The review systematizes modern concepts and substantiates the role of radionuclide lymphoscintigraphy in assessing the lymphatic component in chronic venous insufficiency of the lower extremities. Given the limitations of anatomically oriented techniques (ultrasound diagnostics, magnetic resonance lymphangiography, and indocyanine green fluorescence lymphography), radionuclide lymphoscintigraphy provides a reproducible assessment of lymphatic drainage, detects early abnormalities, distinguishes between venous and lymphatic contributions to the development of edemas, and enables to monitor the effect of therapy. Special attention is paid to the preparation 99mTc-Nanotope as a widely used nanocolloidal radiopharmaceutical with optimal physico-chemical characteristics for quantitative radionuclide lymphoscintigraphy, as well as issues of results comparability when using alternative preparations. The key scintigraphic signs of lymphatic dysfunction are systematized and their clinical significance is analyzed. Integration of radionuclide lymphoscintigraphy into examination algorithms for chronic venous insufficiency increases the accuracy of phlebolymphedema verification and supports personalized treatment choice.
Suicide rate is considered an index of social and professional well-being/ill-being. Therefore, studying this index among nuclear workers (NW), a group subordinate to the Federal Medical-Biological Agency of the Russian Federation, is relevant both for image-building purposes and for optimizing psychological support for this category of workers. This two-report cycle (a synthetic study) presents a systematic review, followed by a meta-analysis and pooled analysis, for suicide risk among NW in different countries and gender patterns of this risk (Standardized Mortality Ratio (SMR) compared to the general population). This Report 1 presents, first, a search methodology for sources in a supported bibliographic database for NW in different countries, including PubMed, Embase, Google Scholar, eLibrary, and the reference lists of identified publications. The primary sample, generated based on the search results for all the specified types, totaled 556 sources (many duplicates), allowing for visual analysis of all of them during subsequent selection. Second, the stages of processing the resulting sample in preparation for meta- and pooled analyses are described (selection of studies with only SMR indexes, only the most recent chronological publications for the studied cohorts, elimination of outliers in the samples, and assessment of the epidemiological quality of the remaining studies). None of the four identified USSR/Russian studies (all for the PO ‘Mayak’) were included in the systematic review due to the lack of the necessary risk index. Nevertheless, some qualitative conclusions were reached, according to which, with overexposure to NW from the PO ‘Mayak’ (up to more than 1 and 4 Gy in two studies), an increased risk of suicide was observed; in the absence of high exposure levels, the unweighted risk index was not increased compared to the general population for male. A reverse ‘gender paradox’ was also observed, with the fatal suicide rate among female NW at the PO ‘Mayak’ being higher than among males, while a direct ‘gender paradox’ (a multiple higher suicide rate for males and a multiple higher rate of suicide attempts for females) has been described for the populations of almost all countries since the 19th century. For foreign NWs, two study samples were created, corresponding to 15 nuclear installations (from five countries; 62% from the USA) for both male NW and female NW (coincidence). Further meta-analyses and pooled analyses of SMR for suicides in foreign NW, as well as a comparison of their risk for male and female cohorts to test for the reverse ‘gender paradox’, will be presented in Report 2.
Sentinel lymph node biopsy (SLNB) is the standard procedure for early breast cancer (BC), however its role in patients with locally advanced tumors (cT4N0) after neoadjuvant hormonal or chemotherapy remains a subject of discussion. The data on this type of patients is limited and the rate of false-negative results exceeds 10%/ Purpose of the study: to assess the diagnostic accuracy SLNB in patients with cT4N0M0 (ycN0) breast cancer after neoadjuvant therapy. Our single-center prospective cohort study included 50 consecutive patients with cT4N0M0 breast cancer who received NALT followed by mastectomy with SLNB followed by level I-II axillary lymph node dissection (ALD). A radioguided method (99mTc-albumine nano colloid) was used to identify sentinel lymph nodes. The detection rate of sentinel lymph nodes, the level of false-negative results (FNR), sensitivity, and negative predictive value were evaluated. The univariate regression analysis was conducted to determine the factors that affect the frequency of false-negative results. The detection rate was 96% (48/50). Metastatic lymph nodes were detected in 15 of 48 patients 31.3% during SLNB. After ALD metastasis were detected in 19 of 48 patients (39,5%). False negative rate (FNR) was 8,3% it the cohort. Sensitivity was 82,6%, Specificity 100%, and negative predictive value was 91,5%. Total accuracy was 92,3%. If 1 or 2 sentinel lymph nodes were removed FNR was 30,8% (4/13), if 3 or more lymph nodes were detected, FNR was 0% (0/35) (p=0,012). In univariate regression analysis only in the number of removed SLN increases the frequency of FNR. Patient’s age, BMI, molecular subtype, tumor grade, type of neoadjuvant therapy (chemo/hormonal) didn’t affect the accuracy of SLMB. The radioguided SLMB demonstrates acceptable diagnostic accuracy in patients with cT4N0 breast cancer after neoadjuvant therapy, which allows it to be an alternative to ALD, if at least three SLN are removed. A. Petrovsky, M. Kurbanova, M. Frolova, V. Amosova, E. Artamonova, I. Stilidi. The accuracy of sentinel lymph node biopsy in locally advanced breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-01-23.
