Tyumen Regional Oncological Dispensary

Objective: to re-evaluate the efficacy and safety of lenvatinib with pembrolizumab in unselected Russian renal cell carcinoma (RCC) patients, included in the phase IV study, in a median follow-up extended to 17.1 months. The primary end point was progression-free survival (PFS), secondary end points were overall survival (OS), objective response rate (ORR) and duration of response (DOR), disease control rate (DCR) and its duration, as well as safety.Materials and methods. The study included medical data of 165 patients with verified advanced RCC who received lenvatinib with pembrolizumab in 36 centers of the Russian Federation from 05.02.2018 to 25.07.2024. The median age was 60 (20–76) years, the male to female ratio was 2.3:1. The majority of patients had Karnofsky performance status ³80 % (74.6 %), clear cell RCC (93.3 %) without sarcomatoid differentiation (93.3 %), metachronous metastases (50.9 %) localized in >1 organ (75.2 %), were nephrectomized (63.0 %) and did not receive antitumor therapy (91.0 %). At the time of lenvatinib with pembrolizumab therapy start 40 patients (24.2 %) were classified into International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable prognostic group, 92 (55.8 %) in the intermediate prognostic group, and 33 (20.0 %) in the poor prognostic group. The median follow-up was 17.1 (1.5–72.9) months.Results. The median PFS achieved 24.0 (18.7–29.3) months, 17-month PFS 60.5 %. The median OS was 48.9 (18.5– 79.2) months, 17-month OS – 76.1 %. Objective response was registered in 46.0 % of patients including 2.4 % complete responders; the DCR was 92.1 %. The median DOR was 16.6 (2.1–72.9) months, duration of disease control –14.3 (2.1–72.9) months. Confirmed dynamics of change in the sum of tumor foci diameters was recorded in 152 patients, while the median change was –25 % (from –100 % to +29 %). Any decrease in the sum of tumor foci diameters occurred in 69.1 % of cases. The incidence of any adverse events (AE) was 78.2 %, severe AE – 24.2 %, and serious AE – 9.7 %. Immune-mediated AEs developed in 17.0 % of cases and AE grades 3–4 in 6.7 % of cases. Mortality from AEs was 1.2 %.Conclusion. Compared with the registration study, in real-world clinical practice in patients with advanced RCC the lenvatinib with pembrolizumab provides a lower ORR with comparable PFS and OS rates and demonstrates a satisfactory safety profile.

Background. Prostate cancer (PCa) is one of the most common cancers of men. In 2022, 48,025 new PCa cases and 12,896 deaths from the disease were reported in Russia. Metastatic castration-resistant PCa still is one of the common causes of death in men.Aim. To evaluate prevalence of homologous recombination repair gene (HRR) mutations in patients with metastatic castration-resistant PCa in Russia and to identify differences in clinical characteristics and treatment outcomes of patients with these mutations and without them.Materials and methods. The study included 329 patients with metastatic castration-resistant PCa from 20 centers. Patients underwent molecular genetic analysis using next-generation sequencing to identify mutations in 14 HRR genes. The mutation status was determined in 3 routine laboratories and further validated in a central independent laboratory.Results. The HRR gene mutations were detected in 59 (19.28 %) of 329 patients. The most common were ATM mutations – in 14 (4.57 %), BRCA2 – in 14 (4.57 %), BRCA1 – in 6 (1.96 %). All the patients received first-line therapy, with newgeneration antiandrogens and taxanes being used most frequently. The patients with HRR gene mutations had nearly1.5 times lower median of progression-free survival (PFS) with first-line therapy: 12.8 months vs. 20.8 months in patients without mutations (p = 0.048). There was statistically significant difference in PFS between the observed groups with first-line therapy depending on the treatment group. In patients of general group having been treated with new-generation antiandrogen therapy, the median of PFS was 22 months, while in patients who had received taxanes it was 8.22 months (p <0.05). In patients with HRR gene mutations having been treated with first-line antiandrogenes of novel generation, the median of PFS was 20.5 months, while in patients without mutations the PFS median was 23.1 months (p = 0.14). In patients with mutations and having been treated with first-line taxanes, the PFS median was 6.15 months, while in patients without mutations it was 8.55 months (p = 0.4).Conclusion. In our ADAM study in the Russian population, the proportion of carriers of the HRR gene mutations was slightly lower (19.28 %) than that reported in published randomized trials. There is also a different distribution structure and frequency of the most frequent mutations. Patients with the HRR gene mutations exhibited worse PFS rates and more aggressive course of the disease, which requires a special approach to treatment of this group of patients.

