Introduction . Incidence of brain metastases rises in recent years. Local control after surgical resection of brain metastases is a priority for patients with limited intracranial disease and controlled primary tumor. Surgery should be combined with other methods because of the high risk of local recurrences. Aim . To analyze the overall survival (OS) and influencing factors for patients with brain metastasis after combined therapy. Materials and methods. The retrospective study included 196 patients with stable systemic cancer or available systemic therapy in cases of progressive disease. All patients had from 1 to 3 brain metastasis. Overall survival and influencing factors after surgical and combined therapy were analysed. Results . Median OS for the entire cohort was 16.9 months. The highest levels of OS were achieved for patients with renal cancer (median OS 32.5 months). For patients with non-small cell lung cancer, breast cancer, melanoma and other cancers OS were 18.8; 19.9; 11.0 and 15.3 months, appropriately. Age, continuation of local therapy in brain (surgical intervention, stereotactic radiosurgery), using of the cisplatin for patients with non-small lung cancer brain metastasis were independent factors that have influenced OS. Conclusion . Application of combined therapy for brain metastasis can provide reasonable OS for patients with controlled systemic disease. Using of the cisplatin as a part of combined therapy provide statistically meaningful rise in OS for patients with non-small lung cancer brain metastasis.

Stereotactic radiosurgery (SRS) demonstrates satisfactory results in terms of local tumor control and survival of patients with choroidal melanoma. At the same time, there are practically no studies aimed at establishing the dependence of the frequency and severity of SRS complications on the initial characteristics of the tumor and dose parameters of radiosurgery. The aim of this study was to analyze the incidence of post-radiation complications, as well as the relationship between the clinical characteristics of the tumor and the dosimetric parameters of stereotactic radiosurgery and secondary glaucoma. Material and methods. The prospective study included 43 patients with cT1-3N0M0 choroidal melanoma. The median prescribed dose per tumor margin at 50% isodose was 30 Gy, (23-35 Gy). The immediate effect of the treatment was assessed as positive in all the cases, except for increased blood flow according to Doppler ultrasound data, an increase in tumor size by more than 20% of the previously determined lesion according to MRI. Univariate and multivariate regression analyzes were performed using the Cox proportional hazards model, ROC analysis for statistically significant variables. Results. During the follow-up period (median was 16 months), an objective tumor response to treatment was recorded in 100% of cases. Secondary cataract after SRS developed in 4 (9.3%) cases, post-radiation retinopathy - in 9 (20.9%) cases, secondary retinal detachment - in 7 (16.3%) cases, secondary glaucoma - in 6 (14%) cases. After SRS during the observation period, the eyeball was preserved in 90.7% of patients. For the tumor volume parameter, the area under the curve was 0.92 (95% CI 0.84-1.00) with a cut-off point of 800 mm3. With a tumor volume less than this indicator, no cases of secondary glaucoma were detected. In the case of tumors with a volume equal to or greater than the calculated value, secondary glaucoma developed in 71% of cases. For the tumor thickness parameter, the area under the curve was 0.78 (95% CI 0.63-0.93) with a cut-off point of 7.6 mm. With a tumor thickness of less than 7.6 mm, the incidence of secondary glaucoma was 5% during the observation period, with a tumor thickness greater than this indicator - 72%. Conclusion. In the treatment of tumors with a volume of more than or equal to 800 mm3 and/or a thickness of more than or equal to 7.6 mm, radiosurgery as a monomethod is not recommended; it is necessary to resort to a combined method, including, along with SRS, tumor endoresection.

Introduction. The initial detection of regional and/or distant metastases in patients with newly diagnosed prostate cancer (PCa) is important for the management and disease prognosis. Conventional diagnostic imaging methods have certain limitations and do not allow a comprehensive assessment of the tumor spread. In recent years the use of positron emission tomography combined with computed tomography (PET/CT) with ligands of the prostate-specific membrane antigen (PSMA) has been rapidly expanding in oncological practice. The aim of the study was to analyze the diagnostic performance of 18F-PSMA-1007 PET/CT for the detection of metastases in patients with newly diagnosed prostate cancer. Material and methods. The study included 52 patients with newly diagnosed high-risk PCa, who underwent 18F-PSMA-1007 PET/CT. In all patients, there were no regional and/or distant metastases according to results of conventional imaging methods (bone scan, computed (or magnetic resonance) tomography of the pelvis). The conclusion about the presence or absence of metastases was made based on pathomorphological verification (in 27 patients) or using all available imaging and clinical follow-up as a reference. Results. Of the 52 patients included in the analysis, 26 (50.0%) had PCa metastases. Of these, 25 (48.1% of total cases) patients had true positive 18F-PSMA-1007 PET/CT. False-positive findings occurred in 2 cases. The positive predictive value of the method was 96.1%. In a univariate analysis of factors associated with true-positive PET/CT results, only the T-stage and Gleason score demonstrated statistically significant predictive value (p<0.05). According to multivariate analysis, only the Gleason score was statistically significantly associated with true positive findings on 18F-PSMA-1007 PET/CT (p=0.03). The most unfavorable in terms of the risk of detecting metastases was the group of patients with a Gleason score 7 (4+3) -10 (metastasis rate was 62.2%). Conclusion. 18F-PSMA-1007 PET/CT is an informative method for the detection of metastases in patients with newly diagnosed high risk PCa. 18F-PSMA-1007 PET/CT may be recommended in patients with Gleason score 4+3 or higher due to the high probability of regional and/or distant metastases, which were not detected by conventional methods.

