Proton beam therapy: the hope and the hype

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1 Proton beam therapy: the hope and the hype Professor Karol Sikora Chief Medical Officer Proton Partners International WelshConfed18

2 Protons The hope and the hype Professor Karol Sikora Chief Medical Officer Welsh NHS Confederation Conference 7 February 2018

3 The Evolution of Precision RT Cobalt, hand planning Cobalt to LINAC, computerisation Set geometric volumes to conformal MLC - refined conformal IMRT, IGRT, VMAT Protons, auto-contouring, SABR, breath-hold, objective QA, peer review of plans, MRI - LINAC, Adaptive RT Auto-planning and optimisation big data

$RT Improving selectivity - biology Biological optimisation Designer fractionation Combination with systemic CTX/ITX Increasing dose - reducing toxicity 2060 Local therapy Single fraction Radiosurgery$

4 4 Radiotherapy to 2030 Improving geometry - physics Multimedia imaging Understanding differential sensitivity IMRT-IGRT increased precision Particle therapy - Bragg peak Auto contouring and adaptive RT Improving selectivity - biology Biological optimisation Designer fractionation Combination with systemic CTX/ITX Increasing dose - reducing toxicity 2060 Local therapy Single fraction Radiosurgery - SABR Tumour reduction prior or after CT/ITX

5 Extending the Location of Cancer Services Impact Palliative and social care CANCER CENTRE Symptom control Community centres including expanded range of IV infusions and RT Radiotherapy and chemotherapy Time

7 Future Radiotherapy Networks Day centres for cancer care including RT Global networks for RT planning and delivery Rapid diffusion of high level expertise Real time QA and eradication of variability Platform for innovation in RT Training vehicle for technical staff Quality care closer to home Cost effective

proximal distal Combine multiple proton beams with different energies to create a Spread Out Bragg Peak uniform dose across tumour lower dose to

8 proximal distal Combine multiple proton beams with different energies to create a Spread Out Bragg Peak uniform dose across tumour lower dose to healthy tissue in front of tumour zero dose to healthy tissue behind tumour But costs are high Advantages of Protons Spread Out Bragg Peak (SOBP)

9 Cumulated number of patients Number of centres operational Global PBT centres/patients 2017 (actual) 2020 (expected ) increase PBT centres % Treatment rooms % LINACS 13,000 15,000 13% year 1990 first hospital multi-room Loma Linda - USA 2001 first commercial PBT system MGH, USA 1995 first PBS PSI, Switzerland

10 Indications for PBT Hard indications, mainly paediatric Tumours where a significant proportion of patients may benefit Patients where the anatomy of tumour and OAR favour protons VALUE = CLINICAL GAIN (tumour control - toxicity) COST OF TREATMENT

11 Estimates of Proton Demand in the UK Study Population Proton/year Proton/ photon Predicted proton UK Machines UK Georgia ,737 20% 18, Sweden 9.7 2,220 14% 12, Italy ,023 13% 11, Holland ,000 10% 9, Rhode Island 10% 9, Lyon 6.2 5,270 12% 10, UK 64 1, % 1, : 150,000 total RT courses 90,000 radical 2: 500 patients per machine annually 6 days, 12 hours a day, 20F per patient

12 Proton therapy as planned % of radical RT by NHS NHS 2020 HOLLAND SWEDEN ITALY DENMARK FRANCE USA USA

13 Current NHSE PBT Overseas Programme Currently the NHSE pays treatment centres overseas to treat eligible patients Referral to USA mainly Jacksonville Currently being reviewed and potentially expanded medulloblastoma Procurement process Essen Ref:

15 Rutherford Cancer Centres PBT indications All NHS England indications All brain tumours Prostate Left sided breast internal mammary nodes Head and neck Rectum and anus Oesophagus Lung Pancreas Lymphoma

