In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival (EFS) and pathologic complete response in patients with resectable non-small cell lung cancer (R-NSCLC), with a safety profile consistent with the individual agents. We report EFS from a second planned interim analysis, interim disease-free survival (DFS) and overall survival (OS), and safety, after all patients completed/discontinued treatment. In this phase III, double-blind, placebo-controlled study, patients with treatment-naïve R-NSCLC (stage II-IIIB [N2]) were randomly assigned (1:1) to neoadjuvant platinum-based chemotherapy plus durvalumab/placebo (once every 3 weeks, four cycles) presurgery and then adjuvant durvalumab/placebo (once every 4 weeks, 12 cycles). Efficacy was analyzed in the modified intention-to-treat population (n = 740; for DFS, its resected subpopulation), which excluded patients with documented EGFR/ALK aberrations. As of May 10, 2024 (median follow-up, 25.9 months [censored patients]), EFS benefit favoring the durvalumab arm remained consistent (hazard ratio [HR], 0.69 [95% CI, 0.55 to 0.88]). Numerical improvement in DFS (HR, 0.66 [95% CI, 0.47 to 0.92]) and OS (HR, 0.89 [95% CI, 0.70 to 1.14]) favored the durvalumab arm. Maximum grade 3/4 adverse events occurred in 15.4% and 10.6% of the durvalumab and placebo arms, respectively, during adjuvant treatment. These results further support perioperative durvalumab plus neoadjuvant chemotherapy as a new treatment option.

4624 Background: In the Phase 3 POTOMAC study (NCT03528694), 1 year of D in combination with BCG (I + M) resulted in a statistically significant and clinically meaningful improvement in disease-free survival vs BCG (I + M) alone, with a manageable safety profile, in patients (pts) with BCG-naive, high-risk NMIBC. We report a planned updated 5-year OS analysis and PROs. Methods: Eligible pts were randomized 1:1:1 to D + BCG (I + M), D + BCG (I only), or BCG (I + M). Secondary endpoints included 5-year OS and PROs, evaluated every 8 weeks by EORTC QLQ-C30 and every 4 weeks by EORTC QLQ-NMIBC24 and PRO-CTCAE. Prespecified priority subscales were global health status/quality of life (GHS/QoL), physical functioning, and fatigue for QLQ-C30; and urinary symptoms, intravesical treatment (tx) issues, future perspective/worries, and sexual functioning for QLQ-NMIBC24. Change from baseline (CFB; mixed model for repeated measures) was assessed; a ±10-point score was considered clinically meaningful. Results: At data cutoff Oct 3, 2025 (median follow-up 72 months), the OS HR was 0.81 (95% CI, 0.54–1.19) with a 5-year OS rate of 87.6% (95% CI, 83.5%–90.8%) for D + BCG (I + M) vs 86.3% (95% CI, 82.1%–89.6%) for BCG (I + M). Median OS was not reached in either arm. For PRO analyses (data cutoff Apr 3, 2025), QLQ-C30 and QLQ-NMIBC24 baseline compliance rates were ≥74% and ≥79%, respectively, with similar baseline scores between arms. Overall, both arms showed deterioration in QLQ-C30 adjusted mean CFB scores, with suggested clinically meaningful deterioration for fatigue with D + BCG (I + M); however, the difference between arms was small (Table). Overall QLQ-NMIBC24 adjusted mean CFB scores were numerically small and similar between arms (Table). PRO-CTCAE measures were similar between arms. Conclusions: Addition of 1 year of D to BCG (I + M) continued to show no detriment to OS at >5.5 years of follow-up and had no major impact on PROs for pts with BCG-naive high-risk NMIBC. Clinical trial information: NCT03528694 . Subscales D + BCG (I + M)Adjusted mean CFB (95% CI) a BCG (I + M)Adjusted mean CFB (95% CI) a Estimated difference of means (95% CI) QLQ-C30 GHS/QoL b −7.6 (–9.19, −6.07) −4.9 (–6.46, −3.41) −2.7 (–4.85, −0.54) Physical functioning b −5.5 (–6.76, −4.15) −2.8 (–4.11, −1.56) –2.6 (–4.43, –0.81) Fatigue c 10.1 (8.32, 11.90) 6.1 (4.37, 7.88) 4.0 (1.50, 6.46) QLQ-NMIBC24 Urinary symptoms c 1.7 (−0.06, 3.41) 0.4 (−1.27, 2.15) 1.2 (–1.19, 3.65) Intravesical tx issues c 1.5 (−0.38, 3.28) 2.7 (0.89, 4.50) −1.2 (−3.79, 1.29) Future perspective/worries c −5.5 (−7.54, −3.39) −3.2 (−5.29, −1.19) −2.2 (−5.11, 0.66) Sexual functioning b 2.2 (0.47, 3.91) 1.1 (–0.60, 2.80) 1.1 (−1.30, 3.48) a Higher scores indicate better health (GHS/functioning) or greater burden (symptoms). b Positive difference favors D + BCG (I + M). c Negative difference favors D + BCG (I + M).

