hereditary BRCA1-associated ovarian cancer (OC).MethodsTwelve OC patients, who could not be treated by primary debulking surgery owing to extensive tumor spread, were given neoadjuvant cisplatin (100 mg/m2) and mitomycin C (10 mg/m2) every 4 weeks for 3 (n = 9), 2 (n = 2), or 4 (n = 1) cycles.ResultsThe decrease of tumor burden and complete surgical cytoreduction were achieved in all patients. Pathologic complete response, defined as the absence of tumor cells in surgically removed tissues, was observed in 2 (17%) of 12 cases. Retrospective analysis of 62 OC in BRCA1 mutation carriers subjected to conventional neoadjuvant chemotherapy schemes revealed 36 objective tumor responses (58%) and 37 instances (60%) of complete cytoreductive surgery; however, none of these patients demonstrated pathologic complete response.ConclusionsThe combination of cisplatin plus mitomycin C showed promising results in BRCA1-driven OC and therefore deserves further clinical evaluation.

The conference "Results and prospects of development of new polyphenolic drugs for cancer patients" took place at the N.N. Petrov National Medical Research Center of Oncology (PNMRCO) on May 31, 2017, and gathered researchers involved in development and evaluation of medicinal products based on the novel lignin-derived soluble polyphenolic polymer BP-Cx-1. BP-Cx-1 is the platform for a portfolio of innovative pharmacological products such as BP-C1, BP-C2 and BP-C3.

Distribution of cancer-predisposing mutations demonstrates significant interethnic variations. This study aimed to evaluate patterns of APC and MUTYH germ-line mutations in Russian patients with colorectal malignancies. APC gene defects were identified in 26/38 (68%) subjects with colon polyposis; 8/26 (31%) APC mutations were associated with 2 known mutational hotspots (p.E1309Dfs*4 [n = 5] and p.Q1062fs* [n = 3]), while 6/26 (23%) mutations were novel (p.K73Nfs*6, p.S254Hfs*12, p.S1072Kfs*9, p.E1547Kfs*11, p.L1564X and p.C1263Wfs*22). Biallelic mutations in MUTYH gene were detected in 3/12 (25%) remaining subjects with polyposis and in 6/90 (6.7%) patients with colorectal cancer (CRC) carrying KRAS p.G12C substitution, but not in 231 early-onset CRC cases negative for KRAS p.G12C allele. In addition to known European founder alleles p.Y179C and p.G396D, this study revealed a recurrent character of MUTYH p.R245H germ-line mutation. Besides that, 3 novel pathogenic MUTYH alleles (p.L111P, p.R245S and p.Q293X) were found. Targeted next-generation sequencing of 7 APC/MUTYH mutation-negative DNA samples identified novel potentially pathogenic POLD1 variant (p.L460R) in 1 patient and known low-penetrant cancer-associated allele CHEK2 p.I157T in 3 patients. The analysis of 1120 healthy subjects revealed 15 heterozygous carriers of recurrent MUTYH mutations, thus the expected incidence of MUTYH-associated polyposis in Russia is likely to be 1:23 000.