1. Division of Radiation Oncology,
ASTRO 2016
Chumpot kakanaporn
Division of Radiation Oncology,
Siriraj Hospital, Mahidol University

2. University of Maryland President and CEO, Xcision Medical Systems, LLC
Cedric Yu, PhD
Professor
University of Maryland
President and CEO, Xcision Medical Systems, LLC
Richard Maughan, PhD
Emeritus Professor
University of Pennsylvania
Bulent Aydogan, PhD
Associate Professor & Director of Medical Physics
University of Chicago
Thomas Delaney, MD
Medical Director, Francis H. Burr Proton Therapy Center, MGS
Harvard Medical School
Stephen Hahn, MD
Professor and Chair of Radiation Oncology, UT MD Anderson Cancer Center

6. A) Yes
B) No

8. A) Yes
B) No

9. A. False
B. True

11. The work of the Massachusetts General Hospital has tested a number of hypotheses:

12. The answer is mixed.
•There is undoubtedly less of a “dose bath” to the anterior and posterior tissues but
•More radiation passes through the femoral heads and
•High-dose volume is actually a little larger with protons than IMRT (because of beam uncertainty)

13. •Two regions associated with morbidities
•the prostatic urethra
•peri-prostatic nerve bundles are treated equally with the two techniques.
•The volume of rectum treated dose not depend on the delivery technique. Likely to depend more on
•image guidance
•choice of margins
•use of a rectal balloon

14. A) Yes
B) No

15. VMAT
New Photon RT

16. VMAT
4π RT
IMPT

17. A) Lung
B) Esophagus
C) Prostate
D) GBM

18. A) It can provide better dose conformality
B) It has biological advantage
C) We have clinical evidence
D) No, it will not be.

19. A) Economics
B) Lack of clinical evidence
C) Organ motion, uncertainties etc.
D) Technology has not matured yet

20. Proton Will Be the Eventual Standard for Radiation Treatment
Photons Will Define the Future of RT
Cedric Yu, D.Sc
Proton Will Be the Eventual Standard for Radiation Treatment
Richard L Maughan, Ph.D.

21. Photons Will Define the Future of RT
Cedric Yu, D.Sc

22. Has Photon RT Reached it limits?
Future: Inject New Freedom into Photons,
NOT Wide Adoption of Protons

23. Why Not Protons? • Technology
• More complicated, therefore harder to advance
• Physics
• Penumbra, Bragg Peak uncertainty
• Sensitive to anatomical variations
• Interplay effects with organ motion
• Biology
• RBE uncertainty
• Economy

24. Proton Treatment Facility
Treatment time per patient at UMD: ~30 minutes
Less time for single room solutions

25. Treatment Control
1. At a given time, only one room can have proton beam
2. All treatments in all rooms are centrally controlled
3. Techniques common with photons are difficult with protons
– Arcs
– MRI guidance
– Motion tracking/gating

26. Why Not Protons? • Technology
• More complicated, therefore harder to advance
• Physics
• Penumbra, Bragg Peak uncertainty
• Sensitive to anatomical variations
• Interplay effects with organ motion
• Biology
• RBE uncertainty
• Economy

27. Lateral Penumbra
The dose penumbra at deeper depth is less steep for Proton beam (6-10mm) than for photon beams

28. Effects of large penumbra
S.J. Gandhi et al: Practical Rad Oncol

29. Why Not Protons? • Technology
• More complicated, therefore harder to advance
• Physics
• Penumbra, Bragg Peak uncertainty
• Sensitive to anatomical variations
• Interplay effects with organ motion
• Biology
• RBE uncertainty
• Economy

30. LET

31. Economy: Simple Proton Math
60 patients/day ≈ 12,000 Tx/yr ≈ $12M/yr
Service ≈ $4M/yr,
Electricity etc. ≈ $1M/yr,
Salary (40 employees) ≈ $7M/yr
Initial capital $ must be FREE for it to work!

32. Economy and Societal Considerations
Any country can only devote a certain percentage of GDP to health care, building a large number of proton centers may hurt healthcare as a whole.

