В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

Рекомендации Восточно-Европейской группы по изучению сарком. В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

Background In the ARIEL4 trial of rucaparib versus standard-of-care chemotherapy in patients with relapsed BRCA- mutated ovarian carcinoma, the primary endpoint was met, showing improved investigator-assessed progression-free survival with rucaparib. Here, we present the final overall survival analysis of the trial and other post-progression outcomes. Methods This open-label, randomised, controlled phase 3 trial was done at 64 hospitals and cancer centres in 12 countries, including Brazil, Canada, Czech Republic, Hungary, Israel, Italy, Poland, Russia, Spain, Ukraine, the UK, and the USA. Eligible patients were women aged 18 or older with BRCA1 or BRCA2-mutated ovarian carcinoma and had received at least two previous chemotherapy regimens. Patients had to have evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) criteria and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (2:1) using an interactive response technology and block randomisation (block size of six) and stratified by progression-free interval after the most recent platinum- containing therapy to receive oral rucaparib (600 mg twice daily administered in 28-day cycles) or chemotherapy on the basis of platinum-sensitivity status. In the chemotherapy group, patients with platinum-resistant disease (progression-free interval >= 1 to <6 months) or partially platinum-sensitive disease (progression-free interval >= 6 to <12 months) received weekly paclitaxel (starting dose 60-80 mg/m2 on days 1, 8, and 15). Patients with fully platinum-sensitive disease (progression-free interval >= 12 months) received the investigator's choice of platinum- based chemotherapy (single-agent cisplatin or carboplatin, or platinum-doublet chemotherapy), in 21-day or 28-day cycles. The primary endpoint (previously reported) was investigator-assessed progression-free survival, assessed in the efficacy population (all randomly assigned patients with deleterious BRCA1 or BRCA2 mutations without reversion mutations) and in the intention-to-treat population (all randomly assigned patients). Overall survival was a prespecified secondary endpoint and was analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned study treatment. The cutoff date was April 10, 2022. This study is registered with ClinicalTrials.gov, NCT02855944; enrolment is complete and the study is closed. Findings Between March 1, 2017, and Sept 24, 2020, 349 eligible patients were randomly assigned to receive rucaparib (n=233) or chemotherapy (n=116). 332 (95%) of 349 patients were white and 17 (5%) patients were other or of unknown race. In the chemotherapy group, 80 (69%) of 116 patients crossed over to receive rucaparib. Median followup was 412 months (IQR 378-446). At data cutoff for this final analysis (April 10, 2022), 244 (70%) of 349 patients had died: 167 (72%) of 233 in the rucaparib group and 77 (66%) of 116 in the rucaparib group. Median overall survival was 194 months (95% CI 152-236) in the rucaparib group versus 254 months (214-276) in the chemotherapy group (hazard ratio 13 [95% CI 10-17], p=0047). No new safety signals were observed, including during crossover to rucaparib. The most common grade 3-4 adverse events across treatment groups included anaemia or decreased haemoglobin (reported in 59 [25%] of 232 patients in the rucaparib group and seven [6%] of 113 in the chemotherapy group), and neutropenia or decreased neutrophil count (in 26 [11%] of 232 in the rucaparib group and 16 [14%] of 113 patients in the chemotherapy group). Serious adverse events were reported in 66 (28%) of 232 patients in the rucaparib group and 14 (12%) of 113 patients in the chemotherapy group. Ten treatment-related deaths were reported in the rucaparib group, two of which were linked to judged to be related to rucaparib (cardiac disorder and myelodysplastic syndrome), and one death related to treatment was reported in the chemotherapy group, with no specific cause linked to the treatment. Interpretation These data highlight the need for a better understanding of the most appropriate treatment for patients who have progressed on a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, and the optimal sequencing of chemotherapy and PARP inhibitors in advanced ovarian cancer. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd.All rights reserved, including those for text and data mining, AI training, and similar technologies.

