Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04842409 |
| Other study ID # |
SAFE-FORWARD |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 30, 2021 |
| Est. completion date |
December 8, 2022 |
Study information
| Verified date |
July 2023 |
| Source |
Azienda Ospedaliero-Universitaria Careggi |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
SAFE-FORWARD is an observational prospective cohort study. Patient population included both
invasive and ductal carcinoma in situ (DCIS) breast cancer receiving ultra-hypofractionated
whole breast irradiation (26 Gy in 5 fractions) after breast conserving surgery, as per
physician choice. Adjuvant endocrine therapy as per local policy is allowed. Main exclusion
criteria are mastectomy with or without breast reconstruction, neoadjuvant and/or adjuvant
chemotherapy, and needs for a tumor bed radiation boost.
All enrolled patients will be prospectively monitored for 12 months, receiving a complex
cardiological assessment before radiation therapy (RT) start (baseline), and at 2-, 6-, and
12-month after RT end of treatment. Both acute- , defined as adverse events recorded within
the first 90 days since RT start, and early-late toxicity, will be scored according to EORTC
(European Organisation for Research and Treatment of Cancer)/Radiation Therapy Oncology Group
(RTOG) and CTCAE (v.5) scales.
Patients will undergo six-monthly follow-up clinical visits for the first 5 years and annual
follow-up visits thereafter up to 10 year, as per clinical local practice. Breast cosmesis
will be evaluated through the use of BCCT.core tool and assessment of the health-related
quality of life will be performed through the EORTC quality of life questionnaire (QLQ) C30
and BR45 modules questionnaires at baseline, at the end of RT treatment, at 2- and 6-month.
Description:
This prospective cohort study aims to assess heart toxicity and safety using a 1-week
radiation schedule regimen of 26 Gy in five daily fractions.
The primary endpoint was defined as detection of any subclinical impairment in myocardial
function and deformation (decrease ≥10%) measured with standard and 3-dimensional (3D)
echocardiography and left ventricular (LV) global longitudinal strain (GLS).
Cardiac assessment. Medical history, electrocardiogram (EKG), clinical examination with
specific attention to signs of heart failure, New York Heart Association (NYHA) class and
Canadian angina grading scale score were recorded during each visit. Transthoracic
echocardiography was performed with a commercially available system (EPIQ, X5-1 transducer,
Philips Healthcare, Andover, Massachusetts). All measurements were performed and reported
accordingly to the American Society of Echocardiography (ASE) and the European Association of
Cardiovascular Imaging (EACVI) recommendations. Each measure was averaged over three cardiac
cycles. Two-dimensional LVEF (2D-LVEF) was measured by Simpson rule, throughout apical 4- and
2-chamber views. LV mass was calculated from LV oriented M-mode tracings using the Devereux
formula, ASE convention, and was indexed to body surface area (BSA). Diastolic function was
evaluated by left atrial volume index, systolic pulmonary pressure, mitral inflow E/A
pattern, E/A ratio, E velocity deceleration time, annular tissue Doppler e', and E/e' ratio.
After optimizing image quality, maximizing frame rate, and minimizing foreshortening, which
are all critical to reduce measurement variability, GLS measurements were made in the three
standard apical views and averaged. LV 4-, 3-, and 2-chamber views were acquired during
breath hold. From apical long-axis view to visualize aortic valve closure, using opening and
closing clicks of the aortic valve the timing of aortic valve opening and closing on
continuous wave (CW) Doppler imaging respect to EKG R wave was measured. Full-volume
six-cycles gated acquisition breath hold images of left ventricle were acquired for Q-lab
analysis to obtain end-diastolic volume, end systolic volume, indexed to BSA (EDVI and ESVI)
and 3D-LVEF. Q-lab version in this study was 10.5. All echocardiography data was stored
including the original Digital Imaging and Communications in Medicine (DICOM) images. All
scans were read jointly by two experienced board certified echocardiographers who were
blinded to all clinical characteristics. Systemic arterial pressure was measured
simultaneously with echo measurements, by means of an arm-cuff sphygmomanometer.
