Journal of Modern Oncology

Background. Cervical cancer (CC) is among the four most common malignancies among the female population. For a long time, platinum-based chemotherapy was the standard of care and practically the only option available. However, treatment outcomes for patients with metastatic and recurrent CC remained poor. The use of immune checkpoint inhibitors significantly increased progression-free survival and overall survival in this group of patients. Currently, pembrolizumab is a priority option in treating patients with metastatic, persistent, recurrent CC with CPS ≥ 1 and is included in international and Russian clinical guidelines.

Aim. To evaluate the efficacy and safety of a pembrolizumab biosimilar (Pembroria®) in patients with metastatic, persistent and recurrent CC in the interim analysis of the PERFECTION observational study.

Materials and methods. The study included a group of 51 patients diagnosed with stage IV CC. The treatment efficacy was analyzed using the Fleming method with the objective response rate criterion according to RECIST 1.1. Safety was assessed by the incidence of adverse events (AEs) and serious AEs according to the CTCAE 5.0 toxicity scale.

Results. At stage g2, an objective response was reported in 24 (47.1%) patients, which exceeded the target threshold (22 responses). 5 (9.8%) patients experienced immune-mediated AEs, a total of 6 cases, including 1 case of grade 3 AE. The overall objective response rate was consistent with KEYNOTE-826, but the AE rate was lower (34.5% in KEYNOTE-826).

Conclusion. Pembroria® has demonstrated efficacy comparable to that of the original pembrolizumab product and an acceptable safety profile. Differences in the incidence of immune-mediated AEs associated with Pembroria® require further study, considering the duration of observation and sample size. The results support using Pembroria® in routine clinical practice.

Background. Patients undergoing surgical treatment for gastrointestinal tumors often suffer from symptoms of cachexia and sarcopenia. Preoperative preparation, or “prehabilitation”, is a potentially effective new approach to managing these patients.

Aim. To evaluate whether multimodal prehabilitation decreases postoperative complications and improves functional recovery in cachexic patients undergoing gastrointestinal cancer surgery, in comparison to usual clinical care.

Materials and methods. This prospective cohort study included data on 36 patients who underwent surgical treatment for gastrointestinal cancer from 2022 to 2023 at our cancer hospital. Sarcopenia and cachexia were assessed preoperatively using modern international consensus criteria. Patients participated in remote comprehensive prehabilitation program which encompassed nutritional and psychological support and supervised exercise. After prehabilitation functional results were assessed. Also, the 30-day postoperative complication rate measured according to the Clavien–Dindo criteria as well as 30-day and 90-day mortality.

Results. After prehabilitation, 24 (66.6%) patients showed a statistically significant decrease in 400 m walking time (p = 0.028); 25 (69.4%) patients gained weight from 0.5 to 6 kg (p < 0.001).

Conclusion. Multimodal remote prehabilitation can improve functional status in patients with gastrointestinal cancer and cachexia.

Cancer-associated thrombosis (CAT) is one of the most frequent and dangerous complications of malignancies, ranking 2nd among the causes of death in cancer patients. The article presents an overview of current data on the pathogenesis of thrombosis in cancer patients, including the key role of tumor cells, inflammatory cytokines, neutrophil extracellular traps, and dysregulation of hemostasis. CAT epidemiology, individual (age, comorbidities, mobility) and tumor-dependent (location, stage, histology) risk factors, as well as the effect of various types of anticancer therapy, including chemotherapy, surgery, and the use of central venous catheters, are considered. Particular attention is paid to modern approaches to the prevention and treatment of CAT, including direct oral anticoagulants, their advantages over low molecular weight heparins, and data from large randomized trials (CARAVAGGIO and API-CAT). The review includes an analysis of international and Russian clinical guidelines (ASCO, NCCN, RUSSCO), focusing on the need for an individual approach, considering the clinical situation, the risk of bleeding, and drug interactions. The presented data emphasize the importance of timely detection of CAT and rational choice of therapy to reduce the risk of complications and improve the prognosis in cancer patients. The presented data emphasize the importance of timely detection of CAT and rational choice of therapy to reduce the risk of complications and improve the prognosis in cancer patients. In addition, a reduced dose of apixaban (2.5 mg twice daily) after 6 months of therapy was found to be effective in preventing the recurrence of venous thromboembolism and reducing the incidence of clinically significant bleeding compared to the full dose.