AIMS:This study aimed to develop a novel aziridine-1,3,5-triazine derivative combining DNA-alkylating aziridine rings with a benzimidazole-containing fragment associated with PARP-related chemotypes. MATERIALS AND METHODS:The synthesis of target (4,6-di(aziridin-1-yl)-N-(2-(4-((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)ethyl)-1,3,5-triazin-2-amine (7) was achieved through a multi-step approach, involving the synthesis of 2-methyl-1-(prop-2-yn-1-yl)-1H-benzo[d]imidazole (3) and subsequent click chemistry reaction with N-(2-azidoethyl)-4,6-di(aziridin-1-yl)-1,3,5-triazin-2-amine (6). Protein modeling, docking and molecular dynamics were performed using the Schrödinger suite. Compound 7 was evaluated for cytotoxicity in vitro (HCT-116, U87, HeLa, A549 and ECV304 cell lines) by MTT assay, genotoxicity in HCT-116 cells by DNA-comet assay, and in vivo in A549 and HCT-116 xenografts in immunodeficient BALB/c Nude mice. RESULTS:Docking/MD suggested a PARP-1 binding mode, with key interactions comparable to established inhibitors such as talazoparib and olaparib. In vitro cytotoxicity assays against HCT-116, U87, HeLa, and A549 cell lines revealed dose-dependent antiproliferative effects, with IC50 values of 14.12, 33.52, 44.60, and 26.4 µM, respectively. In vitro genotoxicity assays showed that incubation of HCT-116 cell line with the compound 7 causes dose-dependent damage to DNA integrity. In vivo, compound 7 inhibited tumor growth in A549 xenografts (up to 75.1%, p < 0.05) and demonstrated dose-dependent activity in HCT-116 xenografts (up to 82.9% TGI at 6 mg/kg, i.v.).
PURPOSE:In FLAURA2, first-line osimertinib plus platinum-pemetrexed induction, with osimertinib plus pemetrexed maintenance, improved progression-free survival versus osimertinib alone in epidermal growth factor receptor (EGFR)-mutated, advanced non-small cell lung cancer (NSCLC; hazard ratio, 0.62; P < 0.001). Combining osimertinib with chemotherapy increased induction grade ≥3 adverse event rates, which reduced during maintenance. We report FLAURA2 patient-reported outcomes (PRO). PATIENTS AND METHODS:Health-related quality of life (HRQoL) was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ) Core 30 (baseline, week 4, week 7, week 10, then every 6 weeks until progression) and QLQ Lung Cancer 13 (baseline, weekly until week 10, then every 3 weeks until progression). Score changes (baseline to progression/19 months) were analyzed by mixed models for repeated measures. Within-patient ≥10-point changes from baseline were considered clinically meaningful. Tolerability was assessed by PRO-Common Terminology Criteria for Adverse Events (CTCAE). RESULTS:Patients had intermediate-to-high baseline functioning and global health status (GHS)/QoL (mean scores ≥63), with mild symptomatology (≤35). Most key scales showed nonclinically meaningful improvements; average least-squares mean (LSM) changes [95% confidence interval (CI)] for GHS/QoL and physical function, respectively, were 3.32 (1.67-4.98) and 2.37 (0.70-4.04) with combination therapy and 7.38 (5.70-9.07) and 6.74 (5.04-8.43) with monotherapy. Improvements in cough were clinically meaningful with combination therapy and monotherapy from week 5 (except monotherapy at week 73); average LSM changes (95% CI) were -13.23 (-14.85 to -11.62) and -11.19 (-12.83 to -9.55), respectively. Nonclinically meaningful deteriorations in fatigue and appetite loss were seen with the combination during induction. Both treatments were similarly well tolerated (PRO-CTCAE). CONCLUSIONS:In FLAURA2, osimertinib monotherapy and combination with platinum-pemetrexed as first-line treatment for EGFR-mutated advanced NSCLC had nonclinically meaningful impacts on HRQoL in mildly symptomatic patients.
