Perm Regional Oncology Center

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.

Objective. To analyze the long-term average values of the birch and cereal pollination periods. Relevance. Fluctuations in the concentration of pollen grains from allergenic plants in the air significantly affect allergy symptoms in sensitive patients, that is why aeropalynological monitoring is so important. Materials and methods. An analysis of aeropallinological monitoring data for the city of Perm from 2010 to 2019 and in 2023 was carried out. For the birch and cereals, an assessment of the main pollination period was made based on 98% of the total annual number of pollen grains (MPP 98) and the pollination season (PS) according to the method of the European Academy of Allergy Clinical Immunology (EAACI). Statistical processing of the obtained data was carried out using the following programs: Microsoft Excel® 2016 was applied for the calculation of the median total pollen grains concentration (p. g.) of the birch and cereals, the duration of pollination of these plants, Statistica 6 was used to determine the differences between median values based on the Mann-Whitney U-criterion. Results. The median total pollen grains concentration of the birch per season was 19,478 [3,024; 32,094] p.g./m3, cereals – 522 [238; 916] p.g./m3, the median duration of the pollination period of the birch was 31 [22; 36] days, cereals – 35 [31; 49] days according to the EAACI method. Statistically significant differences were detected between the duration of cereal pollination when calculated using the MPP 98 and PS methods (p = 0.01). Conclusions. High inter-seasonal variability in the total pollen grains concentration of allergenic plants was determined, the intensity of birch pollination per season in 2013 and 2014 differed by 35 times, that of cereals in 2015, 2016 – by 9 times.

Purpose: to evaluate the hypotensive efficacy and safety of Xenoplast drainage in non-penetrating surgery of primary open-angle glaucoma. Materials and methods. The analysis of the medical records of 157 patients (157 eyes) with primary open-angle glaucoma who underwent hypotensive non-penetrating surgery (non-penetrating deep sclerectomy — NDSE) using Xenoplast drainage (group 1) and without drainage (group 2). The results were evaluated for up to 36 months. Results. The positive effect of the operation, including absolute and relative success, was 96% in group 1 on day 6, then gradually decreased and was 74 % after 36 months. In group 2, the positive effect was 100 % and decreased to 58 % at the appropriate time of follow-up. In both groups, in the early postoperative period, there was a low percentage of eye complications (5.4 % and 4.8 %), typical for non-penetrating antiglaucoma surgeries. The number of descemetogoniopunctures, performed as the second stage of NDSE, was insufficient, both in the 1st group — 42 %, and in the 2nd — 51 %. Conclusion. All of the above points to the advantage of using Xenoplast drainage during non-penetrating deep sclerectomy.

Neuromyelitis optica spectrum disorders (NMOSD, formerly known as opticoneuromyelitis or Devic's disease) are severe chronic autoimmune inflammatory diseases of the central nervous system (CNS) associated with high disability in the absence of adequate treatment. In Russia, no assessment of the medical and social characteristics of this disease and the quality of life of patients has been conducted, which complicates the assessment of the prognosis and the development of medical and social management strategies for these patients.Objective: to analyse the medical and social characteristics and quality of life of patients diagnosed with NMOSD (opticoneuromyelitis).Material and methods. The condition of patients with a confirmed diagnosis of NMOSD or opticoneuromyelitis was assessed using a specially designed questionnaire, which also included questions about patients' attitudes towards their health. The SF-36 international quality of life questionnaire was used to score quality of life. Based on the results of the study, 280 patients diagnosed with NMOSD were surveyed in 21 regions of the Russian Federation.Results. Most patients with NMOSD who are observed by neurologists receive specialised treatment, but half of all patients with NMOSD currently experience some difficulties in obtaining drug therapy. Over the past year, 28.6% of respondents reported an improvement in their health, 39.6% reported no change, and 31.8% reported a deterioration. Self-assessment of health status declines sharply in patients over 55 years of age. The majority (74%) of patients report a decline in vision. Every second patient noted a decrease in vision at the onset of the disease. Severe movement disorders are characteristic, and for the majority (91%) of patients with NMOSD, strenuous physical activities such as running and weight training are not possible. Patients with disability groups I or II are more limited in their physical and mental resources. Patients receiving treatment significantly better assess changes in their health over the past year, both physical and psychological. Those who receive specialized drug therapy have a much better perception of their own health and its prospects. The SF-36 quality of life indices for NMOSD are significantly lower than normal, primarily in terms of physical condition, but also in terms of psychological well-being.Conclusion. In NMOSD, there are pronounced changes in the quality of life of patients, both according to the original questionnaire and according to the SF-36 scale. Receiving timely and adequate treatment significantly improves these indicators and the prognosis.

