Prospective Randomized Trial Comparing 2 Devices for Deep Inspiration Breath Hold Management in Breast Radiation Therapy: Results of the BRAVEHeart Trial.

Purpose: The Breast Radiotherapy Audio Visual Enhancement for sparing the Heart (BRAVEHeart) trial prospectively randomized patients with left-sided breast cancer to 1 of 2 deep inspiration breath hold biofeedback devices: a novel chest surface tracking system and an abdominal block tracking system. The primary hypothesis was that the accuracy of chest tracking would be higher than that of abdominal tracking as the chest is a more direct surrogate of the breast target. Methods and Materials: Patients with left-sided breast cancer were treated in deep inspiration breath hold with intensity modulated radiation therapy delivery. Patients were randomized to either the novel chest surface system or abdominal block system for active management of breath hold with visual feedback. On both trial arms, the unallocated system was monitored passively. A total of 239,296 cine electronic portal imaging device images were analyzed retrospectively to extract the chest wall position. Treatment accuracy was quantified as the deviation of the internal chest wall during treatment relative to the planned position from the digitally reconstructed radiograph. The correlation between motion of the external surrogate and internal chest wall was calculated per-breath hold. Ease of use was assessed with questionnaires for both radiation therapists and patients and appointment length recorded. Results: Data from 26 participants were available for analysis. No difference was found in delivered treatment accuracy between arms. Across all patients and fractions, the median correlation between internal chest wall movement and external surrogate was 0.69 for the chest surface and 0.17 for the abdominal block. Patients found it easy to follow visual feedback from both systems. No difference was found in appointment length between arms. Conclusions: No statistical evidence was found for superior treatment accuracy, satisfaction, or appointment length for the novel chest surface tracking device compared with the abdominal block system. During deep inspiration breath hold, the median per-breath hold correlation of internal chest wall movement to the motion of the chest surface was higher than the median correlation of the abdominal block to the chest surface.

BRAVEHeart: a randomised trial comparing the accuracy of Breathe Well and RPM for deep inspiration breath hold breast cancer radiotherapy.

BACKGROUND: Deep inspiration breath hold (DIBH) reduces radiotherapy cardiac dose for left-sided breast cancer patients. The primary aim of the BRAVEHeart (Breast Radiotherapy Audio Visual Enhancement for sparing the Heart) trial is to assess the accuracy and usability of a novel device, Breathe Well, for DIBH guidance for left-sided breast cancer patients. Breathe Well will be compared to an adapted widely available monitoring system, the Real-time Position Management system (RPM). METHODS: BRAVEHeart is a single institution prospective randomised trial of two DIBH devices. BRAVEHeart will assess the DIBH accuracy for Breathe Well and RPM during left-sided breast cancer radiotherapy. After informed consent has been obtained, 40 patients will be randomised into two equal groups, the experimental arm (Breathe Well) and the control arm (RPM with in-house modification of an added patient screen). The primary hypothesis of BRAVEHeart is that the accuracy of Breathe Well in maintaining the position of the chest during DIBH is superior to the RPM system. Accuracy will be measured by comparing chest wall motion extracted from images acquired of the treatment field during breast radiotherapy for patients treated using the Breathe Well system and those using the RPM system. DISCUSSION: The Breathe Well device uses a depth camera to monitor the chest surface while the RPM system monitors a block on the patient's abdomen. The hypothesis of this trial is that the chest surface is a better surrogate for the internal chest wall motion used as a measure of treatment accuracy. The Breathe Well device aims to deliver an easy-to-use implementation of surface monitoring. The findings from the study will help inform the technology choice for other centres performing DIBH. TRIAL REGISTRATION: ClinicalTrials.gov NCT02881203 . Registered on 26 August 2016.

The MANGO study: a prospective investigation of oxygen enhanced and blood-oxygen level dependent MRI as imaging biomarkers of hypoxia in glioblastoma.

Background: Glioblastoma (GBM) is the most aggressive type of brain cancer, with a 5-year survival rate of ~5% and most tumours recurring locally within months of first-line treatment. Hypoxia is associated with worse clinical outcomes in GBM, as it leads to localized resistance to radiotherapy and subsequent tumour recurrence. Current standard of care treatment does not account for tumour hypoxia, due to the challenges of mapping tumour hypoxia in routine clinical practice. In this clinical study, we aim to investigate the role of oxygen enhanced (OE) and blood-oxygen level dependent (BOLD) MRI as non-invasive imaging biomarkers of hypoxia in GBM, and to evaluate their potential role in dose-painting radiotherapy planning and treatment response assessment. Methods: The primary endpoint is to evaluate the quantitative and spatial correlation between OE and BOLD MRI measurements and [18F]MISO values of uptake in the tumour. The secondary endpoints are to evaluate the repeatability of MRI biomarkers of hypoxia in a test-retest study, to estimate the potential clinical benefits of using MRI biomarkers of hypoxia to guide dose-painting radiotherapy, and to evaluate the ability of MRI biomarkers of hypoxia to assess treatment response. Twenty newly diagnosed GBM patients will be enrolled in this study. Patients will undergo standard of care treatment while receiving additional OE/BOLD MRI and [18F]MISO PET scans at several timepoints during treatment. The ability of OE/BOLD MRI to map hypoxic tumour regions will be evaluated by assessing spatial and quantitative correlations with areas of hypoxic tumour identified via [18F]MISO PET imaging. Discussion: MANGO (Magnetic resonance imaging of hypoxia for radiation treatment guidance in glioblastoma multiforme) is a diagnostic/prognostic study investigating the role of imaging biomarkers of hypoxia in GBM management. The study will generate a large amount of longitudinal multimodal MRI and PET imaging data that could be used to unveil dynamic changes in tumour physiology that currently limit treatment efficacy, thereby providing a means to develop more effective and personalised treatments.