Introduction. A lung immune prognostic index (LIPI) is one of the available models that showed association with immune checkpoint inhibitors (ICI) outcomes. The disadvantage of this model is the presence of intermediate prognostic group. This single-center retrospective study aims to validate the modified lung immune prognostic index (mLIPI) to more accurately predict of the response to immunotherapy and exclusion of intermediate prognostic group from the model. The primary endpoint was progression free survival (PFS).

Aim. Validation of modified lung immune prognostic index (mLIPI) to more accurately predict of the response to immunotherapy.

Materials and methods. Baseline neutrophil-to-lymphocyte ratio, lactate dehydrogenase, hemoglobin, platelets, and fibrinogen level were collected from 195 patients treated with ICI in monotherapy or combination in N.N. Blokhin NMRCO. Univariate and multivariate subgroups analysis by Cox regression model was performed. The median follow-up time was 39.5 months.

Results. In univariate analysis hemoglobin levels below 110 g/l (HR = 1.78, 95% CI 1.51–6.46), platelet count greater than 2 normal values (HR = 4.97, 95% CI 1.19–20.63), neutrophil-to-lymphocyte ratio of 3 or more (HR = 1.39, 95% CI 1.02–1.89), lactate dehydrogenase level is higher than normal values (HR = 1.54, 95% CI 1.1–2.14) and fibrinogen level is greater than 2 normal values (HR = 1.96, 95% CI 1.06–3.64) were significantly associated with worse PFS. In univariate and multivariate analysis, a combination of any 2 or more factors was significantly associated with worse PFS (“poor” mLIPI prognosis group): HR = 2.04 (95% CI 1.43–2.94) and HR = 2.26 (95% CI 1.55–3.32), respectively. At the same time, out of 44 patients with mLIPI 2 or more, 19 (44%) had a LIPI score of 1 (intermediate prognosis group LIPI). The median PFS for the “good” and “poor” mLIPI prognosis groups was 8.4 months (CI 95% 6.6–10.2) and 4 months (CI 95% 2.4–5.6) (p < 0.001), respectively. The 3-year PFS for the “good” and “poor” mLIPI prognosis groups was 24.5 and 3.4% respectively.

Conclusions. The basic mLIPI score has a predictive value. The combination of any two unfavorable factors (not only the ratio of neutrophils to lymphocytes and LDH level) significantly correlates with worse immunotherapy outcomes in patients with metastatic NSCLC.

Introduction. Small cell lung cancer (SCLC) accounts for approximately 15–20% of all lung cancer cases. The addition of PD-L1 inhibitors to platinum-etoposide chemotherapy has become the standard of care first-line treatment of SCLC. IMpower133 study revealed that immune-related adverse events (irAEs) were observed in 33.3% of patients, with only 4% of cases discontinuing treatment owing to irAEs, which indicates an acceptable safety profile.

Aim. To analyse the toxicity profile of atezolizumab in combination with chemotherapy in the first-line treatment of patients with small cell lung cancer in real-world clinical practice.

Materials and methods. This prospective/retrospective, non-randomized, single-site study included 157 patients aged 32 to 84 years with advanced SCLC, who received atezolizumab + carboplatin/cisplatin + etoposide as first-line chemoimmunotherapy over the 2019 to 2025 period at the S. S. Yudin City Clinical Hospital. 101 (65.6%) patients showed a satisfactory ECOG performance status (ECOG 0-1), whereas 54 (34.4%) patients showed ECOG PS of 2-3.

Results. Grade 3-4 irAEs were diagnosed in 8 patients (5.1%). 14 patients (8.92%) were assigned to receive systemic glucocorticosteroid therapy. Five (3.18%) patients required complete discontinuation of immunotherapy due to immune-related toxicity.

Conclusions. In real-world clinical practice, the combination of atezolizumab and chemotherapy demonstrated an acceptable and manageable toxicity profile, even when used in patients with a baseline reduced performance status and aggravated medical history.

