oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2020-19-6-46-56oncotomsk-1639Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESИЗУЧЕНИЕ ДИНАМИКИ ОПУХОЛЕВОГО КРОВОТОКА ДЛЯ ОЦЕНКИ РАННЕГО ОТВЕТА РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ НА НЕОАДЪЮВАНТНУЮ ХИМИОТЕРАПИЮSTUDY OF CHANGES IN TUMOR BLOOD FLOW FOR THE ASSESSMENT OF EARLY RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN BREAST CANCER PATIENTSПавловМ. В.PavlovM. V.

онколог

SPIN-код: 5342-3978. Author ID (Scopus): 57193805010 Россия, 603126, г. Нижний Новгород, ул.Деловая,11/1

Россия, 603950, г. Нижний Новгород, пл. Минина и Пожарского, 10/1

MD, Oncologist

Author ID (Scopus): 57193805010

11/1, delovaya street, 603126-Nizhny Novgorod, Russia

10/1, minina square, 603950-Nizhny Novgorod, Russia

pavlov.med88@gmail.comРыхтикП. И.RykhtikP. I.

кандидат медицинских наук, заведующий отделом лучевой диагностики

Author ID (Scopus): 55164736000

Россия, 603001, г. Нижний Новгород, Нижневолжская набережная, 2

MD, PhD, Head of Diagnostic Imaging Department 

Author ID (Scopus): 55164736000.

2, Lower Volga Embankment, 603001-Nizhny Novgorod, Russia

ИльинскаяО. Е.IlyinskayaO. E.

заведующая патологоанатомическим отделением

SPIN-код: 2870-6177 Россия, 603126, г. Нижний Новгород, ул.Деловая,11/1

MD, Head of the Department of Pathology

11/1, Delovaya Street, 603126-Nizhny Novgorod, Russia

СубочевП. В.SubochevP. V.

кандидат физико-математических наук, старший научный сотрудник

SPIN-код: 6178-7859. Researcher ID (WOS): E-4918-2014. Author ID (Scopus): 12241506200

Россия, 603950, г. Нижний Новгород, ул. Ульянова, 46

PhD, Senior Researcher

Researcher ID (WOS): E-4918-2014. Author ID (Scopus): 12241506200

46, Ulyanov Street, 603950-Nizhny Novgorod, Russia

КрейнинаЮ. М.KreininaYu. M.

доктор медицинских наук, ведущий научный сотрудник

SPIN-код: 3270-7053. Author ID (Scopus): 7801460523. ORCID: 0000-0002-7229-594 Россия, 117997, г. Москва, ул. Профсоюзная, 86/2

MD, DSc, Leading Researcher

Author ID (Scopus): 7801460523. ORCID: 0000-0002-7229-594

86, Profsoyuznaya Street, 117997-Moscow, Russia

https://orcid.org/0000-0003-0434-4372МасленниковаА. В.MaslennikovaA. V.

доктор медицинских наук, профессор

SPIN-код: 7511-8393. Researcher ID (WOS): S-2734-2016. Author ID (Scopus): 9841297600Россия, 603950, г. Нижний Новгород, пл. Минина и Пожарского, 10/1

MD, PhD, DSc, Professor

Researcher ID (WOS): S-2734-2016. Author ID (Scopus): 9841297600

10/1, Minina square, 603950-Nizhny Novgorod, Russia

ГБУЗ НО «Нижегородский областной клинический онкологический диспансер»; ФГБОУ ВО «Приволжский исследовательский медицинский университет» Минздрава РоссииРоссияNizhny Novgorod Regional clinical oncology dispensary; Privolzhsky Research Medical UniversityRussian FederationФБУЗ «Приволжский окружной медицинский центр» ФМБА РоссииРоссияVolga Region Medical CenterRussian FederationГБУЗ НО «Нижегородский областной клинический онкологический диспансер»РоссияNizhny Novgorod Regional Clinical Oncology DispensaryRussian FederationФГБНУ «Федеральный исследовательский центр Институт прикладной физики Российской академии наук»РоссияInstitute of Applied Physics RASRussian FederationФГБУ «Российский научный центр рентгенорадиологии» Минздрава РоссииРоссияRussian Scientific Center of RoentgenoradiologyRussian FederationФГБОУ ВО «Приволжский исследовательский медицинский университет» Минздрава РоссииРоссияPrivolzhsky Research Medical UniversityRussian Federation2020281220201964656Copyright © Павлов М.В., Рыхтик П.И., Ильинская О.Е., Субочев П.В., Крейнина Ю.М., Масленникова А.В., 20202020Павлов М.В., Рыхтик П.И., Ильинская О.Е., Субочев П.В., Крейнина Ю.М., Масленникова А.В.Pavlov M.V., Rykhtik P.I., Ilyinskaya O.E., Subochev P.V., Kreinina Y.M., Maslennikova A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/1639Введение

Введение. В течение последних 20 лет произошло изменение подходов к лечению рака молочной железы, в частности существенное повышение роли лекарственной терапии. Ответ на неоадъювантную химиотерапию рассматривается в настоящее время как суррогатный биомаркер, который позволяет оценить течение и прогноз заболевания. Для решения данной задачи необходимо проводить оценку функциональных и метаболических изменений опухолевой ткани в процессе лечения. Ультразвуковая допплерография – это неинвазивный, доступный и недорогой метод визуализации, который можно безопасно использовать для повторных измерений.

