University of Birmingham. Complete control of respiratory motion: mechanical ventilation is the way forward for Radiotherapy and Medical Imaging.

Size: px

Start display at page:

Download "University of Birmingham. Complete control of respiratory motion: mechanical ventilation is the way forward for Radiotherapy and Medical Imaging."

Maryann Hines
5 years ago
Views:

1 University of Birmingham Complete control of respiratory motion: mechanical ventilation is the way forward for Radiotherapy and Medical Imaging.

Multidisciplinary team Dr Michael Parkes, Physiologist, Prof Stuart Green, Dr Jason Cashmore, Medical Physics Dr Tom Clutton-Brock, Anaesthesia + Intensive Care Medicine Dr Qamar Ghafoor Oncology

of a conscious/unmedicated patient s breathing & regularize it for ~ 1hour Parkes (2016).

2 Multidisciplinary team Dr Michael Parkes, Physiologist, Prof Stuart Green, Dr Jason Cashmore, Medical Physics Dr Tom Clutton-Brock, Anaesthesia + Intensive Care Medicine Dr Qamar Ghafoor Oncology (lung cancer) Dr Andrea Stevens Oncology (breast cancer) Dr Arjan Bel- Academic Medisch Centrum, Amsterdam Clinical Research Facility Key points A mechanical ventilator can now take complete control of a conscious/unmedicated patient s breathing & regularize it for ~ 1hour Parkes (2016). Reducing the within-patient variability of breathing for radiotherapy delivery in conscious, unsedated cancer patients using a mechanical ventilator. Br J Radiol 89, Patients can breath-hold safely for ten times longer (>5 minutes) than currently asked to do (~ 20 secs) (with help from a mechanical ventilator) Parkes (2016a&b). Safely achieving single breath-holds of >5 minutes in cancer patients: feasibility and applications for radiotherapy. Br J Radiol 89, Consider how we might best apply mechanical ventilation to photon & proton beam delivery.

Clinical justification for our research The major problem in radiotherapy and diagnostic imaging :- Patients breathe during radiotherapy, thoracic and abdominal tumours move by up

3 Clinical justification for our research The major problem in radiotherapy and diagnostic imaging :- Patients breathe during radiotherapy, thoracic and abdominal tumours move by up to 3.5cm so healthy tissue has to be irradiated to guarantee irradiation of all tumour, healthy tissue damage - L breast cancer (heart) and other vital tissues. Examples of movement:-

4 Current attempts to solve the respiratory motion problem 1. Ignore the breathing and irradiate the entire movement path beyond the tumour to guarantee treating the tumour. 2. Abdominal compression to restrict the range of motion during breathing. 3. Gate treatment within the breathing cycle 4. Tumour tracking strategies 5. Repeated treatments during multiple short (~20 secs) breath-holds (DIBH). Current Radiotherapy concept of a breath-hold does not correspond with basic physiology. ~22 s breath-hold (Roth, 2011). = regular breathing at ~3 times a minute! We physiologists measure breath-holds in minutes.

5 We use a mechanical ventilator to offer two novel & revolutionary solutions 1. Train the patient to let a mechanical ventilator take complete control of their breathing, Parkes (2016). The ventilator then delivers regularized breaths of constant frequency & volume. The ventilator makes tumour movement predictable & improves tracking prediction of tumour position (and hence dealing with any lag issues). The ventilator could even feed forward to an accelerator, telling the accelerator where the tumour will be to treat predetermined tissue volumes. 2. Could give each entire radiotherapy treatment session in a single prolonged breath-hold (>5 minutes), Parkes (2016a&b). Use a ventilator to hyperventilate to cause hypocapnia (and add 60% oxygen to inspired gas) to perform one single >5 minute breath-hold- Abolishes all rhythmic breathing movements in the treatment session. Why haven t single prolonged breath-holds been considered before? Breath-hold physiology not taught at medical school....because prolonged breath-holds had no clinical application... Physiologist... for the first time, single prolonged breath-holds could have a major clinical application in radiotherapy and imaging.

6 Part 1. What is normal breath-hold duration? 3 Time (mins.) Mean ± range 2 Can you breath-hold until you pass out? No! (Schneider, 1930) it is practically impossible for a man at sea level to voluntarily hold his breath until he becomes unconscious No! Never seen it. Nor reported. Simple safety precautions to ensure it will never happen. Competitive breath-hold divers. 1 Useful knowledge to reassure patients. 0 A. 318 USAF pilots Schneider (1930) Breath-hold from air, max inflation in Parkes (2006) 1 minute breath-hold is just a starting point

7 Single prolonged breath-holds (with preoxygenation and hypocapnia) are safe. During a single ~9 minute breath-hold- not much happens! (Parkes 2014) Spontaneous breathing Mechanical ventilation blood pressure gradually rises 8.7 minutes Parkes (2014) BJR 12 inexperienced healthy subjects, mean breath-hold duration 5.5 ±0.5se min. Normal mean blood gases at breakpoint (still 98% O 2 saturated, normal PetCO 2 levels (43 ± 2 se mmhg) mean sbp 166±4 mmhg). No gasping, no distress, no dizziness nor disturbed breathing in the post breath-hold period. We defined safety limits for patients for single prolonged breath-holds. Safety equipment- monitor SpO 2 and blood pressure non-invasively. Stop if SpO 2 < 94% or sbp > 180 mmhg. conservative 12 minutes!

The key to breath-holding appears to in the diaphragm muscle. But almost nothing is known about the physiology of the diaphragm muscle, because it is so inacessible.

8 The key to breath-holding appears to in the diaphragm muscle. But almost nothing is known about the physiology of the diaphragm muscle, because it is so inacessible. Why is the diaphragm important for breath-holding in Radiotherapy? Because patients feel safe learning to fight a sensation from a muscle! (They would be much more cautious if they were fighting the sensation of asphyxia!) Picture courtesy of Hugh Turvey, Artist in Residence, British Institute of Radiology

How long can cancer patients perform a single breath-hold? (Parkes, 2016a) N=15 female patients with breast cancer (. available). Volunteer patients. Aged 37-75 (average 54, 4 were 60+).

9 How long can cancer patients perform a single breath-hold? (Parkes, 2016a) N=15 female patients with breast cancer (. available). Volunteer patients. Aged (average 54, 4 were 60+). none younger available Exclusion criteria no hypertension, no coronary artery disease, non-smokers, no asthma no obesity, no epilepsy no diabetes. very cautious! All undergoing radiotherapy (each experiment preceded by a treatment session), 12 had undergone chemotherapy (2 with Herceptin). recumbent Conscious, unmedicated, lying listening to music Deliberately mechanically hyperventilate (over-ventilate) to induce safe hypocapnia, (drop PCO 2 from ~40 to 20 mmhg) and preoxygenate (inhale 60% O 2 ). Then switch off the ventilator and tell the patient to inhale and breath-hold (with mask still on). Parkes et al, 2016 & a

10 Mean duration of single breath-holds in 15 cancer patients (Parkes 2016a) 6 practice room (WTCRF) ns on breast board (Radiotherapy room) Mean breath-hold duration (minutes ±se) day 1 ** ** ** 75 yr old! Patients almost never reached our safety limits. Normal mean blood gases at breakpoint (SpO 2 = 100 ± 0 se %, PetCO 2 = 35 ±2 se mmhg) sbp at breakpoint 168 ± 4 mmhg 2 1 *** *** 0 0 first ever breathhold, air. max. inflation, air. max. inflation, 60% O 2. max. inflation, 60% O 2 & hypocapnia. *P<0.01, ** P< 0.001, ns p>0.05 Parkes et al, 2016b So no gasping, no distress, dizziness nor disturbed breathing afterwards. Always willing to come back each time and have another go.

11 No rhythmic chest movement during breath-holding, but all thoracic and abdominal organs will move slightly! Parkes (2016b). Towards the ultimate radiotherapy goal-"freezing" the tumour in a known postion during radiotherapy. Int J Rad Oncol Biol Phys. In Press Some non-rhythmic movement continues during breath-holding because 1). Initial settlement of the diaphragm and organs at the start of breath-holding 2). Lungs deflate slowly by ~ 250 ml/min. why? (gaseous O 2 is extracted from alveolar air, but cannot be replaced by equal amounts of gaseous CO 2 returning from venous blood, because alveoli are no longer refreshed, so there is no partial pressure gradient) Importance in Radiotherapy for all breath-holds. Presumption that tumours make no movement during breath-holding- incorrect. But much less movement than during free breathing. Emerging data showing clear heart and lung dosimetric benefits for breast cancer of multiple short breath-holds (DIBH) Boda-Heggemann (2016). Int J Rad Oncol Biol Phys 94, We think the single prolonged breath-hold of >5 minutes has much more to offer.

12 Small linear chest shrinkage during single prolonged breath-holds (Parkes 2016a) Polygraph record of the longest breath-hold (6.6 minutes) under simulated treatment conditions. (markers on shirt) initial chest settlement A-P linear shrinkage slope -1.6 mm/min. S-I slope 0.2 mm/min. L-R heart rate bpm PetCO 2 mmhg slope -1.0 mm/min. All patients mvv Mean anterior-posterior (z) movement of L breast marker mean mm/min -1.9 ± 0.3 mm/min, spontaneous n=15 Blood pressure mmhg Mean superior-inferior (y) movement of all markers 0.1 ± 0.1mm/min, n=11 SpO 2 % Mean left- right (x) movement of all markers -0.6 ± 0.2mm/min, 50 seconds n=11

