Background. Adjuvant targeted therapy (ATT) with a combination of dabrafenib and trametinib after radical surgical treatment in patients with stage III skin melanoma (SM) with a BRAF V600 mutation reduces the risk of disease recurrence. The effectiveness of this approach has been demonstrated in randomized clinical trials, and also confirmed in several large non-Russian real-world (RW) studies. Aim. To evaluate, in RW settings, the effectiveness of ATT with a combination of dabrafenib and trametinib after definitive surgical treatment in patients with BRAF V600-positive SM in Russia. Materials and methods. The RATIONALE study is a prospective, non-interventional, multicenter RW study. The follow-up duration for the study was 1 year. Patients with SM older than 18 years who had previously started dabrafenib and trametinib therapy no more than 8 weeks prior to Visit 1 were included in the study. The paper presents results from the analysis of Cohort 1 only (patients who received dabrafenib and trametinib in the adjuvant setting). Results. The cohort included 214 patients with BRAF V600-mutated SM of stages IIIA–D and IV resectable. At the time of therapy initiation, the majority of patients were stage IIIc (54.7%) or IIIb (22.0%). The most common mutation – BRAF V600E – occurred in 66.3% of cases, while the second most common variant – BRAF V600 not otherwise specified – was detected in 31.3%. One-year overall survival for all included patients was 94%, one-year relapse-free survival was 84%, and one-year distant metastasis-free survival was 86%. No previously listed adverse events were reported. Adverse events led to therapy discontinuation in only 11.7% of cases. ATT did not reduce patients' quality of life. In the subgroup analysis, the effectiveness of the combination of dabrafenib and trametinib after removal of distant metastases (equivalent to stage IV resectable) was found, in particular, the one-year relapse-free survival rate was 83%, and the one-year overall survival rate was 100%, which is comparable to these indicators for stage IIIB-D (72–86 and 78–100%, respectively). Conclusion. The effectiveness and favorable safety profile of the combination of dabrafenib and trametinib in ATT after radical surgical treatment was confirmed in a population of Russian patients with SM in the RW settings.

Background. A Russian phase IV observational study was initiated to evaluate the efficacy and safety of lenvatinib with pembrolizumab (Len-Pembro) in patients with advanced renal cell carcinoma (RCC) receiving therapy in real-world practice. This article is based on the results of the third analysis conducted with a median follow-up of 23.1 months and reflects data on the efficacy and safety of Len-Pembro in Russian patients. Aim. To evaluate the real-world efficacy and safety of Len-Pembro in patients with advanced RCC with a median follow-up increased to 23.1 months. The primary outcome of the study was progression-free survival (PFS), the secondary outcomes included overall survival (OS), progression-free survival on next-line therapy (PFS2), objective response rate (ORR), duration of response, as well as safety. Materials and methods. The study included data from 165 patients with verified advanced RCC who received Len-Pembro at 36 centers in the Russian Federation from February 05, 2018 to July 30, 2025. The median age was 60 (20–76) years, and 70.3% of the participants were male. Most patients (74.6%) presented with Karnofsky performance score of ≥80%, metachronous metastases (50.9%) of clear cell RCC (93.3%) in 1 organ (75.2%), and had not received any anticancer treatment (91.0%). The IMDC favorable prognosis group included 40 (24.2%), intermediate – 92 (55.8%), and unfavorable prognosis – 33 (20.0%) patients. The median follow-up reached 23.1 (0.5–72.9) months. A total of 110 (66.7%) patients completed Len-Pembro therapy, and 51 (30.9%) patients received next-line treatment. Results. Median PFS reached 25.8 (95% confidence interval – CI 17.0–34.5) months, 23-month PFS – 52.6%; median OS was 39.9 (95% CI 26.9–52.8) months, 23-month OS – 73.1%; median PFS2 was 33.2 (95% CI 23.4–41.1) months, 23-month PFS2 – 66.9%. The ORR was 49.1%, including 3.0% of complete responses, and the disease control rate was 89.1%. The median duration of response reached 29.7 (95% CI 24.9–34.6) months. The incidence of any adverse events (AEs) was 78.8%, severe AEs occurred in 29.1%, fatal AES – in 1.2%, immune-related AEs – 17.0%, severe immune-related AEs – 6.7%. Conclusion. In real-world practice, with increased follow-up duration, the values of PFS, OS, and PFS2 were comparable to those obtained in the registrational study, with a lower ORR and a satisfactory safety profile of the combination of Len-Pembro in advanced RCC.