Background. The results of the study of new imidazotriazine derivatives are presented to support their use as antitumor agents, including for breast cancer (BC) chemotherapy. The study is relevant due to the high prevalence and mortality of BC and other socially significant cancers. Antitumor drugs have limitations in their efficacy due to the primary or acquired drug resistance. As a result, 30% to 50% of patients do not receive adequate treatment, determining the need to develop new antitumor drugs.

Aim. To evaluate the antitumor potential of 5 new imidazotriazine derivatives by testing their cytotoxic (CTA) and cytostatic (CSA) activity on BC cell cultures.

Materials and methods. Culture of MCF-7, MDA-MB231, BT474, and MCF-10a cells and determination of CTA and CSA of imidazotriazine derivatives at concentrations ranging from 0.25 to 10.0 mmol/L.

Results. For the MCF-7 culture, the maximum cell survival inhibition by the comparator (temozolomide) was 2.44, and the concentration causing 50% cell death (IC50) was 6.81 mmol/L; for other cell cultures, CTAs were slightly lower. Imidazotriazine 2 and imidazotriazine 3 showed values below or close to temozolomide; IC50 was not achieved in most cases. These two derivatives were considered to have low CTA and moderate CSA. Imidazotriazine 4 and imidazotriazine 5 showed higher activity than the comparator and were considered compounds with moderate CTA and CSA. Finally, imidazotriazine 1 showed the highest CTA and CSA values with a maximum cell survival inhibition of 4.35 and an IC50 of 1.94 mmol/L.

Conclusion. Based on the results of the in vitro study, five new imidazotriazine derivatives have CTA and CSA in the following ascending order: imidazotriazine 2, imidazotriazine 3 < temozolomide < imidazotriazine 4 < imidazotriazine 5 < imidazotriazine 1. Therefore, 4-aminoimidazo[5,1-c][1,2,4]triazine-3,8-dicarboxylic acid diethyl ether (imidazotriazine 1) is the most promising new imidazotriazine derivative and is recommended for further preclinical studies.

Background. Renal cell carcinoma (RCC) associated with von Hippel-Lindau syndrome (VHL) is characterized by multifocal bilateral involvement of the renal parenchyma and is the leading cause of death in this category of patients due to disease progression or the development of end-stage chronic kidney disease.

Aim. To analyze the treatment outcomes of patients with RCC associated with VHL syndrome.

Materials and methods. The ambispective study included data of 30 patients treated with VHL-associated RCC from 2016 to 2024. In 23 (76.7%) cases, VHL syndrome was classified as type 1, and in 7 (23.3%) as type 2B. Non-metastatic RCC at the initial diagnosis was detected in 28 (93.3%) patients and metastatic RCC in 2 (6.7%). Extrarenal manifestations of VHL syndrome occurred in all patients. Watchful waiting was used in 6 (20.0%) patients, surgical treatment of renal parenchyma tumors in 21 (70.0%), metastasectomy – in 2 (6.7%), and systemic antitumor therapy in 3 (10.0%). Treatment of extrarenal manifestations of VHL syndrome included surgical interventions in 20 (66.7%) patients, radiation therapy in 8 (26.7%), and laser therapy in 9 (30.0%). The median follow-up for all patients from the RCC detection was 46.6 [1-249.5] months.

Results. The four-year overall (OS) and disease-specific (DSS) survival rates for all 30 patients were 93.3% and 93.3%, respectively. In 28 patients with primary non-metastatic RCC, the 4-year metastasis-free survival (MFS) was 74.2%. In 21 patients after radical surgery for the primary non-metastatic renal cell carcinoma, the 4-year OS was 88.9%, DSS was 88.9%, relapse-free survival (RFS) was 62.9%, local recurrence-free survival was 53.9%, and MFS was 63.6%. In patients with distant metastases, the 4-year OS was 66.7%. Two (6.7%) patients developed terminal chronic kidney disease requiring permanent hemodialysis.

Conclusion. VHL-associated RCC is a chronic disease with a torpid course, allowing to recommend organ-sparing treatment of primary tumors and metastasis-directed therapy of oligometastases. Antiangiogenic therapy is effective in metastatic RCC.

Background. More than 630,000 people die annually worldwide as a result of HIV, while malignant neoplasms (MN) are steadily coming to the fore among the causes of death. At the moment, there is not enough data on the treatment of HIV-infected cancer patients.

Aim. To analyze the experience of treating HIV-infected patients with solid MN who underwent therapy at the Tsyb Medical Radiological Research Centre from 2018 to 2024.

