Keyword: Cancer

ABSTRACT: Introduction: Neutrophil extracellular traps (NETs) are web-like structures composed of decondensed chromatin and neutrophil granule proteins. Accumulating evidence suggests that NETs are involved in tumor progression, invasion, and metastasis in breast cancer. Therefore, investigating changes in NET formation during anticancer therapy and their potential use as a marker of treatment efficacy is of particular interest.
Objective: To evaluate the dynamics of induced NET formation during neoadjuvant endocrine therapy (NET) in patients with hormone receptor (HR)-positive breast cancer and to determine its association with changes in primary tumor size.
Materials and Methods: The study included 50 patients with stage II–III HR-positive breast cancer who received neoadjuvant endocrine therapy for 3–6 months. Endocrine therapy included letrozole and toremifene (Fareston); in a subset of patients, toremifene was combined with ovarian suppression using triptorelin (Diphereline). Induced NET formation in peripheral blood was assessed using the method developed by I.I. Dolgushin with pyrogenal stimulation, followed by May–Grünwald azure-eosin staining and microscopy. NET-forming neutrophils were counted per 100 neutrophils. Primary tumor size was assessed by ultrasonography (US) and mammography (MMG). Statistical analysis included the Wilcoxon signed-rank test, Friedman test, and Spearman’s rank correlation.
Results: In the three-time-point analysis of patients with serial measurements (n=32), the median number of induced NETs was 2 [0; 15] at baseline, 0 [0; 1.5] after 3 months, and 2 [0; 6] after 6 months of neoadjuvant endocrine therapy; the overall change did not reach statistical significance (p=0.051). After 3 months of treatment, a reduction in primary tumor size was observed. On US, the median tumor size decreased from 25.0 [22.0; 36.25] to 21.0 [18.0; 27.25] mm (p<0.001), while on MMG it decreased from 29.0 [21.5; 36.5] to 24.0 [18.0; 30.5] mm (p=0.049). The median relative reduction was 16.0% and 11.8%, respectively. No statistically significant correlation was found between changes in NET formation and the percentage change in tumor size after 3 months: US, rₛ=0.139, p=0.351; MMG, rₛ=0.015, p=0.918.
Conclusion: Changes in induced NET formation were observed during neoadjuvant endocrine therapy, with the lowest values recorded after 3 months of treatment. However, no association was established between changes in NET formation and the degree of primary tumor size reduction. These interim findings do not support the use of induced NET dynamics as a standalone marker of radiological response to neoadjuvant endocrine therapy and warrant further evaluation in a larger cohort.

ABSTRACT: Introduction: Cervical cancer remains a significant problem in the structure of cancer morbidity and mortality among women in the Republic of Tajikistan. During the period from 2014 to 2025, the average age-standardized incidence rate (ASIR) was 11.68 per 100,000 female population, and the age-standardized mortality rate (ASMR) was 6.80 per 100,000. The highest average age-specific incidence rates were recorded in the 55–64 age group, at 32.16 per 100,000 women. To reduce this burden and in line with the World Health Organization's Global Strategy for the Elimination of Cervical Cancer, the Government of Tajikistan officially launched a mass human papillomavirus (HPV) vaccination campaign in October 2025. Objective: To evaluate the initial results of the implementation, coverage, safety profile, and public perception of the first national HPV immunization campaign targeting adolescent girls aged 10–14 years in the Republic of Tajikistan.
Materials and Methods: Following the vaccination campaign conducted in October 2025, a comprehensive assessment was carried out. The study analyzed official statistical data from the Republican Center for Immunoprophylaxis, covering a target population of 542,268 girls. In December 2025, a formal Post-Introduction Evaluation (PIE) was conducted at 16 immunization centers and 22 medical facilities to assess logistics, cold chain management, and healthcare worker preparedness. In addition, Rapid Convenience Monitoring (RCM) was implemented in 140 schools across 28 districts for operational decision-making, during which 8,834 girls were interviewed using structured teacher-administered questionnaires to identify behavioral and social factors influencing vaccination.
Results: The overall coverage of the national campaign reached 95.5%, with 507,114 girls vaccinated. Specifically, coverage was 91.1% among the cohort of 10-year-old girls (routine vaccination) and 96.7% among the cohort aged 11–14 years (catch-up vaccination). The vaccine safety profile was excellent, with 48 minor adverse events following immunization (AEFI) reported, accounting for 0.009%. The school-based RCM survey confirmed high coverage rates (91.5% in surveyed schools) and demonstrated strong public support, with 81% of parents endorsing the initiative. The main barriers among the unvaccinated minority were parental refusal (17.0%) and absence from school on the day of vaccination (16.3%). PIE results highlighted strong political leadership, a reliable cold chain infrastructure, and effective interaction between parents and educators, although minor local vaccine supply delays were also noted.
Conclusion: The rapid integration and exceptionally high vaccination coverage against HPV mark a critical public health achievement for Tajikistan. The first national campaign has successfully laid the foundation for achieving international cervical cancer elimination targets. To sustain the results achieved, future efforts should focus on local microplanning, continued community awareness initiatives to address vaccine hesitancy, and ensuring reliable supply chains for routine immunization.

