Tony Lomax Head of Medical Physics Paul Scherrer

Tony Lomax : : Head of Medical Physics : : Paul Scherrer Institute Dose delivery International Conference on Medical Accelerators and Particle Therapy – 4 -6 th September 2019

Overview of presentation 1. Proton therapy and its delivery 2. Improving lateral penumbra 3. Reducing treatment times 4. Protons for FLASH? 5. Summary Page 2

Overview of presentation 1. Proton therapy and its delivery 2. Improving lateral penumbra 3. Reducing treatment times 4. Protons for FLASH? 5. Summary Page 3

Proton therapy and its delivery Why protons for cancer therapy? 15 MV photons SOBP extent Dose target 177 Me. V protons Depth

Proton therapy and its delivery Making protons useful (1): Passive scattering 1 st scatterer 2 nd scatterer Target Range shifter wheel (fixed SOBP extent across field) Drift space

Proton therapy and its delivery Passive scattering for ocular tumours – a success story • Irradiation of eye tumors • > 7000 patients treated @ PSI • > 20% of all patients treated with proton world-wide • Tumor control rate of 98%

Proton therapy and its delivery Making protons useful (2): Pencil beam scanning Magnetic scanner Proton pencil beam Target Patient Change energy Pedroni et al 1995, Med. Phys. 22: 37 -53.

Proton therapy and its delivery Passive scattering and Pencil beam scanning compared Passive scattering Pencil beam scanning (PBS) Fixed SOBP extent

Proton therapy and its delivery The bottom line – Clinical results with PBS (PSI) Skull base tumours 222 Patients 7 y Local control: 80% Ependymomas 50 Patients 5 y Local control: 78% Sacral chordomas 36 Patients 5 y Local control: 66%

Proton therapy and its delivery The success of PBS By end of 2018, there are over 90 PBS treatment rooms around the world

Overview of presentation 1. Proton therapy and its delivery 2. Improving lateral penumbra 3. Reducing treatment times 4. Protons for FLASH? 5. Summary Page 11

Improving penumbra Lateral penumbras for proton therapy PS - Collimated PBS – Un-collimated 80 -20% penumbra

Improving penumbra Contour scanning The conventional approach: Rectilinear scanning Meier et al 2017, Phys. Med. Biol. 62 2398 -2416

Improving penumbra Contour scanning A more logical approach: Contour based Meier et al 2017, Phys. Med. Biol. 62 2398 -2416

Improving penumbra Contour scanning Rectilinear (A) Contour (B) Difference (B-A) Brainstem dose reduced by ~10% with contour scanning Meier et al 2017, Phys. Med. Biol. 62 2398 -2416

Improving penumbra Collimation for PBS proton therapy? PS - Collimated PBS – Un-collimated PBS – Collimated 1. 2 1. 0 0. 6 0. 4 Collimator Collimated PBS Collimator 0. 8 0. 2 0. 0 6 4 2 0 2 4 6 Winterhalter 2018, PMB 63(2): 025022

Improving penumbra Collimation for PBS proton therapy? Collimated contour scanning 0. 8 0. 6 0. 4 0. 2 0. 0 Meier et al 2017, Phys. Med. Biol. 62 2398 -2416 Collimator 1. 0 Collimator Relative dose 1. 2 6 4 2 0 2 Profile (cm) 4 6

Improving penumbra Collimated (energy specific) contour scanning Uncollimated PBS (A) Contour + collimation (B) Difference (B-A) Brainstem dose reduced by ~20% Winterhalter 2018, PMB 64(1): 015002

Overview of presentation 1. Proton therapy and its delivery 2. Improving lateral penumbra 3. Reducing treatment times 4. Protons for FLASH? 5. Summary Page 19

Reducing delivery times E. g. Line/continuous scanning Spot (discrete) scanning David Meer and Grischa Klimpki, PSI

Reducing delivery times E. g. Line/continuous scanning Spot (discrete) scanning c. f. ‘Step-andshoot’ c. f. ‘Slidingwindow’ Line (continuous) scanning David Meer and Grischa Klimpki, PSI

Reducing delivery times Line/continuous scanning Expected Discrete Continuous Treatment times for 0. 6 Gy delivered to a 300 ml target volume Spot scanning – 23 s Line scanning – 10 s David Meer and Grischa Klimpki, PSI

Reducing delivery times Spot reduction 4 field IMPT plan Bragg peaks (spots) for field 1 ~8250 spots per field Do we need so many ‘spots’?

