Mechanical ventilation for radiotherapy

Radiotherapy remains a major treatment for most tumour types and it takes minutes to delivery each radiotherapy dose. The major problem is that patients continue to breathe during these minutes of treatment, so all tumours in the chest and abdomen move with breathing during treatment. This respiratory motion necessitates having to irradiate healthy tissue surrounding the tumour in order to guarantee tumour irradiation. The principal side effects of radiation are: first the damage to all nearby healthy tissue (that limits the duration of any one treatment session), secondly the particular damage to nearby vital organs at risk (usually major blood vessels, airways and gastrointestinal tract).
Chest and abdominal cancer treatment is a major burden in Western healthcare medicine so improvement in its delivery is of major importance to society.
In the United Kingdom I previously developed 2 potentially major advances in respiratory motion management. First to use non-invasive mechanical ventilation in conscious, unmedicated patients to regularize their breathing pattern. This makes constant the size and timing of each breath. Hence it could be much easier for radiotherapy machines to target tumours accurately and to avoid hitting healthy tissue. Secondly, to prolong breath-hold duration by 5 fold by combining hypocapnia induced by mechanical ventilation with breathing 60% oxygen. Hence respiratory motion could be greatly reduced and potentially abolished.
The overall scientific and training objectives of the project were to collaborate with a range of radiotherapy technicians (RTTs), medical physicists and oncologists to
• Train Netherlands staff to deliver my techniques of non-invasive mechanical ventilation to regularize patients breathing and of prolonged breath-holds
• Train healthy volunteers and patients in the Netherlands to accept non-invasive mechanical ventilation
• Use magnetic resonance imaging (MRI) on volunteers and patients to collect data to quantify the improved management of internal motion of relevant structures in the chest and abdomen
• Use this motion quantification to demonstrate objectively the reductions in tumour motion during mechanical ventilation compared to current treatment during spontaneous breathing
• Use simulated treatment plans to quantify the reductions in estimated radiation dose to healthy tissue that mechanical ventilation will achieve and hence make the case for clinical implementation of mechanical ventilation
• Disseminate this information to relevant clinical staff (radiotherapy technicians [RTTs], medical physicists and medical oncologists) and patient groups to encourage adoption of mechanical ventilation

The final period conclusions (the main scientific and technical achievements and innovation outputs) are that
• Netherlands RTTs were successfully trained to use mechanical ventilation with 60% O2 to prolong breath-hold durations of patients by fivefold and to regularize breathing patterns of patients
• During this fellowship we have invented 3 new strategies to improve my techniques for respiratory motion management,
1) Netherlands RTTs were trained to deliver a new and simpler protocol to double breath-hold duration in patients, by administering 60% O2 (without mechanical ventilation). We have written, obtained approval and implemented a clinical protocol for its routine clinical use
2) Regularization at 60 breaths per minute (60 brpm) with positive end- expiratory pressure (PEEP) to further minimize tumour motion
3) Abolishing the chest deflation that normally occurs during my prolonged breath-holds. This is achieved by using the mechanical ventilator to re-inflate the chest during a breath-hold)
• We have also established that mechanical ventilation at higher frequencies (up to 400 brpm) using a jet ventilator offers no further clinical benefits
• We are collecting data on internal organ movement with MRI to quantify reductions in organ motion these will achieve. We have begun worldwide dissemination at international conferences, with international publications and have raised funding to continue this important work beyond the term of the Marie Sklodowska-Curie Fellowship.
• We have developed the software necessary to convert our MRI images into simulated treatment programs and started to create simulated treatment plans
• We are initiating new clinical research projects to reduce respiratory motion management that will continue over at least the 2 years following my Marie Sklodowska-Curie Fellowship

The current state of the art for respiratory motion management is by delivering radiotherapy without motion management (merely during spontaneous breathing)
• over multiple short breath-holds (maximum of 30 seconds) while inhaling room air
• when trying to follow (track) tumour movement indirectly by tracking the chest surface
• when trying to track tumour movement directly with MRI
My progress beyond the state of the art is
• introducing a protocol approved for routine clinical practice in Amsterdam to achieve multiple prolonged breath-holds by inhaling 60% oxygen in patients who cannot otherwise breath-hold
• raising the worldwide recognition of breath-holding with 60% oxygen as a safe clinical protocol
• Promoting worldwide the use of mechanical ventilation at 60 breaths per minute for radiotherapy
• Promoting worldwide the use of chest reinflation during prolonged (> 5 minute) breath-holds to minimize or abolish respiratory motion
• Establishing a preclinical trial in healthy volunteers and in patients that is measuring internal organs to quantify their motion during 60 breaths per minute and during chest reinflation during prolonged (> 5 minute) breath-holds and to quantify the dose reduction in their irradiation
The wider societal impact will ultimately be to revolutionize radiotherapy delivery by more accurately targeting radiotherapy to tumours and increasing treatment efficiency by reducing clinical costs.

Periodic Reporting for period 1 - MV for radiotherapy (Mechanical ventilation for radiotherapy)

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