Introduction. Cervical cancer, a malignant tumor that develops from the lining of the cervix. The main etiological factor in the development of this process is highly oncogenic strains of human papillomavirus type 16 and 18. Cervical cancer is 9^th ranks in the prevalence of malignant neoplasms (MNEs) worldwide and 4^th in the female population. In 2024, 426 new cases of cervical cancer were detected in the Krasnoyarsk Territory, which is 2.6% in the overall structure of oncological pathology (14^th place) and 5.0% in the structure of female cancer incidence (6^th place). In the structure of the stages of cervical cancer in the Krasnoyarsk Krai, the proportion of patients with I–II established stages of cervical cancer was 58.1% in 2022, in 2024 has increased to 66.0%. In a dynamic assessment of late stages of cervical cancer, namely III–IV, they accounted for a total of 31.0% in 2020, in 2022 this has increased to 41.9%, which makes this pathology even more actual in terms of diagnosis and choice of treatment approaches.

Aim. To evaluate the effectiveness of pembrolizumab immunotherapy in a patient with PD-L1-positive status, progressive cervical cancer after radical chemoradiotherapy and platinum-containing chemotherapy and its effect on the patient’s prognosis and epidemiological parameters of oncology.

Materials and methods. The analysis of GLOBOCAN data and reference books “Malignant neoplasms in Russia” is conducted. The results of the studies of KEYNOTE-158 and KEYNOTE-826 were used, as well as our own data obtained from the results of patient treatment.

Results. According to GLOBOCAN, cervical cancer ranks 4th among oncological diseases in women. In 2024 16.3 thousand new cases were identified in the Russian Federation. The Krasnoyarsk Krai demonstrates a high incidence rate. Modern treatment approaches, including the use of immunotherapy, have shown effectiveness and stabilization of the process after 19 courses.

Conclusions. Pembrolizumab immunotherapy is effective in patients with PD-L1-positive status, recurrent or metastatic cervical cancer, allows to achieve long-term stabilization and improve the prognosis.

Introduction. Hepatocellular carcinoma (HCC) is a rare disorder in Russia, but its 1-year mortality rate is comparable to that of pancreatic cancer, reflecting its high aggressiveness and poor prognosis. Atezolizumab combined with Bevacizumab (A + B) is the standard of care for hepatocellular carcinoma (HCC) with a high objective response rate (ORR).

Aim. To evaluate the potential of systemic immunotargeted therapy (ITT) with a combination of A+B to downstage advanced HCC and convert nonsurgical candidates into eligible candidates for transplant, i.e. the state that meets the criteria for orthotopic liver transplantation (OLT), and to explore the safety after ITT.

Materials and methods. A real-world retrospective study to evaluate the efficacy of A+B therapy in converting patients with advanced HCC to a state amenable to surgical treatment and outcomes of OLT was conducted. The results of 12 patients with BCLC-B3 and C hepatocellular carcinoma who received A + B therapy at standard doses from January 1, 2019, to May 2024 at the Russian cancer center and the transplant center were presented. The effectiveness of therapy, the median number of ITT cycles administered, changes in the alpha-fetoprotein (AFP) levels, the safety profile, and progression-free survival (PFS) and overall survival (OS) rates were assessed.

Results. The median number of ITT cycles administered was 8. The median waiting period for OLT after completion of ITT was up to 2 months. The median alpha-fetoprotein (AFP) level decreased from 1975 to 8.2 ng/mL. A complete response was observed in 1 case (8.3%), HCC stage was downstaged to Milan Criteria in 2 cases (16.7%), and to University of California, San Francisco (UCSF) Criteria in 3 cases (25%). The results demonstrated 1-, 3-, and 5-year overall survival rates of 91.7%, 73%, and 73%, respectively. The mortality rate was 33.3%, or 4 out of 12 cases, with 2 of these deaths not being associated with tumor progression.

Conclusion. In our retrospective study, A + B systemic therapy demonstrated high efficacy and safety and may represent a promising treatment option for conversion therapy of inoperable HCC.