Chemotherapy is an integral part of drug treatment of patients with metastatic breast cancer (mBC), regardless of the biological subtype of the tumor, and the availability of a large number of effective drug treatment options can significantly increase life expectancy. Intensive neoadjuvant and adjuvant chemo ± targeted therapy, as well as pretreatment for the metastatic form of the disease, can significantly reduce the effectiveness of subsequent lines of chemotherapy, which complicates the choice of treatment options. That is why the results of modern observational studies of real clinical practice are of exceptional value. Ixabepilone is a semi-synthetic analogue of epothilone B, used for locally advanced or metastatic breast cancer when previous therapy is ineffective.The purpose of this study is to evaluate the efficacy and tolerability of ixabepilone alone and in combination with chemoor target drugs in real clinical practice in the Russian Federation.Methods. A multicenter, non-interventional, retrospective study of ixabepilone therapy in routine clinical practice in patients with locally advanced or metastatic breast cancer with ineffectiveness of previous therapy NIRMA (CLO1418141) included 101 patients who received ixabepilone as monotherapy and in various combinations in the 1st and subsequent lines of therapy from 01.01.2021 to 31.12.2023 in 15 oncological institutions of the Russian Federation.Results. The median of previous therapy lines for metastatic disease was 3. Ixabepilone therapy was administered alone (n=58), in combination with capecitabine (n=30), or in combination with trastuzumab (n=13). The median PFS was 5.77 months. [95 % CI 5.31–6.07] The objective response rate was 35.64 % (36/101), including 1 complete and 35 partial responses. Disease control rate in intensively pre-treated patients with mBC reached 84.16 % (84/101). Adverse events (AE) of any severity were recorded in 25.74 % of cases. The main adverse events with ixabepilone were neutropenia and peripheral polyneuropathy. In no case did toxicity lead to early discontinuation of treatment or death. In patients with mBC progression after anthracyclines and taxanes, the combination of ixabepilone with capecitabine or ixabepilone with trastuzumab demonstrates extremely high disease control rates in modern Real Clinical Practice (RCP). Ixabepilone monotherapy is an option of choice in patients with breast cancer progression after anthracyclines, taxanes and capecitabine.

Objective: The aim of the NiSaXPA study is to evaluate the quality of diagnosing, socio-demographic characteristics and treatment tactics of patients with axial psoriatic arthritis (axPsA) in real-world clinical practice in the Russian Federation.Material and methods. The study involved 600 patients from 21 clinical centers in the Russian Federation.Results and discussion. The diagnosis of axPsA was confirmed in 357 (59.5%) of 600 patients according to the centralized expert assessment. All 357 patients with axial lesions met criteria of the clinical guidelines for the treatment of patients with PsA. Of these, 201 (69%) patients had radiologically significant sacroiliitis (SI) according to Kellgren and 103 (59.2%) had active SI according to magnetic resonance imaging. The presence of syndesmophytes was confirmed in 119 (43.9%) patients. Inflammatory back pain was observed in approximately 80% of patients, most commonly in the lumbar and cervical spine. "Silent" sacroiliitis were found in 1.1–3.5 % of cases. 26.8% of patients were positive for HLA-B27. In the 6 months prior to the study, high PsA activity was present in 21.6% of patients according to the rheumatologist's assessment, while high activity according to the BASDAI index was found in 71.9 % of patients, and moderate and high activity according to the DAPSA index – in 82.7%. On the 24th week of observation, the number of patients with low activity according to BASDAI doubled and reached 66.3 %, while low activity and remission according to the DAPSA index amounted to 52.5% and 8.1% of patients, respectively. In most cases (about 27%), patients with axial manifestations were prescribed interleukin (IL) 17A inhibitors, about 14% of patients received tumor necrosis factor-α inhibitors, and about 4% received IL23 inhibitors.Conclusion. In 40.5% of patients, axial skeletal involvement in PsA was over-diagnosed due to misinterpretation of clinical and imaging data. The vast majority of patients (77%) were treated with synthetic disease-modifying antirheumatic drugs, mainly methotrexate, which do not affect the activity of spondylitis. Biologic disease-modifying antirheumatic drugs (bDMARDs) were taken by 46.5% of patients. Switching therapy to bDMARDs led to a significant reduction in disease activity.In order to improve the quality of medical care, the Russian clinical guidelines for the treatment of patients with PsA and the algorithms for the diagnosis of axial involvement need to be comprehensively implemented.

