ANTthracycline-induced Inflammation and OXidative Stress: 10-year Follow-up (ANTIOX-10)
2026년 6월 25일 업데이트: RODRIGO CASTILLO, University of Chile
Long-Term Effects of Anthracycline Chemotherapy on Inflammatory Cytokines, Redox Status, and Ventricular Function in Breast Cancer Survivors
The goal of this observational study is to learn about the long-term effects of anthracycline chemotherapy on inflammation, oxidative stress, and heart function in adult women with breast cancer.
The main questions it aims to answer are:
- Do inflammatory cytokine levels change after anthracycline chemotherapy and remain altered many years after treatment?
- Are long-term markers of oxidative stress and antioxidant capacity associated with changes in heart structure or function after anthracycline exposure?
This study does not include a comparison group. All participants were previously treated with anthracycline-based chemotherapy as part of their standard cancer care.
Participants will:
- Provide blood samples for the measurement of inflammatory cytokines and oxidative stress-related biomarkers
- Undergo a clinical cardiovascular evaluation
- Receive a transthoracic echocardiogram to assess heart function, including measures of systolic and diastolic function and myocardial deformation
- Participate in a long-term follow-up assessment approximately 10 years after their initial cancer treatment
연구 개요
상태
완전한
상세 설명
- Study design and population. This is a prospective, observational translational study including adult patients with breast cancer undergoing anthracycline-based chemotherapy at a single tertiary-care center. Patients are evaluated longitudinally to assess subclinical cardiovascular alterations associated with anthracycline exposure. All participants are managed according to standard oncologic and cardiologic care pathways.
Echocardiographic assessment. Transthoracic echocardiography is performed by experienced cardiologists following current American Society of Echocardiography (ASE) recommendations. Studies are acquired at predefined time points, including baseline (prior to anthracycline exposure) and long-term follow-up. Left ventricular systolic function is assessed using biplane left ventricular ejection fraction (LVEF) calculated by the modified Simpson method. Diastolic function parameters include transmitral inflow velocities, tissue Doppler-derived mitral annular velocities, E/e' ratio, and left atrial volume index (LAVI).
Left ventricular global longitudinal strain (GLS) is assessed at long-term follow-up using semi-automated speckle-tracking techniques. Right ventricular-pulmonary artery coupling is explored using the Tricuspid Annular Plane Systolic Excursion (TAPSE)/Pulmonary Artery Systolic Pressure (PASP) ratio. All measurements are performed offline, and segments with inadequate image quality are excluded from analysis.
- Blood sample collection and processing. Peripheral venous blood samples are collected under standardized conditions at baseline (pre-anthracycline), early after chemotherapy exposure, and at long-term follow-up. Samples are obtained using chilled anticoagulant-containing tubes, centrifuged according to protocol, aliquoted, and stored at -80 °C until biochemical analyses are performed. All samples are processed under identical experimental conditions to minimize analytical variability.
- Oxidative stress and antioxidant parameters. Plasma antioxidant capacity is assessed using the Ferric Reducing Ability of Plasma (FRAP) assay at predefined time points. Activities of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, are determined in erythrocyte lysates using commercially available assay kits according to manufacturers' instructions. Lipid peroxidation and intracellular redox status are evaluated using established biochemical methods. Results are normalized to protein concentration when applicable.
- Inflammatory and proinflammatory cytokines. Circulating cytokines and growth factors are quantified in plasma samples using multiplex bead-based immunoassays. Measurements are performed at baseline and early after anthracycline exposure following standardized manufacturer protocols. Analyte concentrations are calculated based on standard curves generated for each biomarker.
- Data integration and quality control. Clinical, echocardiographic, and biochemical data are collected using predefined case report forms. Data quality is ensured through consistency checks and verification procedures. All laboratory analyses and imaging measurements are performed blinded to clinical outcomes.
- Exploratory analyses Echocardiographic parameters are integrated with biochemical markers of oxidative stress and inflammation for exploratory mechanistic analyses aimed at identifying associations between myocardial deformation indices and biological signatures of anthracycline-related cardiotoxicity.
연구 유형
관찰
등록 (실제)
17
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
아니
샘플링 방법
비확률 샘플
연구 인구
Adult women with breast cancer treated at Hospital del Salvador, Santiago, Chile.
Patients were consecutively recruited between 2010 and 2013 from a prospective cohort of individuals initiating anthracycline-based chemotherapy.
A protocol amendment approved by the local ethics committee allowed long-term follow-up of the original cohort at 10 years for cardiovascular, inflammatory, and oxidative stress assessment.
