N. A. Abramova’s research while affiliated with Tomsk National Research Medical Center and other places

Giant cell tumor of bone is a locally aggressive primary bone neoplasm affecting patients aged 20–50 years. Neoplastic stromal cells have a phenotype of immature osteoblasts synthesizing various cytokines and molecular factors leading to excessive activation of osteoclastogenesis and increased osteolysis in giant cell tumor of bone. Long-term treatment with denosumab is recommended for unresectable or disseminated disease. A clinical case of long-term treatment with denosumab of initially generalized giant cell tumor of the right ischial bone with metastases to the lungs is presented. Stabilization of the process was first recorded 3 months after the start of therapy and has been maintained to date. The patient was transferred to a maintenance regimen 3 years after the start of treatment. The treatment was not accompanied by adverse events characteristic of bone-modifying agents. Long-term use of denosumab allowed effective control of the tumor process and maintenance of satisfactory quality of life of the patient. Maintenance regimen of denosumab administration was not accompanied by a decrease in treatment effectiveness.

Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein‑4 (CTLA‑4) and programmed cell death protein‑1 (PD‑1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.

Purpose of the study . An analysis of changes in the expression of the VEGF neoangiogenic factor in the tumor tissue of patients with squamous cell carcinoma of the oral mucosa receiving targeted therapy with cetuximab and chemotherapy. Patients and methods . We performed an immunohistochemical study of tumor samples obtained from 60 patients with squamous cell carcinoma of the oral mucosa T3-4N0-1M0. The main group comprised 30 patients who received therapy with cisplatin and fluoruracil plus cetuximab. The control group included 30 patients receiving standard chemotherapy without targeted therapy. Each group was divided into two subgroups with different treatment efficacy: patients sensitive to treatment ( n = 17 in the group with cetuximab and n = 12 in the group without cetuximab) and resistant to treatment ( n = 13 in the group with targeted therapy and n = 18 in the group with standard chemotherapy). Results . Quantification of the VEGF expression demonstrated minimal numbers of vessels stained positively for this marker in the field of view in patients of the main group sensitive to chemotherapy and cetuximab. The value was 5.3 times lower than initial values, and 4.3 times lower than in the subgroup of patients resistant to the treatment (the data were statistically significant, р = 0.0132 and р = 0.0455, respectively). In the control group, patients who were sensitive to the treatment showed 1.4 times lower values than initially ( р = 0.921), and patients who were resistant to the treatment had 1.1 times lower values than initial values ( р = 0.936). The data were not statistically significant. Conclusions . The study showed that the number of microvessels in patients resistant to chemotherapy and cetuximab was 4.3 times higher than in patients with effective targeted therapy ( р = 0.0455). The differences in the control group were not statistically significant.

Purpose of the study . An analysis of parameters of the blood coagulation system in breast cancer patients after coronavirus disease. Materials and methods . 50 breast cancer patients were divided into groups: the main group included 30 patients after coronavirus disease, the control group 1–20 patients without confirmed COVID‑19, and control group 2–20 non-cancer women after corona‑ virus disease. All cancer patients received appropriate chemotherapy. The following parameters were studied: activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), prothrombin index (PTI), fibrinogen, soluble fibrin monomer complexes (SFMCs), thrombin time (TT), antithrombin III, D-dimer and plasminogen, fibrin degradation products. Blood tests were performed 4–6 weeks after the infection and two negative PCR test results for COVID‑19. Results . Patients of the main group demonstrated differences in INR values after treatment in the subgroups with asymptomatic disease (Me = 1.24) and with mild symptoms (Me = 0.97) U = 10; Z = 2.766; р = 0.0057, in subgroups with asymptomatic disease (Me = 1.24) and with moderate to severe symptoms (Me = 0.98) U = 26.5; Z = 2.199; р = 0.027, and in TT values in subgroups with asymptomatic disease (Me = 14.5) and with moderate to severe symptoms (Me = 16.5) U = 18.5; Z = –2.725; р = 0.0064. The comparison of the parameters in patients after COVID‑19 before (Me = 0.83) and after treatment (Me = 0.4) showed differences in the D-dimer values in patients with moderate to severe disease U = 6.5; Z = –2.2861; р = 0.022 towards their decrease after the therapy. Differences were found in APTT values between the main group (Me = 30.65) and control group 1 (Me = 27.85) U = 119; Z = 3.574; р = 0.00035, in antithrombin values between the main group (Me = 94) and control group 1 (Me = 106) U = 112; Z = 3.713; р = 0.00021, and in SFMCs values between the main group (Me = 17) and control group 1 (Me = 8) U = 180.5; Z = 2.356; р = 0.018. Conclusions . Determination of plasminogen levels can become an independent factor in detecting thrombotic risk in cancer patients who recovered from COVID‑19. Previous infection with COVID‑19 should be considered an additional risk factor for venous thromboembolic complications for cancer patients.