Reducing delivery times Spot reduction Conventional PBS Spot reduced Spot reduction optimisation Lomax et al, ESTRO 2003, Geneva van de Water et al. Physics in Medicine & Biology 2013, 58 Belosi et al, PTCOG 57, Cincinnati, 2018

Reducing delivery times Spot reduction Conventional PBS Spot reduced Spot reduction optimisation ~8250 spots per field Lomax et al, ESTRO 2003, Geneva van de Water et al. Physics in Medicine & Biology 2013, 58 Belosi et al, PTCOG 57, Cincinnati, 2018 ~380 spots per field

Reducing delivery times Does this reduce treatment time? Conventional 6 Gy/s Conventional plan Spots/field Delivery time/field (s) Belosi et al, PTCOG 57, Cincinnati, 2018 ~8250 ~50

Reducing delivery times Does this reduce treatment time? Conventional 6 Gy/s Spot reduced Spot reduction Spots/field Delivery time/field (s) Belosi et al, PTCOG 57, Cincinnati, 2018 Conventional plan Spot reduced plan ~8250 ~380 ~50 ~28 6 Gy/s

Overview of presentation 1. Proton therapy and its delivery 2. Improving lateral penumbra 3. Reducing treatment times 4. Protons for FLASH? 5. Summary Page 28

Protons for FLASH? The FLASH effect – Whole brain irradiation of mice Irradiation: 10 Gy @ 0. 1 – 5 MGy/s (4. 5 Me. V electrons) Endpoints: Memory preservation (Recognition ratio) … result in ~20% increase in memory preservation… Dose rates > 30 Gy/s… Montay-Gruel et al Radiother Oncol 2017; 124: 365– 369 Page 29

Protons for FLASH? Proton dose rates Energy specific beam intensities at PSI Beam intensities 3300 Gy/s! without monitoring/ regulatory limitations 60 Gy/s 6 Gy/s Limited by monitoring and regulatory issues!

Protons for FLASH? PBS proton therapy for FLASH – How can we best exploit these intensities? Single energy (230 Me. V) [%] 107 95 80 60 40 20 Clinical Van de Water 2019, Acta Oncolgica Spot-reduced Shoot through Range compensated/ spot reduction

Protons for FLASH? PBS proton therapy for FLASH – How can we best exploit these intensities? Single energy (230 Me. V) [%] 107 95 80 60 40 20 Clinical Van de Water 2019, Acta Oncolgica Spot-reduced Shoot through Range compensated/ spot reduction

Protons for FLASH? PBS proton therapy for FLASH – How can we best exploit these intensities? Single energy (230 Me. V) [%] 107 95 80 60 40 20 Clinical Van de Water 2019, Acta Oncolgica Spot-reduced Shoot through Range compensated/ spot reduction

Protons for FLASH? PBS proton therapy for FLASH – How can we best exploit these intensities? Single energy (230 Me. V) [%] 107 95 80 60 40 20 Clinical Van de Water 2019, Acta Oncolgica Spot-reduced Shoot through Range compensated/ spot reduction

Protons for FLASH? Estimated dose rates for 6 Gy fraction Single energy (230 Me. V) [%] Dose distributions 107 95 80 60 40 20 Clinical Dose rate distributions Van de Water 2019, Acta Oncolgica Spot-reduced Shoot through Range compensated/ spot reduction

Protons for FLASH? Estimated dose rates for 6 Gy fraction Single energy (230 Me. V) [%] Dose distributions 107 95 80 60 40 20 Clinical Dose rate distributions Van de Water 2019, Acta Oncolgica Spot-reduced Shoot through Range compensated/ spot reduction

Protons for FLASH? Estimated dose rates for 6 Gy fraction Single energy (230 Me. V) [%] Dose distributions 107 95 80 60 40 20 Clinical Dose rate distributions Van de Water 2019, Acta Oncolgica Spot-reduced Shoot through Range compensated/ spot reduction

Protons for FLASH? Estimated dose rates for 6 Gy fraction Single energy (230 Me. V) [%] Dose distributions 107 95 80 60 40 20 Clinical Dose rate distributions Van de Water 2019, Acta Oncolgica Spot-reduced Shoot through Range compensated/ spot reduction

Summary • The 3 D localization of the Bragg peak allows for high degrees of modulation, leading to exquisite levels of dose conformation • PBS is currently the most flexible and (now) most widely used delivery modality • But improvements are still necessary… • Reducing treatment times • Improving lateral penumbra • FLASH compatible PBS • … • Whatever, there are still lots of interesting developments to be done in accelerators, beam delivery, medical physics, biology and clinics…

Thanks for your attention.