Vol 28, No 7 (2021)

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC), which necessitates regular screening for colonic epithelial dysplasia. The pathophysiology of IBD-associated colorectal cancer is reduced to the carcinogenic effect of inflammation. This review describes the epidemiology and pathophysiology of IBD-associated CRC. The strategy of managing IBD patients with the aim of detecting dysplasia in the early stages and preventing colorectal cancer from the standpoint of domestic and foreign clinical guidelines of leading medical communities is considered in detail. The literature search was carried out in PubMed and Google Scholar systems using the keywords: ulcerative colitis, Crohn's disease, colorectal cancer, pathophysiology, genetic predisposition, microbiota, risk factors, screening, recommendations. We have focused on clinical guidelines and studies published over the past years, and offer their review to general practitioners, gastroenterologists and coloproctologists for use in daily practice.

Alpelisib is a new drug registered in Russia in 2020 for patients with luminal HER2- metastatic breast cancer with a confirmed mutation in the PIK3CA gene, who have developed resistance against the background of previous endocrine therapy. The results of the SOLAR-1 and BYLieve trials demonstrated not only the effectiveness of the drug, but also new types of toxicity inherent in this therapy. To date, recommendations for the prevention and treatment of the most common adverse events, which make it possible to use the drug as safely as possible, have been developed. This article presents our own clinical experience with the use of Alpelisib with an emphasis on dermatological toxicity, as well as an overview of current recommendations devoted to this problem.

The standard treatment for diffuse large B-cell lymphoma (DLBCL) is R-CHOP immunochemotherapy. About 60% of patients are completely cured by 1st-line therapy; primary-resistant forms account for about 15%, recurrence of the disease with the highest frequency in the first two years after diagnosis occurs in 25% of patients. Treatment outcomes for high-risk DLBCL (aalPI) patients are suboptimal. The search to achieve complete long-term remission during 1st-line therapy continues. The advantage of high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in 1st-line treatment of DLBCL remains controversial. A meta-analysis of randomized and retrospective trials revealed only short-term improvement in survival with 1st-line HDCT with auto-HSCT in patients with high intermediate and high risk DLBCL. The benefits of HDCT with auto-HSCT in terms of long-term survival were noted only in retrospective studies in achieving a complete response (PET-CT) after induction chemotherapy (CT). Early consolidation of HDCT with auto-HSCT in patients with high-risk DLBCL, taking into account only clinical factors, does not lead to an improvement in survival and increases the risk of grade 3-4 adverse events. Identification of clinical, morphological and genetic factors of the effectiveness of anticancer therapy and prognosis will make it possible to determine the optimal strategy for DLBCL therapy. Further prospective studies of predictive and prognostic factors to identify patients in whom early consolidation of HDCT with auto-HSCT of the first complete remission may become the optimal method of choosing therapy are required.

While combined hormone therapy is the generally accepted standard regardless of the patient’s menopausal status in advanced ER+ HER2 breast cancer, in the case of neoadjuvant therapy for locally advanced forms, chemotherapy with the inclusion of anthracyclines and taxanes remains the standard. The objective of this review was the scientific substantiation of the advisability of using combined hormone therapy at the preoperative stage of treatment of this category of patients. After analyzing the information presented in electronic databases (PubMed, MEDLINE, BMS), as well as studying active clinical trials on the ClinicalTrials.gov portal, we concluded that most of the studies related to neoadjuvant hormone therapy were carried out on a population of postmenopausal patients. In this regard, a randomized controlled clinical trial to study the efficacy and safety of a new method of preoperative treatment in premenopausal women with ER+ HER2-locally advanced breast cancer was initiated.

Background. Squamous cell carcinoma of the tongue and oral floor mucosa is one of the most common localizations of tumors of the head and neck, which is characterized by rapid growth, aggressive course, high mortality, and unfavorable prognosis. Objective. Determination of activating mutations in the KRAS gene in the extracellular DNA of blood plasma in patients with squamous cell carcinoma of the tongue and oral floor mucosa during chemotherapy (CT) with targeted therapy with cetuximab or during standard CT without targeted therapy. Methods. Data on 60 patients who underwent chemotherapy in combination with targeted therapy with cetuximab or standard chemotherapy were analyzed. Depending on the effectiveness of treatment, all patients, according to the RECIST 1.1 criteria, were divided into 2 subgroups: sensitivity to treatment (partial regression and stabilization), and resistance (progression). Before the start of antitumor treatment and after 2 cycles, blood samples with a volume of 9 ml were collected in 2 stages. Plasma was isolated by double centrifugation. All extracellular DNA samples were isolated from blood plasma according to the protocol using the cobas cfDNA Sample Preparation Kit. The presence/absence of 7 activating mutations in the second exon of the KRAS gene was detected by Digital Droplet PCR using the KRAS Screening Multiplex kit (Bio-Rad, USA). The data were analyzed using the QuantaSoft v1.7.4 software. Results. It was revealed that when resistance to chemotherapy and cetuximab develops, the ratio of the mutant KRAS type increased by 1.9 times compared to the initial values (p=0.009), exceeding the same indicator in the subgroup with sensitivity by 3.1 times (p=0.049), while the frequency of occurrence of the mutant type of the KRAS gene in the studied sample decreased by 1.5 times (p=0.05), and increased by 3.5 times compared with the subgroup with sensitivity (p=0.0045). The use of cetuximab resulted in a decrease in the frequency of mutations in the KRAS gene and in an increase in the ratio of the number of DNA copies of the mutant KRAS type to the wild type. Conclusion. Thus, it can be concluded that even before the start of treatment, patients resistant to chemotherapy and cetuximab were characterized by an increased occurrence of mutations in the KRAS gene and, obviously, a large number of tumor cells carrying mutations in this gene. Determination of activating mutations in the KRAS gene in the extracellular DNA of blood plasma makes it possible to predict the development of resistance to targeted therapy at the stages of treatment.

