Fluorescence of the Polymethine Dye Tiks and Diagnostics af Cancert

It is shown that the fluorescence of the polymethine dye TIKS, whose absorption and fluorescence bands are located in the spectral region of transmission of biological tissues, can be recorded from a depth of up to 1.5 cm of an animal’s body. The intensity of the fluorescence recorded from the surface of the animal’s body in intravenous injection of the dye (1–2 mg/kg) is in direct proportion to its concentration in tumor nodes and muscles. In rapidly growing tumors, a high (up to 3.6) degree of contrast of the content of the dye is attained in tumor tissues as compared to the surrounding normal tissues. Over the course of 7 days after the injection, the dye is practically completely removed from both the tumor and normal muscular tissues. From the change in the fluorescence intensity in scanning the surface one can determine the regions of localization of tumor nodes against the background of the surrounding normal tissues and the presence of regions with a nonuniform distribution of the dye

Treatment of patients with bone marrow metastases: the present state of the problem

The paper reviews the data available in the literature on the identification of tumor cells in bone marrow and peripheral blood in different tumors and breast cancer. Analysis of the majority of investigations suggest that the presence of tumor cells in the bone marrow correlates with early disease recurrences and lower survival; to detect bone marrow tumor cells is one of the most important approaches to early identifying metastases and improving the results of treatment for breast cancer. The paper gives the results of an investigation conducted at the N.N. Aleksandrov Republican Research and Practical Center for Oncology and Medical Radiology in 2008 to 2014, which established that the presence of cancer cells in the bone marrow is a poor prognostic sign: the 3-year relapse-free survival of patients with the unaffected and affected bone marrow was 88.7 and 69.3 %, respectively (p < 0.01)

The effect of hypoxia on photocytotoxicity of tics tricaebocyanine dye in vitro

To evaluate the effect of cell oxygenation on photocytotoxicity of a novel tricarbocyanine indolenine dye covalently bound to glucose (TICS). Methods: HeLa cells were incubated with 5 µM TICS, 2 h later irradiated by laser at 740 nm with a light dose of 10 J/cm2, delivered at a power density of 10, 20, 25 or 30 mW/cm2, in air or in argon atmosphere, and then scored for viability. Results: The photocytotoxicity of TICS increased dramatically as the power density was reduced. Under hypoxia TICS-photosensitized cell death was determined but its value was lowered, compared to photoirradiation in the air. Conclusion: Photosensitizing effect of TICS is only partially dependent on the oxygenation of tumor cells

Whole-Body Diffusion-Weighted Magnetic Resonance Imaging and Positron Emission Tomography Combined with Computed Tomography in the Staging of Lymphomas

Objective – to compare the diagnostic efficiency of whole-body diffusion-weighted magnetic resonance imaging (DW-MRI) and positron emission tomography combined with computed tomography (PET/CT) in the staging of lymphomas.Material and methods. The prospective study enrolled 92 adult patients with Hodgkin's lymphoma or non-Hodgkin's lymphoma. Before treatment, all the patients underwent whole-body DW-MRI and PET/CT. The techniques were compared for their efficiency in diagnosing damage to lymph nodes (LNs) and organs and in determining the stage of lymphoma.Results. The sensitivity, specificity, and accuracy of DW-MRI in diagnosing a lesion in the enlarged LNs were 98.2%, 99.9%, and 99.3%, respectively; those of PET/CT were 99.4%, 100.0%, and 99.8%. ROC analysis showed that the efficiency of the techniques in diagnosing a lesion in the enlarged LNs did not differ (p>0.06). The sensitivity of DW-MRI and PET/CT in diagnosing a lesion in the unenlarged LNs was 77.8% and 88.1%, respectively (p<0.001). The sensitivity, specificity, and accuracy of DW-MRI in diagnosing lung damage were 73.3%, 98.7%, 94.6%; those of PET/CT were 86.7%, 98.7%, and 96.7%; those for the spleen were 54.8%, 98.3%, 83.3% and 100.0%, 100.0%, 100.0%; those for bone marrow (BM) were 87.1%, 96.4%, 93.0% and 64.5%, 87.3%, 79.1%,; those for all organs were 72.9%, 98.1%, 91.4% and 80.0%, 96.6%, 92.2%. The ROC analysis indicated that the efficiency of the techniques in diagnosing a lesion in the lung did not differ (p>0.3), that of PET/CT for the spleen was higher (p <0.0001); that of DW-MRI for BM was higher (p<0.0008); that for all organs did not differ (p>0.35). DW-MRI and PET/CT could determine the correct stage of lymphoma in the same number of patients (86%). The new lymphoma staging algorithm involving whole-body DW-MRI in all patients, PET/CT, and BM biopsies according to the established indications made it possible to determine the correct stage of lymphoma in 95% of patients.Conclusion. Whole-body DW-MRI has comparable efficiency to PET/CT in the staging of lymphoma. The new lymphoma staging algorithm based on whole-body DW-MRI is superior to PET/CT and PET/CT with BM biopsy