In the phase III AEGEAN trial, perioperative durvalumab (D) + neoadjuvant (neoadj) chemotherapy (CT) significantly improved event-free survival and pathological complete response versus neoadj CT alone with a manageable safety profile in patients (pts) with resectable (R) NSCLC. We report updated safety from AEGEAN with ∼9 months additional study follow-up. Adults with treatment (Tx)-naïve R-NSCLC (stage II–IIIB[N2]; AJCC 8th ed.) were randomised 1:1 to receive platinum-based CT + D or placebo (PBO) IV (Q3W, 4 cycles) before surgery (Sx), followed by adjuvant (adj) D or PBO (Q4W, 12 cycles) post-Sx. This ad hoc safety analysis was required by US health authorities to support regulatory filing. Adverse events (AEs; graded per NCI CTCAE v5.0) were assessed for each protocol-specified Tx period in all randomised pts who received ≥1 Tx dose. Overlapping with the adj period, the post-Sx period was defined as the date of Sx (inclusive) to the earliest of 90 days post-Sx or the first dose of subsequent anticancer Tx. 799/802 randomised pts received study Tx. As of 14 Aug 2023 (data cutoff), median overall Tx duration was 44.9 and 36.6 weeks in the D and PBO arms, respectively. 704/799 (88.1%) had completed 4 cycles of neoadj D/PBO, 651/802 (81.2%) had undergone Sx, and 337/799 (42.2%) had completed adj D/PBO; only 7/799 pts (0.9%) remained on adj Tx. The rate of max. grade 3/4 any-cause AEs was similar between Tx arms during the neoadj and overall Tx periods (Table); max. grade 3/4 any-cause AEs occurred less frequently during the post-Sx and adj periods. Most pts with AEs leading to discontinuation of D/PBO or CT had such events in the neoadj period, and of those pts with AEs leading to death, most had such events during the post-Sx period (Table). Table: 123PAE, n (%)NeoadjuvantPost-SxAdjuvantOverallD n=401PBO n=398D n=325PBO n=326D n=266PBO n=254D n=401PBO n=398Any365 (91.0)357 (89.7)235 (72.3)219 (67.2)223 (83.8)190 (74.8)387 (96.5)379 (95.2)Possibly related to Txa,b330 (82.3)313 (78.6)83 (25.5)36 (11.0)128 (48.1)74 (29.1)350 (87.3)325 (81.7)Max. grade 3/4130 (32.4)145 (36.4)55 (16.9)41 (12.6)41 (15.4)27 (10.6)174 (43.4)172 (43.2)Leading to death8 (2.0)4 (1.0)13 (4.0)9 (2.8)4 (1.5)2 (0.8)23 (5.7)15 (3.8)Leading to Tx discontinuationa54 (13.5)31 (7.8)––26 (9.8)10 (3.9)78 (19.5)40 (10.1)Serious83 (20.7)66 (16.6)61 (18.8)51 (15.6)40 (15.0)26 (10.2)156 (38.9)126 (31.7)aD/pbo or CT. bInvestigator-assessed causality. Open table in a new tab aD/pbo or CT. bInvestigator-assessed causality. There were no new safety signals observed for perioperative D + neoadj CT at this update, and the adj D portion of the AEGEAN regimen was well tolerated in pts with R-NSCLC.