33. Developing photon RT is the right route!

34. How to Improve Photon Plan Quality?
“The DVHs or subsequently derived biological scores depend on the total number of strata, ....”
In coplanar IMRT and VMAT, we are only using independent apertures!
Is it true that increasing the number of independent apertures will improve plan quality?

35. 4π RT

36. 4p RT for Liver Cancer
Peng Dong et al: Int J Rad Oncol Biol Phys. 85(5), 2013

37. Compared with 4π RT
Dong P, Int J Radiat Oncol Biol Phys 2013; 85:1360-6
S.J. Gandhi et al: Practical Rad Oncol

38. Compared with 4π RT for Lung Cancer Coplanar
Dong P, et al. Int J Radiat Oncol Biol Phys 2013; 86(3):pp

39. Compared with 4π RT: Prostate Cancer

40. Conclusions
• Lack of improvements in photon dosimetry over last 20 years led people to mistakenly think that photon RT has reached its limits
• By adding IMRT fields from non-coplanar angles, 4p RT has shown better than proton dose distributions
• The high costs of acquiring and operating proton facilities makes widespread use economically unfeasible
• Shortcomings of protons in physics and biology cannot be improved with technology, which is already complicated and hard to improve
• Therefore, the dosimetric advantage of protons will be short-lived, the future of RT will be defined by photons

41. Proton Will Be the Eventual Standard for Radiation Treatment
Photons Will Define the Future of RT
Cedric Yu, D.Sc
Proton Will Be the Eventual Standard for Radiation Treatment
Richard L Maughan, Ph.D.

42. Proton Will Be the Eventual Standard for Radiation Treatment
Protons II: Physics Perspective
Richard L Maughan, Ph.D.
ASTRO Annual Meeting
September 25, 2016

43. The Rationale -Improved Dose Distribution
It looks obvious –no brainer
But is it?
Obviously not or we wouldn’t be here today!
To understand why it’s not obvious we need to understand how proton beams are delivered

44. Proton Beam Delivery Options
Proton beams have small lateral dimensions and a sharp Bragg peak in the depth dimension. They are also monoenergetic.
To be clinically useful for treating large tumors the beam must be spread both in the lateral direction and in depth.
There are two beam delivery options most commonly used today, these are:
1.Passive Scattering
2.Modulated Scanning (aka Pencil Beam Scanning –PBS)

45. Passive Scattering
Passive scattering requires beam modifying devices to shape the beam.

46. Pencil Beam Scanning
For PBS we do not need scatterers, a modulator or a customized aperture and compensator.
All we need is the proton beam and some bending magnets to provide lateral tumor coverage
And a means of varying the energy of the beam entering the treatment room to provide coverage in the depth dimension.

47. Pencil Beam Scanning PBS produces proximal edge conformality
A full set, with a
homogenous dose
conformed distally
andproximally

48. PBS Has Many Advantages
PROs:
Eliminates the need for custom apertures and compensators.
• Can treat deeper depths because no energy is lost in scatterers.
• Can treat larger fields without matching.
• Produce fewer neutrons.
• But most importantly it gives better treatment plans because
Conforms dose better to the proximal side of the target.
Allows for IMPT
CONs:
How to deal with moving targets?

49. Protons Are a Newer Modality Than You Think
The total number of patients treat with protons at the end of 2014 was approximately 120,000.
Of these about 25,000 were patients receiving treatment for ocular tumors.
It is estimated that less than 7,500 of the 120,000 patients were treated with pencil beam scanning (PBS).
Most of the PBS patients have been treated using techniques which deliver a uniform dose across the field.
But the ultimate proton dose conformality may be achieved with IMPT and very few patients have been treated with this technique, probably less than 2,500.

50. Vision Tree Question YES b) NO
Do you believe that the physical advantages of proton beam therapy delivered with pencil beam scanning (i.e. lower entrance dose, Bragg peak and no exit dose) over conventional x-ray therapy should be sufficient to justify its more wide spread application for treating curative patients
YES
b) NO

51. How Do We Realize The Full potential Of Proton Therapy?
Implement the most advanced treatment delivery techniques; PBS and Intensity Modulated Proton Therapy (IMPT).
Improve range uncertainty: pretreatment through improved stopping power determination using innovative imaging techniques and through range verification during and post treatment.
Provide improved treatment planning algorithms.
Provide less expensive equipment options.
Demonstrate clinical efficacy through clinical “trials”, but using the most advanced delivery techniques.