Despite significant advances in the treatment of patients with EGFR-positive metastatic non-small cell lung cancer (NSCLC), a number of unanswered questions remain. EGFR tyrosine kinase inhibitors (EGFR TKIs), both monotherapy and in combination regimens, are undoubtedly the optimal first-line therapy and can significantly improve long-term outcomes. After disease progression with targeted therapy, we typically use standard platinum-based therapy or a quadruple regimen (atezolizumab, paclitaxel, carboplatin, and bevacizumab), which limits our options. Further treatment is limited to cytostatics, typically used alone, with expectedly low efficacy. Thus, there is an unmet need for subsequent lines of therapy for these patients. The objective of this study was to present the results of clinical and preclinical studies of datopotamab deruxtecan to confirm its benefit in patients with metastatic EGFR-positive NSCLC. The phase I clinical trials TROPION-PanTumor01 and TROPION-PanTumor02 demonstrated encouraging results and satisfactory tolerability in a cohort of patients with NSCLC. In the randomized TROPION LUNG01 study, datopotamab deruxtecan, administered at a dose of 6 mg/kg intravenously every 3 weeks, was compared with docetaxel in a population of previously treated patients with non-small cell lung cancer. The clear advantage of datopjtamab over docetaxel, especially in patients with EGFR mutations, led to its further study in this cohort of patients in the Phase II TROPION LUNG 05 trial. Subsequently, a pooled analysis of the efficacy of datopotamab deruxtecan was conducted in EGFR-positive patients participating in the TROPION LUNG01/05 trials. Datopotamab demonstrated the best results to date in terms of immediate efficacy, progression-free survival, and overall survival in pretreated EGFR-positive patients. The drug was well-tolerated. These results led to the approval of datopotamab deruxtecan for clinical use in patients with EGFR-positive NSCLC following progression on EGFR-TKIs and platinum-based chemotherapy, opening the door to further personalized therapy.

The identification and understanding of various signaling pathways involved in the pathogenesis of malignant neoplasms, particularly breast cancer (BC), have significantly transformed the therapeutic landscape of this disease. Hormone receptor-positive (HR⁺) HER2-negative (HER2⁻) metastatic BC (mBC) is the most common but biologically heterogeneous subtype, which largely accounts for the variability in response to endocrine therapy. In patients without visceral crisis, endocrine therapy remains the preferred treatment option due to its higher efficacy and better tolerability compared with chemotherapy. Activation of the AKT signaling pathway promotes tumor cell growth, proliferation, and survival, leading to the development of endocrine resistance. PIK3CA and AKT mutations, as well as PTEN loss, are among the most frequent alterations, occurring in approximately 20–40% of patients with early-stage BC and in up to 40% of those with metastatic disease. As an AKT inhibitor, capivasertib has shown promising results in both preclinical studies and clinical trials, either as monotherapy or in combination with fulvestrant. The FAKTION trial demonstrated the efficacy and safety of capivasertib combined with fulvestrant, particularly in patients with alterations in the PI3K/AKT/PTEN signaling pathway. The CAPItello-291 study confirmed these findings, leading to the approval of this combination for the treatment of HR⁺/HER2⁻ breast cancer harboring PI3K/AKT/PTEN pathway alterations. Several clinical trials are currently underway to evaluate the efficacy of capivasertib, including that in the first-line treatment of patients with HR⁺/HER2⁻ mBC harboring PI3K/AKT/PTEN pathway alterations.