BACKGROUND: Adrenalectomy is the only possible method of radical treatment of adrenocortical cancer, and surgical approach (laparotomy or laparoscopy) remains a subject of debate. AIM: To evaluate one-year mortality in patients with adrenocortical cancer and determine its relationship with age, stage of the disease, tumor characteristics according to computed tomography results, and surgical approach. MATERIAL AND METHODS: In the Perm Regional Clinical Hospital, over the past 7 years, 107 patients have been operated on for adrenal tumors, of which 15 (14.01%) people were diagnosed with adrenocortical cancer. Adrenalectomy was performed by open (11) and laparoscopic (4) approaches. The results were assessed by the number of local relapses of the disease and life expectancy. Statistical analysis was carried out using standard application programs Statistica for Windows 10.0. Nonparametric methods of descriptive statistics were used. To determine the relationship between individual pairs of characteristics and the degree of its severity, the Spearman correlation coefficient (r) was calculated. RESULTS: Stage I of the disease according to the ENSAT classification was found in 1 case, II — in 7, III — in 5, IV — in 2 cases. The size of tumors removed laparoscopically was significantly smaller (p=0.042) compared to those operated on with an open approach. One-year survival rate was 80%. Surgical approach and combined operations did not affect one-year mortality (r=0.277; p=0.298 and r=–0.462; p=0.071). A relationship was found between lethal outcomes and age (r=–0.539; p=0.030), and the rate of washout of the contrast agent from the tumor in the delayed phase when performing computed tomography (r=–0.845; p=0.034). In case of lethal outcomes, the rate of washout of the contrast agent was the lowest. The life expectancy of patients depended on the stage of the disease (r=–0.590; p=0.016). CONCLUSION: One-year mortality in patients with adrenocortical cancer was 20% and had a moderate positive correlation with age, stage of the disease and a strong correlation with tumor characteristics based on bolus-enhanced computed tomography, but had no relationship with the chosen surgical approach.

Purpose: To evaluate the proportion of BRCA1 / 2 mutations in patients with serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum in Russia, to evaluate the percentage of germinal and somatic mutations, to identify the spectrum of mutations in BRCA1 / 2 genes, to evaluate clinical and morphological features of the BRCA-associated ovarian cancer (OC).Patients and methods: The study enrolled patients of 18 years and older with newly diagnosed serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum. Biological material (blood, tumor tissue) was collected, followed by molecular genetic analysis. The method of mutations detecting in the blood were: allele-specific PCR, high-resolution melting (HRM), Sanger sequencing method. Advanced genetic testing included the use of generation sequencing (NGS) and multiplex amplification of ligated probes (MLPA). The collection of clinical data, family history, clinical and morphological characteristics of the tumor was performed.Results: 500 patients were included in the study, the evaluation of BRCA1 / 2 mutations was performed in 496 patients (99,2 %). The frequency of BRCA1 / 2 mutations in the Russian patient population was 28,4 % (n = 141 / 496). The incidence of germinal mutations was 23,5 % (n = 117 / 141), and somatic — 4,8 % (n = 24 / 141). Frequent mutations in the Russian population were identified in 50 % of cases. When analyzing the ethnicity of patients in the Russian Federation BRCA-associated OC was most common in Russian (83,6 %, n = 118 / 141), Ukrainian (4,2 %, n = 6 / 141) and Tatar (3,5 %, n = 5 / 141) women. A family history of cancer was detected in 44 % of patients (n = 62 / 141) with BRCA1 / 2 mutations.Conclusions: Due to the high frequency of germinal and somatic BRCA1 / 2 mutations in the Russian patients it is recommended to conduct the advanced testing methods not only in blood samples but also in tumor tissue.