Background. Hepatocellular carcinoma (HCC) is one of the most aggressive tumor diseases, with an annual increase in morbidity and mortality. Therefore, the studies for effective treatment options is crucial. The evolution of HCC treatment and the priority of immunotherapy in the first line of advanced HCC leave questions about the place and effectiveness of tyrosine kinase inhibitors in the first line of antitumor therapy. Aim. This study evaluated the efficacy and tolerability of lenvatinib in patients in the first line treatment advanced HCC in real clinical practice. Materials and methods. The retrospective study included 41 patients who received targeted therapy with lenvatinib as the first line for unresectable HCC in medical institutions of the Russian Federation and were observed at Blokhin National Medical Research Center of Oncology. Results. The median progression-free survival in patients treated with lenvatinib was 13.9 months. The median overall survival (OS) was 27.3 months. One-year OS was 80%. Two-year OS was 56%. The best response to treatment in our study was stabilization in 67% of cases, and disease progression during therapy was observed in 23% of cases, assessed using mRECIST. Conclusion. In a selected cohort of patients with advanced HCC, tyrosine kinase inhibitors (in particular lenvatinib) was studied and the efficacy of lenvatinib treatment was demonstrated in key survival indicators in the first line of HCC therapy in real clinical practice. There was also a low incidence of adverse events leading to discontinuation of therapy and dose reduction.

Cancer-associated thrombosis (CAT) is one of the most frequent and dangerous complications of malignancies, ranking 2nd among the causes of death in cancer patients. The article presents an overview of current data on the pathogenesis of thrombosis in cancer patients, including the key role of tumor cells, inflammatory cytokines, neutrophil extracellular traps, and dysregulation of hemostasis. CAT epidemiology, individual (age, comorbidities, mobility) and tumor-dependent (location, stage, histology) risk factors, as well as the effect of various types of anticancer therapy, including chemotherapy, surgery, and the use of central venous catheters, are considered. Particular attention is paid to modern approaches to the prevention and treatment of CAT, including direct oral anticoagulants, their advantages over low molecular weight heparins, and data from large randomized trials (CARAVAGGIO and API-CAT). The review includes an analysis of international and Russian clinical guidelines (ASCO, NCCN, RUSSCO), focusing on the need for an individual approach, considering the clinical situation, the risk of bleeding, and drug interactions. The presented data emphasize the importance of timely detection of CAT and rational choice of therapy to reduce the risk of complications and improve the prognosis in cancer patients. The presented data emphasize the importance of timely detection of CAT and rational choice of therapy to reduce the risk of complications and improve the prognosis in cancer patients. In addition, a reduced dose of apixaban (2.5 mg twice daily) after 6 months of therapy was found to be effective in preventing the recurrence of venous thromboembolism and reducing the incidence of clinically significant bleeding compared to the full dose.