The efficacy of targeted therapy in rare epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer is debatable. However, due to introduction of NGS technology into clinical practice, patients with non-small cell lung cancer (NSCLC) harbouring rare EGFR mutations are being identified more often. We report here the case demonstrating the absence of EGFR mutations at the initial stage of diagnosis of metastatic lung adenocarcinoma in November 2024. The chemotherapy consisting of pemetrexed, carboplatin, and bevacizumab was initiated in December 2024. During treatment, a comprehensive genomic profiling test (Foundation One Liquid CDx Roche) was performed to evaluate a patient’s blood for circulating tumour DNA (ctDNA). A rare EGFR E114K extracellular domain mutation and mutations in the cell cycle checkpoint kinase 2 (CHEK2) – V335fs*14, PTPN11 – G503V, and TP53 splice site 375G > T were identified. Osimertinib at a dose of 80 mg daily has been administered since April 2025. After the sixth course of polychemotherapy and targeted therapy (PCT+TT) in May 2025 and with due account for stabilization based on 18F-FDG PET-CT findings, the patient continued to receive the maintenance chemotargeted therapy with pemetrexed and osimertinib, showing disease stability. Most studies that led to the introduction of tyrosine kinase inhibitors excluded patients with rare EGFR mutations. Moreover, for many mutations, it is still unclear whether they are disease activating or merely incidental findings. Nevertheless, the available separate data suggest that osimertinib, EGFR tyrosine kinase inhibitor (EGFR-TKI), has clinical efficacy in rare EGFR mutations.

Currently oncologists have numerous anti-HER2 drugs available, the sequential use of which ensures long-term disease control in metastatic HER2-positive breast cancer. These drugs belong to various classes, including monoclonal antibodies, tyrosine kinase inhibitors, and antibody–drug conjugates, which feature a fundamentally new mechanism of action. In these conjugates, the cytostatic agent is linked to the monoclonal antibody via a special linker. This structure allows the monoclonal antibody (trastuzumab) to recognize targeted tumor cells (HER2-positive), bind to the HER2 receptor, and the antibody–receptor complex is then internalized into the cell. The active cytostatic agent is then released and exerts its effect directly on the tumor cell. One of the most effective conjugates to date is trastuzumab deruxtecan (T-DXd). It has been studied in numerous trials and demonstrated high objective response rates, with progression-free survival and overall survival significantly higher than with standard treatment options. This article presents a clinical case of the use of T-DXd as a sixth-line therapy in a patient with metastatic HER2-positive breast cancer involving the lungs and brain, who had failed to respond to previous treatments, a rare occurrence. As the disease progressed, the patient’s cough and shortness of breath worsened with standard treatments, forcing her to leave work and significantly impairing her quality of life. When brain metastases were detected, she was prescribed T-DXd, and for the first time after all treatments, positive dynamics in the lung tumor process were observed, leading to a significant improvement in her well-being.

Synchronous multiple primary malignancies (MPM) represent an increasingly relevant challenge in oncology due to rising the incidence and complexity of selecting optimal therapy. Germline mutations in BRCA1/2 genes are associated with a higher risk of breast and ovarian cancers and may serve as predictors of sensitivity to systemic therapies, including platinum-based chemotherapy and PARP inhibitors. We present a case of a 63-year-old female patient with MPM, including stage IV serous ovarian carcinoma with metastases in mediastinal lymph nodes, stage IIA breast carcinoma, and signet-ring cell gastric carcinoma stage IIB. Next-generation sequencing (NGS) identified a germline BRCA1 mutation (c.5382_5383insC). The patient received six cycles of paclitaxel plus carboplatin chemotherapy, resulting in a significant reduction of ovarian and breast tumor lesions by more than threefold and stabilization of the gastric tumor as assessed by imaging. Following partial response, radical surgical treatment was performed, including distal subtotal gastrectomy with D2 lymphadenectomy, hysterectomy with bilateral salpingo-oophorectomy, and right mastectomy. Considering the detected BRCA1 mutation, maintenance therapy with the PARP inhibitor olaparib was administered for 24 months in combination with aromatase inhibitors. During two years of follow-up, no disease progression was observed, the therapy was well tolerated, and adverse effects were limited to grade 1 anemia. This case highlights the clinical value of molecular genetic testing and a multidisciplinary approach in patients with MPM. Identification of a germline BRCA1 mutation allowed for selection of an effective systemic therapy, including platinum-based agents and a PARP inhibitor, achieving durable remission in the context of multiple synchronous primary tumors. The report underscores the importance of personalized treatment strategies for patients with synchronous multiple malignancies.

Introduction. Chemotherapy-induced nausea and vomiting remain among the most unpleasant and dangerous side effects. Netupitant/palonosetron (Akynzeo) is an effective and convenient combination therapy for the prevention of nausea and vomiting in patients receiving chemotherapy with moderate to high emetogenic potential.