Цель исследования. Оценить содержание сурвивина в моче как диагностического маркера рака мочевого пузыря (РМП); изучить прогностическое значение полиморфизма -31G>C (rs9904341) в промоторной области гена BIRC5 в отношении агрессивности течения РМП среди населения Красноярского края. Материалы и методы. Иммуноанализом определен сурвивин в 43 образцах мочи пациентов: с РМП — 27, другим вариантом злокачественного новообразования — 4, воспалительными заболеваниями мочеполовой системы и доброкачественной гиперплазией — 8, здоровых — 4. Разработанным авторами способом на основе биолюминесцентного анализа генотипированы образцы ДНК 285 пациентов с РМП и 183 здоровых доноров. Количественные данные сравнивали U-тестом Манна-Уитни, критерием χ2 Пирсона — частоты генотипов среди случаев РМП и контролей. Ассоциацию между полиморфизмом и РМП оценивали по отношению шансов с 95 % доверительным интервалом, p < 0,05 считали значимым. Результаты. Установлено, что определение сурвивина в моче позволяет разделять пациентов с РМП и здоровых с чувствительностью 66,7 % и специфичностью 100 %. Повышенное содержание сурвивина обнаружено в образцах пациентов с воспалительными заболеваниями и доброкачественными гиперплазиями мочевыводящих путей. Показано, что полиморфизм -31G>C (rs9904341) для пациентов Красноярского края при оценке риска возникновения РМП и развития рецидива заболевания не является значимым. Носительство аллеля GG является возможным предиктором агрессивного течения заболевания с быстрым прорастанием в мышечную стенку мочевого пузыря (48,7 % vs 35,7 %, p = 0,02). Заключение. Сурвивин является хорошим преддиагностическим маркером для выявления пациентов с заболеваниями мочевых путей: его повышенный уровень в моче может указывать на развитие злокачественных (в т. ч. РМП) и доброкачественных гиперплазий, а также воспалительных заболеваний уротелия. Разработка отечественной «аларм» тест-системы по определению сурвивина в моче для быстрой и неинвазивной диагностики перспективна. Полиморфизм -31G>C (rs9904341) можно рассматривать как предиктор агрессивного течения РМП.

Early detection of breast cancer with the help of systematic mammographic screening makes it possible to identify lesions whose treatment is more effective and, in general, more favorable for the quality of life. The further tactics of diagnosis and treatment depend on the timeliness and correctness of the diagnosis. The quality control of the research should be carried out by experts of specialized reference centers. The article presents the experience of the Krasnoyarsk Territory on the double reading of mammograms.

Цель исследования. Оценить содержание сурвивина в моче как диагностического маркера рака мочевого пузыря (РМП); изучить прогностическое значение полиморфизма -31G>C (rs9904341) в промоторной области гена BIRC5 в отношении агрессивности течения РМП среди населения Красноярского края. Материалы и методы. Иммуноанализом определен сурвивин в 43 образцах мочи пациентов: с РМП — 27, другим вариантом злокачественного новообразования — 4, воспалительными заболеваниями мочеполовой системы и доброкачественной гиперплазией — 8, здоровых — 4. Разработанным авторами способом на основе биолюминесцентного анализа генотипированы образцы ДНК 285 пациентов с РМП и 183 здоровых доноров. Количественные данные сравнивали U-тестом Манна-Уитни, критерием χ2 Пирсона — частоты генотипов среди случаев РМП и контролей. Ассоциацию между полиморфизмом и РМП оценивали по отношению шансов с 95 % доверительным интервалом, p < 0,05 считали значимым. Результаты. Установлено, что определение сурвивина в моче позволяет разделять пациентов с РМП и здоровых с чувствительностью 66,7 % и специфичностью 100 %. Повышенное содержание сурвивина обнаружено в образцах пациентов с воспалительными заболеваниями и доброкачественными гиперплазиями мочевыводящих путей. Показано, что полиморфизм -31G>C (rs9904341) для пациентов Красноярского края при оценке риска возникновения РМП и развития рецидива заболевания не является значимым. Носительство аллеля GG является возможным предиктором агрессивного течения заболевания с быстрым прорастанием в мышечную стенку мочевого пузыря (48,7 % vs 35,7 %, p = 0,02). Заключение. Сурвивин является хорошим преддиагностическим маркером для выявления пациентов с заболеваниями мочевых путей: его повышенный уровень в моче может указывать на развитие злокачественных (в т. ч. РМП) и доброкачественных гиперплазий, а также воспалительных заболеваний уротелия. Разработка отечественной «аларм» тест-системы по определению сурвивина в моче для быстрой и неинвазивной диагностики перспективна. Полиморфизм -31G>C (rs9904341) можно рассматривать как предиктор агрессивного течения РМП.