ABSTRACT: Objective: To evaluate the medical-organizational and clinical effectiveness of optimizing comprehensive diagnostics and follow-up care for patients with cervical intraepithelial neoplasia (CIN) through the introduction of a specialized digital module into the national Health Management Information System (HMIS/DHIS2) of the Republic of Tajikistan.
Materials and Methods: An analysis was conducted on the results of diagnosis, treatment, and dynamic follow-up of 542 patients with morphologically verified CIN1–3/Tis, aged 20 to 65 years, examined during 2023–2026. The main group using the digital system (n=82) was compared with a control group managed through paper-based documentation (n=460). The developed Digital Module for Early Diagnosis (DMED) of cervical cancer enabled the integration of 51 specialized cervical pathology units at district and city health centers, HPV diagnostics laboratories, cytology laboratories, and the State Institution "Republican Oncological Scientific Center" (ROSC). Time intervals for completing stages of medical care and the proportion of patients under follow-up care were assessed.
Results: The use of automatic tracking algorithms through the DMED for cervical cancer reduced the total diagnostic and treatment time interval (from abnormal visual screening through extended diagnostics to organ-preserving treatment with LEEP/cone biopsy) from 68.4 ± 5.2 to 21.2 ± 2.4 days (p < 0.001). The proportion of women lost to follow-up decreased from 34.2% to 6.1%. All 5 cases of invasive cervical cancer detected using the DMED were diagnosed at stage I of the disease.
Conclusion: The implementation of the DMED for cervical cancer optimizes the organization of gynecologic oncology care, eliminates lost links in patient referral pathways, and ensures a high level of monitoring of the health status of patients with precancerous pathology of the cervix.

ABSTRACT: Introduction: The main method for preoperative assessment of colorectal cancer (CRC) liver metastases remains intravenous contrast-enhanced computed tomography (CT); however, its sensitivity is limited, especially for lesions smaller than 10 mm, and neoadjuvant chemotherapy further reduces it. The characteristic CT appearance of a metastasis is hypodensity in the portal phase and a rim of enhancement at the lesion edge, which can be enhanced by injecting contrast material directly into the hepatic arteries. CT-arteriohepaticography (CT-AHG) is potentially more effective, including during drug treatment, but data on its sensitivity after chemotherapy are virtually absent.
Objective: To compare the diagnostic efficacy of CT-AHG and intravenous contrast-enhanced CT in the detection and characterization of CRC liver metastases in patients after neoadjuvant chemotherapy.
Materials and Methods: This single-center prospective study included 22 patients with CRC and liver metastases who underwent both imaging methods prior to liver resection at the N.N. Petrov National Medical Research Center of Oncology. The unit of analysis was the lesion. The reference standard was targeted histological examination of each resected lesion. CT and CT-AHG were evaluated independently, using animated images, by radiologists with more than 5 years of experience, one for each "patient–method" pair. For each method, sensitivity, specificity, and predictive values with 95% Clopper–Pearson confidence intervals (CIs) were calculated for 129 included lesions. The difference in sensitivities was reported with 95% CI (patient-level bootstrap) and tested using McNemar's exact test.
Results: With combined use of CT and CT-AHG (a lesion was considered positive if detected by at least one method), sensitivity was 80.8% [72.6–87.4], which was 10.0 percentage points (95% CI: +2.4 to +17.9) higher than the sensitivity of CT alone. Individually, sensitivity was 70.8% [61.8–78.8] for CT and 73.3% [64.5–81.0] for CT-AHG. The difference between them was −2.5 percentage points (95% CI: −9.5 to +6.8) and was not statistically significant (p = 0.66). For lesions smaller than 10 mm, sensitivity was 35.3% for CT versus 50.0% for CT-AHG; for lesions 10 mm or larger, sensitivity was 84.9% and 82.6%, respectively.
Conclusion: The sensitivity of CT-AHG does not differ significantly from that of intravenous contrast-enhanced CT; however, the combination of methods improves sensitivity by 10.0 percentage points. Therefore, CT-AHG should be considered as a complement to CT, rather than a replacement for it.

ABSTRACT: Introduction: The extent of surgery for colorectal cancer (CRC) liver metastases is currently planned on a lesion-by-lesion basis, making lesion-by-lesion assessment of the diagnostic efficacy of radiological methods important. Such studies are few in number: they are labor-intensive, and lesions detected by different methods are difficult to correlate with each other. Typically, the correspondence between radiological findings and histological conclusions is established by liver segment or anatomical landmarks, which is unreliable in cases of multiple lesions.
Objective: To develop a methodology for lesion-by-lesion correlation of radiological data, intraoperative findings, and histological examination based on a three-dimensional liver master model.
Materials and Methods: A single-center study at the N.N. Petrov National Medical Research Center of Oncology included 18 patients with CRC liver metastases who underwent intravenous contrast-enhanced CT, CT-arteriohepaticography (CT-AHG), MRI with hepatobiliary contrast agent, and MR-arteriohepaticography (MR-AHG) 1–7 days prior to liver resection. Using 3D Slicer software, a master model—a three-dimensional reconstruction of the liver with numbered lesions—was constructed from CT data. Lesions detected by at least one imaging method, including those only visible prior to chemotherapy, were mapped onto the model. The lesion number linked the label on images, the surgeon's finding on intraoperative ultrasound (IOUS), and the gross specimen. Correspondence between model lesions and the gross specimen was established by a consensus of the radiologist, surgeon, and pathologist based on location relative to the capsule, resection margin, and vessels.
Results: In 18 patients, 147 lesions were mapped on the master models: median 5.5 per patient (range 1–27). Sixteen patients had more than one lesion. A total of 111 lesions were histologically verified (median 3.5 per patient), of which 103 were metastases; 36 non-resected lesions were excluded from accuracy calculations. The model enabled independent correlation of the four imaging methods: sensitivity was 77.7% for CT, 69.9% for CT-AHG, 56.3% for MRI, and 50.5% for MR-AHG; with combined assessment (at least one method), sensitivity was 90.3%: 93 of 103 metastases were detected, while 10 were missed by all methods. No additional lesions were identified on the gross specimen outside the master model.
Conclusion: When performing liver resection for CRC metastases, the master model provides a unified coordinate system from preoperative images to the gross specimen and continuous lesion numbering. This enables rigorous lesion-by-lesion verification in cases of multiple lesions, where segmental correspondence alone is insufficient.

