1. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Future directions and current challenges of proton therapy Tony Lomax, Centre for Proton Radiotherapy, Paul Scherrer Institute, Switzerland CT after 5 weeks Planning CT

2. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Overview of presentation 1.State-of-the-art proton delivery 2.Current challenges 3.New directions in proton therapy 4.Summary

3. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 State-of-the-art proton delivery Passive scattering Range-shifter wheel Collimator Compensator Target Patient Scatterer

4. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Spot scanning Pedroni et al, Med Phys. 22:37-53, 1995 Target Magnetic scanner ‘Range shifter’ plate Patient Proton pencil beam State-of-the-art proton delivery

5. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 The present and future of proton therapy? Passive scattering (patched fields) Collimators and compensators required for each field Intensity Modulated Proton Therapy (IMPT) Fully automated delivery (scanning) State-of-the-art proton delivery

6. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Sarcoma – 12 year old boy Delivered single field plan 9 field IMRT plan Factor 6 lower integral dose for protons State-of-the-art proton delivery

7. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Integral dose and secondary cancer risk State-of-the-art proton delivery K Haeller, PSI N Tarbell, ASTRO, 2008 Study comparing 503 proton patients to 1591 photon patients (treated 1974-2001) showed a 50% reduction in secondary tumours in proton patients

8. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Overview of presentation 1.State-of-the-art proton delivery 2.Current challenges 3.New directions in proton therapy 4.Summary

9. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 The advantage of protons is that they stop. Range uncertainty The disadvantage of protons is that we don’t always know where… 10% range error Current challenges: range uncertainty

10. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 S. Mori, G. Chen, MGH, Boston Current challenges: range uncertainty Tumour shrinkage Initial Planning CT GTV 115 cc 5 weeks later GTV 39 cc

11. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Planning CT CT after 5 weeks Beam stops at distal edge Beam overshoot S. Mori, G. Chen, MGH, Boston Tumour shrinkage Current challenges: range uncertainty

12. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Patient weight changes 3 field IMPT plan to an 8 year old boy Note, sparing of spinal cord in middle of PTV Planning CT New CT During treatment, 1.5kg weight gain was observed Max range differences: SC 0.8cm CTV 1.5cm Francesca Albertini and Alessandra Bolsi (PSI) Current challenges: range uncertainty

13. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Current challenges: range uncertainty CT artefacts Many patients referred for RT post-operatively and with metal (titanium) stabilisation How accurately can we calculate proton ranges in such CT data sets?

14. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Months 0.2.4.6.8 1 0102030405060 Without implant (n = 13) Implants (n =13) 3-yr, 5-yr 100% 3-yr 69% 5-yr 46% Chordomas and chondrosarcomas of the spinal axis Rutz et al 2007, IJROBP, 67, 512-520 Current challenges: range uncertainty

15. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Martin von Siebenthal, Phillipe Cattin, Gabor Szekely, Tony Lomax, ETH, Zurich and PSI, Villigen What is the effect of organ motion on proton therapy? 4D-CT derived from 4D-MRI Current challenges: organ motion Organ motion

16. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Organ motion and passive scattering Current challenges: organ motion Images courtesy of Thomas Bortfeld, MGH, Boston Parallel opposed photons Single field photons Single field protons

17. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Organ motion and passive scattering Current challenges: organ motion Images courtesy of Thomas Bortfeld, MGH, Boston Parallel opposed photons Single field photons Single field protons

18. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Martin von Siebenthal, Phillipe Cattin, Gabor Szekely, Tony Lomax, ETH, Zurich and PSI, Villigen A scanned beam in a moving patient. 4D-CT derived from 4D-MRI Current challenges: organ motion Organ motion and scanning

19. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Nominal (static) dose Calculated with ‘real’ motion from 4D-MRI of volunteer Organ motion and the ‘interplay’ effect Current challenges: organ motion

20. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Dose (%) Volume (%) 70 80 90 100 110 120 0 20 40 60 80 100 Dose (%) Volume (%) 70 80 90 100 110 120 0 20 40 60 80 100 Motion patient 1 Amplitude ~ 11mm Motion patient 2 Amplitude ~ 8mm Organ motion and the ‘interplay’ effect Current challenges: organ motion Scanning is particularly sensitive to organ motion

21. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Adenoid cystic carcinoma with node involvement Current challenges: treatment gantries Tricky to do without a gantry…

22. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Current challenges: treatment gantries Avoiding density heterogeneities Heterogeneity index Each point is a different field calculated for the same skull base case A comparison of MC and analytical dose calculations as a function of density heterogeneities

23. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Field Applied plan‘Standard’ plan Gantry angle Table angle Density heterogeneit y index Gantry angle Table angle Density heterogeneit y index 1-45-90 20.4 -90-120 28.2 2-100 12.9 -90-60 30.2 3-120 12.7 600 26.2 Avoiding density heterogeneities Current challenges: treatment gantries

24. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Current challenges: treatment gantries 3.5m diameter PSI gantry 1 7m diameter PSI gantry 2 12m diameter Loma Linda 15m diameter Heidelberg Could this be the main limit to the spread of particle therapy?

25. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Overview of presentation 1.State-of-the-art proton delivery 2.Current challenges 3.New directions in proton therapy 4.Summary

26. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 New directions in proton therapy 1.Possible improvements to passive scattering 2.Dealing with range uncertainties 3.Organ motion and scanning

27. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 New directions in proton therapy 1.Dealing with range uncertainties 2.Organ motion and scanning 3.Gantry design

28. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Imaging for range Ospedale San Rafaele, Milan Francesca Albertini, PSI kV-CT MV-CT (Hi-Art) MV-CT Proton radiograph Proton DRR Proton radiography Uwe Schneider, Zurich Alexander Tourovsky, PSI Measured PET activation Calculated PET activation Activation PET Katia Parodi, Thomas Bortfeld MGH, Boston Dealing with range uncertainties

29. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Robust planning techniques Tumour Spinal cord Lomax et al.:Med. Phys. 28(3): 317-324, 2001 Example paraspinal case Nominal plan 10% overshoot Dealing with range uncertainties

30. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 3 patched, intensity modulated fields.......give a homogenous dose without the use of fields that abut distally against the spinal cord Robust planning techniques Lomax et al.:Med. Phys. 28(3): 317-324, 2001 Dealing with range uncertainties

31. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 10% overshoot plans IMPT Single field IMPT Nominal plans Single field IMPT plan Nominal Overshoot Nominal Overshoot Relative dose Relative volume D tol DVH analysis Spinal cord Robust planning techniques Dealing with range uncertainties

32. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Range adapted proton therapy Dealing with range uncertainties Alessandra Bolsi, PSI

33. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Work of Alessandra Bolsi. Dealing with range uncertainties Alessandra Bolsi, PSI Range adapted proton therapy

34. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Alessandra Bolsi, PSI Dealing with range uncertainties Range adapted proton therapy

35. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Dealing with range uncertainties Alessandra Bolsi, PSI Range adapted proton therapy

36. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 New directions in proton therapy 1.Dealing with range uncertainties 2.Organ motion and scanning 3.Gantry design

37. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Repaint scanned beam many times such that statistics dictate coverage and homogeneity of dose in target (c.f. fractionation) Organ motion and scanning Rescanning

38. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Rescanning 4s period Re-scanning in presence of Cos 4 motion with 1cm amplitude Cylindrical target volume Re-scanned different times to same total dose Scan times calculated for realistic beam intensities and dead times between spots Analysis carried out for different periods of motion Marco Schwarz, Silvan Zenklusen ATREP and PSI Not always improving homogeneity with number of re-scans! Organ motion and scanning

39. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Rescanning The ‘synchronicity’ effect Very preliminary results A ‘real’ effect for perfectly regular breathing? Could well be less of an issue when breathing is more irregular For regular breathing, could be avoided by selecting the re- scanning period to avoid effect or varying period scan-to-scan Probably not a big issue in reality See presentation from Silvan Zenklusen, Saturday Organ motion and scanning

40. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Track motion of tumour using scanning system based on some anatomical/physiological signal Tracking Organ motion and scanning

41. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Steven van de Water, PSI/TUDelft Tumour Tracking Plot of dose homogeneity as function of RMS position error due to motion and ‘imperfect’ tracking Cos 4 motion with varying detection delays and tracking accuracies ~ 150ms delay Vedam et al 2004 Organ motion and scanning

42. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Steven van de Water, PSI/TUDelft Tumour Tracking Re-tracking – tracking the tumour repeatedly within one fraction E.g. 4 times ~ 150ms delay Vedam et al 2004 Organ motion and scanning

43. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 New directions in proton therapy 1.Dealing with range uncertainties 2.Organ motion and scanning 3.Gantry design

44. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Still rivers systems single room proton facility Gantry design DWA based proton tomotherapy Probably the biggest step forward for particle therapy would come from a significant reduction in gantry size To stay competitive with other therapies for the next 25 years, treatment gantries will almost certainly be necessary

45. PAUL SCHERRER INSTITUT Future directions and current challenges of proton therapy Tony Lomax, Oxford, 2008 Summary Although passive scattering is still the preferred choice for proton therapy, scanning and IMPT will become more widespread in the next years (c.f. MD Anderson) To what extent can scattering be improved through the use of automated field hardware (MLC’s etc)? Range uncertainty and organ motion (particularly for scanning) remain the main challenges to proton therapy and much interesting and exciting work is still to be done in organ management, range imaging and adaptive proton therapy The field is ripe for new input, ideas and innovations…