Background. Metronomic chemotherapy regimens involving the continuous administration of chemotherapeutic agents in low doses may have additional clinical efficacy due to the activation of the antitumor immune response, while not leading to suppression of the functions of the immune system. Objective. Evaluation of the immunological efficacy of metronomic chemotherapy according to the cyclophosphamide+methotrexate (CM) regimen in combination with immunotherapy with the autologous dendritic cell vaccine CaTeVac in patients with soft tissue sarcomas (STS). Methods. The study included 25 patients with metastatic STS, who received CaTeVac in mono-regimen (n=13) in combination with metronomic therapy with cyclophosphamide and methotrexate (CaTeVac-CM) (n=12) as one of the stages of systemic treatment at the N.N. Petrov National Medical Research Center of Oncology in the 2013-2019. The immunological parameters and survival rates of this group of patients were assessed. Results. The only difference between the groups was found in the number of regulatory T-lymphocytes (T-reg), which significantly decreased during CaTeVac-CM therapy (p=0.0315). The median overall survival in patients receiving CaTeVac-CM was higher than in the group receiving only CaTeVac and amounted to 38.6 and 6.8 months, respectively (p=0.0074). The time to progression also significantly differed between groups and was 5.5 and 2.9 months, respectively (p=0.0416). Conclusion. The addition of metronomic chemotherapy according to the CM regimen to immunotherapy with the autologous dendritic cell vaccine CaTeVac increases the survival rates of patients by reducing the T-reg level. The combination of immunotherapy with metronomic chemotherapy may provide a new approach to the systemic therapy of patients with metastatic STS.

Background. The incidence of nutritional deficiency (ND) among patients with locally advanced gastric cancer (LAGC) ranges from 40 to 60%, sarcopenia - 30%. The evaluation of the effect of ND and sarcopenia on the efficacy of neoadjuvant chemotherapy (NACT) in patients with LAGC is extremely important. Objective. Assessment of the prognostic role of ND and sarcopenia in patients with LAGC treated with NACT. Methods. Retrospective analysis of data on 100 patients with LAGC, mean age 56.9 (45.9-67.9) years, who received NACT at the N.N. Petrov National Medical Research Center of Oncology for the period from 2013 to 2018 was performed. ND, sarcopenia, the incidence of complications against the background of NACT, objective response, pathomorphological regression, 5-year event-free and overall survival were assessed. Results. Before the beginning of the NACT, ND was registered in 47% of cases, after the NACT - in 62%; sarcopenia - in 11 and 22%, respectively. Partial regression was observed in 71% of patients without ND versus 41.9% in the group with ND (p=0.001). The pCR rate in patients without ND was 23.7% versus 4.8% in the group with ND (p<0.001). Febrile neutropenia developed 7.8% in the group without ND versus 27.2% in the group with ND (p=0.001). The 5-year event-free survival in patients without ND was 45.1% versus 15.1% in the group with ND (p=0.026); 5-year overall survival - 63.9% versus 24.5%, respectively (p=0.043). The presence of sarcopenia in patients did not affect all of the above parameters. Conclusion. According to the data of a retrospective analysis, ND is an unfavorable prognostic factor for the effectiveness of NACT in patients with LAGC.