ABSTRACT: Background: The rapid population growth of Astana has been accompanied by an increasing demand for specialized cancer care. Cancer prevention, early diagnosis, improvement of treatment strategies, and enhancement of patients’ quality of life and survival remain key priorities of the oncology service.
Objective: To assess major changes in the organization, capacity, and technological development of the oncology service in Astana over a 15-year period.
Materials and Methods: A retrospective analysis of the main organizational indicators of the State Enterprise on the Right of Economic Management “Multidisciplinary Medical Center” of the Akimat of Astana over a 15-year period was performed. Changes in patient volume, staffing, implementation of modern diagnostic and treatment technologies, screening, and cancer prevention activities were evaluated.
Results: Over 15 years, the nearly threefold increase in the population of Astana was accompanied by a substantial rise in the workload of the oncology service. Despite a planned outpatient capacity of 380 visits per day, the actual number reached up to 1,300 patients daily. The total number of employees increased from 250 to 864, including 177 physicians and 318 nursing professionals. Modern laboratory and radiation diagnostic methods, immunohistochemical and cytochemical testing, targeted therapy, and immunotherapy were introduced into clinical practice. Linear accelerators, angiographic systems, and video endoscopic equipment expanded the capabilities of radiation therapy, diagnostic procedures, and minimally invasive treatment. Cancer screening, follow-up programs, and public cancer awareness initiatives were further developed to support early detection of malignancies.
Conclusions: Over the 15-year period, the oncology service in Astana substantially expanded its workforce and technological capacity while responding to rapid population growth and increasing demand for cancer care. The implementation of modern diagnostic and treatment technologies, development of screening programs, and strengthening of human resources provide a foundation for further improvements in the accessibility and quality of oncology care.

ABSTRACT: Tumor cells release biomarkers such as CD44 into the bloodstream, offering opportunities for minimally invasive monitoring of tumor progression. However, conventional analytical methods often suffer from insufficient sensitivity and a limited dynamic range, which hinders reliable detection of such biomarkers in complex biological fluids. Optical fiber biosensors are particularly attractive alternatives, offering high sensitivity, low cost, chemical inertness, and diverse surface functionalization strategies, making them well suited for detecting clinically relevant circulating tumor biomarkers that require sensitive, quantitative analysis. CD44, a cell adhesion glycoprotein whose soluble form (solCD44) is elevated in several cancers including breast cancer (BC), was selected as a model biomarker for this study owing to its well-established diagnostic relevance.
Here, we report the development of a graphene oxide-coated fiber-optic biosensor based on a semi-distributed interferometric sensing platform for the highly sensitive detection of solCD44. A total of 46 sensors were fabricated and characterized for their sensitivity to refractive index changes in the surrounding medium. The sensor surface was subsequently functionalized with anti-CD44 antibodies, and successful biofunctionalization together with antibody specificity was confirmed using several complementary techniques, including atomic force microscopy (AFM) and ELISA.
The optimized biosensor exhibited a wide dynamic detection range, spanning attomolar concentrations up to 100 nM, with a limit of detection (LOD) as low as 175 aM in spiked serum. Specificity was confirmed by comparison with non-functionalized sensors and healthy control samples. To validate its practical clinical applicability, the biosensor was further tested in human serum samples from breast cancer patients, showing significantly higher signal in cancer patients than in healthy controls. Successful detection of solCD44 in urine additionally demonstrated the biosensor's compatibility with multiple biological matrices. Together, these findings establish this fiber-optic biosensor as a promising platform for highly sensitive, label-free, and minimally invasive detection of cancer biomarkers, with strong potential for clinical translation and point-of-care diagnostic systems.

ABSTRACT: Background: Tumor-related bleeding in bladder cancer is a serious complication that may limit the feasibility of standard surgical treatment, particularly in patients with comorbidities. Chemoembolization of the inferior vesical arteries is a minimally invasive technique combining local administration of an antineoplastic agent with embolization of the vessels supplying the tumor.
Objective: To evaluate the outcomes of chemoembolization of the inferior vesical arteries in patients with bladder cancer complicated by bleeding.
Materials and Methods: From 2020 to November 2024, chemoembolization of the inferior vesical arteries was performed in 12 patients with bladder cancer at the State Enterprise on the Right of Economic Management “Multidisciplinary Medical Center” of the Akimat of Astana. The procedure was performed using doxorubicin (Adriamycin) at a dose of 50 mg or cisplatin at a dose of 50 mg. Treatment efficacy was assessed based on the patients’ general condition, presence of gross hematuria, changes in laboratory blood parameters, and tumor size evaluated by computed tomography, ultrasonography, and cystoscopy.
Results: At two months after chemoembolization, no episodes of gross hematuria were observed, and laboratory blood parameters showed improvement. After two chemoembolization sessions, tumor size decreased by more than 25% on average, as assessed by computed tomography, ultrasonography, and cystoscopy. Six patients underwent surgical treatment three months after the first chemoembolization procedure: transurethral resection in four patients, open bladder resection in one, and cystectomy in one. Histopathological examination of the resected tumor tissue demonstrated treatment-induced tumor necrosis. Three patients with advanced disease were referred for further chemoradiotherapy. Three patients with early-stage disease remained under surveillance with a recommendation for intravesical chemotherapy.
Conclusions: Chemoembolization of the inferior vesical arteries may be considered a minimally invasive method for controlling tumor-related bleeding in patients with bladder cancer, particularly when major surgical intervention is limited by comorbidities. The findings suggest that this approach may be promising; however, the small sample size and limited follow-up period warrant further investigation to determine the optimal number of treatment sessions and assess long-term efficacy.