Introduction. The addition of durvalumab after chemoradiation therapy in unresectable stage III non-small-cell lung cancer (NSLC) is a new standard of care.Aim. Study the features and outcomes of durvalumab maintenance treatment after chemoradiotherapy in patients with unresectable stage III NSCLC in the real-world clinical practice in Russia.Materials and methods. 50 patients with unresectable III stage NSCLC after concurrent or sequential chemoradiotherapy (CRT) were enrolled in this observational retrospective study. Median follow up time at primary analysis was 12.4 months.Results. A mean age of the patients in the study was 61.2 years (58.4-64.1; 95% CI). Most of the patients had received sequential CRT (76%, n = 38). Median time of durvalumab start from the end of CRT varied from 22 to 50 days (overall - 35 days). Estimated median PFS and OS were 10.86 months (7.78-14.01, 95% CI) and 26 months (20.19-31.81, 95% CI), respectively. There was a trend toward increased PFS in patients with smoking history: 12 months (9.79-14.2; 95% CI) versus 4,9 months (0.0-12.47; 95% CI), p = 0.2. Half of the patients without smoking history (5/10) had targetable mutations (EGFR ex 19, ALK, ROS1, cMET). Most common reported adverse events of special interest were pneumonitis grade 1-2 (36%, n = 18), leading permanent treatment discontinuation to in 6% of patients (n = 3). There were no reported cases of grade 3-4 adverse events.Conclusions. Real-world characteristic of patients in our study were different from PACIFIC trial. Sequential CRT is the most frequent treatment option in locally advanced unresectable NSCLC in Russia. Estimated PFS was shorter than in PACIFIC, but there were less cases of pneumonitis.

Objective: implementation of value-based approach and development of adherence to treatment in patients with non-melanoma cancer.Material and methods. The observational, single-arm, prospective, long-term single-center study of the quality of life and patients’ experience was performed. It included 42 patients aged from 42 to 82 years. Validated questionnaires were used: Patient-Reported Outcome Measures (PROMs) (as a decision support tool), Patient-Reported Experience Measures (PREMs) (3 months after treatment to assess the patient's experience).Results. Mean concern about appearance was 43.5 points (Rasch psychometric model). Younger patients (r=–0.398, p=0.009) and female patients (r=–0.475, p=0.001) were more concerned about appearance. In 10 cases (24%), the involvement was estimated as 4 points, in 18 cases (43%), it was 3 points, in 14 cases (33%), it was 2 points. Older patients were less involved in the choice of treatment method (r=–0633, p<0.001). The level of satisfaction with communications was more than 50 points. The use of a patient-oriented algorithm of communication has a positive effect on a patient's experience.Conclusion. The heads of oncological care are recommended to evaluate the patient's experience on a regular basis, create conditions for patients to choose treatment methods according to their individual needs, analyze the outcomes obtained by the introduction of validated questionnaires on the appropriate nosological profile and take these results into account in treatment. Further studies of the degree of influence of different factors on a patient’s choice of treatment method are needed, as well as conducting studies among other groups of patients with non-melanoma skin cancer (located in other parts of the body, larger than 2 cm).

Background: A lightning strike causes macro- and micromorphological changes in the human body as a whole due to a combination of several damaging factors. Clinical case: Using an example from the forensic medical expert practice demonstrating the possibilities of a comprehensive approach (autopsy, biochemical, histological, and medico-forensic investigations) to the diagnosis of trauma arising from atmospheric electricity exposure. Conclusion: Complex assessment based on a wide range of laboratory studies made it possible to diagnose at a qualitatively new level, reasonably reconstruct circumstances of the injury that occurred in conditions of nonobviousness, and constructively solve a wider range of issues in the interests of the investigating authorities and court.