Aim. To evaluate the efficacy of clinically used regimens for the prevention of nausea and vomiting associated with highly emetogenic antitumor chemotherapy for bladder cancer (netupitant/palonosetron and aprepitant/ondansetron).

Materials and methods. We prospectively analyzed the experience of concomitant antiemetic therapy in 47 patients receiving gemcitabine-cisplatin antitumor chemotherapy for urothelial carcinoma of the bladder. Response rates were calculated in the acute (0–24 h), delayed (24–120 h), and overall phases of the first GC cycle.

Results and discussion. Complete response rates with oral netupitant/palonosetron and aprepitant/ondansetron were 86.9% and 87.5% in the acute (p = 0.2), 82.6% and 75.0% in the delayed (p = 0.02), and 78.3% and 70.8% in the overall (p = 0.04) phases, respectively. Breakthrough vomiting within 120 hours after cisplatin administration occurred in 17.4% of patients in the netupitant/palonosetron group and 20.8% in the aprepitant/ondansetron group (p = 0.25). All cases of breakthrough vomiting developed between days 3 and 5. The incidence of adverse events (AEs) was comparable between the netupitant/palonosetron (65.1%) and aprepitant/ondansetron (62.3%) groups. Most patients (95.7%) rated their AEs as mild to moderate. There were no deaths during the follow-up period. Despite the small sample size, our results are consistent with the current literature data.

Conclusions. Netupitant/palonosetron is highly effective in the prevention of chemotherapy-induced nausea and vomiting. Its oral administration and single dose make it unique, distinguishing it from more complex previous-generation antiemetic therapy regimens. Modern antiemetic prophylaxis can improve the quality of life of most patients; however, further study of the problem of chemotherapy-induced nausea and vomiting is needed.

Introduction. The development of febrile neutropenia (FN) is associated with high mortality and significant healthcare costs. Currently, granulocyte colony-stimulating factors (G-CSF) are recommended for patients with at least one clinical risk factor for FN in chemotherapy (CT) regimens with an intermediate risk of complications (10–20%). The question remains open as to how optimally FN prevention is carried out and how the use of G-CSF affects the budget of a medical institution in the treatment of patients with an intermediate risk of complications.

Aim. To assess the impact of primary FN prevention on the costs of a medical institution and on survival rates in patients undergoing intermediate-risk CT regimens.

Materials and methods. A retrospective analysis of 252 patient medical records was conducted (average age 66.8 years; 52% women, 48% men). A model was developed to assess the impact on the budget of a medical institution, taking into account direct medical costs for prevention, laboratory and instrumental studies, and treatment of episodes of neutropenic complications, as well as patient death by the time of analysis.

Results. Direct costs per patient for FN prevention amounted to 53,095.26 RUB and were 6% higher (3,212.16 RUB) compared to the group without prevention. Primary FN prevention led to a reduction in episodes of neutropenia, with a risk difference in the FN prevention group -26.1 (95% CI -35.6; -14.1), p < 0.001. As a result, one-year survival in the neutropenia prevention group was statistically significantly lower at 66.1% (41 out of 62), and costs per patient were 33% lower (19,840.44 RUB) compared to the group without prevention.

Conclusion. The prescription of primary prevention using G-CSF is associated with a reduction in the frequency of neutropenia development and an improvement in both immediate and long-term outcomes, positively affecting the institution’s budget.

Introduction. Atezolizumab, bevacizumab, and chemotherapy (ABCP) is a standard of care for advanced non-squamous NSCLC, including post-TKI patients with EGFR/ALK mutations. Real-world data on ABCP efficacy in Russia are limited.

Aim. To evaluate OS and PFS in real-world NSCLC patients who received ≥4 cycles of first-line ABCP followed by atezolizumab-bevacizumab (AB) maintenance.

Materials and methods. REACT is an observational, retrospective, multicenter study of adult patients with advanced NSCLC (diagnosed 2021–2023) who received ≥4 ABCP cycles and started AB maintenance. Key endpoints included ORR, PFS, and OS.