Стереотаксическая радиохирургия (СРХ) демонстрирует удовлетворительные результаты в отношении локального контроля опухоли и выживаемости пациентов с меланомой хориоидеи. В то же время практически отсутствуют исследования, направленные на установление зависимости частоты и тяжести осложнений СРХ от начальных характеристик опухоли и дозовых параметров радиохирургии. Целью настоящего исследования стал анализ частоты развития постлучевых осложнений, а также взаимосвязи клинических характеристик опухоли и дозиметрических параметров стереотаксической радиохирургии и вторичной глаукомы. Материал и методы. В проспективное исследование были включены 43 пациента с меланомой хориоидеи cT1-3N0M0. Медиана предписанной дозы на край опухоли по 50% изодозе составила 30 Гр (23-35 Гр). Непосредственный эффект лечения оценивался как положительный во всех случаях, кроме усиления кровотока, по данным УЗИ, в режиме допплеровского картирования, увеличения объема опухоли более чем на 20% от ранее определяемого очага поражения, по данным МРТ. Был проведен однофакторный и многофакторный регрессионный анализ с использованием модели пропорциональных рисков Кокса, ROC-анализ для статистически значимых переменных. Результаты. За период наблюдения (медиана составила 16 месяцев) объективный ответ опухоли на лечение был зарегистрирован в 100% случаев. Вторичная катаракта после СРХ развилась в 4 (9,3%) случаях, постлучевая оптикоретинопатия – в 9 (20,9%) случаях, вторичная отслойка сетчатки – в 7 (16,3%) случаях, вторичная глаукома – в 6 (14%) случаях. После проведения СРХ за период наблюдения глазное яблоко удалось сохранить у 90,7% пациентов. Для параметра объема опухоли площадь под кривой составила 0,92 (95% ДИ 0,84-1,00) с точкой отсечения 838,1 мм3. При объеме опухоли менее данного показателя не выявлено ни одного случая развития вторичной глаукомы. В случае опухолей объемом, равным или превышающим рассчитанное значение, вторичная глаукома развилась в 71% случаев. Для параметра толщины опухоли площадь под кривой составила 0,78 (95% ДИ 0,63-0,93) с точкой отсечения 7,6 мм. При толщине опухоли менее 7,6 мм частота вторичной глаукомы составила 5% за период наблюдения, при толщине опухоли больше указанного показателя – 72%. Выводы. При лечении опухолей объемом более или равным 800 мм3 и/или толщиной более или равной 7,6 мм применение радиохирургии в качестве монометода не рекомендовано, необходимо прибегать к комбинированному методу, включающему, наряду с СРХ, эндорезекцию опухоли.

Here we report the results of the second interim analysis of a randomized prospective multi-center clinical study aimed to evaluate safety and efficacy of p62/SQTM1-encoding plasmid applied as an adjuvant to chemotherapy in patients with advanced platinum-resistant ovarian cancer. P62 encoding plasmid acts as an classic anti-cancer DNA vaccine and it also lowers chronic inflammation thus rendering tumor cells more susceptible to immune response and chemotherapy. A prospective randomized study was started in 2020. Chemotherapy (Gemcitabine 1000 mg/m2 days 1,8 every 3 weeks) was administered in both arms. In the Chemo arm (n = 20) it was the only treatment, and in the Plasmid arm (n = 20) the same chemo was supplemented with p62-plasmid (2.5 mg i.m. weekly). To data cut-off, the median follow-up was 11.1 months in Efficacy-Evaluable Set. The median progression-free survival (PFS) was 2.7 and 6.6 mo in Chemo and Plasmid arms respectively (p Log-Rank = 0.018). Noteworthy, as of today, 35% of patients in the plasmid group did not progress with the longest PFS recorded so far is 24 months. The tumor response was assessed according to the RECIST 1.1 criteria. No complete responses were observed in either group. The objective response rate was higher in the Plasmid arm: partial response (PR) - 5.0% and 20.0%, stable disease (SD) - 40.0% and 60.0%, disease progression - 55.0% and 20.0%, and disease control rate (PR and SD) - 45.0% and 85.0% in Chemo and Plasmid arms respectively (p = 0,001). One patient in the Plasmid arm underwent complete cytoreduction with no evidence of disease progression. No Grade 3-4 toxicities were observed in both arms. All adverse effects were managed by conventional medications. No treatment delays or interruptions due to plasmid-related adverse events were registered. The interim results of this study show that adding p62/SQSTM1-encoding plasmid to standard Gemcitabine chemotherapy for advanced platinum-resistant ovarian cancer is a novel treatment approach which is safe, well-tolerated and effective: it improves ORR, DCR, and PFS. The long-lasting PFS in some patients is typical for immunotherapeutic agents. The study is ongoing.