Introduction. Current guidelines (NCCN, ESMO, RUSSCO) for the treatment of breast cancer (BC) with the disease progression recommend performing a repeat biopsy with a reassessment of immunohistochemical (IHC) status. However, due to the weak evidence base, the indications and clinical significance of repeat biopsies are not clear, and repeated IHC examinations of histological specimens have not yet been introduced into routine practice. The dependence of the change in the tumor immunophenotype on its clinical and biological characteristics, and hence the potential markers for deciding to perform a repeat biopsy, remain poorly studied. Aim. To evaluate phenotypic variability of luminal BC based on comparison of repeat biopsies of recurrent/metastatic lesions with biopsies of primary tumors before treatment, and to study the effect of this variability on the treatment of the disease. Materials and methods. Between 2019 and 2024, 100 patients with early luminal A and B BC underwent a core biopsy of the primary tumor before treatment and a biopsy of a recurrent or metastatic lesion after the disease progression. In our study, the influence of the main clinical and morphological factors (patient's age, tumor differentiation degree, localization of metastases, presence of the driver mutations in the BRCA1/2 and PIK3CA genes, IHC subtype of the tumor, as well as administered chemotherapy, antihormonal, and radiation therapy) on the frequency of detection of discordance between paired biopsies was determined. The impact of discordance detection on further treatment approaches was also assessed. Results. Discordance of the IHC study results between the primary tumor before treatment and recurrent/metastatic lesions was found in 57% of cases, of which 37 cases were associated with a change in the tumor subtype, 20 cases with the loss/acquisition of IHC parameters that do not lead to conversion. Tumor subtype conversion was observed in 37% of cases. The luminal A subtype was the most unstable; in 54% (20/37) of cases, it converted into the luminal B subtype. The IHC discordance detection led to a treatment change in 48% of cases (27/57). There was no statistically significant effect of the studied clinical and morphological factors (see materials and methods) on the probability of discordance detection. However, the probability of conversion by multivariate analysis was significantly less in the luminal B subtype (70% less than in luminal A subtype) [odds ratio (OR) lumА/lumВ = 0.30, 95% confidence interval 0.10-0.80; p = 0.018], and adjuvant antihormonal therapy with tamoxifen was associated with a 79% reduction in the probability of conversion when compared with adjuvant treatment with aromatase inhibitors [OR IA/TAM = 0.29 (95% confidence interval 0.10-0.82); p = 0.024]. Conclusion. Performing a repeat biopsy in patients with luminal BC can reveal the discordance of IHC characteristics in 57% (57/100) of patients and the therapy-induced tumor subtype conversion in 37% (37/100) of patients, which led to a change in treatment approaches in more than 1/3 of cases (48%, 27/57). Risk factors for conversion of the IHC subtype include the luminal A subtype of the primary tumor and adjuvant antihormonal therapy with aromatase inhibitors. For this category of patients, a repeat biopsy is necessary since it helps to individualize further anti-tumor treatment.

Background. Cervical cancer (CC) is among the four most common malignancies among the female population. For a long time, platinum-based chemotherapy was the standard of care and practically the only option available. However, treatment outcomes for patients with metastatic and recurrent CC remained poor. The use of immune checkpoint inhibitors significantly increased progression-free survival and overall survival in this group of patients. Currently, pembrolizumab is a priority option in treating patients with metastatic, persistent, recurrent CC with CPS ≥ 1 and is included in international and Russian clinical guidelines. Aim. To evaluate the efficacy and safety of a pembrolizumab biosimilar (Pembroria®) in patients with metastatic, persistent and recurrent CC in the interim analysis of the PERFECTION observational study. Materials and methods. The study included a group of 51 patients diagnosed with stage IV CC. The treatment efficacy was analyzed using the Fleming method with the objective response rate criterion according to RECIST 1.1. Safety was assessed by the incidence of adverse events (AEs) and serious AEs according to the CTCAE 5.0 toxicity scale. Results. At stage g2, an objective response was reported in 24 (47.1%) patients, which exceeded the target threshold (22 responses). 5 (9.8%) patients experienced immune-mediated AEs, a total of 6 cases, including 1 case of grade 3 AE. The overall objective response rate was consistent with KEYNOTE-826, but the AE rate was lower (34.5% in KEYNOTE-826). Conclusion. Pembroria® has demonstrated efficacy comparable to that of the original pembrolizumab product and an acceptable safety profile. Differences in the incidence of immune-mediated AEs associated with Pembroria® require further study, considering the duration of observation and sample size. The results support using Pembroria® in routine clinical practice.

Background. Secondary hyoid tumors are extremely rare. There are few documented reports of metastases into hyoid in patients with distant localizations of malignancies, such as breast, lung, kidney, liver, and sigmoid colon cancers. The article describes a rare case of metastases of advanced gastric cancer to the hyoid bone. Aim. To present a clinical case of isolated metastatic lesion of the hyoid bone in a patient with primary advanced gastric cancer, demonstrating the possibility of increasing the duration and quality of life using polychemotherapy. Results. A 54-year-old male with synchronous pain in the throat and epigastrium when swallowing solid food and weight loss underwent esophagogastroduodenoscopy, which showed a defect in the mucosa along a small curvature in the middle third of the stomach. Histological examination showed colloid cancer. Combined positron-emission and X-ray computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) revealed a gastric tumor with radiopharmaceutical hyper uptake, serous membrane invasion and involvement of paragastric, celiac, retroperitoneal, and mediastinal lymph nodes. The entire hyoid bone was swollen with fragmentary cortex destruction. Stage IV gastric cancer cT4bN3аM1 was diagnosed with metastases to the hyoid bone, mediastinal, and retroperitoneal lymph nodes. The patient received eight cycles of polychemotherapy with the XELOX regimen and reported the resolution of sore throat and epigastric pain. The results of PET/CT with 18F-FDG showed sclerosis of the cortical layer of the hyoid bone and no abnormal radiopharmaceutical uptake. The patient has been alive for 13 months. Conclusion. Hypoglossal bone metastases are extremely rare in patients with advanced colloid cancer. Such case was described for the first time. The method of choice for diagnosing and assessing the extent of the tumor is PET/CT with 18F-FDG. Palliative polychemotherapy can increase the duration and improve the quality of life.