16 Paediatric medulloblastoma Advantages of Protons they stop

17 Tomotherapy IMPT Advantages of Protons Mengingioma

heart Increased life expectancy, phase II, MD Anderson Lung Cancer PBT reduces

18 Clinical Reality Solution with PT Side effects: pneumonitis heart disease Reduction of Side effects: Reduced dose to contra-lateral lung Reduced dose to heart Increased life expectancy, phase II, MD Anderson Lung Cancer PBT reduces dose to heart and contra-lateral lung Phase III randomised trial ongoing RTOG 1308

19 Left breast IMRT

20 Left breast IMPT

loss of taste/loss of weight 50% less feeding

21 IMRT IMPT Side effects: Fatigue/loss of taste/loss of weight Feeding tube during treatment Long-term swallowing issues Reduction of Side effects: Reduced fatigue, loss of taste/loss of weight 50% less feeding tubes during treatment Reduced swallowing issues Head and neck Cancer PBT reduces xerostomia and dysphagia Phase II/III randomised trial ongoing NCT

22 Prostate VMAT

23 Prostate IMPT

24 Prostate nodes VMAT

25 Prostate nodes IMPT

26 122 active PBT trials >50,000 patients

27 Cancer Endpoint Patients Completion Adv NSCLC OS, toxicity Adv NSCLC OS Adv NSCLC TTF Early prostate PSA, toxicity Gd 4 glioma TTF Oesophageal PFS Early breast CVS toxicity, OS Oropharyngeal Toxicity, OS Randomised proton-photon trials (Mishra et al, IJRO, 97, 228, 2017)

29 IBA Proteus One single room 230MeV 220 Gantry (180 to -40 ) with PBS + CBCT

30 Rigging in one day

31 Enhances privacy and staff workflow Welcome Clinical Desk Anesthesia / Admin Set-up Prepare Irradiation LINAC like control desk

32 PBT Commissioning Newport

33 Our network of centres South Wales North East Thames Valley North West

34 Gulf International Cancer Centre

35 UCLH Proton Beam Therapy Centre SEPTEMBER 2017 JANUARY 2018

36 Rutherford PBT provision 2020

37 Network of treatment centres One clinical team across multiple sites: Site-based staff and central staff all using shared central system Standardised protocols and treatments processes defined by setup PCs on site access O.I.S & T.P.S servers in datacentre via Citrix One planning team across multiple sites : each physicist & dosimetrist has own laptop (plug into large screens): use Citrix client to run O.I.S, T.P.S., other centralized software Outlook, Office etc. work in a centre, at home, anywhere all planners/checkers can plan/check for any patient/any site Lync/Business Skype calling & screen-sharing for planning, review, training Mentorship and peer review from UPenn, Philadelphia

38 Centralised servers Oncologists can work remotely: access via citrix client on PC, laptop, Macbook, ipad, tablet, broadband, 4G: Treatment Planning (TPS) contouring, plan review Record & Verify (OIS) plan approval, IGRT review, documentation Treat patients on any site Shared resources for all sites: benefits of upgrades, new functionality immediately available to all staff/sites changes in process/setup apply to all (paperless working) data from all sites stored and analysed in one location Disaster Recovery has many more options. (and collectively cheaper)

39 Proton uncertainties Magnitude of lateral penumbra Distal edge degradation RBE across Bragg peak Range inaccuracies in delivery Importance of integral dose reduction Secondary neutron production Correlation of optimal planning to NTCP

Conclusion 10% patients having radical RT optimal with PBT PPI is building a network of 6 UK proton centres Full integration of clinical systems across all sites Central storage of all clinical,

40 Conclusion 10% patients having radical RT optimal with PBT PPI is building a network of 6 UK proton centres Full integration of clinical systems across all sites Central storage of all clinical, imaging and RT data Mix of NHS, PMI and self pay patients Funding in place for 6 UK centres - beam on Q International model with Abu Dhabi and Dublin Selection for proton based on double planning and NTCP

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