Введение. Первоначальное обнаружение регионарных и/или отдаленных метастазов у пациентов с впервые выявленным раком предстательной железы (РПЖ) важно для выбора тактики лечения и прогноза заболевания. Традиционные методы диагностической визуализации имеют определенные ограничения, а также не позволяют комплексно оценить распространенность опухолевого процесса. В последние годы в онкологической практике стремительно расширяется применение позитронноэмиссионной томографии, совмещенной с компьютерной томографией (ПЭТ/КТ), с использованием лигандов к простатическому специфическому мембранному антигену (prostate specific membrane antigen – PSMA). Цель исследования. Изучить диагностические возможности ПЭТ/КТ с 18F-PSMA-1007 в обнаружении метастатического поражения у пациентов с впервые выявленным РПЖ с высоким риском прогрессирования. Материал и методы. В исследование были включены 52 пациента с впервые выявленным РПЖ высокого риска прогрессирования, которым выполнена ПЭТ/КТ с 18F-PSMA-1007. У всех пациентов отсутствовали данные в пользу регионарных и/или отдаленных метастазов по результатам стандартных методов обследований (остеосцинтиграфия с использованием 99mTc-метилендифосфонатов, компьютерная (или магнитно-резонансная) томография таза). Окончательные выводы о наличии либо отсутствии метастазов делались на основании патоморфологической верификации (у 27 пациентов) либо данных обследований в динамике на фоне проводимой терапии. Результаты. Из 52 включенных в анализ пациентов у 26 (50,0%) имели место метастазы РПЖ. Из их числа у 25 (48,1% от общего числа случаев) пациентов получены истинно-положительные результаты ПЭТ/КТ с 18F-PSMA-1007. Ложно-положительные находки имели место в 2 случаях. Положительное предсказательное значение метода составило 96,1%. При проведении моновариантного анализа факторов, ассоциированных с истинно положительными результатами ПЭТ/КТ, только уровень степени местной распространенности и сумма Глисона продемонстрировали статистически значимое прогностическое значение (p<0,05). По данным мультивариантного анализа только сумма Глисона была статистически значимо ассоциирована с истинно-положительными находками при ПЭТ/КТ с 18F-PSMA-1007 (р=0,03). Наиболее неблагоприятной в отношении риска выявления метастазов была группа пациентов с суммой Глисона 7 (4+3)-10 (частота метастазов составила 62,2%). Заключение. ПЭТ/КТ с 18F-PSMA-1007 – информативный метод обнаружения метастатического поражения у пациентов с впервые выявленным РПЖ из группы высокого риска прогрессирования. Выполнение ПЭТ/КТ с 18F-PSMA-1007 может быть рекомендовано при значении суммы Глисона 4+3 и выше ввиду высокой вероятности наличия не определяемых стандартными методами регионарных и/или отдаленных метастазов.

CMF (Cyclophosphamide 600mg/m2 + Methotrexate 40mg/m2 + Fluorouracil 600mg/m2, IV, day 1 and 8, every 4 weeks) remains a chemotherapeutic modality effective for metastatic triple-negative breast cancer (mTNBC). A plasmid encoding p62/SQTM1 reduces chronic inflammation, changes the tumor microenvironment, and increases the number of tumor-infiltrating lymphocytes. Dosing of the plasmid preserved the lives of 10 out of 11 dogs with breast cancer. In a human phase I/IIa trial, it demonstrated an excellent safety profile and limited cancer progression.