ABSTRACT: Introduction: Given the difficulties in assessing response of the primary tumor and metastatic lesions in gastric cancer patients using standard RECIST 1.1 criteria, there is a need to search for new biomarkers to evaluate treatment efficacy, especially at early stages after therapy initiation. Perfusion computed tomography is a functional imaging technique that provides qualitative and quantitative information about tumor microcirculation and can serve as a tool for predicting or assessing treatment response, helping to optimize and individualize subsequent patient management.
Objective: To evaluate the role of perfusion CT (PCT) in monitoring response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer.
Materials and Methods: The results of PCT in 28 patients aged 36 to 76 years with histologically confirmed gastric cancer who received combined treatment at the A.F. Tsyb Medical Radiological Research Center between June 2023 and June 2026 were analyzed. Baseline CT, supplemented by perfusion imaging, was performed before treatment initiation to assess tumor extent and obtain baseline perfusion parameters. Follow-up PCT was performed before surgery to evaluate treatment efficacy and changes in perfusion parameters.
Patients were divided into 2 groups: 12 of 28 patients with regression grade 1a/b according to the scale established by K. Becker (2003) were considered "responders" to neoadjuvant chemotherapy, and 16 of 28 patients with regression grade 2/3 were considered "non-responders." Quantitative PCT analysis was based on interpretation of perfusion parameter values automatically calculated from the region of interest (ROI) placed within the tumor. The following PCT parameters were analyzed: blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area (PS).
Results: The obtained perfusion data were subjected to both qualitative and quantitative analysis. Qualitative analysis included interpretation of parametric perfusion maps automatically generated by the software for each perfusion parameter. For each group, the significance of changes in each parameter was assessed using the paired Wilcoxon test. In patients who responded to treatment, a statistically significant decrease in BF, BV, and PS perfusion parameters was observed (p < 0.05). In patients who did not respond to treatment, none of the parameters changed significantly (p > 0.1 for all). Differences in BF and BV dynamics between groups were highly significant (p < 0.01), with significantly greater changes in responders. For PS, the difference was also significant (p = 0.04), although less pronounced. When assessing the prognostic value of baseline PCT parameters, none of the parameters reached statistical significance (p > 0.05); only PS showed a weak trend toward lower values in the responder group.
Conclusion: CT perfusion parameters reflect tissue vascularization and can serve as objective quantitative biomarkers of tumor response to neoadjuvant treatment. Baseline low PS values are associated with a likelihood of clinical response to preoperative chemotherapy in gastric cancer. Further studies with larger sample sizes are needed to clarify the prognostic role of PCT.

ABSTRACT: Introduction: Sarcopenia is associated with an unfavorable prognosis in cancer patients, especially in the presence of concurrent nutritional deficiency risk. CT-based sarcopenia assessment remains the gold standard for non-invasive evaluation of muscle mass; however, its routine use is limited by the high labor intensity of manual muscle segmentation on CT images.
Objective: To determine the prognostic value of preoperative CT-based sarcopenia assessment, performed using a developed software assistant, as a predictor of postoperative complications in patients with gastric and pancreatic tumors.
Materials and Methods: The study was conducted in two stages. At the first stage, a muscle tissue segmentation model was trained on 610 CT images (Dice coefficient on the training set — 0.95). A program was developed as an integrated information system incorporating computer vision algorithms, which identifies a single axial slice at the L3 level and performs subsequent semantic segmentation using convolutional neural networks. Thus, the muscle tissue area at the L3 vertebral level was automatically calculated with adjustment for the square of the patient's height, and the skeletal muscle index (SMI) was computed.
At the second stage, using this software module, sarcopenia was assessed preoperatively in 65 patients with gastric cancer and 55 patients with pancreatic cancer who subsequently underwent gastrectomy and pancreaticoduodenal resection, respectively. Sarcopenia was defined as SMI values of < 52.4 cm²/m² for men and < 38.5 cm²/m² for women. The severity of postoperative complications was assessed according to the Clavien–Dindo classification. Differences were considered statistically significant at p < 0.05.
Results: The prevalence of sarcopenia was evaluated in both groups: in patients with gastric cancer it was 77% (50 out of 65 patients), and in patients with pancreatic cancer – 73% (40 out of 55), indicating a considerable prevalence of this condition in this patient population.
The crude relative risk of overall postoperative complications (RR = 0.94; 95% CI 0.60–1.47; p > 0.05) and pancreatic fistulas in particular (RR = 0.64; 95% CI 0.33–1.26; p > 0.05) in pancreatic cancer patients with sarcopenia did not differ from that in patients without sarcopenia, indicating comparable complication rates in both groups.
In gastric cancer patients, the overall rate of postoperative complications also did not correlate with the presence of sarcopenia (p = 0.392); however, severe complications (≥ IIIb by Clavien–Dindo) were observed only in patients with sarcopenia (p < 0.001).
Conclusions: Thus, the inclusion of automated CT-based sarcopenia assessment in preoperative workup may help identify a high-risk group of cancer patients for severe postoperative complications, enabling optimization of personalized management strategies. However, multivariate analysis accounting for other clinical factors is required; further studies with validation on larger cohorts are necessary to justify the implementation of this method into clinical practice.