Сравнение диагностической эффективности магнитно-резонансной томографии с диффузионно-взвешенным исследованием всего тела и позитронной эмиссионной томографии/компьютерной томографии при определении степени регрессии лимфомы после завершения химиотерапии: Минская шкала и шкала Довиль

Introduction. Positron emission tomography/computed tomography (PET/CT) is a recommended technique for tumor response evaluation in lymphoma after treatment. The possibilities of the whole body magnetic resonance imaging with diffusion-weighted imaging (MRI-DWI) for tumor response evaluation in lymphoma are not well studied. Objective: to compare the diagnostic effectiveness of whole body MRI with a diffusion-weighted imaging (MRI-DWI) and PET/CT in determining tumor response in lymphoma after the end of chemotherapy. Materials and methods. A prospective study included 105 adult patients with lymphoma whounderwent whole body MRI-DWI and PET/CTafter the end of chemotherapy and who were followed-up for at least 6 months. To interpret the MRI-DWI, the 5-level scale (Minsk scale) proposed by us was used. Categories 1–3 were considered a sign of complete tumor response, categories 4–5 were a sign of non-complete response. Results. According to the reference standard, complete tumor response was established in 77% of patients, non-complete response in 23%. The assessment of the tumor response in MRI-DWI and PET/CT matched in 89% of patients. The agreement of MRI-DWI (k =0,76, p=0,000) and PET/CT (k =0,78, p=0,000) with the reference standard is good. The sensitivity, specificity, accuracy, positive and negative prognostic value of MRI-DWI were 66,7%, 100,0%, 92,4%, 100,0%, 91,0%, PET/CT — 83,3%, 95,1%, 92,4%, 83,3%, 95,1%, respectively. The diagnostic effectiveness of the methods is not significantly different (p=0,32). The most common reason for the incorrect determination of the tumor response in MRI-DWI was non-enlarged lymph nodes, and in PET/CT — metabolically active non-tumor diseases. 3-year progression-free survival with negative and positive MRI-DWI results was 93% and 25% (p=0,000), 3-year overall survival — 97% and 70% (p=0,011), respectively. Conclusion. Whole body MRI-DWI and Minsk scale are recommended for use in patients with lymphoma to determine tumor response after the end of chemotherapy as a non-irradiative and effective alternative to PET/CT.Введение. Для оценки степени регрессии лимфомы после химиотерапии рекомендуется использовать позитронную эмиссионную томографию/компьютерную томографию (ПЭТ/КТ). Возможности метода магнитно-резонансной томографии с диффузионно-взвешенным исследованием (МРТ-ДВИ) всего тела при оценке степени регрессии лимфомы изучены недостаточно. Цель: сравнить диагностическую эффективность МРТ-ДВИ всего тела и ПЭТ/КТ при определении степени регрессии лимфомы после завершения химиотерапии. Материалы и методы. В проспективное исследование включены 105 взрослых пациентов с лимфомой, которым после завершения химиотерапии выполнили МРТ-ДВИ всего тела и ПЭТ/КТ и которые находились под наблюдением не менее 6 месяцев. Для интерпретации МРТ-ДВИ использовали предложенную нами 5-уровневую шкалу (Минская шкала). Для интерпретации ПЭТ/КТ использовали 5-уровневую шкалу Довиль. Категории оценки 1–3 считали признаком полной регрессии опухолей, категории 4–5 — признаком неполной регрессии. Результаты. Согласно стандарту диагностики полная регрессия опухолей установлена у 77% пациентов, неполная регрессия — у 23%. Оценка степени регрессии при МРТ-ДВИ и ПЭТ/КТ совпала у 89% пациентов. Согласие МРТ-ДВИ (к =0,76, р=0,000) и ПЭТ/КТ (к =0,78, р=0,000) со стандартом диагностики хорошее. Чувствительность, специфичность, точность, положительное и отрицательное прогностическое значение МРТ-ДВИ составили 66,7; 100,0; 92,4; 100,0 и 91,0%, ПЭТ/КТ — 83,3; 95,1; 92,4; 83,3 и 95,1% соответственно. Диагностическая эффективность методов достоверно не различается (р=0,32). Наиболее частой причиной неверного установления степени регрессии при МРТ-ДВИ были неувеличенные лимфоузлы, при ПЭТ/КТ — метаболически активные неопухолевые заболевания. 3-летняя выживаемость без прогрессирования при отрицательном и положительном результатах МРТ-ДВИ составила 93 и 25% (р=0,000), 3-летняя общая выживаемость — 97 и 70% (р=0,011) соответственно. Выводы. МРТ-ДВИ всего тела и Минская шкала рекомендуются к использованию у пациентов с лимфомой для определения степени регрессии опухолей после завершения химиотерапии как нерадиационная и эффективная альтернатива ПЭТ/КТ

