Vol 27, No 7 (2020)

Immune checkpoint inhibitors have heralded the advent of a “new era" in cancer treatment, significantly improving long-term survival of patients. While these novel agents are often well tolerated, they are widely known to cause a unique profile of immune-mediated toxicities. Any organ systems can be harmed be immune therapy, but the skin, gastro-intestinal tract, liver, lungs and endocrine system are most commonly affected. In recent years, an increasing number of atypical and sometimes life-threatening side effects have been reported, which requires early recognition and prompt intervention. This article reviews rare immune-related adverse events, their diagnosis and management.

Most neuroendocrine tumors (NETs) are slow-growing neoplasms, often occurring in people of working age or very young, who need long-term follow-up and treatment. A multidisciplinary approach is currently the optimal method for the diagnosis and management of patients with NETs. It is associated with improving the quality and timing of diagnosis, developing the most rational individual algorithm for treating patients, increasing their survival, reducing treatment costs by eliminating the use of ineffective drugs. The global medical community considers the creation of regional interdisciplinary expert centers (IDEC) to be the global trend and the “gold" standard for the provision of medical care for NETS. In April 2019, in the Russian Federation a project to create an IDEC for the treatment of NETs was launched, and 6 such centers have already been created. The experience of the work of first of them, created on the basis of the M.F. Vladimirsky Moscow Regional Research Clinical Institute (MONIKI), is presented. From September 2019 to May 2020, 56 tumors of various localization were tested there. The problems of determining the somatostatin receptor expression in NETs of various localization in terms of indications for the use of somatostatin analogues are discussed.

Background. Current Russian recommendations for adjuvant therapy for patients with gastric cancer are supported by the results of clinical studies conducted among Asian patient population. Given the discrepancy in the overall survival (OS) of patients of different ethnic groups, we can assume the fundamentally distinctive features of the biology of their tumors. Objective. Evaluation of the long-term results of treatment of patients with locally advanced gastric cancer. Methods For a retrospective analysis, patients with a diagnosis of II - III stage gastric cancer who received treatment from 2009 to 2010 in the St. Petersburg City Clinical Oncology Dispensary were selected. All patients underwent radical surgical treatment (resection/gas-trectomy), followed by adjuvant chemotherapy (ACT) in PF mode (taking into account the standards at the time of treatment initiation) for 4 to 10 weeks. Results. The median survival of patients undergoing complex treatment was 26 months. The number of weeks (4-6) from the initiation of surgical treatment to the onset of ACT did not significantly affect OS. The number of cycles of ACT significantly increases the OS (more than 3 cycles). The degree of tumor differentiation did not significantly affect OS, and the colloid histological type can reliably be a factor in the poor prognosis. Conclusion. The results of a retrospective study among patients of the City Clinical Oncology Dispensary are comparable to those of key international studies and their meta-analyzes. Search for ways to improve results should be through the use of perioperative chemotherapy. Adjuvant therapy remains relevant for those patients in whom the first stage of treatment was surgical due to the complicated course of the disease or for other reasons.

Background. Nab-paclitaxel is a nanodispersed albumin-stabilized paclitaxel. This structure significantly changes the properties of paclitaxel, because albumin provides delivery and accumulation of paclitaxel in tumor tissue, and also affects its undesirable effects. Objective. Evaluation of the efficacy and safety of a combination of gemcitabine and nab-paclitaxel in patients with locally advanced and advanced pancreatic cancer. Methods. The data on treatment with nab-paclitaxel and gemcitabine in standard dosages in 23 patients with locally advanced and advanced pancreatic cancer were analyzed. The direct clinical effect, overall and progression-free survival, and adverse events associated with antitumor therapy were evaluated. Results. The objective antitumor effect (PR) was 26.1% (6), and 73.9% (17 patients) achieved tumor control (PR + CD). The median PFS was 6.0 months, OS - 9.7 months. The most common adverse events included neutropenia (34.7%), thrombocytopenia (34.7%), and anemia (43.5%). Non-hematologic toxicity was much less common. In some patients, complications led to the dose reduction (17.4%), delayed administration of cytostatics (17.3%), and discontinuation of therapy (4.3%). Conclusion Nab-paclitaxel in combination with gemcitabine has demonstrated clinical efficacy in the treatment of locally advanced and advanced pancreatic cancer, comparable to the results of international and retrospective Russian studies. This combination is characterized by a favorable toxicity profile and can be used, among others, in weakened patients with ECOG 2. It is necessary to carefully monitor non-hematological adverse events, because, despite their relative rarity, their severity and nature can significantly affect the treatment of patients with this severe oncopathology

