Nano-X A Smarter and Smaller Cancer Radiotherapy System

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Nano-X A Smarter and Smaller Cancer Radiotherapy System Paul Keall, Ilana Feain, Chun-Chien Shieh, Brendan Whelan, Peter Bennett, Paul Liu, Jeff Barber, Michael Barton, Simon Downes, Michael Jackson, +++ The University of Sydney Page 1

Disclosure of Corporate Partners The University of Sydney Page 2

Nano-X Pty Ltd Disclosure DISCLOSURE: NANO-X PTY LTD The University of Sydney Page 3

The ACRF Image X Institute Eradicating Cancer through Innovation in Imaging and Targeted X ray Therapy Revolutionise cancer imaging University of Sydney Charles Perkins Centre Pioneer functionally targeted radiotherapy Ingham Institute for Applied Medical Research Enable global access to cancer radiotherapy Nelune Comprehensive Cancer Centre The University of Sydney Page 4

Nano-X A Smarter and Smaller Cancer Radiotherapy System Clinical Rationale History Smarter Smaller Science Summary and Future The University of Sydney Page 6

Nano-X A Smarter and Smaller Cancer Radiotherapy System Clinical Rationale History Smarter Smaller Science Summary and Future The University of Sydney Page 7

Cancer is a worldwide problem The University of Sydney Page 8

Radiotherapy is under-utilised around the world Optimal utilisation rate for radiotherapy is 48% Developed countries rate is 20-55% Barton Rad Onc 2014 Delaney Cancer 2005 Developing countries rate is 0-25% 23,000 cancer radiotherapy systems needed in 2035 Barton Lancet Oncol 2006 Atun Lancet Oncol 2015 The University of Sydney Page 9

Radiotherapy is under-utilised around the world Source: IAEA Radiotherapy in cancer care 2017 Number The University of Sydney of people served by each radiotherapy centre by country Page 10

The world is aware of the benefits of radiotherapy Investment in radiotherapy not only enables treatment of large number of cancer cases to save lives; it also brings positive economic benefits. The University of Sydney Page 12

Lean Innovation 1000 $100 $800 Lean thinking: a new way to think about how to organize human activities to deliver more benefits to society and value to individuals while eliminating waste Wikipedia Lean innovation: using lean thinking to develop a new process or product http://www.innovationexcellence.com The University of Sydney Page 13

Conventional Nano-X The University of Sydney Page 14

Nano-X A Smarter and Smaller Cancer Radiotherapy System Clinical Rationale History Smarter Smaller Science Summary and Future The University of Sydney Page 16

Image-guided radiation therapy circa 1956 Fluoroscope Linac Source: The World of Stanford Radiology, O. Linton 2006 Isocentric rotating chair The University of Sydney Page 17

Drivers of patient rotation Cost-effective radiotherapy MRI-Linacs Particle therapy Synchrotron microbeam therapy The University of Sydney Page 18

If patient rotation is such a good idea why isn t everyone doing it? MGH proton system Epley Omniax Nano-X patient system Quantify patient acceptance Rotate patients in lying and sitting position Image during rotation The University of Sydney Page 19

If patient rotation is such a good idea why isn t everyone doing it? P-Cure/Northwestern Medicine Chicago Proton Center Product Genesis for fixed proton, stereotactic brain therapy The University of Sydney Page 20

If patient rotation is such a good idea why isn t everyone doing it? Whelan Med Phys 2017 The University of Sydney Page 21

If patient rotation is such a good idea why isn t everyone doing it? The University of Sydney Page 22

A dedicated, configurable linear accelerator for medical radiation research Australian Research Council Linkage Infrastructure, Equipment and Facilities Grant 2012 $600,000 Paul Keall Michael Jackson Anatoly Rozenfeld Michael Barton Peter Greer Peter Metcalfe David Thwaites Zdenka Kuncic Philip Vial Stephen Bosi Lois Holloway Enid Eslick Simon Downes Clive Baldock The University of Sydney Page 23

The ACRF Image-X Institute: Eradicating cancer through innovation in imaging and targeted X-ray therapy Australian Cancer Research Foundation Research Grant 2015-2020 $2,500,000 Paul Keall Michael Barton Michael Jackson David Thwaites Zdenka Kuncic Roger Fulton Kirsty Foster The University of Sydney Page 24

