Purpose of the study. To evaluate the impact of different management strategies for regional nodal metastases on survival in patients with localized oral cavity cancer (cT1–2N0M0), based on data from the population-based cancer registry of Arkhangelsk Oblast and Nenets Autonomous Okrug (PCR AO and NAO) over the period 2010–2024. Patients and methods . A population-based retrospective cohort study was conducted including 204 patients from the Population-Based Cancer Registry of the Arkhangelsk Region and the Nenets Autonomous Okrug. According to the treatment strategy chosen, patients were allocated to four groups: 1) radical surgery of the primary tumor with prophylactic neck lymph node dissection (n = 63); 2) radical surgery of the primary tumor with neck lymph node dissection followed by adjuvant radiation/chemoradiation therapy (n = 38); 3) radiation/chemoradiation therapy as a standalone treatment (n = 69); 4) radical surgery directed to the primary tumor only, without regional lymph node treatment (n = 34). Survival analysis was performed using the Kaplan–Meier method, the log-rank test, and the Cox proportional hazards regression model. Results . The 5‑year cancer-specific survival rate in the overall cohort was 70.8 % (95 % CI, 63.2–77.1 %). After adjustment for stage, age, sex, morphology, place of residence, and calendar period, the surgery group with elective neck dissection demonstrated the most favorable prognosis. Compared with this reference group, omission of regional lymph node treatment was associated with a 2.9‑fold increase in the risk of death (HR = 2.90; 95 % CI, 1.01–8.37; p = 0.049), while definitive radiotherapy as a standalone modality was associated with a 3.24‑fold increase (HR = 3.24; 95 % CI, 1.42–7.38; p = 0.005). The risk in the adjuvant radiotherapy group did not differ significantly from that in the reference group (HR = 1.63; p = 0.276). Stage II disease (HR = 2.72; p = 0.013) and age 50–69 years (HR = 1.99; p = 0.023) were independent adverse prognostic factors. Conclusion . The results of this population based study demonstrate that radical surgery of the primary tumor combined with prophylactic neck lymph node dissection is the optimal treatment strategy for patients with Stage I–II oral cavity cancer. Omission of regional lymph node treatment or the use of radiation therapy as a standalone method in routine clinical practice are associated with a statistically significant increase in the risk of disease specific mortality.
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: Fournier’s gangrene is a severe condition with a high mortality rate, requiring emergency surgical treatment. Improving its efficacy remains a pressing issue in urology and surgery. AIM: To analyze the clinical course and treatment outcomes of Fournier’s gangrene. MATERIALS AND METHODS: This article presents an analysis of the clinical course and treatment outcomes of 42 patients with Fournier’s gangrene treated in medical institutions in the Arkhangelsk region from 2005 to 2024. All patients were men aged 19 to 93 years (mean age 49.6 years). RESULTS: Spread of gangrene beyond the genital area was observed in 36 patients (85.7%). The purulent process most frequently affected the perineal tissues (22 patients; 52.4%), often extending to the gluteal regions and pelvic soft tissues. Emergency surgical treatment was performed with excision of necrotic tissues. Subsequently, patients required staged surgical debridement at 1–2 day intervals. The number of these procedures ranged from 1 to 8. A total of 139 operations were performed (an average of 3.3 per patient). The maximum skin defect area was 467 cm2, and the length of the largest linear wound measured 109 cm. Seven patients (16.7%) required readmission for delayed reconstructive surgeries. These included urethral fistula repair in three cases, penile urethral stricture repair in one case, orchiopexy in two cases, and colostomy closure in one case. The mean period of hospital treatment was 32.6 days, with a mortality rate of 21.4%. CONCLUSIONS: Hospitalization and initiation of treatment in patients with Fournier’s gangrene should be performed on an emergency basis. Excision of necrotic tissues must be radical, extending into healthy tissues during the initial and subsequent surgical debridement. The outcome of the condition largely depends not only on the timeliness and adequacy of therapeutic measures but also on the severity of immunocompromising predisposing factors and underlying diseases.