Background. Morbidity and mortality from oral squamous cell carcinoma occupy a significant place in the structure of morbidity in Russia. Therefore, the search for informative prognostic factors remains an urgent task for oncologists involved in the treatment of malignant tumors of the oral mucosa. Objective. Determination of the occurrence of DNA of oncogenic viruses in the structure of oral squamous cell carcinoma and to determination of the prognostic role of the detected viruses in the survival rates of patients. Methods. A prospective study included 116 patients with newly diagnosed oral squamous cell carcinoma. In all tumor tissue samples, HSV-I, -II, CMV, EBV, HPV-6, -11, HPV-16 and HPV-18 DNA were detected using real-time PCR. The overall survival (OS) and progression-free survival (PFS) were analyzed. Results. In 54 (46.6%) patients, viral DNA was absent in the tumor structure. In the others, EBV DNA was detected significantly more often - in 40 (34.5%), and HPV(types 6, 11, 16 and 18) - in 48 (41.4%): HPV-6,-11 - in 16 (13, 8%), HPV-16 - in 12 (10.3%), HPV-18 - in 20 (17.2%). HSV-I, -II, and CMV DNA were detected less frequently: HSV-I,-II were detected in 2 (1.7%) patients, CMV - in 5 (4.3%). The median OS of virus-positive patients who underwent non-radical treatment was 15.0 months (95% CI, 12.0-27.0), virus-negative - 10.0 months (95% CI, 5.5-12,0; p=0.0049). The median PFS of virus-positive patients who underwent non-radical treatment was 6.0 months higher than that of virus-negative patients: 11.0 months (95% CI, 9.0-13.5) versus 5.0 months (95% CI, 3.0-6.0; p=0.0053). Conclusion. The analysis suggests that the presence of DNA of the considered types of viruses in the cells of oral squamous cell carcinoma may be a factor in the favorable course of the disease, increasing the survival rates of patients even after nonradical treatment program.

Background. Despite the success of the treatment of oncological diseases, which significantly increase the duration and quality of life of patients, the oncological disease still has a stressful character. The situation of oncological disease affects all the functioning systems of oncologic patients (biological, physical, mental and social), influencing lifestyle in general. Such changes are often accompanied by anxiety-depressive, anti-vital reactions among oncologic patients, which, on the one hand, reflect the process of experiencing a difficult life situation, and on the other hand, create a situation of risk of low adherence to treatment, Objective. Analysis of anti-vital trends among oncologic patients, which allows identifying factors provoking an increase in these trends and evaluating the effectiveness of psychocorrectional measures for anti-vital experiences. Methods. In the period from 2018 to 2020, a study of oncologic patients with anti-vital experiences, depressive and anxious reactions of varying severity was conducted on the basis of the N.N. Petrov National Medical Research Center of Oncology. All patients received individual and group psychological correction as part of a cognitive-behavioral approach. Psychodiagnostic examination of patients was carried out using a clinical diagnostic conversation, the Hopelessness Scale, the hospital Anxiety and Depression Scale before, immediately after and 6 months after psycho-corrective measures. Results. There were two subgroups of patients: the subgroup with severe anti-vital experiences included patients with malignant neoplasms of the gastrointestinal tract (43%), head and neck (36%), lung (21%), 34% of patients had stage III disease, 66% of patients - IV stage. The second subgroup included patients demonstrating mild anti-vital experiences with malignant neoplasms of the mammary gland (39%), organs of the female reproductive system (23%), urogenital system (20%) and lymphoproliferative diseases (18%), 69% of patients had stage II diseases and 31% - stage III. According to the results of the study, it was found that patients of the first subgroup show a high level of hopelessness according to the Beck scale (13.6), coupled with a high level of depression according to HADS scale (10.4, r=2.6 at p=0.041). The second subgroup is characterized by low indicators of hopelessness (4.7, p=0.035), coupled with high rates of anxiety (10.8, p=0.045). Conclusion The risk group for enhancing anti-vital experiences included patients with the following characteristics: male gender, old age, loneliness or social isolation, loss of social-role functioning, time after diagnosis (first year), localization of the tumor process (tumors of the gastrointestinal tract, head and neck , lung), stage of the tumor process (III, IV), physical distress (pain, asthenia). Psychological correction in the framework of cognitive-behavioral therapy in a family, individual and group format is effective to reduce anti-vital experiences within 6 months after the end of psychocorrectional measures