Efficacy and Safety of Trifluridine/Tipiracil Treatment in Patients With Metastatic Gastric Cancer Who Had Undergone Gastrectomy: Subgroup Analyses of a Randomized Clinical Trial

Importance Trifluridine/tipiracil (FTD/TPI) treatment has shown clinical benefit in patients with pretreated metastatic gastric cancer or gastroesophageal junction cancer (mGC/GEJC). Patients who have undergone gastrectomy constitute a significant proportion of patients with mGC/GEJC. Objective To assess the efficacy and safety of FTD/TPI among patients with previously treated mGC/GEJC who had or had not undergone gastrectomy. Design, Setting, and Participants This preplanned subgroup analysis of TAGS (TAS-102 Gastric Study), a phase 3, randomized, placebo-controlled, clinical trial included patients with mGC/GEJC who had received at least 2 previous chemotherapy regimens, and was conducted at 110 academic hospitals in 17 countries in Europe, Asia, and North America, with enrollment between February 24, 2016, and January 5, 2018; the data cutoff was March 31, 2018. Interventions Patients were randomized 2:1 to receive oral FTD/TPI 35 mg/m2 twice daily or placebo twice daily with best supportive care on days 1 through 5 and days 8 through 12 of each 28-day treatment cycle. Main Outcomes and Measures The primary end point was overall survival. This subgroup analysis was conducted to examine potential trends and was not powered for statistical significance. Efficacy and safety end points were evaluated in the subgroups. Results Of 507 randomized patients (369 [72.8%] male; mean [SD] age, 62.5 [10.5] years), 221 (43.6%) had undergone gastrectomy (147 randomized to FTD/TPI and 74 to placebo) and 286 (56.4%) had not undergone gastrectomy (190 randomized to FTD/TPI and 96 to placebo). In the gastrectomy subgroup, the overall survival hazard ratio (HR) in the FTD/TPI group vs placebo group was 0.57 (95% CI, 0.41-0.79), and the progression-free survival HR was 0.48 (95% CI, 0.35-0.65). In the no gastrectomy subgroup, the overall survival HR in the FTD/TPI group vs placebo group was 0.80 (95% CI, 0.60-1.06), and the progression-free survival HR was 0.65 (95% CI, 0.49-0.85). Among FTD/TPI-treated patients, grade 3 or higher adverse events of any cause occurred in 122 of 145 patients (84.1%) in the gastrectomy subgroup and 145 of 190 (76.3%) in the no gastrectomy subgroup: 64 (44.1%) in the gastrectomy subgroup and 50 (26.3%) in the no gastrectomy subgroup had grade 3 or higher neutropenia, 31 (21.4%) in the gastrectomy subgroup and 33 (17.4%) in the no gastrectomy subgroup had grade 3 or higher anemia, and 21 (14.5%) in the gastrectomy subgroup and 10 (5.3%) in the no gastrectomy subgroup hD grade 3 or higher leukopenia. In the gastrectomy subgroup, 94 (64.8%) had dosing modifications because of adverse events vs 101 (53.2%) in the no gastrectomy subgroup; 15 (10.3%) in the gastrectomy group and 28 (14.7%) in the no gastrectomy group discontinued treatment because of adverse events. Treatment exposure was similar between groups. Conclusions and Relevance The FTD/TPI treatment was tolerable and provided efficacy benefits among patients with pretreated mGC/GEJC regardless of previous gastrectomy

Health-related quality of life associated with trifluridine/tipiracil in heavily pretreated metastatic gastric cancer: results from TAGS

