Evaluation of the effectiveness of transarterial chemoembolization irinotecan-loaded with drug-saturable microspheres for the treatment of patients with neuroendocrine tumors with liver metastases

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Abstract

Background: Since 2021, transarterial chemoembolization of the hepatic arteries (TACE) has been included in the recommendations of professional communities for the treatment of metastases of neuroendocrine liver tumors (NEO). However, the heterogeneity of both this group of patients and types of chemoembolization with a limited range of cytostatics used in the treatment makes it difficult to analyze the data and introduce the method into the combination therapy regimens.

Aim: to study the effectiveness of transarterial chemoembolization with irinotecan-loaded drug-saturable microspheres for the treatment of patients with neuroendocrine tumors with liver metastases.

Methods: A retrospective, observational, uncontrolled study of 34 patients with liver metastases from neuroendocrine cancer who underwent 52 TACE with irinotecan-loaded drug-saturable microspheres. Group 1 consisted of 15 patients who already had liver metastases at the time of the primary focus detection, group 2 included 19 patients with liver metastases having appeared some time after the detection of the primary focus. To plan and evaluate the effectiveness of chemoembolization, computed tomography and magnetic resonance imaging were used every 10–15 weeks during the systemic treatment. All the patients received systemic NEO therapy before and after the embolization.

Results: An increase in the progression-free time from 101 [57; 120] and 145 [89; 263] days after chemotherapy up to 300 [134; 344] and 304 [240; 342] days after TACE in groups 1 and 2, respectively, with no difference between the groups (p=0.31 and p=0.57, respectively). We did not find a linear relationship between the doubling time of the tumor and the change in the volume of the tumor lesion (R2=0.1085 and R2=0.0265 in groups 1 and 2). When comparing the intragroup scores, there was a statistically significant difference (p=0.009, p=0.046) in the tumor volume reduction and progression-free time between the patients who underwent TACE immediately and those who underwent TACE after chemotherapy. The diagnostic and angiographic images of liver metastases varied within the same organ and depended on the size of metastases. There were no adverse events after TACE.

Conclusions: TACE with irinotecan-loaded drug-saturable microspheres is an effective method for the treatment of liver metastases of neuroendocrine cancer, allowing one to increase the time without progression.

About the authors

Elena A. Zvezdkina

The Skobelkin Research and Practical Centre for Laser Medicine

Author for correspondence.
Email: zvezdkina@yandex.ru
ORCID iD: 0000-0002-0277-9455
SPIN-code: 8428-4518

MD, PhD, research associate

Russian Federation, 40, Studentcheskaya street, Moscow, 121165

Anna G. Kedrova

Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological Agency; Academy of Postgraduate Education Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological Agency; E.N. Meshalkin National Medical Research Center

Email: kedrova.anna@gmail.com
ORCID iD: 0000-0003-1031-9376
SPIN-code: 3184-9760

MD, PhD, professor

Russian Federation, Moscow; Moscow; Novosibirsk

Dmitry P. Lebedev

Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological Agency

Email: lebedevdp@gmail.com
ORCID iD: 0000-0003-1551-3127
SPIN-code: 4770-5722

doctor for X-ray endovascular diagnostics and treatment

Russian Federation, Moscow

Sergey E. Krasilnicov

E.N. Meshalkin National Medical Research Center

Email: krasilnikov_s@meshalkin.ru
ORCID iD: 0000-0001-8366-6083

Director of the Institute of Oncology and Neurosurgery

Russian Federation, Novosibirsk

Oleg V. Krestyaninov

E.N. Meshalkin National Medical Research Center

Email: o_krestyaninov@meshalkin.ru
ORCID iD: 0000-0001-5214-8996

Head of the Research Department of Endovascular Surgery of the Institute of Oncology and Neurosurgery

Russian Federation, Novosibirsk

Tatevic A. Greyan

Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological Agency; Academy of Postgraduate Education Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological Agency

Email: tatev111@gmail.com
ORCID iD: 0000-0003-4118-3002
SPIN-code: 6952-4709

Oncologist of the oncology department, Senior Lecturer of the Department of Obstetrics and Gynecology

Russian Federation, Moscow; Moscow

Dmitry N. Panchenkov

Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Email: dnpanchenkov@mail.ru
ORCID iD: 0000-0001-8539-4392
SPIN-code: 4316-4651

Doctor of Medical Sciences, Professor, Head of the Laboratory of Minimally Invasive Surgery

Russian Federation, Moscow

Yulia A. Stepanova

A.V. Vishnevsky National Medical Research Center of Surgery

Email: stepanovaua@mail.ru
ORCID iD: 0000-0002-2348-4963
SPIN-code: 1288-6141

Doctor of Medical Sciences, Senior Researcher, Department of Radiation Methods of Diagnosis and Treatment

Russian Federation, Moscow

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Study design. Note: ТАХЭ — transarterial chemoembolization of hepatic arteries; ХТ — chemotherapy.

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3. Fig. 2. Angiography (а): intense contrast of a metastasis with a diameter of 3 cm (white arrow); magnetic resonance imaging (б): the same metastasis with a diameter of 3 cm with slit necrosis in the structure (long arrow), an infiltrative metastasis with a diameter of 0.5 cm with a locally expanded bile duct in the center (3D arrow), the pancreatic tail tumor (triangular arrow); angiography of the pancreatic tumor (в): branched network of afferents (triangular arrows).

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4. Fig. 3. The same patient. Angiographic picture of another metastasis with a diameter of 3 cm (а): several thin recalibrated vessels (arrow) exiting in an atypical place; magnetic resonance imaging of the same metastasis (б): slit necrosis in the structure (arrow).

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5. Рис. 1. Дизайн исследования. Примечание. ТАХЭ — трансартериальная химиоэмболизация печеночных артерий; ХТ — химиотерапия.

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6. Рис. 2. Ангиография (а): интенсивное контрастирование метастаза диаметром 3 см (стрелка); магнитно-резонансная томография (б): тот же метастаз диаметром 3 см с щелевидным некрозом в структуре (длинная стрелка), инфильтративный метастаз диаметром 0,5 см с локально расширенным желчным протоком в центре (объемная стрелка), опухоль хвоста поджелудочной железы (треугольная стрелка); ангиография опухоли поджелудочной железы (в): разветвленная сеть афферентов (треугольные стрелки).

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7. Рис. 3. Тот же пациент. Ангиографическая картина другого метастаза диаметром 3 см (а): несколько тонких перекалиброванных сосудов (стрелка), отходящих в нетипичном месте; магнитно-резонансная томография того же метастаза (б): щелевидный некроз в структуре (стрелка).

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