No correlation between the dose, adverse events, and efficacy was detected in clinical trials of anti-PD-1 antibodies across a range of solid and hematological malignancies. Given that dose reduction with potentially comparable clinical efficacy may improve access to treatment, particularly in low-income regions, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose PD-1 inhibitor monotherapy in relapsed/refractory (r/r) classic Hodgkin lymphoma (cHL). Relevant reports were identified through PUBMED, MEDLINE, Cochrane, ScienceDirect databases, and major international conference proceedings, from inception till December 1, 2024. The risk of bias was assessed independently by two authors using the Joanna Briggs’s critical appraisal checklist for studies reporting prevalence data. Heterogeneity was assessed using Cochran’s Q test, with statistical significance defined as p < 0.05; I2 statistic was used to quantify heterogeneity. Random effects models (Der-Simonian method) was used to pool results from primary studies in the presence of significant heterogeneity. After screening, 13 reports including 148 patients were included in the systematic review. After exclusion of duplicated reports, studies with less than 5 patients, and studies with unextractable data, five studies with a total of 84 patients were included in the meta-analysis. The pooled objective response rate (ORR) with low-dose PD-1 inhibition in r/r cHL, as determined by meta-analysis, was 87

Gastric cancer is an important medical and social problem all over the world. The aggressiveness of the course of this disease is reflected by the high figures of one-year mortality, which is due to both high neglect at the time of diagnosis and unsatisfactory results of surgical treatment of even a localized tumor process, which from a biological point of view casts doubt on the possibility of performing a “radical” operation for this type of malignant tumor. Currently, the “gold standard” has become the conduct of perioperative chemotherapy according to the FLOT scheme for locally advanced stages of gastric cancer, esophagogastric junction and esophagogastric junction and lower esophagus. A further promising direction for improving perioperative chemotherapy is the investigation of immune checkpoint inhibitors (pembrolizumab, atezolizumab and durvalumab) in combination with cytostatics. Today, there are still a number of unresolved issues, including the need to continue such aggressive treatment in the postoperative period with an unsatisfactory pathomorphological response from the tumor. Performing the entire volume of chemotherapy is a difficult task, due to the toxicity of this type of treatment and the weakened condition of the patient after extensive surgery. The significance of the pathomorphological regression of the tumor after neoadjuvant chemotherapy is also unclear. Only 10–15% of patients achieve a complete pathomorphological response. The standard postoperative practice is to carry out the same preoperative chemotherapy regimen, regardless of sensitivity to it. The search for prognostic markers will help to individualize the treatment strategy of such patients and protect patients from excessive toxicity with unjustified continuation of chemotherapy.

In recent years, approaches to the pharmacological treatment of non-small cell lung cancer (NSCLC) have significantly evolved due to a deeper understanding of tumor biology and, consequently, the active development of personalized medicine and the introduction of targeted therapies. The identification of activating mutations, including ALK gene rearrangements, enables long-term objective control, which is particularly crucial in young patients with extensive metastatic disease and brain metastases (BM). The high rate of central nervous system (CNS) metastases characteristic of ALK-positive NSCLC underscores the importance of selecting therapeutic agents with high intracranial activity. Lorlatinib, a third-generation ALK tyrosine kinase inhibitor (TKI), is capable of crossing the blood-brain barrier and effectively suppressing resistance mutations that may develop during treatment with crizotinib or second-generation TKIs. Initially, lorlatinib was used in the second-line and subsequent lines of therapy; however, updated results from the CROWN study have demonstrated its unprecedented efficacy as a first-line treatment, including in patients with BM. Currently, lorlatinib is approved in the Russian Federation for the treatment of ALK-positive advanced NSCLC in both previously treated patients and as a first-line therapy. This paper presents a clinical case of a 49-yearold patient with advanced ALK-positive NSCLC and brain metastases. Following the diagnostic phase, which included videoassisted thoracoscopy and morphological verification, the patient underwent a course of chemotherapy with cisplatin and pemetrexed. Subsequently, based on the results of molecular genetic testing, lorlatinib was initiated at a dose of 100 mg/day. Within a month, a significant regression of CNS metastases was observed. Therapy was accompanied by minimal side effects, including hypercholesterolemia and elevated liver enzymes, which were successfully managed with lipid-lowering agents and physical activity. During targeted therapy, the patient has maintained stable disease for 26 months, showing a strong clinical response without the need for dose reduction. This case report highlights the efficacy and tolerability of lorlatinib in the treatment of ALK-positive NSCLC with BM and underscores its potential in clinical practice.