Background In TAGS, an international, double-blind, phase 3 trial, trifluridine/tipiracil significantly improved overall survival and progression-free survival compared with placebo in heavily pretreated metastatic gastric cancer patients. This paper reports pre-specified quality of life (QoL) outcomes for TAGS. Methods Patients were randomized 2:1 to trifluridine/tipiracil (35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle) plus best supportive care (BSC) or placebo plus BSC. QoL was evaluated at baseline and at each treatment cycle, using the EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires; results were considered valid for analysis only if ≥ 10% of patients completed the questionnaires. Key QoL outcomes were mean changes from baseline and time to deterioration in QoL. A post hoc analysis assessed the association between QoL and time to deterioration of Eastern Cooperative Oncology Group performance score (ECOG PS) to ≥ 2. Results Of 507 randomized patients, 496 had baseline QoL data available. The analysis cut-off was 6 cycles for trifluridine/tipiracil and 3 cycles for placebo. In both treatment groups, there were no clinically significant deteriorations in the mean QLQ-C30 Global Health Status (GHS) score, or in most subscale scores. In a sensitivity analysis including death and disease progression as events, there was a trend towards trifluridine/tipiracil reducing the risk of deterioration of QoL scores compared with placebo. Deterioration in the GHS score was associated with deterioration in ECOG PS. Conclusion QoL was maintained in TAGS, and there was a trend towards trifluridine/tipiracil reducing the risk of QoL deterioration compared with placebo

Long-term efficacy and safety of CT-P6 versus trastuzumab in patients with HER2-positive early breast cancer: final results from a randomized phase III trial

Purpose Equivalent efficacy was demonstrated for the biosimilar CT-P6 and trastuzumab following neoadjuvant therapy for patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer. Following adjuvant treatment, efficacy and safety were comparable between treatments. We report updated safety and efficacy data after up to 3 years’ follow-up. Methods Following neoadjuvant chemotherapy with CT-P6/trastuzumab, patients underwent surgery and continued receiving adjuvant CT-P6/trastuzumab. The primary endpoint (previously reported) was pathological complete response. Time-to-event analyses (disease-free survival [DFS], progression-free survival [PFS], and overall survival [OS]), study drug-related and cardiac adverse events, and immunogenicity were assessed during post-treatment follow-up. Results Most patients entered the follow-up period (CT-P6: 259 [95.6%]; trastuzumab: 269 [96.8%]). After a median follow-up of 38.7 (CT-P6) and 39.6 (trastuzumab) months, medians were not reached for time-to-event parameters; estimated hazard ratios (HRs) and 3-year survival rates were similar between groups. Estimated HRs (95% confidence intervals) for CT-P6 versus trastuzumab were 1.23 (0.78–1.93) for DFS, 1.31 (0.86–2.01) for PFS, and 1.10 (0.57–2.13) for OS (intention-to-treat population). Safety findings were comparable between groups for the overall study and follow-up period, including study drug-related cardiac disorders (CT-P6: 22 [8.1%] patients; trastuzumab: 24 [8.6%] patients [overall]) and decreases in left ventricular ejection fraction. Immunogenicity was similar between groups. Conclusion The similarity of the time-to-event analyses between CT-P6 and trastuzumab supports the equivalence in terms of efficacy established for the primary endpoint. CT-P6 was well tolerated, with comparable safety and immunogenicity to trastuzumab. ClinicalTrials.gov: NCT02162667 (registered June 13, 2014

Comparison of diagnostic effectiveness of X-ray computed tomography, magnetic resonance imaging and diffusion-weighted magnetic resonance imaging in the differentiation of residual tumors and posttherapeutic masses in patients with lymphoma after treatment

We conducted prospective study of the effectiveness of X-ray computed tomography (CT), magnetic resonance imaging (MRI) and MRI with diffusion-weighted imaging (MRI-DWI) with apparent diffusion coefficient (ADC) maps calculation for the differentiation of residual tumors and posttherapeutic masses in 40 adult patients with lymphoma. Whole body CT and MRI-DWI were performed before and after treatment.The effectiveness of lesions size criterion for CT and MRI, visual and quantitative criteria for MRI-DWI were investigated. Residual lesions signal intensity on DWI images and ADC maps was compared with paraspinal muscles signal intensity. The accuracy of the overall tumor response estimation was 38 % for CT, 48 % for MRI, 68 % for MRI-DWI with visual assessment of DWI images, 93 % for MRI–DWI with visual assessment of ADC maps. CT density of the lymph node lesions before treatment and residual masses after treatment did not differ significantly – 40.4 ± 9.4 and 37.2 ± 10.5 Hounsfield units respectively (p = 0.08), whereas ADC (×10–3 mm2/s) increased significantly from 1.04 ± 0.40 to 2.01 ± 0.82 (p < 0.0001). ADC of postherapeutic masses was significantly higher than that of residual tumors – 2.32±0.62 and 1.04 ± 0.66 respectively (p < 0.0005). MRI-DWI with visual assessment of ADC maps is the most effective method for differentiation of residual tumors and posttherapeutic masses in patients with lymphoma after treatment. Usefulness of quantitative analysis of ADC values requires further investigation