Materials and methods. The study included 154 patients, median follow-up – 35 months. The average age of the patients was 45.4 (30–78) years; 86 (55.8%) women prevailed. The following diagnoses were most often made: cervical cancer (n = 30, 19.5%), thyroid cancer (n = 22, 14.3%), breast cancer (n = 16, 10.4%), head and neck tumors (n = 24, 15.6%). In half of the patients, early stages (I–II) of MN were confirmed – 78 (50.6%), generalized tumor process in the onset of MN was observed only in 34 (22%) patients. The majority of patients – 136 (88.3%) had AIDS. HIV infection was confirmed at various times before the development of MN – from 6 to 279 months, on average after 114 months. The majority of patients have stage 4 HIV – 124 (80.6%). Suppressed viral load – less than 50 copies of viral RNA in 1 ml of blood, was detected in 96 (62.3%) patients. At the time of the start of specific antitumor treatment, the vast majority of patients – 132 (85.7%) have received antiretroviral therapy (ART), another 22 (14.3%) patients started taking ART after an oncological diagnosis. The level of CD4+ cells at the onset of MN was determined in all patients, ranged from 54 to 1036 cells/ml, with an average value of 454 and a median of 401 cells/ml. There were 12 (7.8%) patients with CD4+ cell count less than 200 per µl. Viral hepatitis (B or C) was previously detected in 24 (15.6%) patients, tuberculosis – in 6 (3.8%).

Results. Surgical treatment was performed in 82 (53.3%) patients, of which 74 (90.3%) patients received surgery as a stage of program therapy, and for 8 (9.7%) patients surgical treatment was an independent type of therapy. Radiation/chemoradiotherapy was performed in 50 (32.5%) patients, of which 31 patients received it as a stage of program treatment (62%), and for the remaining 19 (38%) patients, radiation treatment was an independent type of therapy. Antitumor drug therapy was performed in 66 (42.8%) patients: neoadjuvant therapy in 12 (18.1%) patients, adjuvant therapy in 22 (33.3%) patients, palliative chemotherapy therapy in 32 (48.6%) patients. Complications of antitumor therapy were observed in 18 (27.3%) patients, complications of surgical treatment were observed in 1 (1.2%) patient, complications of radiation therapy were identified in 14 (36.8%) patients from the EBRT group, complications of chemoradiotherapy were observed in 6 (50%) patients. During the follow-up, 4 (2.6%) deaths of patients with combined pathology were registered: in two cases, death occurred due to the progression of a malignant tumor, in the other two – due to severe infectious complications during antitumor therapy.

Conclusion. Thus, it is possible for oncological patients with HIV to undergo the entire volume of antitumor treatment, equal to that of patients without HIV, which allows achieving the same oncological results. Appropriate therapy becomes possible with adequate prevention of infectious complications, monitoring of ART, and monitoring drug interactions.

Background. Modern methods of treatment of late-stage ovarian cancer (III–IV) are based on the immediate and maximum surgical removal of all manifestations of the tumor process. However, in some cases, surgical treatment has to be performed after neoadjuvant chemotherapy. Differences in the effectiveness of treatment with both approaches are the subject of discussion in oncogynecology.

Aim. Analysis of overall survival and progression-free survival in patients with late-stage ovarian cancer (IIIC–IVB) depending on the timing and optimality of cytoreductive surgery.

Materials and methods. A retrospective analysis of 467 patients with stage III–IV ovarian cancer who received comprehensive treatment at the Primorsky Regional Oncological Dispensary in the period 2004–2021.

Results. Significant advantages in overall survival and progression-free survival were in patients with ovarian cancer of stages IIIC–IVB, who underwent primary cytoreduction (PCR), compared with patients who underwent interval cytoreduction. With suboptimal PCR volume, the overall survival rate is significantly lower than with full or optimal PCR. There is a tendency to better OS and IBD in patients with PCR in full and optimal volume, compared with patients who underwent PCR in full or optimal volume. Neoadjuvant chemotherapy in patients with serous ovarian carcinoma of low-grade IIIC–IVB stages significantly worsens immediate and long-term treatment results.

Conclusion. In patients with advanced ovarian cancer, performing primary cytoreduction in full or optimal volume is the main treatment. Neoadjuvant chemotherapy is justified only as a therapy of despair in severe general condition or extreme prevalence of the disease.