Nano-X: A new class of cancer radiotherapy system National Health & Medical Research Council Development Grant 2017-2019 $825,000 Paul Keall Ilana Feain Thomas Mackie Philip Prather Ben Wright Ricky O Brien Michael Jackson Michael Barton Peter Bennett The University of Sydney Page 25

Nano-X A Smarter and Smaller Cancer Radiotherapy System Clinical Rationale History Smarter Smaller Science Summary and Future The University of Sydney Page 26

The era of real-time radiotherapy: Tipping point is integration on a standard linac Dedicated systems Standard linac The University of Sydney Page 27

What real-time tools are available on standard linacs today? Multileaf collimator Hit the target X-ray imaging system Find the target The University of Sydney Page 28

A Kilovoltage Intrafraction Monitoring (KIM) patient treatment The University of Sydney Page 29

KIM achievements Treated patients Cancer sites >70 patients, >1000 fractions Prostate/Lung/Liver/Pancreas Continents Linacs North America/Europe/Australia 3 models 7 total Adaptation Gating (68) MLC tracking (5) Accuracy Phantoms <1mm, <1 degree Patients <1mm, <1.5 degrees Kim Phys Med Biol 2017 Kim AAPM 2017 The University of Sydney Page 30

MLC Tracking is 1 of 4 Real-Time Adaptation Systems Robotic linac CyberKnife Synchrony Clinical 2004 Gimbaled linac Vero/ Mitsubishi Clinical 2011 Robotic couch Clinical 20?? Widely available MLC Clinical 2013 Widely available Smallest, lightest 6 DoF Deformation The University of Sydney Page 31

Clinical status of MLC tracking Prostate Oct 2013 June 2015 Calypso-guidance Lung SABR July 2015 - Calypso-guidance Prostate SABR Nov 2016 - KIM-guidance 28 patients (858 fx) 7/20 patients (29 fx) 6 patients (70 fx) The University of Sydney Page 32

Nano-X A Smarter and Smaller Cancer Radiotherapy System Clinical Rationale History Smarter Smaller Science Summary and Future The University of Sydney Page 33

Nano-X key difference Only substantive difference and challenge is rotating the patient: Balance relative discomfort with clinical and economic gain Addressing via three clinical studies: An investigation into the patient experience of rotation in upright and lying positions completed 15-patient Omniax study Quantification of patient deformation during rotation MRI study using prototype patient rotation device The patient experience of rotation Nano-X prototype patient rotation device study The University of Sydney Page 34

Comparison of bunker sizes Conventional bunker Nano-X bunker Footprint Concrete required Conventional 54 m 2 102 m 3 Nano-X 17 m 2 35 m 3 Eslick TCRT 2014 The University of Sydney Page 35

Nano-X A Smarter and Smaller Cancer Radiotherapy System Clinical Rationale History Smarter Smaller Science Summary and Future The University of Sydney Page 36

Standard radiotherapy Nano-X radiotherapy Motion in radiotherapy Organ movement between imaging and treatment/between treatments Patient movement during treatment Organ movement during treatment due to e.g. breathing Patient movement during rotation (sliding at certain angles) Organ movement due to rotation (deformation from gravity) The University of Sydney Page 37

Science measure and correct for gravitational effects Shieh AAPM 2017 The University of Sydney Page 38

Science measure and correct for gravitational effects Conventional CBCT Uncorrected Nano-X Corrected Nano-X The University of Sydney Page 39

First prototype The University of Sydney Page 40

Recent Milestones Nov 2016 Jan 2017 March 2017 May 2017 June 2017 Animal rotation studies Linac installation Linac commissioning Patient rotation system installation Software control and integration The University of Sydney Page 41

Nano-X A Smarter and Smaller Cancer Radiotherapy System Clinical Rationale History Smarter Smaller Science Summary and Future The University of Sydney Page 42

Summary We are building a smarter and smaller Nano-X cancer radiotherapy system Real-time image guided radiotherapy is at the core of the design Future New patient rotation studies Veterinary treatments Build first clinical system Improve the global access to and quality of cancer radiotherapy Number of people served by each radiotherapy centre by country The University of Sydney Page 43