ABSTRACT: Introduction. The expansion of indications for trastuzumab deruxtecan following the DESTINY-Breast06 trial has increased the clinical relevance of minimal HER2 membrane staining that was previously included within the HER2 0 category. In the current CAP protocol, HER2 0 is further subdivided into 0 with no membrane staining and 0+ with membrane staining, corresponding to the HER2-ultralow phenotype. Conventional HER2 immunohistochemistry (IHC) has historically been focused on identifying HER2 overexpression, whereas assessment of very low levels of HER2 staining is less reproducible. This places greater emphasis on the distinction between HER2 0 with no detectable expression (HER2-null), HER2-ultralow, and HER2 IHC 1+.
Objective. To determine the frequency of HER2-ultralow expression among invasive breast carcinomas initially classified as HER2 0, to assess patterns of reclassification on repeat review, and to evaluate concordance between the initial and repeat standard HER2 status.
Materials and Methods. A retrospective single-center study included 241 cases of invasive breast carcinoma without prior neoadjuvant therapy diagnosed between January and July 2026. Initial HER2 status was assessed by IHC in routine clinical practice according to the 2023 ASCO/CAP recommendations, and all slides were subsequently reviewed by a second pathologist. IHC was performed using the HER2 antibody clone 4B5 (Ventana). During repeat assessment, HER2 0 cases were further subclassified as HER2-null or HER2-ultralow. For concordance analysis, both subcategories were combined within the conventional HER2 0 category. Overall percent agreement and Cohen’s κ coefficient were calculated. Clinicopathological associations were evaluated in an exploratory analysis.
Results. The initial HER2 distribution was as follows: 0 in 112/241 cases (46.5%), 1+ in 66 (27.4%), 2+ in 24 (10.0%), and 3+ in 39 (16.2%). Following repeat review, HER2-ultralow expression was identified in 55/241 cases (22.8%). Among the 112 tumors initially classified as HER2 0, 61 (54.5%) were categorized as HER2-null, 44 (39.3%; 95% CI, 30.7–48.5%) as HER2-ultralow, and 7 (6.2%) were reclassified as HER2 1+. Standard HER2 status changed in 22/241 cases (9.1%), with 20/22 discrepancies (90.9%) occurring at the HER2 0↔1+ boundary. Overall agreement was 90.9%, with a Cohen’s κ of 0.864. Among tumors initially classified as HER2 0 with known hormone receptor (HR) status, HER2-ultralow expression was identified in 35/80 (43.8%) HR-positive tumors and 2/16 (12.5%) HR-negative tumors (OR, 5.44; 95% CI, 1.16–25.55; p=0.024). No statistically significant differences were observed according to histologic grade or Ki-67 proliferation index.
Discussion and Conclusions. HER2-ultralow expression was identified in 39.3% of tumors initially classified as HER2 0, a proportion comparable with that reported in recent retrospective studies. Changes in HER2 classification occurred predominantly at the HER2 0↔1+ boundary, highlighting the diagnostic vulnerability of the lower range of HER2 expression. Although concordance for conventional HER2 categories was high (κ=0.864), this analysis does not assess the reproducibility of distinguishing HER2-null from HER2-ultralow because interobserver agreement specifically at this boundary was not evaluated. These findings emphasize the heterogeneity of the HER2 0 category and support the importance of standardized assessment and explicit reporting of minimal HER2 membrane staining in routine pathologic practice.
 

ABSTRACT: Introduction: Papillary thyroid cancer (PTC) is characterized by a favorable prognosis; however, disease recurrence remains a clinically significant problem among adolescent and young adult (AYA) patients. The prognostic role of molecular alterations in this age group remains insufficiently studied, especially in Central Asian populations.
Objective: To evaluate clinical-pathological and molecular factors associated with PTC recurrence in young adult patients from Kazakhstan.
Materials and Methods: This retrospective multicenter study included 246 patients with histologically confirmed PTC. Tumor tissue samples obtained between 2016 and 2020 were collected at three specialized oncology centers in Kazakhstan: the Kazakh Institute of Oncology and Radiology (Almaty), the Center for Nuclear Medicine and Oncology (Semey), and the Multidisciplinary Center of Oncology and Surgery (Ust-Kamenogorsk). Clinical-pathological characteristics and molecular genetic alterations were analyzed in relation to recurrence risk and survival outcomes. Multivariate regression analysis and time-to-event methods were used to identify factors associated with recurrence, progression-free survival (PFS), and overall survival (OS).
Results: In the AYA subgroup, none of the evaluated clinical-pathological or molecular factors retained a statistically significant association with recurrence after multivariate adjustment. TERT promoter alterations demonstrated the largest estimated association with recurrence (odds ratio [OR] 9.05; 95% confidence interval [CI] 1.00–59.86; p = 0.333); however, statistical significance was not reached. In the overall cohort, the presence of lymph node metastases demonstrated the most pronounced trend toward worse PFS (hazard ratio [HR] 9.61; 95% CI 0.92–100.49; p = 0.059). No statistically significant clinical-pathological or molecular predictors of overall survival were identified.
Conclusions: The risk of PTC recurrence in young adult patients is characterized by heterogeneity and cannot be fully assessed based on clinical-pathological factors alone. TERT promoter alterations may have potential prognostic significance. Larger prospective studies in the Central Asian population are needed to clarify the role of molecular markers and improve individual risk stratification.

ABSTRACT: Introduction: Germline mutations in the BRCA1 and BRCA2 genes are an important hereditary risk factor for the development of breast cancer. The spectrum of pathogenic variants of these genes is characterized by pronounced ethnic and population specificity, including the presence of founder mutations. Data on the spectrum of germline BRCA1/BRCA2 variants in the Kazakh population remain limited, which hinders their application in clinical practice and genetic counseling.
Objective: To study the spectrum of germline mutations in the BRCA1 and BRCA2 genes in patients with breast cancer and women with a family history in the Kazakh population and to identify the founder mutation.
Materials and Methods: The study included 544 women of Kazakh ethnicity with breast cancer or a family history of cancer. DNA was isolated from peripheral blood lymphocytes according to the manufacturer's protocol. Exons and adjacent intronic regions of the BRCA1 and BRCA2 genes were sequenced by NGS. Variants were classified by clinical significance, and their spectrum and distribution by gene, type, and localization were analyzed.
Results: Of the 544 examined patients, 178 (32.7%) were found to have mutations in the BRCA genes. Mutations in the BRCA1 gene were detected in 35 patients (19.7%), in the BRCA2 gene — in 119 patients (66.8%), and mutations in both genes — in 24 patients (13.5%).
The study identified a total of 125 BRCA gene variants. Sequence analysis revealed 37 pathogenic variants in 81 patients, 83 likely pathogenic variants in 104 patients, 1 likely benign variant in 6 patients, 2 benign variants in 6 patients, and 2 variants of uncertain clinical significance in 2 patients.
Among BRCA1 gene variants, the most common was a deletion of exon 6, detected in 11 patients (6.1%). Deletions of exons 2, 13, and 20 were found in 7 patients each (3.9%), while deletions of exons 8 and 23, as well as variants BRCA1 c.3214delC and BRCA1 c.1044_1045insC, were found in 3 patients each (1.7%).
Among the identified BRCA2 gene variants, the most common was a deletion of exon 16, detected in 37 patients. The variant c.24_27delGCCAinsCG was identified in 15 patients, c.2600_2601insA in 12 patients, and c.9241_9242insA in 11 patients.
Conclusions: The spectrum of germline BRCA1/BRCA2 mutations in the Kazakh population is characterized by a predominance of BRCA2 gene variants. Deletion of exon 16 of the BRCA2 gene was identified as a founder mutation.