Here we report the first intermediate analysis of a randomized prospective multi-center clinical study aimed to evaluate safety and efficacy of p62/SQTM1-encoding plasmid applied as an adjuvant to chemotherapy in patients with advanced platinum-resistant ovarian cancer. Previously we reported that the p62-plasmid reduces chronic inflammation, changes the tumor microenvironment, and increases the number of tumor-infiltrating lymphocytes. In a phase I/IIa study in patients with refractory solid tumors, the plasmid demonstrated high degree of safety and preliminary indications of efficacy.

Background. Patients suffering from prostate cancer (PCa) with a high risk of progression need the most active treatment tactics. Escalation of radiation dose, larger daily fractions radiation therapy (including high-dose-rate interstitial brachytherapy (HDR-BT)) is a promising approach to the treatment of PCa. Objective of the study . Comparative assessment of the long-term treatment results of patients with PCa with a poor prognosis after external beam radiotherapy (EBRT) and combined radiation therapy, depending on risk factors. Materials and methods . 207patients who received a course EBRT and HDR-BT with EBRT (combined RT) on a radical program for the first detected PCa at the N.N. Alexandrov National Cancer Center of Belarus in 2013—2015 inclusive. All patients were belonged to the group of high and very high risk of progression according to the criteria of the NCCN (National Comprehensive Cancer Network), all were treated with neoadjuvated hormone therapy (medical or surgical castration). The patients were stratified into two groups: HDR-BT with EBRT and EBRT. When conducting combined RT, HDR-brachytherapy was performed in single fraction with a dose of 11.5 Gy, for EBRT it was used as a conventional fractionation (single dose of 2 Gy, total — 44 Gy) and hypofractionation (single dose of 3 Gy, total — 36 Gy). Patient that were not who not included in the combined RT protocol were treated with EBRT under a radical program in a total dose of 78—80 Gy. Results . It was established that in the group of patients after EBRT the median survival was not achieved, the 5-year adjusted survival (AS) was 85.2 + 5.6 %. In the combined RT group, the median survival was also not reached, the 5-year-old AS was 92.2 + 5.9 %. It was found that for the patients with a Gleason score of 7 or more, a significant difference in the AS index was obtained in favor of the HDR-BT with EBRT: the 5-year AS of patients of this subgroup who were exposed to combined RT was 84.6 + 9.8 %, while after EBRT, the 5-year-old AS was 71.0 + 11.2 %. In the subgroup of patients with Gleason sum 7—10, combined RT was associated with statistically significantly better long-term results in compared with EBRT. Conclusion. The application of the method of combined RTfor patients suffering from PCa with a high risk is characterized with satisfactory long-term treatment results.

Рак мочевого пузыря (РМП) занимает 9 место в мире среди всех злокачественных новообразований и является второй по частоте опухолью в онкоурологической практике.Ежегодно в мире регистрируется более 430 тыс.новых случаев, Резюме.Мышечно-инвазивный рак мочевого пузыря (МИРМП) с неблагоприятным прогнозом (категории рТ3-4N0 либо pN+) характеризуется высокой агрессивностью течения опухолевого процесса и смертностью.В настоящее время в рамках комплексного лечения данной патологии наряду с радикальной цистэктомией (ЦЭ) используется неоадъювантная (НХТ) либо адъювантная химиотерапия (АХТ), главным образом, на основе цисплатина, характеризующаяся высокой токсичностью и умеренной эффективностью.У пациентов с МИРМП с неблагоприятным прогнозом, которым не проводилась НХТ, после радикальной ЦЭ предлагается применять режимы M-VAC (цисплатин, адриамицин, метотрексат и винбластин), GC (гемцитабин, цисплатин) или CMV (цисплатин, метотрексат и винбластин).Данные исследований, в том числе и проспективного рандомизированного исследования, проведенного в Республиканском научно-практическом центре онкологии и медицинской радиологии им.Н.Н.Александрова, показали, что наибольшая эффективность АХТ отмечается в подгруппе пациентов без метастатического поражения регионарных лимфоузлов.

Objective is study on the clinical efficacy of the treatment method using polychemotherapy in the docetaxel + vinorelbine regimen in patients with prostate cancer of stage III–IV without distant metastases.Materials and methods. The study included 112 patients, who underwent radical prostatectomy on prostatic adenocarcinoma in the period 2006–2010 at N.N. Alexandrov National Cancer Center of Belarus.Results. The developed scheme of chemotherapy after radical prostatectomy showed its effectiveness in patients with the spread of a tumor characterized by the criterion pT3b–4pN0 or pT3apN0 with Gleason sum ≤7 and prostatic specific antigen level before operation >20 ng/ml. In patients with pT3aN0 tumor with a Gleason sum ≤7 and prostatic specific antigen level before surgery <20 ng/ml, adjuvant chemotherapy is not justified.