Safety of Ultra-hypofractionated Whole Breast Irradiation After Breast-conserving Surgery
Condition: Breast Cancer; Radiotherapy Side Effect
MeSH terms: Breast Neoplasms
Study type: Observational

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.
    

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.
    

Intervention name(s): Whole breast irradiation
Intervention type(s): Radiation
Intervention description(s): Whole breast irradiation using an ultra-hypofractionated schedule (26 Gy in 5 fractions)
Observational model: Cohort
Time perspective: Prospective
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.
      
Keywords: Breast Cancer; Radiotherapy; Safety