ABSTRACT: Introduction: Differentiated thyroid cancer (DTC) is characterized by a favorable prognosis in most cases. However, the development of radioiodine refractoriness significantly worsens the disease course, limits the effectiveness of standard therapy, and is associated with an increased risk of progression. In this regard, the search for molecular genetic markers that allow early identification of patients at high risk of developing an aggressive radioiodine-refractory phenotype is a relevant area of research. Integration of molecular and clinical-pathological characteristics of the tumor may improve the accuracy of risk stratification and contribute to personalization of treatment strategy.
Objective: To evaluate the relationship between molecular genetic alterations, including BRAF and TERT promoter mutations, and clinical-pathological characteristics of radioiodine-refractory differentiated thyroid cancer.
Materials and Methods: A retrospective single-center study was conducted, including 167 patients with DTC treated between 2021 and 2023. The study was performed in the Republic of Kazakhstan among patients treated at the Radionuclide Therapy Department of the Center for Nuclear Medicine and Oncology, Health Department of the Abai Region. Depending on the response to radioiodine therapy, patients were divided into two groups: radioiodine-sensitive DTC (n = 130) and radioiodine-refractory DTC (n = 37). Multivariate analysis was performed to identify independent predictors of radioiodine refractoriness. The discriminatory ability of the prognostic model was assessed using ROC analysis.
Results: The development of radioiodine refractoriness was associated with clinical-pathological signs of aggressive disease course, including elevated levels of thyroglobulin and/or antibodies to thyroglobulin, the presence of lymphogenous metastasis, and the need for more extensive surgical intervention. Individual BRAF and TERTp mutations did not demonstrate independent statistically significant prognostic value. At the same time, the simultaneous presence of BRAF and TERTp mutations was significantly associated with the development of radioiodine refractoriness. The integrated clinical-molecular model demonstrated good discriminatory ability (AUC = 0.796) and outperformed the model based solely on clinical-pathological characteristics, indicating the additional prognostic value of molecular profiling.
Conclusions: The inclusion of molecular genetic profiling in comprehensive clinical-pathological assessment may improve the accuracy of risk stratification, contribute to early identification of patients with potentially aggressive disease course, and serve as a basis for personalization of treatment strategy.

ABSTRACT: Background: Lung cancer leads cancer mortality in Kazakhstan: the International Agency for Research on Cancer estimates 2,798 new cases and 2,617 deaths for 2024. Randomised trials show that low-dose computed tomography screening lowers lung cancer mortality, but population screening brings heavy reading workloads and many false positives. This review examines the published evidence on artificial intelligence in this setting.
Objective: To review published evidence on artificial intelligence in low-dose computed tomography lung cancer screening, with implications for programmes in Kazakhstan and Central Asia.
Materials and Methods: Narrative review of peer-reviewed publications, 2011 to August 2026, in PubMed and publisher databases. Screening trials required a mortality endpoint; artificial intelligence studies required histological outcomes, an expert panel reference standard or randomisation. Included: the National Lung Screening Trial (2011), the Dutch-Belgian screening trial (2020), Sybil (2023), the United Kingdom Lung Cancer Screening trial validation (2025), the 4-IN-THE-LUNG-RUN feasibility study (2025) and a prospective single-centre randomised trial (2026).
Results: The National Lung Screening Trial reduced lung cancer mortality by 20.0 percent (95 percent confidence interval 6.8 to 26.7) versus chest radiography; 96.4 percent of positive screens were false positives. The Dutch-Belgian trial reported a ten-year lung cancer mortality rate ratio of 0.76 (95 percent confidence interval 0.61 to 0.94) among male participants versus no screening. Neither trial used artificial intelligence. Sybil predicted one-year cancer risk from one scan with areas under the receiver operating characteristic curve of 0.92, 0.86 and 0.94 in three retrospective cohorts. In 1,252 United Kingdom baseline scans, an artificial intelligence first reader detected all 31 histologically confirmed cancers, one below its volume threshold (negative predictive value 99.8 percent), with an estimated maximum workload reduction of 79 percent. In 3,678 European baseline scans, artificial intelligence negative misclassifications were 0.8 percent against 11.1 percent for radiologists; its positive misclassifications were 5.7 percent against 0.5 percent for radiologists. In a randomised trial in asymptomatic individuals, artificial intelligence assistance raised detection of Lung Imaging Reporting and Data System positive nodules from 10.3 to 16.9 percent with no significant change in interpretation time.
Conclusions: The mortality benefit belongs to low-dose computed tomography screening itself; no included artificial intelligence study measured mortality. Evidence is strongest for artificial intelligence as a first reader ruling out negative baseline scans while radiologists read the rest; detection assistance raises nodule yield and positive misclassifications; single-scan risk prediction remains retrospective. For Kazakhstan and Central Asia these applications address the reading capacity and false-positive burden that limit programme feasibility, provided tools are validated locally against histological outcomes.
Keywords: Lung Neoplasms; Early Detection of Cancer; Tomography, X-Ray Computed; Artificial Intelligence; Radiographic Image Interpretation, Computer-Assisted; Kazakhstan