13 Initial organ settlement during multiple short breath-holds (Lens et al., 2016) subject 1 MRI of the diaphragm and pancreatic head during multiple short breath-holds from air (DIBH) with different inflation volumes (0-100% inspiratory capacity) in 16 healthy volunteers subject 2

14 Part 2. More details about mechanical ventilation to regularize patient s breathing. Train... even simpler just to mechanical ventilation during radiotherapy we already have the data. ~inflation volume Parkes 2016 f volume mins # breaths 17 ± 0% 2 ±7% 5 55 ±1.5 mm without trying faster to achieve smaller volume and movement! Don t have to use f= 17.. For n=15 patients, during mechanical ventilation at 16 breaths per minute with the increased inflation volume necessary to cause hypocapnia, mean rhythmic A-P marker movement is ±2.5 ± 1mm. Mean variability in peak position marker is 0.5 ±0.1 mm, trough position marker is 0.4 ±0.0 mm, marker position drift is n.s. from zero. Mechanical ventilation achieved an 85% reduction in mean within-breath variability (sd) of breathing frequency (P<0.05) 29% reduction in mean within-breath variability (sd) of breath volume (P<0.05) But we allowed patients to override the ventilator (they like the freedom to cough or sigh or talk or laugh) If we instruct the patients never to override the ventilator, the reduction in variability will be even greater.

15 Possibility of Synchronizing the ventilator with Accelerator or imaging equipment. patent Breathing pattern feeding forward to Linac accelerator ventilators over-engineered accelerator Linac We are currently raising funds to develop a customised radiotherapy ventilator. Target cost < 5000 per ventilator Dual usage- regularized ventilation single prolonged breath-hold A number of companies are interested Feedback Treatment Ventilator sets breathing pattern Patient Patient breathing pattern monitor

16 Conclusions- Complete control of respiratory motion: mechanical ventilation is the way forward for Radiotherapy and Medical Imaging. Shown how a mechanical ventilator can now 1) take complete control of patient s breathing for ~1hour Parkes (2016). 2) have patients performing a single prolonged breath-hold for > 5 minutes Educate. resistance Parkes (2016a&b). How best we might apply mechanical ventilation to photon and proton beam delivery?

17 Recent breath-holding publications Parkes MJ (2006). Breath-holding and its breakpoint. Exp Physiol 91, Cooper HE, Parkes MJ, & Clutton-Brock TH (2003). CO2-dependent components of sinus arrhythmia from the start of breath-holding in Man. Am J Physiol 285, H841-H Parkes MJ (2012). The limits of breath holding Scientific American 306, Parkes MJ (2012). Do humans really prolong breath-hold duration by lowering heart rate to reduce metabolic rate? Physiology News 88, Parkes MJ (2008). Lack of a role for arterial chemoreceptors in the breakpoint of breath-holding. Physiology News 70, Parkes MJ (2008). So what does cause the breakpoint of breath-holding? Physiology News 73, Parkes MJ (2007). What happens to the central respiratory rhythm during breath-holding? Physiology News 68, Parkes MJ, Green S, Stevens CD, & Clutton-Brock TH (2014). Assessing and ensuring patient safety during breath-holding for radiotherapy. British Journal of Radiology 87, Parkes MJ, Green S, Stevens A, Parveen S, Stephens R, & Clutton-Brock T (2016). Reducing the within-patient variability of breathing for radiotherapy delivery in conscious, unsedated cancer patients using a mechanical ventilator. British Journal of Radiology 89, Parkes MJ, Green S, Stevens AM, Parveen S, Stephens B, & Clutton-Brock TH (2016a). Safely achieving single breath-holds of >5 minutes in cancer patients: feasibility and applications for radiotherapy. British Journal of Radiology 89, Parkes MJ, Green S, Cashmore J, Stevens AM, Clutton-Brock TH, Bel A, Lens E, Lohr F, & Boda-Heggemann J (2016b). Towards the ultimate radiotherapy goal-"freezing" the tumour in a known postion during radiotherapy, Int. J. Rad. Oncol. Biol. Phys. 96, 709, Lens E, Gurney-Champion OJ, Van der Horst A, Tekelenburg DR, van Kesteren Z, Parkes MJ, Van Tienhoven G, Nederveen AJ, & Bel A (2016). Towards an optimal breath-holding procedure for radiotherapy: differences in organ motion during inhalation and exhalation breath-holds. Med Phys 43,

18 University of Birmingham Complete control of respiratory motion: mechanical ventilation is the way forward for Radiotherapy and Medical Imaging.

RESPIRATORY REGULATION DURING EXERCISE

RESPIRATORY REGULATION DURING EXERCISE Respiration Respiration delivery of oxygen to and removal of carbon dioxide from the tissue External respiration ventilation and exchange of gases in the lung Internal