gnckКолопроктологияKoloproktologia2073-75562686-7303Russian Association of Coloproctology10.33878/2073-7556-2024-23-4-48-56gnck-1956Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВлияние неоадъювантной химиотаргетной терапии на течение периоперационного периода у больных колоректальным раком с синхронными метастазами в печеньImpact of neoadjuvant chemotargeted therapy in patients with colorectal cancer and synchronous liver metastases in perioperative periodhttps://orcid.org/0000-0002-2748-0644ДобродеевА. Ю.YunusovaN. V.

Добродеев Алексей Юрьевич — д.м.н., главный научный сотрудник отделения абдоминальной онкологии

пер. Кооперативный, д. 5, г. Томск, 634009, +7 (3822) 41-80-60 

Natalia V. Yunusova

Kooperativny per., 5, Tomsk, 634009

Moskovsky trakt, 2, Tomsk, 634050

dobrodeev@oncology.tomsk.ruhttps://orcid.org/0000-0001-5691-2349КостромицкийД. Н.DobrodeevA. Yu.

Костромицкий Дмитрий Николаевич — к.м.н., старший научный сотрудник отделения абдоминальной ионкологии

пер. Кооперативный, д. 5, г. Томск, 634009

Aleksey Yu. Dobrodeev

Kooperativny per., 5, Tomsk, 634009

https://orcid.org/0000-0002-4701-0375АфанасьевС. Г.KostromitskyD. N.

Афанасьев Сергей Геннадьевич — д.м.н., профессор, заведующий отделением абдоминальной онкологии

пер. Кооперативный, д. 5, г. Томск, 634009

Dmitry N. Kostromitsky

Kooperativny per., 5, Tomsk, 634009

https://orcid.org/0000-0001-6247-3434ТарасоваА. С.AfanasyevS. G.

Тарасова Анна Сергеевна — к.м.н., научный сотрудник отделения абдоминальной онкологии

пер. Кооперативный, д. 5, г. Томск, 634009

Sergey G. Afanasyev

Kooperativny per., 5, Tomsk, 634009

https://orcid.org/0000-0002-9112-6041ЕрмоленкоР. В.TarasovaA. S.

Ермоленко Роман Владимирович — врач-рентгенолог отделения лучевой диагностики

пер. Кооперативный, д. 5, г. Томск, 634009

Anna S. Tarasova

Kooperativny per., 5, Tomsk, 634009

https://orcid.org/0000-0002-0562-3878БабышкинаН. Н.ErmolenkoR. V.

Бабышкина Наталия Николаевна — д.м.н., старший научный сотрудник лаборатории молекулярной онкологии и иммунологии; доцент кафедры биохимии и молекулярной биологии с курсом клинической лабораторной диагностики

пер. Кооперативный, д. 5, г. Томск, 634009

Московский тракт, д. 2, г. Томск, 634050

Roman V. Ermolenko

Kooperativny per., 5, Tomsk, 634009

https://orcid.org/0000-0003-3009-2404ДроноваТ. А.BabyshkinaN. N.

Дронова Татьяна Анатольевна — младший научный сотрудник лаборатории молекулярной онкологии и иммунологии

пер. Кооперативный, д. 5, г. Томск, 634009

Natalia N. Babyshkina

Kooperativny per., 5, Tomsk, 634009

Moskovsky trakt, 2, Tomsk, 634050

https://orcid.org/0000-0003-2060-4840ПономареваА. А.DronovaT. A.

Пономарева Анастасия Алексеевна — к.б.н., научный сотрудник лаборатории молекулярной онкологии и иммунологии

пер. Кооперативный, д. 5, г. Томск, 634009

Tatyana A. Dronova

Kooperativny per., 5, Tomsk, 634009

https://orcid.org/0000-0001-5758-7330ЛарионоваИ. В.PonomarevaA. A.

Ларионова Ирина Валерьевна — к.м.н., старший научный сотрудник лаборатории молекулярной терапии рака

пер. Кооперативный, д. 5, г. Томск, 634009

Anastasia A. Ponomareva

Kooperativny per., 5, Tomsk, 634009

https://orcid.org/0000-0003-4595-4177ЮнусоваН. В.LarionovaI. V.

Юнусова Наталья Валерьевна — д.м.н., главный научный сотрудник лаборатории биохимии опухолей, Научно-исследовательский институт онкологии; профессор кафедры биохимии и молекулярной биологии с курсом клинической лабораторной диагностики