Aim. To analyze newly diagnosed diseases and features of the post-COVID course in patients after a coronavirus disease 2019 (COVID-19) within 12-month follow-up.Material and methods. A total of 9364 consecutively hospitalized patients were included in the ACTIV registry. Enrollment of patients began on June 29, 2020, and was completed on March 30, 2021, corresponding to the first and second waves of the pandemic. Demographic, clinical, and laboratory data, computed tomography (CT) results, information about inhospital clinical course and complications of COVID-19 during hospitalization were extracted from electronic health records using a standardized data collection form. The design included follow-up telephone interviews with a standard questionnaire at 3, 6, and 12 months to examine the course of post-COVID period.Results. According to the ACTIV registry, 18,1% of patients after COVID-19 had newly diagnosed diseases (NDDs) over the next 12 months. Hypertension (HTN), type 2 diabetes and coronary artery disease (CAD) prevailed in the NDD structure. Comparison of the age-standardized incidence of NDDs (HTN, CAD, diabetes) in the post-COVID period in the ACTIV registry with NDD incidence in 2019 according to Rosstat and the expected incidence of NDDs according to the EPOHA study revealed that HTN, diabetes, CAD in patients after COVID-19 were registered more often as follows: HTN by 7,0 and 4,4 times, diabetes by 7,3 and 8,8 times, CAD by 2,3 and 2,9 times, respectively. NDDs most often developed in patients aged 47 to 70 years. Comparison of the actual and expected number of cases of newly diagnosed HTN, CAD and diabetes depending on age showed that the actual number of cases in the population of patients in the ACTIV register is significantly higher than expected for patients aged 45-69 years and for patients with hypertension or diabetes and aged <45 years. Patients with NDDs, compared with patients without NDDs, had a more severe acute COVID-19 course. Statistically significant independent predictors of NDD occurrence (HTN and/or diabetes and/or CAD) within 1 year after hospital discharge were age (direct relationship), body mass index (direct relationship) and glucose levels upon admission to hospital (direct relationship).Conclusion. Available evidence suggests that a strategy for managing COVID-19 survivors should include mandatory screening for early detection of cardiovascular disease and diabetes, which will be key to reducing the risk of further COVID-19 consequences.

Objective. To analyze and evaluate the factors connected with age and territorial distribution among women with unfavorable maternal outcomes.
 Materials and methods. A retrospective epidemiological analysis of official statistics data on all cases of unfavorable maternal outcomes (deceased women and women with near-miss "almost dead") by age and structure at the place of residence (city, village) in comparison with successful outcomes in Perm Krai (PK), Privolzhsky Federal Region (PFR) and the Russian Federation (RF) for 19972020 was carried out.
 Results. In the age structure of deceased women in PK, the main share of 46.7 % was occupied by women aged 2029 and 3039 years, that differed from the comparison group. Among the mothers with successful outcomes in PK, PFR and RF, women aged 2029 years were in the first place 59.3, 62.5 and 60.2 %, respectively, that is 1.3 times higher than the corresponding proportion in MM. In the second place, there were women aged 3039 years 29.6; 27.9 and 29.1 %, respectively, that is 1.6 times less than the deceased women of the corresponding age. The percentage of young mothers aged 1519 was 9.2; 7.7 and 8.9 %, respectively, that is 1.4 times higher than that of the deceased women.
 The age structure of women with failed maternal mortality (FMM) differed slightly from that of deceased women and significantly from all puerperas in PK, PFR, RF. Thus, according to the ave-rage longterm data, the main share of women with FMM was women aged 2029 years 51.8 %. The percentage of puerperas aged 2029 years in PK, Privolzhsky Federal Region and the Russian Federation was 59.3, 62.5 and 60.2 respectively. In the second place in PK are women with FMM aged 3039 years 31.5 %. The share of puerperas aged 3039 years in PK, PFR and RF is 29.6 %, 27.9 % and 29.1 %, respectively. In the third place, there are young puerperas with FMM aged 1519 years 14.8 %. The proportion of such patients in PK, PFR and RF is 9.2, 7.7 and 6.6 %, respectively.
 According to the average longterm data, the proportion of urban residents prevailed among the deceased women 60.0 %. In the rural areas, the proportion of women who died was 40.0 %.
 By the place of residence, the share of women with FMM did not differ from the corresponding data in the MM group and amounted to 57.4 % in the city and 42.6 % in the village. In PK, PFR and RF, this ratio was 72.7 and 27.3 %; 71.6 and 28.4 %; 73.3 and 26.7 % respectively in all the compared territories).
 Conclusions. The risk groups for MM and FMM were women aged 2029 years, residents of the city and village, high-risk group rural women 3039 years.