The aim of the study is to investigate the influence exerted by short-term outpatient pulmonary rehabilitation on functional indices and the course of the perioperative period for patients with lung cancer against the background of COPD Material and methods. According to the study design, lung cancer patients with planned surgical treatment were distributed between groups according to the COPD severity (stages II-IV). At the outpatient stage, evaluation of the pulmonary function and 6-minute walk test were performed. The results of the test and the functional indices were registered with further establishment of the pulmonary rehabilitation procedure complex for the patient. The exercises were performed at home and designed for the duration of two weeks. The complex included cycles of breathing, strength and aerobic exercises with individually adjusted intensity depending on the severity of clinical COPD manifestations and the baseline physical status. Upon completion of the training course, the patients underwent repeated spirometry and the 6-minute walk test. The results obtained were registered and analysed with subsequent surgical treatment of the patients. Results. Minimal changes in functional indices upon completion of the course were registered in patients with COPD stage II, which prevented achievement of statistical significance. Therewith, patients with COPD stages III and IV who had undergone the course of exercises were noted to show statistically reliable improvement of pulmonary function (FEV1) and improvement of the overall physical status, which is testified to by enhanced tolerance to externally imposed physical loads (p<0.01). Apart from that, decreased HR values (p<0.01)) growth of SpO2 values (p<0.01) and decreased shortness of breath (p<0.01) were registered in these groups after the 6-minute walk test. No statistically significant differences in relation to the number of postoperative complications or the term of in-hospital stay were revealed between the groups in the postoperative period. Conclusion. Performance of a pulmonary rehabilitation course during the preoperative period reliably improves functional indices in patients with COPD stage III and IV, which may be of crucial significance for determination of functional operability at the outpatient stage

Parameters of 24-h rhythm in intraocular pressure (IOP) were assessed in patients with stable or advanced primary open-angle glaucoma (S-POAG/A-POAG) and referenced to the phase of “marker” circadian temperature rhythm of each patient. Body temperature and IOP were measured over a 72-h span in 115 participants (65 S-POAG and 50 A-POAG). Retinal Ganglion Cell (RGC) damage was assessed by high-definition optical coherence tomography. The 24-h IOP rhythm in A-POAG patients peaked during the night, opposite to the daytime phase position in S-POAG patients (p < 0.0001). The 24-h IOP phase correlated with RGC loss (p < 0.0001). The internal phase shift between IOP and body temperature gradually increased with POAG progression (p < 0.001). Angiotensin converting enzyme Alu-repeat deletion/insertion (ACE I/D) emerged as a candidate gene polymorphism, which may play a role in the alteration of the circadian IOP variability in advanced glaucoma. To conclude, a reliable estimation of the 24-h rhythm in IOP requires the degree of RGC damage to be assessed. In advanced POAG, the 24-h phase of IOP tended to occur during the night and correlated with RGC loss, being progressively delayed relative to the phase of temperature.

The aim of this work was to identify the causative agent of community-acquired pneumonia and coinfection using PCR study of biomaterial from patients.Materials and methods. PCR testing of 268 samples from 258 patients was carried out to identify RNA/DNA of viral and bacterial pathogens of respiratory infections.Results and discussion. In 43.3 % of samples SARS-CoV-2 RNA was detected, in 4.5 % – RNA/DNA of acute respiratory viral infections pathogens, in one sample – DNA of Mycoplasma pneumoniae. Co-infection was detected only in patients of the anti-tuberculosis dispensary (SARS-CoV-2 and Mycobacterium tuberculosis). In the examined patients with pneumonia, SARS-CoV-2 RNA was significantly more often detected in biomaterial from the lower respiratory tract (52 %) than in respiratory smears (8.5 %). In the first week from the onset of the disease, 19.2 % of positive samples were found, in the second – 56.5 %.