Currently, tumour tissue biopsy to determine RAS/BRAF gene alterations, assess microsatellite instability status, and determine HER‑2/neu gene amplification/hyperexpression is the gold standard of diagnosis and allows the selection of optimal molecularly targeted therapy when considering treatment strategies for patients with metastatic colorectal cancer. However, biopsy does not fully reflect the existing intratumoural heterogeneity and clonal evolution of tumour cells, which can often be the cause of therapeutic failures. In recent years, liquid biopsy has attracted increasing attention as an additional and potentially alternative non-invasive tool for molecular tumour profiling. Assessment of circulating tumour DNA allows changes in the genetic status of the tumour to be monitored and the «burden» of disease to be measured dynamically in real time. Advances in liquid biopsy technology have led to promising new strategies for the management of patients with metastatic colorectal cancer in late-line therapy. The standard drug arsenal in this group of patients is limited to either repeat administration of previously effective therapy or regorafenib and the combination of trifluridine/tipiracil with bevacizumab, which are characterized by limited clinical activity. However, thanks to the discovery of the NeoRAS wild-type phenomenon and the rechallenge strategy of anti-EGFR monoclonal antibodies based on the study of clonal selection and evolution of tumour cells, the administration of epidermal growth factor inhibitors in a molecularly selected by liquid biopsy population is accompanied by good tolerability and efficacy. Numerous clinical studies are ongoing to further understand the mechanisms of tumour resistance and to develop new evidence-based treatment approaches in order to realise the concept of personalised medicine.

Gastric cancer (GC) is one of the most aggressive and unfavorably ongoing malignant neoplasms, occupying the fifth and fourth places in the structure of oncological morbidity and mortality, respectively. Overexpression of the human epidermal growth factor receptor 2 (HER2-neu) is detected in about 20% of patients with advanced GC, which made it possible to successfully use trastuzumab in combination with chemotherapy (CT) in this cohort of patients. The development of resistance to trastuzumab is a serious problem that requires research and development of new therapy targeted to blockHER2-neu. Trastuzumab deruxtecan is an antibody–drug conjugate consisting of an antibody to the HER2-neu receptor and a topoisomerase inhibitor linked by a cleavable tetrapeptide-based linker. The drug has proven its effectiveness as a monotherapy for the treatment of patients with metastatic or locally advanced HER2-positive gastric adenocarcinoma or cardio esophageal junction in the 2nd and subsequent lines of treatment. In the above clinical case a 57-year-old patient with CEС adenocarcinoma with metastatic liver damage, distant lymphnodes and the presence of HER2-neu overexpression is presented. After the standard first-line drug treatment according to the XELOX scheme with trastuzumab, the patient underwent surgical treatment followed by postoperative chemotherapy according to the FOLFOX scheme in combination with trastuzumab. Given the negative dynamics, the next step was 3 injections of nivolumab immunotherapy, which eventually led to the development of autoimmune hepatitis and rapid progression of the disease. Almost the last hope for the patient was the introduction of trastuzumab deruxtecan, which allowed for an objective response, as well as an improvement in the patient’s clinical condition, which led to the achievement of the longest possible progression-free survival (PFS).

INTRODUCTION:Poly (adenosine diphosphate-ribose) polymerase inhibitors can up-regulate programmed cell death-ligand 1 expression and promote immune-mediated responses and may improve efficacy of first-line anti‒programmed cell death protein 1‒based therapies in patients with metastatic squamous NSCLC. METHODS:In this randomized, double-blind, phase 3 trial (NCT03976362), adults with previously untreated stage IV squamous NSCLC received four cycles of induction therapy (pembrolizumab 200 mg every 3 weeks plus carboplatin and paclitaxel or nab-paclitaxel). Patients with disease control were randomized to 31 cycles of pembrolizumab 200 mg every 3 weeks plus olaparib 300 mg orally twice daily or placebo. Dual primary end points were progression-free survival (PFS) and overall survival (OS). PFS was tested at interim analysis 2 (the final PFS analysis); OS was tested at final analysis. RESULTS:A total of 851 patients received induction treatment; 296 were randomized to pembrolizumab plus olaparib and 295 to pembrolizumab plus placebo. At interim analysis 2, with median follow-up of 27.1 months, median (95% confidence interval [CI]) PFS was 8.3 (6.7‒9.7) months in the pembrolizumab plus olaparib group and 5.4 (4.1‒5.6) months in the pembrolizumab plus placebo group (hazard ratio = 0.77, 95% CI: 0.63‒0.93, p = 0.0040 [not significant at a one-sided superiority boundary of p = 0.003]). At final analysis, with median follow-up of 33.4 months, median (95% CI) OS was 19.1 (15.9‒22.2) and 18.6 (16.0‒21.6) months, respectively (hazard ratio = 1.01, 95% CI: 0.83‒1.24, p = 0.5481). Treatment-related adverse events occurred in 76.5% and 65.1% of patients, respectively. CONCLUSIONS:Adding olaparib to pembrolizumab as maintenance therapy for metastatic squamous NSCLC did not significantly improve PFS versus pembrolizumab plus placebo; neither PFS nor OS met the prespecified statistical significance boundary. No new safety signals were identified. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03976362.