Phenotype of urine sediment cells were studied in patients with bladder cancer depending on the cancer stage and recurrence prognosis. In T1N0M0 stage, the number of lymphocytes decreased, in T2N0M0 stage, the most pronounced shift was an increase in the number of erythrocytes. Irrespectively of the disease stage, we observed increased number of innate immunity cells and cells that inhibit antitumor immunity in the composition of the leukocyte fraction of urine sediment cells. At T1N0M0 stage, the epithelial-endothelial fraction was characterized by increased content of cells expressing CD13 marker (responsible for tumor growth and metastasis) and reduced number of cells expressing CD15 marker (responsible for intercellular adhesion). In patients developing relapse of bladder cancer, the number of lymphocytes was decreased in urine sediment cells and the number of epithelial and endothelial cells expressing CD13 marker was increased.

Background. Ionizing radiation is an effective antitumor therapy, but it has a serious negative effect on the immune system requiring the use of radiation reaction prevention and reduction methods. Neutrophils are a sensitive element of the immune system both in interaction with tumor tissue and in response to radiation injury. Aim. To evaluate functional activity of peripheral blood neutrophils by chemiluminescent analysis in patients with anorectal cancer after radiotherapy. Materials and methods. The study included 80 patients with anorectal cancer. Patients received chemo- and radiotherapy with 3D conformal radiotherapy and radiation therapy under visual control, followed by the use of radioprotector and without it. Neutrophil activity determined by chemiluminescent analysis. Results. In patients with anorectal cancer found maximum spontaneous and induced chemiluminescence acceleration. The chemiluminescence activation index with luminol is lower in patients with anorectal cancer, and with lucigenin shows no differences with the control group. The low luminol chemiluminescence maximum intensity, as well as the decrease in the synthesis of reactive secondary oxygen species in enzymatic systems, is likely regulatory intracellular limitations consequence. After treatment, patients with radioprotector showed a decrease in the number of parameters with statistically significant differences with the control group. Undesirable phenomena associated with sodium deoxyribonucleate therapy not detected in anorectal cancer patients during radiotherapy and subsequent observation period. Conclusion. During treatment, differences in chemiluminescence parameters suggest that ionizing radiation affects them in patients with anorectal cancer receiving standard chemoradiotherapy. Use of chemoradiotherapy with a radioprotector leads to indirect restoration of cellular functional activity. This is confirmed by luminol-dependent chemiluminescence faster reaching its maximum and a decrease in the number of significant differences from the control group after the start of the drug treatment.