ABSTRACT: Precision oncology seeks to identify patient-specific therapeutic vulnerabilities; however, conventional genomic profiling is limited by intratumoral heterogeneity and its inability to distinguish functional driver alterations from passenger mutations, often resulting in incomplete prediction of therapeutic response. Recently, the combination of CRISPR functional genomics with single-cell multi-omics has proven to be a paradigm-shifting strategy for understanding context-specific cancer vulnerabilities by causal functional interrogation. The aim of this review is to critically examine recent progress in the integration of these technologies for discovering vulnerabilities in cancer, and introduces a new conceptual model, called the Integrated Functional Precision Oncology (IFPO) Framework, that brings together functional genomic perturbation, single-cell multi-omics, computational systems biology, and clinical translation. Literature was retrieved from Pubmed, Web of Science and Google Scholar and peer reviewed studies published between 2020 and 2025. Key findings from historic and recent research were analyzed to pinpoint methodological innovations, translational studies, limitations, and areas in need of further research. The results reveal that the integrated CRISPR–single-cell platforms, such as Perturb-seq, CROP-seq, and ECCITE-seq, can be used to causally interrogate gene function at the single-cell level, allowing for the identification of context-dependent essential genes, synthetic lethal interactions, regulatory networks, and therapeutic resistance mechanisms. All the evidence suggests that therapeutic response is not merely a function of genomic alterations but also the dynamic interplay between genomic alterations, cellular state, epigenetic plasticity, and the tumor microenvironment. The proposed IFPO Framework integrates these findings into a systems-level model that captures the mechanisms by which these functional perturbations, multimodal molecular profiling, and AI-driven integration of data converge to reveal clinically actionable cancer vulnerabilities. This integrated paradigm transforms precision oncology from descriptive molecular profiling to functional systems oncology and offers directions for further progress of precision cancer treatment based on enhanced biomarker discovery, therapeutic target identification, and prospective clinical translation.

ABSTRACT: ABSTRACT
Background: Diethylnitrosamine (DEN) is a nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties that causes major liver damage and acts as a hepatocarcinogen in rodents. Acacia nilotica and Kigelia africana are plants used in local communities to treat wounds and ulcers.
Objective: This study investigated the effect of aqueous extracts of Kigelia africana and Acacia nilotica on alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and cancer antigen 125 (CA-125) levels in DEN-induced liver cell dysplasia in Wistar rats.
Methods: Forty (40) male Wistar rats, aged 6–8 weeks, were divided into eight (8) groups of five (5) animals each. Liver cell dysplasia was induced with a single intraperitoneal dose of DEN (100 mg/kg) and promoted with oral phenobarbitone (0.25 mg/kg) twice weekly, beginning one week after induction. Group I received clean drinking water; group II received DEN only; group III received DEN + phenobarbitone; groups IV and V received DEN + phenobarbitone + 250 mg/kg and 500 mg/kg of Acacia nilotica respectively; groups VI and VII received DEN + phenobarbitone + 250 mg/kg and 500 mg/kg of Kigelia africana respectively; and group VIII received DEN + phenobarbitone + 10 mg/kg of sorafenib. Blood samples were collected on day 120 for biomarker evaluation, and liver tissue was processed for histopathology.
Results: CEA and CA-125 differed significantly among groups (p < 0.001), although group means largely remained within the physiological reference range; AFP showed no significant difference (p = 0.580). The highest CEA values occurred in the DEN-only and DEN + phenobarbitone groups, while CA-125 was highest in the DEN-only and sorafenib-treated groups. Animals treated with the plant extracts, particularly at the higher dose (500 mg/kg), maintained CEA and CA-125 values close to those of the negative control. Histopathology showed dose-dependent attenuation of DEN-induced changes by both extracts, with the higher dose of Kigelia africana producing near-normal liver architecture.
Conclusion: Both extracts, especially at higher doses, appeared chemoprotective against DEN-induced hepatic changes, supporting further investigation of their underlying mechanisms.

ABSTRACT: Surgery in metastatic cancer has been considered to have a limited role in the treatment of metastatic disease and has generally been reserved for palliative intent. However, as imaging, systemic therapy, surgical techniques, and understanding of the biology of cancer has improved, the role of surgery in the treatment of metastatic disease has evolved. This narrative review will discuss the current state of surgical therapy in metastatic cancer and the indications for such an approach. A discussion of the impact of reducing tumor burden, the concept of oligometastatic disease, and the role of host–tumor interactions will provide a basis for the discussion. The objectives of surgery have evolved from palliation to include longer survival and even potentially curative intent. The primary consideration in the decision to pursue surgical therapy for metastatic disease is proper patient selection, and this requires a thorough evaluation of disease and patient factors, as well as the integration of systemic therapy and other local therapies. While evidence is strongest for metastasectomy in colorectal cancer, there is growing evidence in breast cancer, renal cell carcinoma, lung cancer, and neuroendocrine tumors. As a general rule, the optimal management of metastatic cancer includes a combination of systemic and surgical therapies to maximize benefit for the patient. While there are limitations to the current role of surgical therapy in metastatic cancer, challenges including surgical morbidity, delays in initiation of necessary systemic therapy, and a paucity of high-quality evidence, proper patient selection remains the cornerstone to providing meaningful clinical benefit.