Results. Data from 108 patients were included: 78 patients (72.2%) received ABCP in first line (wild type) and 30 (27.8%) were post-TKI (EGFR/ALK+). Median age 57.6 years; 63.9% male. Baseline metastases: CNS (17.6%), liver (8.3%), bone (33.3%). ORR was 56.5% (59.0% first line); DCR 98.2%. Median PFS was 14.7 months (95% CI 12.4–23.9) in first line group and 9.3 months (95% CI 7.4–14.6) in post-TKI group. Median OS was 34.4 months (95% CI 21.8–NR) in first line group and 24.2 months (95% CI 21.8–NR) post-TKI. 2-year OS rates were 52.7% and 54.4%, respectively. High tumor burden (≥3 sites), large sum of longest diameters, and bone metastases were negative prognostic factors. Age, sex, smoking, and PD-L1 status had no significant impact.

Conclusion. In this cohort, the ABCP regimen was highly effective. Results align with IMpower150 trial for post-TKI patients and demonstrate prolonged survival in the first-line setting.

Introduction. Combined immune-targeted therapy is a new registered approach for treating metastatic melanoma. Identifying subgroups of patients who may benefit more from simultaneous rather than sequential administration of triple combination drugs is of current scientific interest to the medical community.

Aim. To present a 4-year updated analysis of the efficacy and safety of triple therapy with atezolizumab + vemurafenib + cobimetinib (AVC) in patients with BRAF-mutated advanced melanoma in real-world clinical practice in Russia.

Materials and methods. A prospective non-interventional study included 59 patients with metastatic BRAF+ melanoma receiving the triple combination of vemurafenib, cobimetinib, atezolizumab. The primary endpoint was 24-month OS. Additionally, PFS, ORR, and risk factors influencing OS were evaluated. This paper is a 4-year update of a previously published analysis.

Results. The median OS in the entire population was 23.67 months (95% CI 13.19–NR), and the median PFS in the entire population was 14.97 months (95% CI 8.00–24.39). An objective response was recorded in 57.6% of patients. Cox multivariate analysis revealed a significant impact of age, presence of lung metastases, and large tumor mass (10–15 cm vs ≤6 cm) on OS. The presence of liver metastases reduced median survival by more than 2.5 times, but no significant effect was proven. BMI, ECOG ≥ 2, CNS metastases, line of therapy, and PD-L1 did not have a statistically significant effect.

Conclusion. Triple therapy demonstrates high clinical efficacy in patients with metastatic BRAF+ melanoma in real-world clinical practice in the analyzed population of patients with an unfavorable prognosis – CNS involvement, liver involvement, and second-line and subsequent therapy. Age, the presence of lung metastases, and tumor size were found to be prognostic factors affecting survival.

Introduction. In the 21st century, medical imaging evolved from simple assessment of the presence of a pathological sign to quantitative assessment of detected changes. Despite the obvious dependence of diagnostic accuracy on the degree of measurement error, modern classifications of radiologic errors do not single out measurement error as a separate cause of discrepancies between specialists. We consider it necessary to study in detail the size of measurement error of radiologists in conditions close to routine practice and to determine the possibility of the influence of such an error on the formation of the correct patient management tactics.

Aim. To determine radiologist discrepancy in measuring the pulmonary nodule size during opportunistic screening in chest computed tomography (CT).

Materials and methods. A retrospective study was performed on a database containing the 3897 labeled native chest CT studies using a routine protocol. Experts determined the type and mean size of each pulmonary nodule. We used the following statistical methods: intraclass correlation coefficient to evaluate measurement reliability; limits of agreement (Bland-Altman method) to quantify measurement variability. The significance level for all statistical hypotheses was set to 0.05.

Results. The final analysis included 87 CT studies, each containing a single solid pulmonary nodule with a diameter ranging from 6 to 30 mm, independently measured by three radiologists. The median nodule size was 10 mm. The intraclass correlation coefficient was 0.95 with 95% CI (0.93; 0.97). The 95% CI for the maximum absolute difference between observers ranged between (1.5; 1.9) mm.