First-line CHOP-R immunochemotherapy provides long-term progression-free survival (PFS) in 33-96% of patients with diffuse large B-cell lymphoma (DLBCL) depending on the prognosis, but progression or relapse occurs in 30-40% of patients. When carrying out high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT with auto-HSCT) for patients with chemo-sen-sitive recurrence of DLBCL, 5-year event-free survival (EFS) reaches 46%, overall survival (OS) - 53%. To improve the results of HDCT with auto-HSCT, new “rescue" therapy regimens are being studied, as well as modes of supporting remission after HDCT with auto-HSCT. The effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with recurrence of DLBCL after HDCT with auto-HSCT was confirmed by high rates of 3-year PFS and OS - 41 and 53%. Modern ideas about the molecular biological characteristics of DLBCL justify the use of immunotherapy in the treatment of relapses and refractory forms. Modern “rescue" therapies for the DLBCL with high efficacy and low toxicity are especially relevant for patients who are not candidates for HDCT with auto-HSCT, as well as for relapses after HDCT with auto-HSCT. In June 2019, the FDA granted accelerated approval for the use of polatuzumab vedotin in combination with bendamustine and rituximab for the treatment of relapses and refractory forms of DLBCL after two or more lines of previous therapy. In June 2018, the FDA granted granted for pembrolizumab in the treatment of adults and children with relapses and refractory forms of primary mediastinal (thymic) B-cell lymphoma (PMBCL) after two or more lines of previous systemic therapy. The antitumor efficacy of the combination of nivolumab with brentuximab vedotin is significantly higher compared to that of monotherapy with nivolumab/pembrolizumab, brentuximab vedotin: the overall response (OR) rates are 73.0%, 48.0 and 13.3%, complete remissions (CR) - 37% , 13, 0% in PMVCL patients with relapses and refractory forms. In the Phase IIL-MIND study [NCT0239085], the efficacy of tafasitamab (OR - 60%, CR - 43%) is comparable to that of CAR-Tcell therapy in patients with relapses and refractory forms of DLBCL, while tafasitamab has significantly lower toxicity. In order to increase the antitumor effect of immunotherapy, combined modes are being studied, primarily with various mechanisms of action and possible synergistic antitumor activity. The identification of predictive biomarkers will allow to develop an optimal algorithm for the appointment of immunotherapy, which helps to determine the dose, regimen, effectiveness and duration of therapy. Promising areas of DLBCL therapy are associated with the further study of new targets for tumor cells and their signaling pathways.

Currently, immunotherapy is a leader in the treatment of disseminated melanoma, kidney cancer, pulmonary cancer, and is an option for the treatment of some solid tumors. However, in some cases, despite the improvement of clinical responses, immunotherapy is ineffective. The search for predictors of the immune response remains an urgent problem in modern antitumor therapy. This review demonstrates the results of studies describing the possibility of using a number of predictive and prognostic markers with high efficiency in clinical practice.

Background. The presence of HIV infection is a risk factor for many malignant diseases, including skin melanoma. Given the current lack of stabilization of the incidence rates of both skin melanoma and HIV infection, the search for effective and safe methods of treatment with a combination of these diseases is of great social importance. Combination therapy with vemurafenib and cobimetinib serves as a standard of treatment and has high therapeutic potential in patients with metastatic melanoma with BRAF V600 gene mutation. The toxicity profile of the combination of vemurafenib and cobimetinib was acceptable and manageable in the framework of international clinical trials and in real oncological practice; however, the spectrum of adverse events associated with their combined use with antiretroviral drugs is currently unknown. Description of the clinical case. The clinical experience of the combined targeted regimen of vemurafenib+cobimetinib in the treatment of BRAF-positive metastatic skin melanoma in a patient with HIV infection receiving antiretroviral therapy (ARVT) is presented. The treatment was accompanied by pronounced effects of skin toxicity, which may be associated with the drug-drug interaction of targeted therapy with two ARVT drugs (ritonavir, darunavir), which are a powerful inhibitors of the CYP3A4 isoenzyme and have a narrow therapeutic potential. Nevertheless, taking into account the initial degree of melanoma extension at the time of the start of antitumor therapy, the effect obtained and the possibility of correcting toxic effects in an extremely short time, treatment with the combination of targeted drugs vemurafenib+cobimetinib is justified in the considered clinical situation. The general condition of patient is satisfactory and the effect of stabilization of the tumor process maintains after 8 months of treatment. Conclusion. Given the multifactorial nature of HIV infection and oncological diseases, as well as the potential interaction between antiretroviral and anticancer drugs, it is necessary to improve coordination of treatment and communication between oncologists and infectious disease specialists. Also, it is necessary to accumulate clinical experience of combined use of antiretroviral therapy and anticancer drugs to obtain complete information about the effectiveness and safety of treatment in this category of patients.