Safety of Ultra-hypofractionated Whole Breast Irradiation After Breast-conserving Surgery (SAFE-FORWARD)

• ClinicalTrials.gov Identifier: NCT04842409
• Recruitment Status: Recruiting
• First Posted: April 13, 2021
• Last Update Posted: February 1, 2022
• Sponsor: Azienda Ospedaliero-Universitaria Careggi
• Information provided by (Responsible Party): Icro Meattini, Azienda Ospedaliero-Universitaria Careggi

Study Description

Brief 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.

Condition or disease	Intervention/treatment
Breast Cancer; Radiotherapy Side Effect	Radiation: Whole breast irradiation

Detailed 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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 60 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Cardiological Monitoring and Safety of Ultra-hypofractionated Whole Breast Irradiation After Breast-conserving Surgery for Patients Affected by Breast Cancer: an Observational Prospective Cohort Study
• Actual Study Start Date: November 30, 2021
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Groups and Cohorts

Intervention Details:

• Radiation: Whole breast irradiation
  Whole breast irradiation using an ultra-hypofractionated schedule (26 Gy in 5 fractions)

Outcome Measures

Primary Outcome Measures :

1. Change from baseline 3-dimensional left ventricular ejection fraction (3D-LVEF) at 12 months [ Time Frame: Baseline to 12-month ]
   Assessment of 3D-LVEF
2. Change from baseline Global Longitudinal Strain (GLS) at 12 months [ Time Frame: Baseline to 12-month ]
   Assessment of GLS

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients affected by 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 was allowed. Main exclusion criteria were mastectomy with or without breast reconstruction, neoadjuvant and/or adjuvant chemotherapy, and needs for a tumor bed radiation boost.

Criteria

Inclusion Criteria:

• Invasive and ductal carcinoma in situ (DCIS) breast cancer
• Indication to ultra-hypofractionated whole breast irradiation
• Written informed consent
• Aged more than 18 years old

Exclusion Criteria:

• Neoadjuvant and adjuvant chemotherapy
• Tumor bed radiation boost prescription

Contacts and Locations

Contacts

Contact: Lucia Paolini; +39-055794 ext 7019; rt.datamanager@sbsc.unifi.it

Contact: Virginia Votino; +39-055794 ext 7019

Locations

Italy

Azienda Ospedaliero-Universitaria Careggi, Florence University; Recruiting

Florence, Italy, 50134

Contact: Lucia Paolini +39-055794 ext 7019 rt.datamanager@sbsc.unifi.it

Principal Investigator: Lorenzo Livi, MD, Prof

Principal Investigator: Icro Meattini, MD, Prof

Sponsors and Collaborators

Azienda Ospedaliero-Universitaria Careggi

Investigators

• Principal Investigator: Icro Meattini, MD, Prof; AOU Careggi
• Principal Investigator: Lorenzo Livi, MD, Prof; AOU Careggi

More Information

• Responsible Party: Icro Meattini, M.D., Associate Professor, Azienda Ospedaliero-Universitaria Careggi
• ClinicalTrials.gov Identifier: NCT04842409
• Other Study ID Numbers: SAFE-FORWARD
• First Posted: April 13, 2021
• Last Update Posted: February 1, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Icro Meattini, Azienda Ospedaliero-Universitaria Careggi:

Breast Cancer; Radiotherapy; Safety

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases