Evaluation of Myocardial Injury After Anthracycline Chemotherapy in Osteosarcoma Patients Using CMR

July 2, 2020 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University
using a contrast-enhanced (CE) cardiac magnetic resonance imaging(CMR) which included the measurement of T1 mapping, T2 mapping, T2* mapping and late gadolinium enhancement(LGE) sequences, as well as LVEF and extracellular volume(ECV) to evaluate the respective changes before and after anthracycline chemotherapy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Osteosarcoma is the most common primary malignant bone tumor in children and young adults and accounts for 5% of all pediatric malignancies. The long-standing chemotherapy regimen of doxorubicin and cisplatin with or without methotrexate remains a standard treatment of osteosarcoma.But anthracyclines such as doxorubicin have a notorious cardiotoxic side effect, which causes chemotherapy-related cardiac dysfunction(CTRCD). The American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) defines it as a decrease in left ventricular ejection fraction (LVEF) of more than 10% to below the lower limit of normal, which is considered an LVEF of 53%, despite symptoms.

Cardiac magnetic resonance imaging is the gold standard for detection of ventricular volume and function. The parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease and is capable of in vivo tissue characterization.

In this study, the investigators used a contrast-enhanced (CE) cardiac magnetic resonance imaging(CMR), which included the measurement of T1 mapping, T2 mapping, T2* mapping and late gadolinium enhancement(LGE) sequences, as well as LVEF and extracellular volume(ECV) to evaluate the respective changes before and after anthracycline chemotherapy.

Study Population:

This prospective study was conducted at the Second Affiliated Hospital, School of Medicine, Zhejiang University. All chemotherapy naive patients whose biopsy results show high grade osteosarcoma were considered. Patients with underlying heart disease, severe hypertension, diabetes mellitus and previous history of gadolinium contrast agent allergy were excluded.Patients were treated with a standard chemotherapy protocol containing anthracyclines.

Study Protocol:

All patients underwent a contrast-enhanced (CE) cardiac magnetic resonance imaging(CMR), including measurement of LVEF, T1mapping, T2mapping, T2*mapping, ECV, LGE before starting chemotherapy (baseline), after neoadjuvant chemotherapy treatment, at the end of treatment (within 1 month), or whenever required by the clinical situation. These times points corresponded to scheduled oncological controls.

The CMR protocol included a standard segmented cine steady-state free-precession sequence, a T2 gradient spin-echo mapping sequence, a T2* gradient spin-echo mapping sequence, native and post-contrast T1 mapping sequences, and late gadolinium enhancement (LGE) sequence. The imaging parameters for the standard segmented cine steady-state free-precession sequence were as follows: field of view (FOV) 340 X340 mm², slice thickness 8 mm , repetition time (TR) 34.84ms, echo time (TE) 1.14ms, flip angle 67°, voxel size 1.8 X1.8 mm, and number of excitation. The imaging parameters for the T2-gradient-spin-echo mapping sequence were FOV 340X 340 mm², acquisition voxel size 1.8 X1.8 mm², slice thickness 8 mm, 8 echo times ranging from 6.7 to 53.6ms, and flip angle 70°. The T2* mapping sequence parameter were FOV 340X340 mm², acquisition voxel size 1.3X1.3mm², slice thickness 8mm, 8 echo times ranging from 2.22 to 17.48 (2.22,4.4,6.58,8.76,10.94,13.12,15.3,17.48), and flip angle 20°. The T1 mapping sequence (Modified Look-Locker Inversion recovery [MOLLI]) was acquired before and 10 min after contrast administration. All MOLLI sequences were based on a 5(3)3 scheme using a single shot steady-state free precession readout sequence (TR/TI/TE/flip angle 291.84ms/183ms/1.22ms/35°) with an in-plane acquisition resolution of 1.2 X1.2 mm² and an 8mm slice thickness. LGE imaging was performed 8 min after intravenous administration of 0.2mmol/kg gadopentetate dimeglumine contrast agent using a 3-dimensional inversion-recovery spoiled turbo field echo sequence (TR/TE/flip angle 813.6ms/1.09ms/40). Inversion time was adjusted before acquisition using a look-locker scout sequence with different inversion times to ensure proper nulling of the healthy myocardium signal.

The primary end point of the study was completion of chemotherapy with anthracycline drugs.

The secondary end point was cardiotoxicity. The time of occurrence of cardiotoxicity was recorded. Cardiotoxicity was defined as an LVEF reduction >10% from baseline, or LVEF <53%.

The following cardiac events were also considered as secondary end points: cardiac death, acute coronary syndromes, acute pulmonary edema, overt HF, and life-threatening arrhythmias.

Study Type

Observational

Enrollment (Anticipated)

55

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310000
        • Recruiting
        • 2nd Affiliated Hospital, School of Medicine, Zhejiang University
        • Contact:
        • Contact:
          • ZHAOMING YE, Doctor
          • Phone Number: +8613606501549

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 50 years (ADULT, CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All chemotherapy naive patients whose biopsy results show high grade osteosarcoma undergoing an anthracycline agent as part of their chemotherapy regimen without the underlying heart disease.

Description

Inclusion Criteria:

  • All chemotherapy naive patients whose biopsy results show high grade osteosarcoma undergoing an anthracycline agent as part of their chemotherapy regimen
  • Informed consent has been signed

Exclusion Criteria:

  • Strict contraindications to contrast-enhanced cardiac magnetic resonance imaging
  • Underlying heart disease:myocardial infarction, heart failure, valvular disease or cardiomyopathy
  • Acute or chronic kidney failure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Completion of chemotherapy with anthracycline drugs
Time Frame: Through study completion, an average of 6 months.
Chemotherapy regimen completed.
Through study completion, an average of 6 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Cancer therapy-related cardiac dysfunction
Time Frame: From start of anthracycline therapy up to 6 months of anthracycline completion
Cancer therapy-related cardiac dysfunction was defined as an LVEF reduction >10% from baseline, or LVEF <53%
From start of anthracycline therapy up to 6 months of anthracycline completion

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes of T1 mapping values
Time Frame: At timepoints 0 months, 2 months and 6 months (corresponding to the chemotherapy regimen controls)
Change in T1 mapping values before and after anthracyclin chemotherapy
At timepoints 0 months, 2 months and 6 months (corresponding to the chemotherapy regimen controls)
Changes of T2 mapping values
Time Frame: At timepoints 0 months, 2 months and 6 months (corresponding to the chemotherapy regimen controls)
Change in T2 mapping values before and after anthracyclin chemotherapy
At timepoints 0 months, 2 months and 6 months (corresponding to the chemotherapy regimen controls)
Changes of T2* mapping values
Time Frame: At timepoints 0 months, 2 months and 6 months (corresponding to the chemotherapy regimen controls)
Change in T2* mapping values before and after anthracyclin chemotherapy
At timepoints 0 months, 2 months and 6 months (corresponding to the chemotherapy regimen controls)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 1, 2019

Primary Completion (ANTICIPATED)

December 1, 2021

Study Completion (ANTICIPATED)

December 1, 2021

Study Registration Dates

First Submitted

June 28, 2020

First Submitted That Met QC Criteria

July 2, 2020

First Posted (ACTUAL)

July 8, 2020

Study Record Updates

Last Update Posted (ACTUAL)

July 8, 2020

Last Update Submitted That Met QC Criteria

July 2, 2020

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-523

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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