ABSTRACT: Prostate cancer still remains one of the most common cancers in men worldwide, and it is a great therapeutic challenge, especially in the field of immunotherapeutics. The tumour microenvironment (TME) is immunologically “cold” in prostate cancer, and influenced by intrinsic molecular characteristics of the disease such as androgen receptor (AR) signalling, PTEN loss, and lineage plasticity towards neuroendocrine prostate cancer (NEPC). Together, these aspects inhibit antigen presentation, block the entry of cytotoxic T cells and help to establish spatially organised immunosuppressive niches, providing a rational explanation for the clinical variability and partial efficacy of immune-based therapies.
Traditional bulk genomic approaches have provided important insights into tumour biology but are unable to capture the cellular and spatial complexity of tumour–immune interactions. These developments have been spurred by recent advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, which allow to detect individual cell subpopulations within intact tumour tissues, such as exhausted T cells co-expressing PD-1, TIM-3, LAG-3 and TIGIT, immunosuppressive SPP1+ macrophages and various cancer-associated fibroblast subpopulations. These technologies have identified specific immune exclusion sites, stromal–epithelial immune silencing barriers, and therapeutic resistance and immune evasion regulatory programs in the context of prostate cancer specifically.
However, there are still many technical challenges that need to be overcome, such as the lack of patient samples and their demographic diversity, data integration, lack of spatial characterisation of bone metastases and difficulties in clinical translation. Comprehensive multi-omics atlases, AI-driven spatial pattern recognition, functional validation of potential targets and prospective clinical trials based on biomarkers are all important areas for future research. They show significant potential for the creation of better, personalized immunotherapeutic treatment for prostate cancer.

ABSTRACT: This study was conducted to investigate histological outcomes of patients with locally advanced colorectal cancer involving the urinary bladder, ureters or prostate. Initial cohort included 45 patients but 10 patients were eliminated from the study due to absence of medical records or non-confirmed colon adenocarcinoma. Finally, the study included 35 patients who underwent colon surgery plus either partial or complete bladder resection, partial ureter resection or prostate resection in time period between 2016 and 2025. Data on patient characteristics and results of histological examination were collected retrospectively. Among patients, who underwent colon surgery plus cystectomy (n=27), only in 48% cases confirmed histological invasion was detected. Overall R0 resection was achieved in 94% cases. These data correspond to literature reviewed findings. True lower urinary tract invasion occurred in approximately half of locally advanced colorectal cancer cases, while en bloc resection achieved high R0 rates, supporting resection when invasion is uncertain.

ABSTRACT: Type 2 diabetes mellitus is associated with an increased risk of several malignancies, prompting interest in the potential oncologic effects of antidiabetic therapies, particularly metformin. This study evaluated cancer-related adverse event reporting associated with metformin compared with other antidiabetic agents using real-world pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS) between Q1 2023 and Q4 2024. A disproportionality analysis was conducted on over 3.2 million reports, including 66,187 metformin cases and 55,257 comparator cases comprising GLP-1 receptor agonists, SGLT2 inhibitors, sulfonylureas, and insulin. Reporting odds ratios (ROR), proportional reporting ratios (PRR), information components (IC), and chi-squared tests were applied across twelve pre-specified cancer types.
Metformin was associated with significantly lower reporting of hepatocellular carcinoma (ROR 0.377, 95% CI 0.181–0.782) and pancreatic carcinoma (ROR 0.669, 95% CI 0.493–0.908). In contrast, increased reporting signals were observed for prostate cancer (ROR 2.065, 95% CI 1.435–2.972), leukaemia (ROR 2.388, 95% CI 1.155–4.939), and breast cancer (ROR 1.404, 95% CI 1.023–1.926). Drug-specific comparisons indicated relatively lower overall cancer reporting for metformin compared with sitagliptin and empagliflozin, but higher reporting compared with insulin. Temporal analyses demonstrated variability in reporting patterns across study quarters.
These findings represent disproportionality signals reflecting reporting associations rather than causal effects and may be influenced by reporting bias, residual confounding, and differences in healthcare utilization. Overall, the results suggest a heterogeneous, cancer-type-specific reporting profile for metformin and highlight the value of pharmacovigilance analyses in generating real-world safety signals. Further confirmation in prospective and mechanistic studies is required.

ABSTRACT: Cervical cancer remains a leading cause of cancer-related mortality in Sub-Saharan Africa, where it disproportionately affects women due to late-stage diagnoses. Despite the availability of preventive measures such as screening and HPV vaccination, uptake remains critically low. This systematic review and meta-analysis aimed to estimate the pooled prevalence and identify key predictors of cervical cancer screening uptake across Sub-Saharan Africa. A comprehensive search of databases including PubMed, Google Scholar, African Journal Online (AJOL) and ScienceDirect identified 27 studies involving a total of 357,586 women. Our results revealed that the overall prevalence of cervical cancer screening uptake was 21.2% (95% CI: 16.2%, 27.2%). Key predictors of uptake included education, healthcare access, awareness of cervical cancer, age, and integration with other health services like HIV care. This study underscores the urgent need for tailored interventions to address barriers such as lack of awareness, financial constraints, and cultural stigma. The findings provide crucial evidence to guide policy and public health strategies aimed at increasing screening rates and reducing the cervical cancer burden in the region.

ABSTRACT: Spatial tumour heterogeneity, which denotes the changes in cellular and molecular attributes across distinct locations within a tumour, significantly influences cancer diagnosis and treatment resistance. The heterogeneity of tumour cells inside a singular mass facilitates tumour development, metastasis, and the ineffectiveness of standard therapy. Comprehending the geographical distribution of tumour cells is crucial for formulating more efficient treatment regimens. Diverse methodologies are employed to investigate spatial heterogeneity, encompassing modern imaging techniques such as MRI, PET, and multiplexed imaging, alongside omics approaches including genomes, transcriptomics, and proteomics. These instruments offer insights into the tumour microenvironment and facilitate the identification of resistant subpopulations. The amalgamation of imaging and genomic data via radiogenomics has emerged as a viable methodology, providing an extensive perspective on the spatial and molecular intricacies of tumours. Principal findings reveal that spatial heterogeneity fosters medication resistance by establishing microenvironments characterised by varying oxygen levels, immunological infiltration, and genetic alterations, hence complicating the efficacy of monotherapy strategies. Hypoxic environments and immunological evasion significantly contribute to treatment resistance. Addressing geographical heterogeneity has the potential to enhance cancer treatments. By analysing the molecular and geographical characteristics of tumours, physicians can customise therapies more efficiently, minimising resistance and improving therapeutic results. This methodology signifies a vital advancement in precision medicine, providing more individualised and efficacious cancer therapies in the future.