52. Range Uncertainty Why is there range uncertainty?
•Because there is no direct information on the stopping power of protons in the different body tissues.
How do we determine stopping power now?
•By calibrating stopping power against Hounsfield number from a CT. The problem is that HU is proportional to electron density, but stopping power is dependent on the exact atomic composition of tissue ( i.e. the exact percentage of H, O, C, N etc) and this is not proportional to electron density.
How does this effect range uncertainty?
•Many factors effect overall range uncertainty but stopping power is a major contributor. Improving stopping power uncertainty, could lead to improved treatment plans through reducing planning margins.

53. Future of Proton Therapy
PBS and IMPT.
•With improved knowledge of stopping power/range.
•Delivered with improved treatment planning.
•Verification of range.
All these improvements are in progress and will be available within the near future and will result in significant improvements in beam targeting, further leveraging the proton dose distribution advantage.

54. Prospects For New Technologies
Some Innovative Accelerator Technologies to Reduce Capital Costs
Wakefield/Laser Accelerators
Cyclotrons with Yokeless Magnets

55. Laser Accelerator for Protons

56. Yokeless Magnet 1990 Yokeless Cyclotron Patent.
“There is no iron yoke for the magnet and the weight and size are consequently much reduced and the cyclotron is highly transportable.”
The design was for a 17 MeV proton cyclotron.
MIT Paper:

57. Prospects of New Accelerator Technology
New technology accelerators are likely to be long term solutions –greater than 10 years.
Therefore, we must look at other options for capital cost containment based on the existing technology –cyclotrons, synchrotrons and synchrocyclotrons.
The solution seems to be compact design and simple systems:
•Simplifying the system by delivering pencil beam scanning only reduces costs
•Compact accelerators –superconducting cyclotrons and compact synchrotron designs
•Compact gantries –with or without superconducting magnets
•Fixed beam delivery with the patient in a chair

58. Compact Solutions

59. Growth in Number of Single Room Facilities

60. Growth in Number of Proton Facilities

61. Vision Tree Question
Given that one room PBS proton therapy systems are now available and that many of the most recent sales have been for this type of facility, how likely do you think it is that your Institution would consider providing proton beam therapy for your patients.
a) Definitely
b) Very likely.
c) Reasonably likely.
d) Reasonably unlikely
e) Very Unlikely.
f) Definitely not.

62. Conclusions
Although many patients have benefited from proton treatment with passively scattered beams, the number of anatomical sites has been limited. PBS and IMPT allow the scope of proton therapy to be increased.
Advances in imaging allow for better stopping power determination, combined with range verification and improved treatment planning will lead to improved dose targeting.
Future “trials” and comparisons should use PBS and IMPT to provide the best dose distributions.

63. “Proton Will Be the Eventual Standard for Radiation Treatment”.

64. “Proton Will Be the Eventual Standard for Radiation Treatment”.
What is Standard?
Is the Standard: 3-D Conformal, IMRT / Rapid Arc, SRS, SBRT, Brachytherapy or Proton Therapy?
Is the standard the one of these modalities used to treat the most patients with curative intent?
It doesn’t really matter. What matters is that whatever treatment a patient receives it is the one best suited to their situation.
All these modalities have a role, it is our job to make the treatment fit the patient’s disease in the best possible way.
The physics tells us that proton beams have the potential to produce the best dose distributions, does this make protons the choice to be the most used modality in curative cases?

65. Final Comment At Penn Proton is the Standard for Radiation Treatment.
At the University of Pennsylvania we have a fully integrated photon and proton department:
•5 Linacs + 5 Proton treatment rooms, under one roof.
•Physicians have equipoise –they decide which is the most appropriate treatment with no pressure.
On Friday, September 16, 2016 we had 214 patients under treatment:
•Photons -117
– ~88Curative (including ~10 to15 SBRT)
– ~29Palliative
•Protons -97
– 97 Curative
– 0 Palliative
At Penn Proton is the Standard for Radiation Treatment.

66. ขอบคุณค่ะ.