Breast Fractionation Study - Standard Versus Investigational Fractionation Trial - Nodal Radiation

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the difference in fatigue, quality of life and radiation morbidity between hypofractionated and conventional radiation to the breast, chest wall and regional lymph nodes post mastectomy or lumpectomy

Detailed Description
-----------------
Breast cancer is the most commonly diagnosed cancer in Australia. Radiotherapy to the breast, chest wall and regional lymph nodes for breast cancer after surgery can reduce the risk of local recurrence by 50% and reduce breast cancer mortality. Traditionally, radiotherapy is delivered in a large number of small doses i.e. 25 treatment sessions over 5 1/2 weeks. Another approach is to give a lower number of larger doses i.e. 15 sessions over 3 1/2 weeks (hypofractionated radiotherapy). Several studies in Europe and Asia have investigated hypofractionated radiotherapy to the chest wall, breast and regional lymph nodes following surgery for breast cancer, and found that it is equally effective to standard treatment, with similar side effects. These two approaches have not been directly compared in Australia. This trial is to compare these two approaches, to determine whether hypofractionated radiotherapy is better tolerated by patients.

Official Title
-----------------
Standard Versus Investigatioinal Fractionation Trial - Nodal Radiation

Conditions
-----------------
Breast Cancer, Post Mastectomy

Intervention / Treatment
-----------------
* Radiation: Hypofractionated radiotherapy VS Standard/Conventional fractionation radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years and older ECOG performance status 0-2 Ability to understand and willingness to sign a written informed consent document Stage pT1-3, pN0-3, M0 histologically proven breast cancer no matter the status of ER/PR/HER2 receptor testing Managed with either mastectomy or breast conserving surgery Suitable for radiation therapy to the breast/chest wall and regional lymph nodes Neoadjuvant and adjuvant systemic therapy with chemotherapy, endocrine therapy and anti-HER2 therapy is accepted Neoadjuvant radiotherapy (reverse sequencing) accepted Breast implants and expanders are accepted Patients with connective tissue disease are allowed if the treating radiation oncologist finds radiation therapy indicated Life expectancy minimum 10 years Patients with non-breast malignancies are accepted if the patient has been disease free for five years and/or has a low risk of recurrence as estimated by the treating radiation oncologist (to be determined at initial patient appointment) Exclusion Criteria: Prior radiotherapy to the ipsilateral breast or chest wall Pregnancy or lactation Radiosensitivity syndrome Permanent pacemaker/defibrillator within radiotherapy field Oncoplastic surgery where boost volume unacceptable (clinician discretion) Conditions indicating that the patient cannot go through radiation therapy or follow up, or a condition where the treating oncologist thinks the patient should not participate in the trial (for example, language barriers)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hypofractionation Arm<br>40Gy / 15 fractions, 2.67Gy per fraction, over 3.5 week (9 fractions per fortnight) | Radiation: Hypofractionated radiotherapy VS Standard/Conventional fractionation radiotherapy<br>* The purpose of this study is to investigate toxicity following standard conventional fractionation versus moderately hypofractionated radiotherapy to the breast, chest wall and regional lymph nodes<br>|
| Other: Standard /Conventional fractionation Arm<br>50Gy / 25 fractions, 2Gy per fraction, over 5.5 week (9 fractions per fortnight) | Radiation: Hypofractionated radiotherapy VS Standard/Conventional fractionation radiotherapy<br>* The purpose of this study is to investigate toxicity following standard conventional fractionation versus moderately hypofractionated radiotherapy to the breast, chest wall and regional lymph nodes<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | Changes in patient reported fatigue at six weeks post commencing radiotherapy compared to baseline fatigue score. Fatigue score is rated as fatigue that interfered with patients' normal daily activities from all of the time, most of the time, a good bit of the time, some of the time, a little of the time, hardly any of the time, none of the time with the all of the time being the worst outcome | six weeks post radiation treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in patients' quality of life | Changes in patients' quality of life during radiotherapy and follow up period are captured by questionnaires. The questions are for examples how difficult is it in planning or being able to continue your usual activities?, how often have you felt low in energy? The score scales are from all of the time, most of the time, a good bit of the time, some of the time, a little of the time, hardly any of the time, none of the time with the all of the time being the worst outcome | first to 8th weeks post radiation treatment, half yearly for 2 years, annually for 3 years | 
| Number of participants with acute radiation dermatitis in irradiated area | Grade 2 or worse radiation dermatitis | During treatment | 
| Number of participants with ipsilateral arm lymphoedema | The circumference of the ipsilateral arm >=10% increased compared to the other arm defines oedema | 3 years post radiation treatment | 
| Number of participants with ipsilateral arm range of motion | Impaired shoulder movement is present when >20 degrees difference between arms at flexion and/or abduction | 3 years post radiation treatment | 
| Disease Recurrence | Any disease progression or recurrence - location and time of event | 5 years from treatment | 
| Self reported acute & late radiation toxicities | acute radiation toxicities during treatment and late radiation toxicities are captured by questionnaires | first to 8th weeks post radiation treatment, half yearly for 2 years, annually for 3 years | 
| Compare the indirect radiation therapy costs by 2 treatment arms | data of cost of attending treatment, work and lifestyle impact are captured by questionnaires | 4 weeks post radiation treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
radiotherapy, hypofractionation, quality of life