Background. Over the past 20-30 years, great advances in the treatment of gastric cancer (GC) have been made. An important step in the development of new therapeutic agents was the understanding of the role of prognostic and predictive factors, including the significance of the subpopulation composition of immunocompetent cells and tumor biology. Objective. Evaluation of the state of systemic and local immunity before and during drug treatment in patients with gastric adenocarcinoma. Methods. From 2017 to 2018 20 primary patients with metastatic gastric adenocarcinoma received drug therapy at the N.N. Blokhin National Medical Research Center of Oncology. The sampling of biological material (peripheral blood, tumor tissue) was carried out twice (before treatment and during the first control examination, after 3 courses). Using the method of flow cytometry, the degree of infiltration of tumor tissue by lymphocytes (CD45+CD14-TILs); T cells (CD3+CD19-TILs); B cells (CD3-CD19+TILs); NK cells (CD3-CD16+CD56+TILs); CD16 and CD8 effector cells and their cytotoxic potential (CTP) (CD16+Perforin+TILs; CD16CTPTILs), (CD8+Perforin+TILs; CD8CTPTILs); regulatory T cells - NKT cells (CD3+CD16+CD56+TILs), CD4 (CD4+CD25+CD127-TILs) and CD8 (CD8+CD11b-CD28-TILs) regulatory cells were assessed, as well as parameters of systemic and local immunity. Results. An increase in the number of CD8+ T-regulatory cells (5.1-12.1%; p=0.019) in the peripheral blood, and an increase in perforin potential of effector CD16 cells (0.5-4.9%; p=0.030) and their cytotoxic potential (13.2-55.7%; p=0.011) in tumor tissue were factors of a favorable prognosis for progression-free survival (PFS) in patients with metastatic gastric cancer (mGC), When assessing the nature of changes in the indicators of local immunity in the course of chemotherapy, a negative effect of an increase in the content of T cells (22.0- -9.7%; p=0.012), NKT-cells (207.9- -13.8%; p=0.002) and CD4+ T-regulatory cells (190.7- -25.2%; p=0.002) was revealed. On the contrary, an increase in the level of effector CD16 cells during chemotherapy increases the likelihood of surviving PFS - 9 months (-69.5-9.1%; p=0.013). Conclusion. Indicators of local and systemic immunity serve as additional prognostic factors in gastric cancer.

Background. Monoimmunotherapy (mIT) in the 1st line of treatment for non-small cell lung cancer (NSCLC) is performed in patients with a high PD-L1 expression (>50%) or with severe concomitant pathology and contraindications to therapy with platinum drugs with an intermediate level of PD-L1 expression (1-49%). Therapy is carried out up to 2 years of disease progression or intolerable toxicity. An important issue is determining the optimal duration of treatment in order to find a balance between effectiveness, toxicity, cost and burden on the health care system. To date, there are no prospective studies with sufficient power devoted to this issue. Objective. Evaluation of long-term indicators of the effectiveness of the cycle of monotherapy with immune checkpoint inhibitors (ICPI) in the 1st-line therapy shortened for organizational or medical indication in patients with NSCLC. Methods. The analysis included patients with histologically verified inoperable NSCLC who received 1st-line therapy in 2019-2020. ICPI in the 1st line received 25/230 patients (16 men, 9 women; mean age - 65.4 years). PD-L1 level>/=50% was detected in 18 (72%) patients, 1-49% - in 3 (12%), 0% - in 1 (4%), not assessed - in 3 (12%); adenocarcinoma - in 13 (52%), squamous cell carcinoma - in 12 (48%) patients. All patients received therapy with pembrolizumab 200 mg once every 21 days. Results. The mean follow-up period was 13.1 (0.8-26) months. The mean number of injections of immunotherapy (IT, min-max) was 9.5 (1-28). The objective response rate (ORR) in the 1st line was 18 (72%): complete regression - 3 (12%), partial - 8 (32%), stabilization - 7 (28%), not assessed - 7 (28%), 2 (8%) patients died after the 1st injection of IT, 1 (4%) patient was lost for follow-up. Due to the registered progression of the tumor process, treatment was completed in 12 (48%) patients, the mean number of cycles performed was 4.1 (1-16). Before the progression of the disease or until the end of the planned duration, therapy was interrupted by 9 (36%) of 13 patients: six - due to the tightening of the requirements of the epidemiological situation, three - due to refusal to visit medical institutions. The mean follow-up period after the end of treatment was 8.5 (3.0-14.2) months; 6 (67%) patients whose treatment was interrupted not because of disease progression are observed without progression 9.3 (4.0-12,1) months (min-max). PD in 3 (33%) after the mean follow-up period was 9.3 (7.1-13.2) months (min-max). Conclusion. The data obtained indirectly indicate the absence of a tendency towards a decrease in mPFS and mOS in the group of patients with NSCLC who received mIT in the first line of treatment, for whom treatment was discontinued unscheduled, and not continued until 2 years or until the progression of the tumor process recorded.

The world’s population is aging rapidly. Approximately half of all human malignant neoplasms develop in people over 65 years of age. The body of an elderly patient is influenced by three main factors - the actual malignant neoplasm, concomitant diseases and geriatric status. This necessitates the introduction of a systematic and evidence-based integrated approach, including an assessment of the geriatric status of elderly and senile cancer patients into routine clinical practice. Currently, there are many different strategies for choosing the tactics of treating patients in this category, but there are no clinical guidelines approved by Russian oncological organizations. This article presents the most important aspects of the systemic therapy of patients with solid and lymphoproliferative neoplasms in the elderly and senile age, and the main methods of complex geriatric examination.