The HeartSpare Plus 1B Trial

Study Overview
=================
Brief Summary
-----------------
This study aims to compare the resource impact, acute toxicity and feasibility of different pan-lymph node radiotherapy techniques. Radiotherapy using wide tangents with the patient in breath hold will be compared against volumetric modulated arc therapy (VMAT) in free breathing in the main trial. A parallel study will asses the accuracy of VMAT treatments using voluntary deep inspiratory breath hold compared to an active breathing controlled breath hold device.

Detailed Description
-----------------
Following publication of results of two large randomised clinical trials, pan-lymph node radiotherapy (pan-LN RT) (including treatment of the internal mammary chain) is set to become standard treatment in patients with lymph-node positive breast cancer. Traditional pan-LN RT techniques deliver high radiation doses to the heart and lungs which can cause long-term side-effects in women many years after their treatment. Modern techniques including breath-holding and volumetric-modulated arc therapy (VMAT) can reduce doses to heart and lungs but the investigators do not yet know which technique(s) are best in terms of resource costs, short to medium-term side-effects, and day to day accuracy. This study will compare the time taken to deliver pan-LN RT using breath-holding versus VMAT and will collect side-effect data up to one year following treatment as well as modelling long-term cardiac risks based on heart doses delivered. The results of the main study will help guide clinicians and departments in selecting the best pan-LN RT techniques for their patients. A parallel study will evaluate the combination of breath-hold and VMAT using a machine-based technique called the active-breathing controlled (ABC) device against a more simple voluntary breath-hold technique were patients simply take a breath in and hold it for up to 20 seconds at a time. These techniques will be compared in terms of their day-to-day accuracy. If the simpler technique proves as accurate as the ABC-technique, this will establish the simpler technique as a less resource-intensive standard of care adoptable by other radiotherapy departments.

Official Title
-----------------
The HeartSpare Plus 1B Trial: A Randomised Phase II Trial Comparing the Resource Impact, Acute Toxicity and Feasibility of Different Pan-lymph Node Radiotherapy Techniques for Breast Cancer Patients

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Radiation: WT_vDIBH
* Radiation: VMAT_FB


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years Female or male Invasive carcinoma of the breast (left or right-sided) Breast conservation surgery or mastectomy Axillary staging and/or dissection pT1-T4,N1-2,M0 disease Histological involvement of axillary lymph nodes Indication for radiotherapy to the IMC, axillary levels I-III and/or level IV Patient able to tolerate breath hold Performance status 0-1 Exclusion Criteria: Contralateral and/or previous ipsilateral breast cancer, irrespective of date of diagnosis Past medical history of malignancy except (i) basal cell skin carcinoma, (ii) CIN cervix uteri, (iii) non-breast malignancy allowed if treated with curative intent and at least 5 years disease free Previous radiotherapy to any region above the diaphragm

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: WT_vDIBH<br>Wide tangent radiotherapy in voluntary deep inspiratory breath hold | Radiation: WT_vDIBH<br> <br> |
| Active Comparator: VMAT_FB<br>Volumetric modulated arc therapy in free breathing. | Radiation: VMAT_FB<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Linear Accelerator time | Patient mounting couch to linear accelerator being turned off | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute toxicity - Skin | CTCAE grading | 5 weeks | 
| Acute toxicity - lung (pneumonitis) | CTCAE grading | 5 weeks | 
| Acute toxicity - oesophagitis | CTCAE grading | 5 weeks | 
| Acute toxicity - fatigue | EORTC QLQ-C30 + FA13 | 5 weeks | 
| Acute toxicity - quality of life | EORTC QLQ-C30 + BR23 | 5 weeks | 
| Intermediate toxicity - lung (pneumonitis) | CTCAE pneumonitis assesment | up to 1 year | 
| Intermediate toxicity - fatigue | EORTC QLQ-C30 + FA13 | up to 1 year | 
| Intermediate toxicity - quality of life | EORTC QLQ-C30 | up to 1 year | 
| Intermediate toxicity - lymphoedema/ shoulder dysfunction | EORTC BR23 | up to 1 year | 
| Organ at risk dose - ipsilateral lung | mean dose to the ipsilateral lung (Gy) measured using DVH | Immediate | 
| Organ at risk dose - contralateral lung | mean dose to the contralateral lung (Gy) measured using DVH | Immediate | 
| Organ at risk dose - heart | mean dose to the heart (Gy) measured using DVH | Immediate | 
| Organ at risk dose - contralateral breast | mean dose to the contralateral breast (Gy) measured using DVH | Immediate | 
| Organ at risk dose - thyroid | mean dose to the thyroid (Gy) measured using DVH | Immediate | 
| Organ at risk dose - humeral head | mean dose to the humeral head (Gy) measured using DVH | Immediate | 
| Organ at risk dose - brachial plexus | maximum dose to the brachial plexus (Gy) measured using DVH | Immediate | 
| Organ at risk dose - Left anterior descending coronary artery | maximum dose to the Left anterior descending coronary artery (Gy) measured using DVH | Immediate | 
| Organ at risk dose - oesophagus | maximum dose to the oesophagus (Gy) measured using DVH | Immediate | 
| Time taken to plan and check radiotherapy |  | Immediate | 
| Inter-fraction reproducibility | Distance - shift from planning CT on CBCT (mm) | 3 weeks |