пер. Кооперативный, д. 5, г. Томск, 634009

Московский тракт, д. 2, г. Томск, 634050

Irina V. Larionova

Kooperativny per., 5, Tomsk, 634009

Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences ; Siberian State Medical University of the Ministry of Health of RussiaRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of SciencesRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук ; ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава РоссииРоссияCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of SciencesRussian Federation2024211220242344856Copyright © Добродеев А.Ю., Костромицкий Д.Н., Афанасьев С.Г., Тарасова А.С., Ермоленко Р.В., Бабышкина Н.Н., Дронова Т.А., Пономарева А.А., Ларионова И.В., Юнусова Н.В., 20242024Добродеев А.Ю., Костромицкий Д.Н., Афанасьев С.Г., Тарасова А.С., Ермоленко Р.В., Бабышкина Н.Н., Дронова Т.А., Пономарева А.А., Ларионова И.В., Юнусова Н.В.Yunusova N.V., Dobrodeev A.Y., Kostromitsky D.N., Afanasyev S.G., Tarasova A.S., Ermolenko R.V., Babyshkina N.N., Dronova T.A., Ponomareva A.A., Larionova I.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.ruproctology.com/jour/article/view/1956ЦЕЛЬ

ЦЕЛЬ: оценить влияние неоадъювантной химиотаргетной терапии на течение периоперационного периода у больных колоректальным раком с синхронным метастатическим поражением печени.

ПАЦИЕНТЫ И МЕТОДЫ

ПАЦИЕНТЫ И МЕТОДЫ: с сентября 2020 г. проводится пилотное проспективное исследование, в которое было включено 30 больных колоректальным раком с синхронным метастатическим поражением печени (мКРР). Комбинированное лечение включало 3 курса неоадъювантной химиотерапии (НАХТ) по схеме FOLFOXIRI с добавлением таргетных препаратов — цетуксимаб (24 больных с wtKRAS) и бевацизумаб (6 больных с mtKRAS), после чего проводилось радикальное хирургическое лечение.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ: клинико-рентгенологический эффект НАХТ по метастазам в печени был представлен полным — 4 (13,3%) и частичным регрессом — 26 (86,7%), по первичной опухоли в виде частичного регресса — 30 (100%). Нежелательные явления НАХТ зафиксированы у 12 (40%) больных, из них в 1 (3,3%) случае отмечена токсичность III степени. Через 3–4 недели после завершения НАХТ у 30 (100%) больных проведены радикальные оперативные вмешательства (R0), из них у 28 (93,3%) были симультанные операции по поводу первичной опухоли и метастазов в печени. Послеоперационные осложнения развились у 21 (70%) больного, включая осложнения I ст. по Сlavien-Dindo — 22 (73,3%) и IIIa ст. — 2 (6,7%). При патоморфологическом исследовании в 1 (3,6%) случае был подтвержден полный ответ метастазов в печени (pCR), в первичной опухоли наиболее часто выявлялся лечебный патоморфоз 3 ст. (TRG3 по Mandard A.M.) — 23 (76,7%). У 2 (6,7%) больных с полным клинико-рентгенологическим ответом метастазов в печени, которым резекция печени не проводилась, через 12 месяцев признаков прогрессирования заболевания отмечено не было.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ: при мКРР с синхронным поражением печени проведение НАХТ по схеме FOLFOXIRI в сочетании с таргетными агентами при умеренном профиле токсичности позволяет получить объективный ответ опухоли, не оказывая при этом негативного влияния на течение периоперационного периода. Для анализа 2-летней безрецидивной и общей выживаемости больных исследование продолжается.

AIM

AIM: assess the impact of neoadjuvant chemotargeted therapy in patients with colorectal cancer and synchronous liver metastases in perioperative period.

PATIENTS AND METHODS

PATIENTS AND METHODS: a pilot prospective study included 30 patients with colorectal cancer and synchronous liver metastases (mCRC). The combined treatment included 3 cycles of neoadjuvant FOLFOXIRI chemotherapy with the addition of targeted agents: cetuximab (24 patients with wtKRAS) and bevacizumab (6 patients with mtKRAS) followed by radical surgery.

RESULTS

RESULTS: the clinical and radiological response of colorectal cancer liver metastases to neoadjuvant chemotherapy (NACT) was complete in 4 (13.3%) patients and partial in 26 (86.7%) patients. Partial response to NACT in the primary tumor occurred in all patients. Adverse events of NACT were detected in 12 (40%) patients, 1 (3.3%) of them produced grade III toxicity. All patients underwent radical surgery (R0) 3–4 weeks after NACT, 28 (93.3%) of them underwent simultaneous colorectal and liver resection. Postoperative complications occurred in 21 (70%) patients, including grade I and grade IIIa complications (according to Сlavien-Dindo classification) — 22 (73.3%) and 2 (6.7%), respectively. Histology revealed pathologic complete response (pCR) of liver metastases in 1 (3.6%) case and pathological grade 3 regression of the primary tumor (TRG3, Mandard A.M.) in 23 (76.7%) patients. Two (6.7%) patients with complete clinical and radiological response of liver metastases, who did not undergo liver resection, had no evidence of disease progression 12 months after the treatment.

CONCLUSION

CONCLUSION: in mCRC with synchronous liver metastases, NACT according to the FOLFOXIRI regimen in combination with targeted agents with a moderate toxicity profile provide significant carcinocidal effect without having a negative impact in the perioperative period. The study is ongoing to analyze 2-year disease-free and overall survival of patients.

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