Adjuvant endocrine therapy is an integral component of treatment for resectable luminal breast cancer. Tamoxifen or aromatase inhibitors monotherapy has been the standard of practice for many years. However, recent studies have shown that the addition of ovarian suppression statistically significantly increases survival rates in patients at high risk for recurrence and with poor prognosis factors. In this literature review, we summarized recent data regarding the role of ovarian suppression in adjuvant therapy for hormone-positive breast cancer. Suppression of ovarian function was most effective in young patients (< 35 years) in the premenopausal stage when adverse prognostic factors were present (indications for (neo)adjuvant CT, G3, etc.) The authors noted that using of aromatase inhibitors instead of tamoxifen in this subgroup significantly reduced the risk of breast cancer recurrence. Ovarian suppression, especially in combination with aromatase inhibitors, was accompanied by an increase in the incidence of adverse side effects, particularly osteoporosis and bone fractures, which can be reduced by prescribing adequate accompanying therapy with OMA. The optimal duration of ovarian function suppression has also not been determined, but a two-year course seems optimal, given the results of large clinical trials. In the protocols performed, there was no significant effect of temporary ovarian suppression on the likelihood of subsequent pregnancy.

Malignant glomus tumor is an extremely rare, aggressive neoplasm, which is contain from modified glomus body’s cells. The correct morphological diagnosis is difficult, and requires careful differential diagnosis between neuroendocrine tumors, pericytic tumors, smooth muscle neoplasms. The literature describes only sporadic clinical observations, a series of cases and the results of a small number of retrospective studies. Due to the rarity of nosology, the optimal treatment strategy for this disease has not been developed. Most cases, surgical treatment is used in a locally common process. Cases of metastasis of a malignant glomus tumor are extremely rare. There is no consensus on the tactics of systemic treatment to date. In this article, we present a clinical case of achieving stabilization of the tumor process after 5 courses of chemotherapy with doxorubicin, ifosfamide in a 49-year-old patient with a malignant glomus tumor of the soft tissues of the left forearm with metastatic lesion of the tissues of the anterior chest wall on the left with spread to the left small pectoral muscle, 3rd rib and pleural cavity, with metastatic lesion lung parenchyma.

Purpose. To study the efficacy and safety of total neoadjuvant chemotherapy (NACT) with the FOLFIRINOX regimen for locally advanced gastric (GC) and cardioesophageal junction (CEJ) cancer. Patients and methods . Patients with histologically confirmed locally advanced gastric adenocarcinoma and CEJ, clinical stage cT3 or higher and/or regional lymph node involvement (cN+), without evidence of distant metastasis were included in our open-label, single-centre, non-randomised study. In the FLOT control group, patients received 4 courses preoperatively and 4 postoperatively with follow-up. I In the FOLFIRINOX group 8 courses of chemotherapy were administered in neoadjuvant mode, followed by surgery and observation. The tumor regression grade was assessed in accordance with Becker, Mandard and G. A. Lavnikova scales. Results. The study included 136 patients, 119 of whom started treatment according to the protocol (ITT population). Fiſty-nine patients were enrolled into the FLOT group and 60 into the FOLFIRINOX group. One-year progression-free survival (PFS) was 67,5 % in the FLOT group and 90,4 % in the FOLFIRINOX group (p = 0,29). The estimated 2-year PFS in the FLOT group was 61,4 % [95 % CI, 48,4–77,9 %]. Median PFS and overall survival (OS) were not reached. The incidence of events (progression or death) was lower in the FOLFIRINOX group (odds ratio [OR] 0,40 [95 % CI 0,16–0,97, p = 0,047]). Adverse prognostic factors regardless of treatment were lymphatic (L1), vascular (V1) and perineural invasion (Pn1), and regional lymph node involvement aſter chemotherapy (ypN+) [p = 0,046; p = 0,014; p = 0,0021; p = 0,04, respectively]. There was no correlation between pathological complete response and survival rates. Conclusion . Total neoadjuvant chemotherapy with the FOLFIRINOX regimen for locally advanced GC/ CEJ demonstrated comparable to the perioperative FLOT one-year PFS rate. No association was found between tumor regression grade and survival outcomes.

