Trial Information

Investigating the Improvement in 4D CT Images Using Audiovisual Biofeedback: An Intra-fraction and an Inter-fraction Evaluation.

JUSTIFICATION Among the various sites affected by cancer, statistics show that lung cancer
is the leading cause of death among both men and women. One major reason for this is that
the treatment of lung cancer has not improved drastically in the past few years. Lung tumors
are also potentially difficult to treat with radiation therapy due the patients' respiration
motion causing the tumor to be mobile.

A1) Detrimental effects of respiration motion Respiration motion affects all tumor sites in
the thorax and abdomen, although the disease of most prevalence and relevance for
radiotherapy is lung cancer. Many studies have been performed to study lung-tumor motion and
methods to compensate for this motion during radiation treatment imaging, planning and
delivery. The significance of the respiration motion compensation techniques is to reduce
the mobility of the tumors and thereby reduce the dose to the surrounding normal structures.
If no motion compensation methods are used then a margin must be added to ensure adequate
coverage of the tumor. Large margins results in radiation delivered to a larger volume of
critical structures.

A2) Compensation techniques Methods that reduce respiration induced intrafraction motion
include active breathing control, voluntary breath-hold, deep inspiration breath-hold,
respiratory gated techniques, and 4D or tumor-tracking techniques.1-6 Active breathing
control and the deep inspiration breath hold involves the patient holding their breath.
While these may improve the reproducibility of the position of the tumor within the lung, it
is not feasible for all patients especially those that have a compromised respiratory
function. Respiratory gating techniques involves turning on the beam during only a small
window of the respiratory cycle. Thus respiratory gating reduces the intrafraction motion
but does not totally eliminate it. During respiratory gating, since the beam is turned on
and off based on the respiration signal, the treatment time may increase up to 35-40%
compared to a regular treatment. Since the patient has to spend more time on the table, this
could introduce more errors due to patient movement on the table. 4D or tumor tracking
techniques has it own share of issues as is discussed in the following paragraph.

A3) During 4D radiotherapy (4DRT) delivery the tumor is continuously tracked with the
radiation beam as they move throughout the respiratory cycle. The benefits of 4DRT are a
reduction in dose to the healthy lung tissue and/or an increase in dose to the tumor. The
gains from 4DRT are clinically measurable, though much development is needed in the various
steps of 4DRT i.e. CT image acquisition, planning and delivery.

During 4D CT image acquisition, images are acquired during different respiration states of
normal breathing.7-9 The quality of images acquired by using the 4D CT image acquisition is
limited by patients respiration pattern. Since the images are sorted based on the patients
respiration motion, any change in pattern could lead to the images being sorted to a
different part of respiration. This effect is reflected as an artifact on the CT image.

Target volumes along with respiration motion can be determined by contouring the target in
the various respiratory states thus obtaining a volume that encompasses an entire breathing
cycle. The efficacy and accuracy of 4D CT will be maximized when patients breathe
reproducibly. However it is well-known that respiration motion varies not only from one day
to the next but also during one fraction.

A4) Effect of irregular breathing For 4D CT, minimizing the variation of patient breathing
within a treatment fraction and from fraction to fraction, i.e., increasing the
reproducibility of patient breathing, is important. Large variation in patient respiration
motion and irregular breathing lead to artifacts in the CT images as shown in. However,
respiration motion amplitude and period vary with time and from patient to patient because
of various anatomic and physiologic factors.

A5) Possible solutions Biofeedback/coaching techniques are being increasingly embedded in
the behavioral treatment of patients with lung disease such as chronic obstructive pulmonary
disease, asthma, and cystic fibrosis. For respiratory gating, several studies suggest that
verbal prompts improve respiration reproducibility. Kini et al.12 concluded that audio
prompts improve the stability of respiration frequency of the patient but does not maintain
the range of respiratory motion, whereas visual prompts control only the regularity of the
displacement and the frequency is not reproducible. Based on the results of Kini et al.12,
combined audio-visual biofeedback was devised to improve the reproducibility of respiration
motion. Recently Neicu et al.13 described results of audio and visual prompting and
demonstrated improvement in the efficacy of so-called synchronized moving aperture radiation
therapy, using respiratory traces from single-patient and volunteer sessions.

George et al.14 concluded based on a 24-patient, multisession study that audio-visual
biofeedback can significantly reduce residual motion variability for a given duty cycle,
thus potentially improving the accuracy of respiratory-gating. From the results of this
study it was seen that audio-visual biofeedback reduced motion by 0.5 cm (0.29 to 0.24 cm)
for exhale breathing and 1.5 cm (0.46 to 0.36 cm) for inhale breathing.