Conclusion. The measurement disperancy between three radiologists for solid pulmonary nodule in chest CT did not exceed the methodologically established threshold for pulmonary nodule growth.

Introduction. 5–10% of breast cancer (BC) cases are associated with germline pathogenic variants (PVs) in predisposition genes. In Russia, detection of “8 frequent” BRCA1,2 variants by PCR is recommended, with next generation sequensing (NGS) performed only at a second stage. Most studies on BC PVs have focused on BRCA1,2, not exploring other candidate genes.

Aim. Analyze the frequency and spectrum of PVs in candidate genes in patients with BC and healthy women with a family history of cancer.

Materials and methods. Results of NGS testing (26-gene panel) on peripheral blood from 291 women were retrospectively analyzed. Participants were divided into 2 groups: 1 – patients with a history of BC (n = 146); 2 – women with 1^st/2^nd degree relatives diagnosed with BC or ovarian cancer (n = 145).

Results. PVs were 2.5 times more frequent in Group 1 (21.2%) vs Group 2 (8.3%), р = 0,0012. BC onset with PVs occurred earlier than in women in whom significant genetic variants were not identified (39.3 ± 1 vs 44 ± 0,9 years, р = 0,01). PV in the BRCA1,2 genes were detected in 14.3% of group 1 and 6.2% of group 2, respectively. The most frequently detected variants were. BRCA1,2 PVs were most frequent (14.3% Grp1, 6.2% Grp2); Most common PVs were in BRCA1: c.5266dupC, c.4035delA. BRCA1,2 PVs comprised only 68,18% of all PVs, confirming importance of testing other genes. CHEK2 PVs were frequent in Group 1 (4.8%), 7 times higher than Group 2 (р = 0,0076). CHEK2:c.1100delC comprised 57% of these. 20.4% were VUS (variants of uncertain significance), often in non-BRCA genes. PVs in Group 2 were 8 times higher than general population rates.

Conclusion. NGS enables detection of a full spectrum of clinically significant variants, requiring high expertise for interpretation.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. The discovery of anaplastic lymphoma kinase (ALK) gene translocations and the subsequent development of targeted therapies have transformed the prognosis for patients with advanced ALK-positive NSCLC accounting for about 3–7% of all NSCLC cases. With the introduction of targeted drugs, particularly tyrosine kinase inhibitors, treatment strategies for these patients have fundamentally changed. Alectinib, a second-generation tyrosine kinase inhibitor, has demonstrated high efficacy and improved progression-free survival as first-line therapy for ALK-positive NSCLC. This article presents a clinical case of a durable response to alectinib in a 43-year-old female patient with advanced ALK-positive lung adenocarcinoma with metastases to the lungs, pleura, and liver. First-line treatment with alectinib resulted in rapid and profound regression of tumor lesions, achieving a complete radiological response that has been maintained for 4 years. The therapy was characterized by a manageable safety profile. This observation demonstrates the potential for achieving long-term disease control and converting advanced ALK-positive NSCLC into a chronic, manageable condition with the use of alectinib as first-line therapy.

Cholangiocellular carcinoma is a heterogeneous group of malignant neoplasms of the biliary tract. It accounts for approximately 3% of all gastrointestinal tumors and is the second most common primary liver tumor after hepatocellular carcinoma. Surgery is the only cure. Surgical treatments are among the most complex in hepatopancreatobiliary surgery. Standard first-line therapy with gemcitabine-based chemotherapy has demonstrated a modest improvement in survival in patients with advanced cholangiocellular carcinoma. Despite its role as the cornerstone of first-line therapy, chemotherapy produces suboptimal response rates, and overall survival highlights the urgent need for improved therapeutic strategies. The TOPAZ-1 trial, which included an immuno-oncology agent, demonstrated an improvement in overall survival. In the case described above, the patient first presented for this condition in 2022. After diagnosis verification, chemoembolization and surgical treatment were performed. Disease progression began in 2023. Based on the progression, chemotherapy in combination with durvalumab was initiated. In the case of local progression, a course of stereotactic radiotherapy was administered. This clinical case demonstrates the results of combining systemic therapy and local control methods. Progression-free survival with durvalumab therapy was 26 months. Thus, this option demonstrated the potential of modern immunochemotherapy and stereotactic radiotherapy.

