Breast cancer Cancer Malignant neoplasm of breast
Conditions
Sponsors
Institute of Cancer Research
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 20/11/2024: 1. Age =18 years, female or male 2. Histologically proven invasive breast carcinoma treated with: 2.1. Breast conservation surgery with axillary surgery (biopsy or dissection) OR 2.2. Mastectomy with axillary surgery (biopsy or dissection)OR 2.3. In the case of an occult breast primary, axillary surgery (biopsy or dissection) only is permissible 3. Recommended to undergo RT to the breast/chest wall +/- axilla +/- IMN 4. Estimated lifetime risk of radiation-induced late cardiac toxicity around 2% or higher* * Calculated from tables of mean heart dose, age and cardiovascular risk factors (pre-existing cardiac disease, other circulatory diseases, diabetes, chronic obstructive pulmonary disease, smoking, body mass index >30 kg/m2)(10). N.B. Mean heart dose is estimated using wide-tangent field placement in deep inspiration breath hold (DIBH)) as this is the commonest technique for IMN RT in the UK and can be carried out quickly to ensure an efficient patient pathway. 5. Ability to provide written informed consent to participate in PARABLE _____ Previous inclusion criteria: 1. Age =18 years, male or female 2. Histologically proven invasive breast carcinoma treated with wide local excision or mastectomy, and any type of axillary surgery 3. Recommended to undergo RT to the breast/chest wall + internal mammary node (IMN) RT; or if pectus excavatum, recommended to undergo RT to the breast/chest wall +/- IMN RT 4. Estimated lifetime risk of radiation-induced late cardiac toxicity =2%* *calculated from tables of mean heart dose, age and cardiovascular risk factors (pre-existing cardiovascular disease, diabetes, chronic obstructive pulmonary disease, active smoker, body mass index > 30kg/m2, chronic pain medication, use of anthracycline chemotherapy). N.B. mean heart dose is calculated from radiotherapy plan using wide tangents in deep inspiration breath hold (DIBH) as this is the most common technique for IMN RT in the UK and can be planned relatively quickly to ensure an efficient patient pathway.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 20/11/2024: 1. Definitive clinical or radiological evidence of metastatic disease. 2. Prior RT to the ipsilateral chest wall, breast and thorax. 3. Connective tissue disorders requiring active medical therapy. (Patients with a history of connective tissue disorders in whom a multidisciplinary team has agreed that the benefits of radiotherapy outweigh the risks may be included. Methotrexate and/or other immune therapies must be stopped during RT or PBT). 4. Concomitant TDM1 or capecitabine is not permitted. 5. Breast tissue expander implants with integrated metallic injection ports are contraindicated and not permitted within PARABLE. _____ Previous exclusion criteria: 1. Definitive clinical or radiological evidence of metastatic disease 2. Prior RT to the ipsilateral chest wall, breast and thorax 3. Connective tissue disorders requiring active medical therapy (Patients with a history of connective tissue disorders in whom a multidisciplinary team has agreed that the benefits of radiotherapy outweigh the risks may be included. Methotrexate and/or other immune therapies must be stopped during RT or PBT) 4. Concomitant TDM1 or capecitabine is not permitted
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Mean heart dose (in Gy) using wide-tangent field placement in deep inspiration breath hold (DIBH) at baseline 2. Patient-reported normal tissue toxicity in the breast measured using the EORTC QLQ-BR23 breast symptoms score at 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Mean lung and contralateral breast doses measured from the treatment plan (PBT or volumetric modulated arc therapy [VMAT]) at baseline 2. Early and late toxicity: skin and oesophageal toxicities assessed by clinician-recorded CTCAE v5.0 weekly on treatment, 2 weeks post-RT then weekly until acute reaction graded as 0 (none) or 1 (mild). Cough and breathlessness will be assessed by clinician-recorded RTOG at 3, 6 and 12 months. 3. Health-related quality of life: late toxicity and health-related quality of life will be assessed by patients using PRO including EORTC QLQ-C30, QLQ-BR23, Body Image Scale and items capturing breast changes resulting from cancer treatments (established in previous trials). Questionnaires will be administered at baseline, 6, 12, 24, and 60 months. 4. Health economic consequences: analysis will utilise the healthcare resource use questionnaire developed for the trial and the EuroQol five-dimensional questionnaire (EQ-5D-5L). These will be collected at baseline, 3, 6, 12, 24 and 60 months. 5. Changes to the planned RT pathway (including delays and re-planning) will be defined as the proportion of patients with a delay to RT or PBT exceeding 4 weeks’ overall treatment time and the proportion requiring re-planning. 6. Second primary cancers (including contralateral breast, lung and oesophagus), defined as proportion of patients with confirmed diagnosis up to 5 years’ follow-up 7. Recurrence and survival, defined as cumulative incidence rates up to 5 years’ follow-up 8. Incidence of major cardiac events will be reported, defined as proportion of patients at 5 years’ follow-up with atherosclerotic coronary heart disease or other heart disease death, myocardial infarction, coronary revascularisation, or hospitalisation for major cardiovascular event (heart failure, valvular disease, arrhythmia, or unstable angina) Mechanistic endpoints: 1. Change in median lung Hounsfield Units per Gy on CT from baseline to 2 years for PBT versus photon RT 2. I | — |
Countries
England, United Kingdom
Outcome results
None listed