Цель исследования – изучение динамики васкуляризации опухоли ультразвуковым  методом в режиме энергетического допплера для оценки раннего ответа рака молочной железы на неоадъювантную химиотерапию.

Материал и методы

Материал и методы. Исследование проводилось на базе ФБУЗ ПОМЦ ФМБА России с мая 2017 по август 2019 г. В исследование были включены 63 больных раком молочной железы, которым проводилась неоадъювантная химиотерапия. Оценка кровотока опухоли с использованием допплеровского сканирования проводилась до начала и перед вторым курсом неоадъювантной химиотерапии. Изменения кровоснабжения опухоли на фоне химиотерапии сопоставлялись с патоморфологическим ответом опухоли после оперативного лечения.

Результаты

Результаты. В подавляющем большинстве случаев (78 %) наблюдалось не зависящее от степени лечебного патоморфоза уменьшение количества опухолевых сосудов после первого курса химиотерапии. В 8 случаях повышения васкуляризации после первого  курса неоадъювантной химиотерапии при гистологическом исследовании удаленной опухоли наблюдалось отсутствие ответа/слабый ответ на лечение при отсутствии перитуморального воспаления, в 5 случаях – резкое увеличение количества сосудов вокруг обширных зон интранодулярного некроза и обусловленного им перитуморального воспаления. В целом сопоставление динамики васкуляризации опухоли и  патоморфологического ответа выявило слабую, хотя и статистически значимую отрицательную корреляцию между изменениями кровоснабжения опухоли на фоне химиотерапии и степенью лечебного патоморфоза.

Выводы

Выводы. Не удалось установить однозначной зависимости между реакцией сосудистого русла и ответом опухоли на цитостатическое воздействие. Повышение количества  опухолевых сосудов при отсутствии перитуморального воспаления оказалось  единственной ситуацией, когда изменения опухолевого кровотока на фоне проведения химиотерапии могут быть однозначно интерпретированы как предиктивный критерий отсутствия/слабого ответа опухоли на лечение.

Background

Background. Over the past 20 years, there has been a change in approaches to the treatment of breast cancer, in particular, a significant increase in the role of drug therapy. Breast cancer response to neoadjuvant chemotherapy is currently considered as a surrogate biomarker, which allows evaluation of the clinical course and prognosis of the disease. To solve this problem, it is necessary to assess the functional and metabolic changes in tumor tissue during treatment. Doppler ultrasound is a non-invasive, affordable, and low-cost imaging technique that can be safely used for repeated measurements.

The purpose of the study was to study vascular changes in the tumor by power Doppler ultrasound for the evaluation of the early breast cancer response to neoadjuvant chemotherapy.

Material and Methods

Material and Methods. From May 2017 to August 2019, 63 patients with breast cancer received neoadjuvant chemotherapy. Changes in the tumor blood flow were assessed before starting the treatment and prior to the second course of neoadjuvant chemotherapy using Doppler scanning. Changes in tumor blood floor after chemotherapy were compared with the pathological tumor response after surgical treatment.

Results

Results. In the vast majority of cases (78 %), there was a decrease in the number of tumor vessels after the first cycle of neoadjuvant chemotherapy independent of the grade of pathological response. In 8 cases with increased vascularization after the first cycle of neoadjuvant chemotherapy, histological examination of the removed tumor showed no response / weak response to treatment in the absence of peritumoral inflammation. In 5 cases, a sharp increase in the number of vessels around large areas of intranodular necrosis and peritumoral inflammation was observed. In general, a comparison of changes in tumor vascularization and pathological response revealed a weak, although statistically significant, negative correlation between changes in the tumor blood flow after neoadjuvant chemotherapy and pathological response.

Conclusion

Conclusion. It was not possible to establish an unambiguous relationship between the reaction of the vascular bed and the tumor response to the cytostatic effect. An increase in the number of tumor vessels in the absence of peritumoral inflammation was the only situation when changes in tumor blood flow during chemotherapy can be unambiguously interpreted as a predictive criterion for the absence / weak response of the tumor to treatment.

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The authors declare that there are no conflicts of interest present.