Malignant tumors of the salivary glands are a rare type of neoplasm in the head and neck region. Adenoid cystic carcinoma of the salivary gland is characterized by a high propensity for perineural invasion and frequent local and distant recurrences. The primary treatment for localized adenoid cystic carcinoma of the salivary gland is surgical removal of the tumor, while radiation therapy is considered the most effective for local recurrences. However, modern treatment methods for recurrent or metastatic adenoid cystic carcinoma of the salivary gland do not always yield the expected results. The disease is rare, which has led to limited understanding of its etiopathogenesis; however, several genetic mutations and biomarkers associated with the onset and/or progression of adenoid cystic carcinoma of the salivary gland have been identified. The discovery of these mutations has made targeted precision therapy possible, with ongoing research and development in this area. This article presents a case history of long-term (25 years) observation and successful treatment of adenoid cystic carcinoma of the salivary gland, which was accompanied by multiple progressions and adjustments in systemic therapy based on the genetic characteristics of the tumor. The aim of this publication is not only to present a rare clinical observation but also to highlight current issues, modern approaches, and emerging trends in the diagnosis and treatment of adenoid cystic carcinoma of the salivary gland.

Hodgkin’s lymphoma (HL) is a rare B-cell lymphoid malignancy. Its clinical presentation is nonspecific and highly variable, which can complicate differential diagnosis. Differential diagnosis of HL includes infectious, autoimmune, and other malignant conditions. With timely treatment, mortality from this disease is extremely low. However, delays in therapy can lead to a worse prognosis and even death. The main symptom of HL is gradually developing asymmetric painless lymphadenopathy, which can remain asymptomatic for a long time. Ninety percent of young adults have lymph node involvement above the diaphragm, while only 10% have lymphoid organ involvement below the diaphragm. This clinical case of HL in a 48-year-old woman demonstrates the difficulties of antemortem diagnosis of this disease. The leading symptoms of the disease were fever and lymphadenopathy of the deep lymph nodes, which were determined by imaging studies. Overestimation of the results of imaging diagnostics, a low initial suspicion for malignancy, the absence of peripheral lymphadenopathy, and, consequently, difficulties in biopsy of the enlarged lymph nodes, along with the addition of coronavirus infection, prevented verification of the diagnosis during life and led to a fatal outcome. This article presents the stages of differential diagnosis and the impact of coronavirus infection on the course of the disease. This clinical case demonstrates the difficulties in interpreting the results of additional imaging diagnostics in HL and the lack of awareness among physicians of the clinical manifestations and diagnostic criteria of this disease.

Gastric cancer is among the most common malignant diseases and ranks fifth in incidence and mortality worldwide according to GLOBOCAN 2022. Gallbladder cancer is significantly less prevalent, ranking 22nd in terms of incidence, with 122 000 new cases reported in 2022. The synchronous occurrence of these malignancies is exceptionally rare. The global literature describes only a limited number of cases addressing therapeutic approaches in patients with synchronous gastric and gallbladder cancers. The present report describes a patient diagnosed with synchronous multiple primary malignancies of the stomach and gallbladder. A comprehensive diagnostic assessment, including endoscopy, histopathological verification, and imaging studies, enabled characterization of the disease and determination of the treatment strategy. The patient received perioperative systemic therapy using the FLOT regimen, followed by gastrectomy with lymph node dissection and cholecystectomy. Systemic therapy was subsequently continued in the adjuvant setting. During follow-up, no signs of disease recurrence were detected. This case highlights the importance of differential diagnosis between primary tumors and metastatic lesions, and underscores the necessity of a multidisciplinary approach when determining treatment strategies for patients with rare combinations of synchronous oncological diseases.