Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04091542 |
| Other study ID # |
EC2019/0127 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 15, 2019 |
| Est. completion date |
February 22, 2021 |
Study information
| Verified date |
January 2023 |
| Source |
University Hospital, Ghent |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
With the HOBBIT trial, the investigators want to develop a technology that allows volunteers
to hold their breath for a long time. This technique will then be taught to patients with
breast cancer to be able to hold their breath long-term during the irradiation. After all,
research has shown that the heart is in a better position when the patient enters her breath
after a deep inhalation, as a result of which there is less unwanted radiation of the heart.
To develop this technique the investigators use healthy volunteers, who are asked several
times to hold their breath as long as comfortable. Before the respiratory arrest the
investigators allow these volunteers to hyperventilate, administer oxygen and cause
hyperinflation of the lungs.
The volunteers come back four times, on four consecutive days. The first day they receive a
short training. Afterwards oxygen is administered for a few minutes while the volunteers are
asked to hyperventilate. Afterwards, by using the learned technique, they must hold their
breath for as long as possible, comfortably. They should hold their breath 3 times in total
with a short break in between. The following days there is always a change in the preparation
protocol, compared to the previous study. Different parameters in the protocol will be
changed for different groups of volunteers, this is based on randomization. In this way the
effect of different parameters in the preparation of the AHS can be investigated. The
investigators will use this information to develop a new protocol for extending the duration
of breathing to two minutes and thirty seconds for use during radiotherapy treatment. The
method for finding the optimal technique is iterative optimization. This method follows a
process of development, testing, feedback and redevelopment cycles. Iteratively, these cycles
of development use the prior research to further elaborate the most promising discoveries and
drop paths that do not produce the desired result. During the development The investigators
listen to the input of different people: doctors, nurses, support staff, engineers and the
participants, to guarantee the usability of the technique on the radiotherapy device. Once
the researchers think they have found a solution that meets all the conditions, a group of
untrained volunteers are asked to implement the technique. With this the investigators
validate the technique for later use in breast cancer patients.
Description:
Radiotherapy (RT) has an established role in breast cancer, complementing surgery and
systemic therapies to prevent recurrences and improve survival. Long-Term follow-up shows
that the beneficial effect on survival is weakened by radiation-induced cardiac and lung
cancer mortality, especially in patients with left sided breast cancer or requiring
irradiation of regional lymph nodes. Cardiac toxicity is of major concern because many
patients receive cardiotoxic systemic treatments like anthracyclines and trastuzumab. Dose
and volume of the heart exposed to radiation correlate with severity of cardiac toxicity. The
heart dose-volume parameters are highest for patients receiving left-side radiotherapy
especially if irradiation of the internal mammary lymph nodes is performed. Risk of (fatal)
ischemic heart attack increases linearly with mean heart dose with no known dose threshold.
In patients who receive left-side local treatment, heart dose is decreased by using prone
positioning or deep-inspiration breath hold (DIBH), or a combination of both.
Previous research has shown that the heart shifts to an anatomical more favorable position in
DIBH, away from the breast, chest wall and internal mammary lymph nodes, reducing heart dose.
This advantage remains in prone positioning. The goal is to prolong the duration of a single
DIBH, to create a long-DIBH (L-DIBH). Possible advantages are better positioning of the
patient, execution of technically more difficult procedures and inclusion of regional lymph
node (locoregional) irradiation. Most patients can't sustain a DIBH long enough to perform
simulation with computed tomography (CT) and delineation during DIBH, so delineation of the
laser lines during CT-simulation is performed on the shallow breathing (SB) scan. During
positioning of the patient on the radiotherapy machine, a daily cone-beam CT (CBCT) is
performed. The duration of this CBCT is 40 seconds, maintaining DIBH during this period is
also hard for most patients. So currently the positioning at the moment of treatment is based
on the SB CT-scan, whilst the DIBH CT-scan is used for treatment. This could potentially
induce suboptimal positioning. Breath hold during CBCT positioning and CT-simulation and
delineation could minimize shifts in treatment position. The current DIBH schedules for whole
breast cancer radiotherapy without inclusion of the lymph nodes, use between three and six
DIBHs of 12 to 18 seconds. Longer DIBH could lead to less DIBHs and faster treatment
execution, which is especially important when the lymph nodes are included in the target
volumes. Locoregional irradiation, including the lymph nodes, requires between 10 and 14
DIBHs of 15-30 seconds which leads to a total treatment time of around 5 minutes. This
represents a substantial physical and mental effort for all but the most able patients.
This research, the first phase of the Hyperventilation Oxygenation Breath hold in Breast
cancer Irradiation Treatment (HOBBIT) trail, will focus on finding a technique to assist
patients to maintain a long DIBH (L-DIBH) during radiotherapy. Other research has shown a
potential increase in duration of breath hold and reduction in rest time between DIBHs using
oxygen in combination with hyperventilation. There is a safe way to prolong DIBH to at least
5 minutes. However, the technique requires a long training period for the patient, and 15
minutes of mechanical ventilation before each treatment session, making the technique very
time consuming and resource intensive. The investigators hope to simplify the technique by
allowing patients to do multiple L-DIBHs during the 5 minutes of treatment time. The
investigators found from preliminary tests that using shorter L-DIBHs has several advantages,
firstly pre-oxygenation and induction of hypocapnia can be achieved in a shorter time,
secondly the duration of training is reduced, and thirdly a the costs are reduced.
Increase in blood pressure is the main risk of L-DIBH. No adverse events of L-DIBH have been
reported. In order to minimize the risks during testing, this research project was developed
in collaboration with the anesthesiology department, to ensure safety of the participants
during L-DIBH. For all subjects, vital parameters will be continuously monitored by medical
staff. Safety boundaries are in place which subjects are not allowed to cross during L-DIBH.
The aim of this research is to develop a new and easy technique for L-DIBH in prone and
supine position, feasible for daily use at our radiotherapy department. The purpose of the
technique is to allow locoregional treatment using a reasonable amount of L-DIBHs, increase
patient positioning and accuracy of radiation treatment, and further significantly reduce
heart toxicity for left sided cancer patients. The HOBBIT trial includes multiple phases. The
first phase is performed on healthy volunteers, different support techniques to prolong DIBH
will be tested. In the second phase the most optimal techniques to perform a L-DIBH will be
validated on breast cancer patients. Around 40 volunteers will be included in the first phase
of the HOBBIT trail, the final amount of volunteers depends on the amount of testing needed
to find a technique which fulfills all criteria for phase two. The second phase of the HOBBIT
trail will include breast cancer patients treated at our radiotherapy center. The
expectations from previous research is that the investigators will see a similar increase in
DIBH time, compared to healthy volunteers. The final goal is the use of the technique during
locoregional radiation therapy at the University Hospital of Ghent.