BCD-217-2/OCTAVA (NCT05732805) is an international, multi-center, randomized, double-blind, placebo-controlled phase III study conducted to access the efficacy and safety of prolgolimab+nurulimab (BCD-217) combination therapy with continued prolgolimab therapy compared to prolgolimab monotherapy as 1st line treatment for patients (pts) with unresectable or metastatic melanoma (un/mM). BCD-217 is a fixed-dose combination of nurulimab (aCTLA-4, 5 mg/ml) and prolgolimab (aPD-1, 15 mg/ml) was recently approved as the 1st line treatment for un/mM in Russia. Here we present the primary analysis of the study. Pts with unresectable or metastatic cutaneous melanoma (IIIC-IVM1a-c) with treatment- naïve for unresectable/metastatic disease were randomized in 2 treatment arms: combination drug containing nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) at a dose of 0.2 ml/kg Q3W during the first four blinded infusions (nuru+prolgo arm) and prolgo arm received prolgolimab monotherapy at a dose of 3 mg/kg Q3W during the first four blinded infusions. Then both arms received prolgolimab maintenance up to two years. The primary endpoint of the study was progression-free survival (PFS). 271 pts were randomized to nuru+prolgo (n=135) or prolgo monotherapy (n=136) arms. After the median of 15.8 mo follow-up the median PFS (mPFS) was 15.4 (10.3; ND) mo in the nuru+prolgo group and 10.8 (4.7; ND) mo in the prolgo monotherapy group (95% CI, HR 0.68 (0.482; 0.957), iRECIST). The mPFS benefit of nuru+prolgo arm compared to prolgo arm are maintained in RECIST 1.1 assessment: 9.9 mo vs 2.8 mo, respectively. ORR and DCR were also higher in NURU+PROLGO arm. mOS was not reached in both groups (95% CI, HR 0,88, (0.50; 1.55)). 12-mos OS was 84% in each arm. Grade 3-4 treatment-related AE were reported in 16.3% of pts in nuru+prolgo arm compared to 14.0% - prolgo arm. Immune-related AEs (irAE) of all grades were reported in 52.6% of cases in nuru+prolgo arm and 32.4% of cases - in prolgo arm (p 0.0007). Majority of them were mild. The proportion of gr.≥3 irAEs was 13.3% vs 5.9% in nuru+prolgo arm and prolgo arm, respectively (p 0.04). Treatment discontinuation due to AE was reported in 9.6% of cases for nuru+prolgo vs 4.4% of cases for prolgo arm. OCTAVA trial resuts demonstrated that the fixed-dose combination of nurulimab + prolgolimab is significantly more effective than aPD-1 monotherapy without a serious deterioration of the safety profile in patients with metastatic or unresectable cutaneous melanoma as 1st line therapy. Lev Demidov, Igor Samoylenko, Galina Kharkevich, Kristina Orlova, Vladimir Moiseenko, Igor Utyashev, Daniil Stroyakovskiy, Vadim Kozlov, Anastasia Mochalova, Svetlana Demidova, Marina Lyadova, Andrey Kutkovich, Pavel Skopin, Nadezhda Kovalenko, Sufia Safina, Vitaliy Volkov, Yulia Semiletova, Vera Vaschenko, Nikolaiy Kislov, Artem Poltoratsky, Irina Shumskaya, Sergey Kolomiets, Alexander Sobolev, Igor Belogortsev, Svetlana Odintsova, Sameer Rastogi, Timur Andabekov, Anastasia Zimina, Konstantin Penkov, Anna Semenova, Alexey Obukhov, Vasiliy Belyakovsky, Oleg Gladkov, Rakesh Neve, Natalia Falaleeva, Elena Poddubskaya, Amale Vaibhav, Dmitriy Kirtbaya, Yana Chapko, Maria Smagina, Irina Sorokina, Yulia Linkova, Arina Zinkina-Orikhan, Fedor Kriukov, Anton Lutsky, Evgenia Mikhailova. Proved clinical benefit of low-dose anti-CTLA4 + anti-PD-1 immunotherapy versus mono anti-PD-1 therapy in patients unresectable or metastatic melanoma: Phase III OCTAVA trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 653.
The objective: to determine the types and prevalence of Mycobacterium tuberculosis DNA mutations associated with resistance to rifampicin, isoniazid, ethambutol, fluoroquinolones and injectable drugs in MDR TB patients in Arkhangelsk Oblast. Subjects and Methods. In Arkhangelsk Oblast, all patients underwent examination by molecular genetic testing and phenotypic methods for drug susceptibility. In 2010-2017 in Arkhangelsk Oblast, 1064 new MDR TB cases were registered. A total of 1340 cases of MDR TB were registered during this period, including 276 cases with recurrent MDR. Mutations associated with resistance to rifampicin ( rpoB gene) and isoniazid ( inhA, katG genes) were identified by Genоtype MTBDR plus (Hain Lifescince); mutations associated with resistance to fluoroquinolones ( gyrA gene), injectable drugs ( rrs gene) and ethambutol ( emB gene) were identified using GenoType MTBDR sl (Hain Lifescince) in accordance with the manufacturer's recommendations. Results. In 2010–2017 among 1064 new MDR TB cases, Mycobacterium tuberculosis mutations associated with simultaneous resistance to rifampicin and isoniazid were detected in 922/1064 (87%) cases; mutations associated with monoresistance to isoniazid were found in 2/1064 people. 1196/1340 (89%) MDR TB cases underwent examination with GenoTуре MTBDRsl. The predominant mutation in the rpoB gene was the S531L mutation (86.6%), the second and third most frequent mutations were D516V (5.3%) and L511P (2.6%), respectively. Mutations in codon 526 were less frequent than the others. In all MDR TB cases, mutations in the katG gene were detected, which were combined with mutations in the inhA gene in 85 (9.2%) cases. Only two cases had isolated mutations in the inhA gene. The predominant mutation among M. tuberculosis isolates associated with resistance to isoniazid was S315T1 (98.8%) in the katG gene, and C15T in the inhA gene. According to the results of our study, mutations in the gyrA gene were present in 13.6% (163/1196; 95% CI 11.7–15.7%) of cases, in the embB gene – in 49.7% (594/1196; 95% CI 46.8–52.5%), in the rrs gene – in 7.1% (85/1196; CI 95% 5.7–8.7%). Among all studied isolates with resistance to fluoroquinolones, the most common mutation in the gyrA gene was D94G (79/163; 48.5%), including cases without wild-type dropout. The A90V mutation was present in 19% of cases. The S91P mutation was detected in 11.7% of isolates. The D94N and D94A mutations occurred in 9.2% and 7.4% of cases, respectively. In 3 cases, two mutations were present simultaneously. All isolates in our study had mutations in the rrs gene associated with high levels of resistance to injectable drugs (A1401G and G1484T). In the rrs gene, the rrs A1401G mutation was most common (81/85; 95.3%), including cases of simultaneous detection of “mutant samples” and “wild type” samples. In 4.7% of cases, the G1484T mutation was detected. In Arkhangelsk Oblast, 81.5% (95% CI 78.1% to 84.5%) of mutations in the embB gene were M306V mutations and 18.5% (95% CI 15.5% to 21.9%) were M306I mutations.
