Reduction of organ motion during radiotherapy by non-invasive mechanical ventilation supported breathing control.

Radiotherapy with or without surgery and chemotherapy is an important treatment for many thoracic and abdominal cancers, including breast and lung cancer, mediastinal tumours, liver tumours, and pancreatic cancer. To minimize the risk of acute and late radiation-associated toxicity, irradiated tissue volumes should be kept as small as possible. However, large and irregular breathing amplitudes during free breathing require large safety margins. To account for respiratory motion and daily anatomical variations, treatment volumes are expanded beyond the tumour to ensure complete target volume irradiation. Consequently, normal tissues surrounding the tumour may be exposed to high radiation doses.
Current clinical practice for a range of thoracic and abdominal cancer patients reduces respiratory motion during radiotherapy while patients perform multiple (~10) and short (~20-35 secs) deep-inspiration breath-holdsfrom room air. The effectiveness depends on patients’ compliance and their response to feedback. Besides, tumour and organ position can vary considerably between multiple short breath-holds, and residual motion occurs. Safety margins are still required.
Non-invasive mechanical ventilation supported regularized breathing can reduce respiratory motion compared to free breathing. Furthermore, combining non-invasive mechanical hyperventilation (causing safe hypocapnia) with pre-oxygenation enables single prolonged breath-holding (≥5 mins). Our pilot study (METC NL64693.018.18) unveiled a residual diaphragm motion during proloonged breath-holding.
In this study, we aim to establish compensated prolonged breath-holding by mechanical re-inflation of oxygen during breath-holding to compensate for gradual lung deflation. High frequency ventilation is a strategy where the subject needs not take any breaths for a prolonged period (~10 mins), since the high frequency oscillation of gasses ensures adequate gas exchange.

Respiratory motion will be maximally reduced during compensated prolonged breath-holding where gradual lung deflation is abolished by mechanical re-inflation of oxygen, and high frequency ventilation is expected to be equally effective. Regularized breathing with lower frequencies is the second best solution to reduce organ motion.

The feasibility to achieve mechanical ventilation supported breathing control strategies in heatlhy volunteers and cancer patients will be demonstrated at four time points:
1. Training session 1
2. Training session 2
3. MRI session 1
4. MRI session 2
At the same time points, subject's comfort with each of the breathing control strategies will be assessed.
The effect of the breathing control strategies on (residual) organ motion in healthy volunteers will be quantified on MR images.
The effect of the breathing control strategies in cancer patients will be quantified in terms of reduced dose to OARs by comparing radiation treatment plans.

Subjects will be trained in approximately two sessions to feel safe and comfortable while being mechanically ventilated via a face mask and viral filter. Step by step they learn to to achieve safely compensated prolonged breath-holds and to undergo high frquency ventilation. In two subsequent sessions, MRIs will be acquired during these procedures.