Despite advances in the early diagnosis of breast cancer (BC), the identification of locally advanced forms continues to be relevant. This is a complex category of patients whose treatment includes the complex use of various methods with significant medical and economic costs, long-term treatment and rehabilitation. A particular difficulty is the treatment in cases of progression of locally advanced forms. Patients with locally advanced BC require a multidisciplinary approach. In the absence of an effect after neoadjuvant drug treatment and the impossibility of performing surgical intervention, patients are treated with induction radiation therapy. The article describes the features of induction radiation therapy in the treatment of progression of primary inoperable BC in a specific clinical example. In case of recurrence of triple negative type of BC, the patient underwent various drug treatment regimens with the inclusion of immunotherapy. Due to the lack of effect from 3 lines of systemic drug treatment, it was decided to conduct radiation therapy. In connection with the identified carrier of a mutation in the BRCA1 gene, targeted therapy with PARP inhibitors was prescribed. Two months after radiation therapy and 1 month after the start of targeted therapy, the patient showed complete resorption of the tumor conglomerate on the anterior chest wall. The use of conformal radiation therapy in case of recurrence of the disease and the absence of the effect of systemic treatment made it possible to completely resorb an exophytic tumor with ulceration and achieve remission within the next 6 months.

Background. Chemoimmunotherapy with the combination of atezolizumab and nab-paclitaxel demonstrates clinical benefit at 12 months in only 45.8% of patients with metastatic triple-negative PD-L1-expressing breast cancer. This emphasizes the relevance of finding predictor markers of high sensitivity to immunotherapy. Since atezolizumab acts through the local immune system, assessing its status prior to therapy administration may be crucial. Aim. The objective of this study was to evaluate the predictor significance of immunological parameters of tumour microenvironment in patients with metastatic triple-negative cancer receiving therapy with atezolizumab in combination with nab-paclitaxel. Materials and methods. Eleven patients with metastatic triple-negative breast cancer, who received atezolizumab in combination with nab-paclitaxel, were included in the study. Among them, five patients exhibited a durable response (progression-free survival 6 months), while six patients had a short response (progression-free survival ≤6 months). Tumour microenvironment parameters (the proportion of immune cells in the microenvironment and their expression of PD-L1 and PD-1) were analyzed by TSA-associated multiplex immunofluorescence (Tyramide Signal Amplification) using the Vectra® 3.0 tissue analysis system and InForm® software (Akoya Bio, USA). Results. The study revealed that CD163+-macrophage counts below 6.475% of all tumor stromal cells were associated with long-term efficacy of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative cancer. Conclusion. The number of CD163+-macrophages in the tumor stroma could potentially serve as a marker for predicting the efficacy of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative cancer.

Exocrine pancreatic insufficiency (EPI) is a condition in which the amount of secreted pancreatic enzymes is insufficient to maintain normal digestion. EPI is a frequent complication of pancreatic or other malignancies. The presence of EPI in a cancer patient may be suggested by symptoms of maldigestion, malabsorption, and alteration of nutritional markers; however, it is important to note that the EPI symptoms may be subtle. In the early stages, EPI may be latent and manifested by malnutrition. However, even in the later stages, the symptoms of EPI may be similar to those of cancer or be masked by the condition after chemoradiation therapy. Antitumor therapy itself may also cause EPI. Enzyme replacement therapy (ERT) is the standard of care for EPI, but it is rarely prescribed to cancer patients. However, supportive therapy plays an essential role in treating cancer patients because the quality of life and life expectancy of patients largely depend on the adequacy of the complex treatment. The review discusses the possible causes of EPI and its diagnosis and treatment in cancer patients. Special attention is paid to ERT regimens, including those for improving digestion and the drug's dosage form. It is shown that pancreatin in minimicrospheres is the drug of choice for ERT, since the minimum particle size facilitates the most physiological digestion process.