설명
Inclusion Criteria:
- Female patients with histologically confirmed breast cancer
- Age between 18 and 75 years
- Indication for anthracycline-based chemotherapy (>200 mg/m²)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Written informed consent signed prior to study participation
- Availability for baseline cardiovascular and biomarker assessment and long-term follow-up
Exclusion Criteria:
- History of heart failure or left ventricular dysfunction (LVEF <53%)
- Known coronary artery disease or clinically significant ischemic heart disease
- History of clinically significant arrhythmias or requirement for antiarrhythmic therapy
- Dilated or hypertrophic cardiomyopathy
- Moderate to severe valvular heart disease (mitral or aortic stenosis or regurgitation)
- Congenital heart disease (including atrial or ventricular septal defects, patent ductus arteriosus, Ebstein anomaly, tetralogy of Fallot, coarctation of the aorta)
- Chronic kidney disease (creatinine >2 mg/dL)
- Hepatic failure (bilirubin >3 mg/dL, albumin <3.5 g/dL, or prothrombin activity <60% in absence of anticoagulation)
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
코호트 및 개입
그룹/코호트 |
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Long-term anthracycline breast cancer cohort
Women with histologically confirmed breast cancer who received anthracycline-based chemotherapy (>200 mg/m²) between 2010 and 2013 at Hospital Salvador, Santiago, Chile.
This cohort was followed longitudinally from baseline pre-chemotherapy assessment and reassessed after 10 years.
The study is observational and no therapeutic intervention was assigned as part of the protocol.
Serial evaluations included echocardiographic parameters, inflammatory cytokines, oxidative stress biomarkers, and cardiac remodeling indicators.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in left ventricular ejection fraction from baseline to 10-year follow-up
기간: From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy
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Assessment of left ventricular systolic function by biplane Simpson method using transthoracic echocardiography.
Left ventricular ejection fraction (LVEF) was measured at baseline (7 days before the first cycle of anthracycline chemotherapy) and at the 10-year follow-up.
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From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy
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Change in left ventricular filling pressure (E/e' ratio) from baseline to 10-year follow-up
기간: From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy
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Assessment of left ventricular diastolic function using the average E/e' ratio obtained by transthoracic echocardiography.
Measurements were performed at baseline (7 days before the first cycle of anthracycline chemotherapy) and at the 10-year follow-up.
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From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Left ventricular global longitudinal strain at 10-year follow-up
기간: 10 years after completion of chemotherapy
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Assessment of left ventricular global longitudinal strain (LVGLS) using speckle-tracking echocardiography at the 10-year follow-up.
Baseline LVGLS measurements were not available; therefore, only long-term values were assessed.
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10 years after completion of chemotherapy
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Left atrial volume index at 10-year follow-up
기간: 10 years after completion of chemotherapy
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Assessment of left atrial volume index (LAVI) by transthoracic echocardiography as an indicator of long-term left atrial remodeling after anthracycline exposure.
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10 years after completion of chemotherapy
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Right ventricular-pulmonary arterial coupling (TAPSE/PASP ratio) at 10-year follow-up
기간: 10 years after completion of chemotherapy
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Assessment of right ventricular-pulmonary arterial coupling using the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio obtained by transthoracic echocardiography.
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10 years after completion of chemotherapy
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Plasma antioxidant capacity measured by ferric reducing ability of plasma assay
기간: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
|
Assessment of systemic antioxidant capacity using the ferric reducing ability of plasma (FRAP) assay.
Plasma samples were obtained at baseline (7 days before the first anthracycline chemotherapy cycle), on day 3 after the first chemotherapy cycle , and at the 10-year follow-up.
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Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
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Erythrocyte antioxidant enzyme activity
기간: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
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Assessment of erythrocyte antioxidant enzyme activity by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities using standardized commercial assays.
These enzymes were evaluated as complementary indicators of endogenous antioxidant defense mechanisms.
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Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
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Markers of oxidative stress and intracellular redox status
기간: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
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Assessment of oxidative stress by measuring plasma 8-isoprostane concentrations and intracellular redox status using the reduced-to-oxidized glutathione (GSH/GSSG) ratio.
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Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
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Inflammatory cytokine profile measured by multiplex immunoassay
기간: Baseline (7 days before the first anthracycline chemotherapy cycle), and day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days).
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Assessment of the systemic inflammatory cytokine profile using a validated MILLIPLEX® multiplex bead-based immunoassay based on Luminex® xMAP® technology.
Plasma cytokines were measured simultaneously as a single multiplex biomarker panel comprising inflammatory cytokines and chemokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ), and additional analytes included in the assay.
This outcome represents the overall inflammatory biomarker profile generated by a single multiplex assay rather than multiple independent outcome measures.
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Baseline (7 days before the first anthracycline chemotherapy cycle), and day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days).
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여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2011년 2월 1일
기본 완료 (실제)
2026년 4월 1일
연구 완료 (실제)
2026년 4월 1일
연구 등록 날짜
최초 제출
2026년 6월 15일
QC 기준을 충족하는 최초 제출
2026년 6월 25일
처음 게시됨 (실제)
2026년 7월 2일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2026년 7월 2일
QC 기준을 충족하는 마지막 업데이트 제출
2026년 6월 25일
마지막으로 확인됨
2026년 6월 1일
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- CEC-SSMO-97-2021
약물 및 장치 정보, 연구 문서
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