Despite their B cell origin, Reed-Berezovsky-Sternberg tumor cells (RBS) in classic Hodgkin's lymphoma (cHL) demonstrate an absolutely unique phenotype. Immunohistochemistry of RBS cells is positive for CD15 antigen in most of cases, CD30, PAX-5; they do not express the T cell antigen CD3, В cell CD19, and in most cases are negative for the B cell antigen CD20, as well as for common leukocyte antigen CD45. Taking into account such unequivocal immunophenotype, RBS cells can be identified by multiparameter flow cytometry. Thus, J.R. Fromm et al. (2006, 2014) have convincingly shown the possibility to identify RBS cells in a puncture and/or biopsy sample of lymphatic nodes in cHL and were of the fair opinion that such rather simple and reproducible technique as flow cytometry could be an additional diagnostic instrument in cHL. We have tested the technique proposed by J.R. Fromm et al. for the assessment of lymphatic node involvement in cHL and used 8 to 10-parameter flow cytometry for detection RBS cells in cHL in 8 biopsy samples of a lymphatic node, and confirmed the feasibility to identify RBS cells by high performance flow cytometry. We also performed morphological and immunohistochemical assessment of the biopsy samples of lymphatic nodes from patients with suspected cHL. The study included clinical cases with immunohistochemically confirmed cHL (n = 8), and the control samples were from those with other diagnoses than Hodgkin's lymphoma. In all cases of cHL we found RBS cells. In future we plan to analyze larger case samples by flow cytometry.

Introduction . Giant cell tumor of bone is a relatively rare, locally aggressive osteolytic skeletal neoplasm with uncertain behavior: recurrence rates up to 70 % and distant metastases occur 2–6 % of cases. Nowadays denosumab is the choice of therapy for patients with unresectable or advanced disease. However, the efficiency, duration or administration and most of all safety of continuous denosumab are not established. Materials and methods . Fourty advanced or unresectable giant cell tumor cases were observed from 2005 till 2020 in N.N. Blokhin National Medical Research Center of Oncology. The average age of pts was 33,6 ± 13,1 years (18–64), and the women and men ratio was about 2,1 : 1. The most commonly affected sites were long bones of the lower extremities (22,5 %), sacrum (22,5 %), long bones of the upper extremities (17,5 %), spine (17,5 %), pelvis (10 %) and others. 70 % of cases were anatomically compounded due to tumor localization and 27,5 % of cases were primary disease. 37,5 % of cases were with pulmonary metastases. Patients underwent computed tomography / magnetic resonance imaging every 3 months during the first three years and then once every six months. Patient received subcutaneous denosumab 120 mg every 4 weeks with a loading dose of 120 mg subcutaneous on study days 8 and 15. After 2 years monthly therapy and confirmed stabilization effect patient then received maintenance therapy: once in three months injection. All patients received daily calcium and vitamin D supplement. Results . Median follow-up was 52,8 ± 41,3 months (3–219 months). The average denosumab injections were 25 ± 16 (4–85). Clinical and radiographically stabilization of the effect occurred on average at 12 ± 8 (4–32) injections. Hypocalcemia was registered in one case (2.5 %). There was significant improvement of Karnofsky scale, Visual analogue scale (VAS) and Watkins scale (p <0.001). 5-year progression-free survival for was 70.1 % (95 % confidence interval 55.7–88.0), the median was not reached. Progression of disease was observed only in subgroup with violations in denosumab administration or its cancellation (32,5 %). 3-year progression-free survival in subgroup with violations in denosumab administration or its cancellation was 10 % (95 % confidence interval 15.5–64.1). In subgroup with continuous denosumab and once in three months injection after 2 years monthly therapy there was no signs of progression. Conclusions . In this study we showed evidence of safety and effectiveness of continuous denosumab for unresectable or advanced giant cell tumor even with once in three months injection therapy. Denosumab for advanced giant cell tumor of bone became a choice of treatment, but we need further investigation for observation long term denosumab effectiveness and complications.