Introduction . Erythropoietin (EPO) application is a pathogenetic method for anemia correction in cancer patients. The purpose of study . Clinical evaluation of the efficacy and safety of Eralfon® (epoetin alpha) in treatment for anemia in patients with malignant solid tumors during medical anticancer therapy. Materials and methods . We analyzed the data on anemia treatment with Eralfon® in 184 patients with malignant solid tumors receiving various medical anticancer therapies. Eralfon® was injected subcutaneously 12 000 IU 3 times per week or 40 000 IU once a week. Clinical antianemic effect, the time to maximum antianemic effect, adverse events (AE) were analyzed. Results . Patients were stratified by the grade of anemia, stages of treatment, presence of bone metastases, bleeding, previous medical and radiation anticancer therapies, dosage of Eralfon®. The time to effect was shorter in patients under 65. There were no significant differences in efficacy depending on the dosing regimen of Eralfon®. Efficacy was lower in patients with advanced tumors, especially in bone metastases. A history of tumor bleeding, chemotherapy and/or radiation therapy prolonged the period of hemoglobin recovery to normal values. Arterial hypertension and venous thrombosis were the most common AE associated with Eralfon®. Eralfon® 12 000 IU 3 times per week caused less frequent complications, with no cases of ossealgia and myalgia. Conclusion . Eralfon® demonstrated clinical efficacy in treatment for anemia in patients with solid malignant tumors receiving medical anticancer therapy. Dosage of 12 000 IU 3 times per week provided better control of the antianemic effect and adverse events.

The development of a new area of antitumor drug therapy, immunotherapy using immune checkpoint inhibitors targeting PD-1/PD-L1, has significantly changed approaches to the treatment of advanced non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated the clinical benefit as well as the long-term effect of these drugs. Currently, the problem of treatment of patients after disease progression against the background of the use of checkpoint inhibitors is relevant. Equally relevant is the issue of choosing the correct and most effective treatment tactics for NSCLC patients with oligoprogression, as well as with abscopal effect. This paper describes a clinical case of a patient with lung adenocarcinoma without driver mutations with PD-L1-positive status, who was treated with nivolumab after second-line chemotherapy for disease progression, and after oligoprogression of the disease into the brain was given stereotactic radiotherapy of metastatic lesion and continued therapy with nivolumab. Partial regression of metastases was achieved with a prolonged effect on the background of continued treatment with nivolumab for 24 months. Tolerability of therapy was satisfactory: no adverse events were observed. The patient retained the result for 1.5 years.

The development of a new direction in anticancer medical therapy – the use of immune checkpoint inhibitors targeting PD-1/ PD-L1 and CTLA-4 – has significantly changed the approach to tumor treatment in the last few years. The PD1 blocker nivolumab in major registered clinical trials improved overall survival, including in metastatic melanoma, with a favorable toxicity profile. However, its efficacy in patients with brain metastases from melanoma was poorly studied, since the inclusion criteria for most clinical trials do not envisage recruiting such patients. The immune-mediated toxicity of immune checkpoint inhibitors is currently well enough studied. However, cases of cutaneous toxicity are quite rare and present certain difficulties for differential diagnosis and treatment. This article presents two cases of effective nivolumab treatment in patients with generalized BRAFwt and BRAFmut cutaneous melanoma. The first case is of interest due to the presence of brain metastases in the patient. Nivolumab therapy helped achieving complete regression of intracranial metastases with the long-term effect. The second case, in addition to effective treatment, demonstrates a rare manifestation of skin toxicity – vitiligo on the face and upper extremities.

Objective . Studying the blood levels of type 1 and 2 insulin-like growth factors in patients with squamous cell carcinoma of the tongue and mouth floor mucosa depending on the therapy effect. Materials and Methods . The study included data from 30 patients with squamous cell carcinoma of the tongue and mouth floor mucosa T3–4N0–1M0 who received chemotherapy cycles together with targeted therapy with cetuximab. Twenty non-cancer donors were examined as well. Depending on the therapy effect, patients were divided into two groups: sensitive and resistant ones. Results . Initial levels of IGF-1 and IGF-2 in the blood serum of patients prior to chemotherapy and targeted therapy with cetuximab were lower than the levels in donors by 53.5 % and 20.3 %, respectively. After chemotherapy and cetuximab therapy, patients with sensitivity to the treatment showed normalization of IGF-1 and its significant increase compared to the initial levels — by 87 %. Levels of IGF-2 were not statistically significantly different from the initial levels and were 32.5 % lower than in donors. The IGF-1 / IGF-2 coefficient was 58 % higher than the initial value. Conclusions . Chemotherapy and cetuximab therapy normalized levels of IGF-1 in patients with sensitivity to the treatment which was demonstrated by an increase in IGF-1 up to the normal blood levels in effective treatment.