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 determine the potential for generating secondary radiation on a hydroxyapatite-wollastonite graft, which has the potential to be used as a marker for postoperative pre-irradiation marking. Materials and methods. During the simulation of a radiotherapy session, the spectrum of secondary radiation generated on the hydroxyapatite-wollastonite graft and polyacrylamide was studied. Polyacrylamide, composed of basic chemical elements similar to those in human soft tissues, was used as an equivalent. Hydroxyapatite-wollastonite was obtained by plasma-reactive sintering of Ca 3 (Si 3 O 9 ) powder mixed with reactive components (CaO and CaHPO 4 HAP). The simulation of radiotherapy was conducted using a TrueBeam Linear Accelerator, developed by Varian Medical Systems, utilizing photon energy of 6 mega-electron volts (MeV) with a portable lead block shield and an aperture of 10 mm in diameter for irradiation. An SKS-50M gamma spectrometer with a high-purity germanium detector was used to record the photon distribution. Instrument readings were summarized in increments of 50 kilo-electron volts (keV) within the range of 0 to 2650 keV and presented graphically. Three measurements were taken in each range, after which the arithmetic mean and mean deviation were calculated. The significance of differences between means was determined using Student's t-test. Results. The secondary radiation from the studied samples in the range of 51–100 keV showed minor differences: hydroxyapatite-wollastonite produced 23.18 ± 2.57 pulses/second compared to polyacrylamide at 21.57 ± 2.37 pulses/second, while at energies of 101–150 keV, hydroxyapatite-wollastonite yielded 21.18 ± 2.51 pulses/second versus polyacrylamide at 22.9 ± 2.41 pulses/second. However, these differences were not statistically significant. Conclusion. The graft of hydroxyapatite-wollastonite micro-particles is considered to be a promising material for precise postoperative/pre-irradiation marking during treatment planning and does not require recalculation of radiation dose.
Objective. To estimate the results of lipopolysaccharide adsorption using a domestic Efferon LPS cartridge in the complex treatment of maternal sepsis and septic shock. Materials and methods. In Perm Regional Clinical Hospital, a comprehensive treatment of 22 patients with maternal sepsis or septic shock was carried out using LPS adsorption with domestic Efferon LPS columns in Perm Regional Clinical Hospital. The results of clinical and laboratory examination were compared before extracorporeal selective adsorption of endotoxin and in 24, 48 and 72 hours. The APACHE and SOFA scales were used. The level of inflammation biomarkers and endotoxin activity were determined. Results. After LPS adsorption, the median SOFA score decreased significantly to 5 (p = 0.00). A distinct decline was observed in the levels of creatinine, lactate dehydrogenase, procalcitonin, interleukins 1b, 8, 10, a tendency to decrease in the amount of C-reactive protein, presepsin, interleukin 6, tumor necrosis factor and endotoxin activity. The maximum effect of LPS adsorption using Efferon LPS columns occurred after the first session. After the second procedure, the severity on SOFA scale, endotoxin activity, procalcitonin and lactate levels decreased insignificantly. In 72 hours, the amount of procalcitonin and lactate tended to increase again. The hospital 28-day mortality rate was 22.73 %. The fatal outcomes correlated with the patients` initial condition. The higher the scores on the APACHE, SOFA scales, the Charlson index, the initial dose of norepinephrine (r = 0.38, p = 0.00; r = 0.37, p = 0.00; r = 0.34, p = 0.00; r = 0.43, p = 0.02, respectively) were, the worse was the result of the comprehensive treatment for maternal sepsis. Improvement of the clinical condition on the SOFA scale, an oxygenation index, and a decrease in vasopressors dose (r = 0.71, p = 0.00; r = -0.54, p = 0.00; r = 0.61, p = 0.00, respectively), as well as the results of laboratory studies (lactate – r = 0.58, p = 0.00; EAA – r = 0.57, p = 0.00; PCT – r = 0.59, p = 0.00) had a medium or strong correlation with the patients` recovery. Conclusions. The inclusion of lipopolysaccharide adsorption with domestic Efferon LPS columns in the comprehensive treatment for maternal sepsis and septic shock makes it possible to achieve a significant improvement in the patients` clinical condition, reduce the level of inflammation biomarkers, endotoxin activity and interleukins.
Aim. To assess the efficacy and safety of lenvatinib plus pembrolizumab for the treatment of mismatch repair-proficient (pMMR) endometrial cancer (EC) in routine clinical practice in Russia.Materials and methods. This multicenter, retrospective, cohort study included 114 patients with recurrent and metastatic EC from 37 cancer centers in Russia treated between December 2020 and November 2024. Patients with histologically verified EC without microsatellite instability were included. The primary endpoint was progression-free survival; the clinical characteristics of the patients were additionally analyzed; the objective response rate and the toxicity profile of therapy were assessed.Results. Median patients’ age was 66.5 (33–83) years. The most common histologic tumor subtype was endometrioid adenocarcinoma (72.8 %); serous adenocarcinoma was diagnosed in 18.4 % of cases, other subtypes – in 8.8 %. The median progression-free survival was 8.15 months (95 % confidence interval 0.4–41.1). Objective response rate was 38.0 %. The median overall survival was not achieved with a median follow-up of 12.23 months. During treatment, dose reduction rate due to adverse events was 50 %. The most frequent adverse events were hypertension (n = 64; 56.1 %), fatigue (n = 45; 39.5 %), and diarrhea (n = 20; 17.5 %).Conclusion. In the conducted study of routine clinical practice in Russian patients with recurrent and metastatic EC without mismatch repair system deficiency (pMMR/MSS), lenvatinib plus pembrolizumab showed good efficacy with a manageable safety profile.
Introduction. This paper examines the treatment outcomes for patients with stage I and II non-small cell lung cancer (NSCLC) in real clinical practice. The frequency of molecular genetic testing of operated patients was determined, and long-term prognoses for the disease were determined depending on the volume of treatment. Aim. To determine the effect of adding adjuvant treatment to radical surgery on the treatment outcomes in real clinical practice – overall and relapse-free survival. To determine the frequency and results of molecular genetic testing in patients with stage I–II NSCLC. Materials and methods. The results were obtained during the study – clinical approbation of lung cancer (CARL-001). The study included 401 patients with stage I–IIB NSCLC. The study included 129 women and 272 men. The median age was 56 years. There were 272 patients with stage I disease, 129 with stage II. 83 patients received combined treatment, 318 patients received only surgical treatment. The median follow-up was 36 months. Results. PD-L1 testing was performed in 31.7% of patients with stage II and in 14% of patients with stage I. The frequency of testing for mutations in the EGFR and ALK genes was 53.6% and 17.0% for stage II and 46% and 14.8% for stage I, respectively. Three-year overall survival of patients with stage IIA and adjuvant chemotherapy was higher compared to stage IIA patients who did not receive adjuvant treatment – 65% vs 69.24%. A similar indicator in patients with stage IIB also showed an advantage from adjuvant treatment 57.69% vs 72.86% in favor of those who received adjuvant. In patients with stage IIA and adjuvant therapy, 3-year relapse-free survival was 53.86% versus 50.0% without adjuvant. Among patients with stage IIB, the same parameter was 53.85% in the group without adjuvant versus 65.71% in the group that received adjuvant therapy. Conclusions. Adjuvant polychemotherapy in patients with stage II disease has a positive effect on long-term treatment outcomes in the form of increased overall and relapse-free survival compared to patients with a similar stage of the disease without adjuvant treatment. Molecular genetic testing of patients with NSCLC allows us to identify the presence of activating mutations and PD-L1 expression, which is important information for planning further treatment tactics.