Purpose : To study the relationship between the -31G/C (rs9904341) polymorphism in the promoter region of the survivin protein gene and the predisposition to bladder cancer (BC) in patients of the Krasnoyarsk region. Material and methods . The allelic composition of the studied gene was determined in a group of 158 BC patients, consisting of 30 women and 128 men (mean age 65.6 ± 10.7, median: 66.5; C 25 –C 75 : 59–72). The control group included 117 healthy donors and consisted of 27 women and 90 men with an average age of 60.2 ± 5.1 (median: 60; C 25 –C 75 : 57–63.25). The allelic composition was determined using the bioluminescent method. A sample with the GC genotype confirmed by sanger sequencing (center for collective use “genomika”, Novosibirsk, Russia) was used as a control. The Mann–Whitney U test was used to compare quantitative data. the studied sample was in Hardy–Weinberg equilibrium (p>0.5). The pearson χ 2 test was used to compare the frequencies of gene variants among BC cases and control samples. The association between variants rs9904341 and BC was assessed in terms of odds ratio (OR) with a 95 % confidence interval (CI); p values<0.05 were considered significant. Results . The allelic composition was determined for the genes of patients and control group participants: GG – 62 (39.2%) vs 43 (36.8%); GC – 82 (51.9%) vs 54 (46.2%); CC – 14 (8.9%) vs 20 (17.15%). The relationship between the presence of the C allele and BC was assessed using the recessive inheritance model, combining all carriers – heterozygotes and homozygotes. The frequency of occurrence of genotypes for patients and the control group was established: GG + GC – 144 (91.1%) vs 97 (82.9%); CC – 14 (8.9%) vs 20 (17.1%). Thus, carriers of the CС genotype were significantly less in patients: OR (95% CI) 0.47 (0.23–0.98), p=0.04. The relationship with tumor invasion was not significant (p=0.08). Conclusion . Based on the results of detecting the rs9904341 (G/C) polymorphism among BC patients of the Krasnoyarsk region, a protective effect of the carriage of the CC genotype was found. In order to study the allelic composition with the threat of recurrence of the disease, additional research is needed.

Purpose: To study the relationship between the -31G/C (rs9904341) polymorphism in the promoter region of the survivin protein gene and the predisposition to bladder cancer (BC) in patients of the Krasnoyarsk region. Material and methods. The allelic composition of the studied gene was determined in a group of 158 BC patients, consisting of 30 women and 128 men (mean age 65.6 ± 10.7, median: 66.5; C25–C75: 59–72). The control group included 117 healthy donors and consisted of 27 women and 90 men with an average age of 60.2 ± 5.1 (median: 60; C25–C75: 57–63.25). The allelic composition was determined using the bioluminescent method. A sample with the GC genotype confirmed by sanger sequencing (center for collective use “genomika”, Novosibirsk, Russia) was used as a control. The Mann–Whitney U test was used to compare quantitative data. the studied sample was in Hardy–Weinberg equilibrium (p>0.5). The pearson χ2 test was used to compare the frequencies of gene variants among BC cases and control samples. The association between variants rs9904341 and BC was assessed in terms of odds ratio (OR) with a 95 % confidence interval (CI); p values<0.05 were considered significant. Results. The allelic composition was determined for the genes of patients and control group participants: GG – 62 (39.2%) vs 43 (36.8%); GC – 82 (51.9%) vs 54 (46.2%); CC – 14 (8.9%) vs 20 (17.15%). The relationship between the presence of the C allele and BC was assessed using the recessive inheritance model, combining all carriers – heterozygotes and homozygotes. The frequency of occurrence of genotypes for patients and the control group was established: GG + GC – 144 (91.1%) vs 97 (82.9%); CC – 14 (8.9%) vs 20 (17.1%). Thus, carriers of the CС genotype were significantly less in patients: OR (95% CI) 0.47 (0.23–0.98), p=0.04. The relationship with tumor invasion was not significant (p=0.08). Conclusion. Based on the results of detecting the rs9904341 (G/C) polymorphism among BC patients of the Krasnoyarsk region, a protective effect of the carriage of the CC genotype was found. In order to study the allelic composition with the threat of recurrence of the disease, additional research is needed.

Background. Apart from surgery and medications, radiation therapy is one of the main treatment methods for malignant tumors of the cervix. However, its use is associated with high incidence of urological complications. In addition, the need for long-term treatment, reduced level of patients’ quality of life promote the necessity to minimize the frequency of urological complications and justify search and study of the most adequate methods of their prevention. Aim. To evaluate the effect of radioprotector sodium deoxyribonucleate on clinical characteristics and quality of life of patients with cervical cancer after radiation treatment. Materials and methods. 80 patients with cervical cancer treated in A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncology Dispensary. Patients received chemoand radiotherapy with the 3D conformal radiotherapy method in combination with intracavity gamma therapy sources of high dose with subsequent application of radioprotector and without it. Results. On the 3rd visit it was found that in patients with cervical cancer using a radioprotector, reduced red blood cells and flat epithelium cells content in the urine sediment, it may be due to the reparative and cytoprotective sodium deoxyribonucleate properties. In the assessment of the life quality after combined therapy completion with radioprotector, 60 % of patients’ responses to the health assessment questions of the last week differed from the comparison group. Undesirable phenomena associated with sodium deoxyribonucleate therapy not observed in cervical cancer patients during radiotherapy and subsequent observation period. Conclusion. Conformal external beam radiation therapy in combination with long-term intramuscular administration of a radioprotector has advantages compared to 3D conformal radiation therapy. This method reduces the severity of post-radiation side effects, increases time to development of hematological toxicity in the context of combination chemoradiotherapy, and reduces urothelial damage caused by chemoradiotherapy.

