The HeartSpare Plus 1B Trial

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Radiation: VMAT_FB; Radiation: WT_vDIBH

• Registration Number: NCT02771353
• Lead Sponsor: Royal Marsden NHS Foundation Trust

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.

Study Timeline

• Study First Submitted: 2016-04-26
• Study First Submitted QC: 2016-05-12
• Study First Posted: 2016-05-13
• Study Start: 2016-12-12
• Primary Completion: 2019-01-15
• Study Completion: 2019-01-15
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-12
• Last Update Posted: 2022-04-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 39

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VMAT_FB	VMAT_FB	Volumetric modulated arc therapy in free breathing.
WT_vDIBH	WT_vDIBH	Wide tangent radiotherapy in voluntary deep inspiratory breath hold

Primary Outcome Measures

Name	Time	Method
Linear Accelerator time	3 weeks	Patient mounting couch to linear accelerator being turned off

Secondary Outcome Measures

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