The article presents a clinical case of treatment of orbital B-cell lymphoma of the extranodal marginal zone. This case report demonstrates the safety and efficacy of ibrutinib monotherapy in patients with relapsed/refractory LMZ previously reported in the PCYC-1121 study. Research and clinical evidence support the use of ibrutinib monotherapy as an alternative to chemotherapy in this patient population with a favorable benefit-risk profile and a convenient once-daily regimen.

The immune system, one of the most important homeostatic organism systems, is actively involved in the protection against malignant tumors. The earliest sighs of immune homeostasis disorders should be invetigated at the cellular level, because of cell functional manifestations depend on the state of intracellular metabolic reactions. The study of lymphocyte NAD(P)-dependent dehydrogenases activity and peripheral blood neutrophils oxygen-dependent metabolism in patients with renal cellular carcinoma (RCC) showed a decrease in the intensity of ribose-5-phosphate and NADH-dependent synthetic processes, inhibition of terminal reactions of glycolysis. Altered activities of the studied enzymes favor an increase in outflow of intermediates of the Krebs cycle on the reaction of amino acid metabolism in peripheral blood lymphocytes. Radical nephrectomy was accompanied by increased activity of glycolysis. The basal level chemiluminescent of peripheral neutrophils of RCC patients response was higher both before and after operations. Stimulation of neutrophils by opsonized zymosan in vitro leads to increase in oxidative metabolism activity, most in 14 days after surgery period. Before and 30 days after surgery, adaptive metabolic capabilities of neutrophilic granulocytes decreased.

Smart analysis of multidimensional data of the physical development of patients with gastric cancer is carried out through the implementation of non-linear up-to-date technique of statistical analysis that is elastic map method. It is shown the data on physique reveal the dynamics of the disease, and support a prognosis for the outcome.

Background. One of the obligate clinical manifestations of pancreatic cancer is chronic pain syndrome, which is realized in 80 % of patients with a progressive course of the disease. Studying the molecular genetic factors that influence the phenotypic realization of chronic pain syndrome in patients with pancreatic cancer is an important step towards personalizing the roadmap.Aims. To study the associative effect of single nucleotide polymorphisms (SNPs) of the OPRM1, ABCB1, IL1B, PTGS2, LOC 541472 genes on the interindividual variability of chronic pain syndrome in patients with pancreatic cancer.Materials and methods. The study included 81 patients aged 18 to 75 years with histological verification, promptly treated for prostate cancer according to the main criterion for inclusion in the study. Molecular genetic studies were performed to determine the allelic variants of rs1799971 of the OPRM1 gene, rs1045642, rs2032582, rs1128503 of the ABCB1 gene, rs1143627 of the IL1B gene, rs5275 of the PTGS2 gene, rs1800795 of the LOC gene 541472. Statistical processing of the results was carried out using the Statistica 10.0 program.Results. Carriers of the homozygous AA genotype of the OPRM1 gene prevailed among the observed patients of the Krasnoyarsk Territory with pancreatic cancer. Genotype AG IL1B showed an increase in the chances of chronic pain by 18,46 times in patients with pancreatic cancer. Carriers of the GG genotypes of the ABCB1 rs1045642 and AA genes of the ABCB1 rs2032582 gene constituted a risk group for the implementation of chronic pain in patients with pancreatic cancer.Conclusions. The study showed that the most significant in terms of increasing the chances of chronic pain in patients with pancreatic cancer are the homo- and heterozygous genotypes of the IL1B and LOC 541472 genes encoding IL-6.