This slide includes physical, biological properties of proton and its advantage over the photon. It also provides information from beam production to treatment planning system of proton therapy, its potential applications, cost effectiveness and demerits.

1. BY Dr Deepak kumar Das
Moderator- Dr Renu Madan
Assistant Professor
PGIMER

2. Radiation therapy
 Established treatment modality since over 100 years [1st
treatment in 1896, one year after discovery of X-ray]
 60-70 % of all cancer patients require radiotherapy as a
modality during their cancer course.
 Curative modality in 25-30% of cancers

3. Types Of Radiation
 Photons
 X ray
 Gamma ray
 Particulate radiation
 Electrons
 Protons
 Neutrons
 Heavy ions

4. THERAPEUTIC RATIO

5. RATIONALE
Relative dose distribution

6.  Constant principle in radiation oncology is that higher or more
intense the radiation dose, the greater the probability of tumour
control
 The primary barrier to maximising local tumour control through
dose escalation or intensification is the risk of damaging normal
tissues either by delivering too high dose or exposing too much of
the normal tissue to radiation.
 In most clinical settings, there is an opportunity for improvement
of therapeutic ratio by increasing disease control or by reducing
toxicity.
 The most direct means of improving the therapeutic ratio is by
reducing dose to non-targeted tissues, which both reduces toxicity
and facilitates dose escalation for increased tumour control
Herein lies the rationale for proton therapy

7. Limitations of Conventional Photon
based treatments
-Significant exit dose
-Dependent biological effect on
oxygen (indirect effect; 70-80%)
-Dose escalation not possible
beyond a limit
-Second malignancies

8. Problem with X-Rays and the promise and
challenge of protons

9. Proton dose distribution
 Depends on the concept of Linear energy transfer (LET)
 LET is defined as dE/dx, where dE is the mean energy
deposited over a distance dx in media.
 The rate of energy loss due to ionisation and excitation
caused by a charged particle travelling in a medium is
proportional to the square of the particle charge and
inversely proportional to the square of its velocity.
 As the particle velocity approaches zero near the end of its
range, the rate of energy loss becomes maximum.
 The sharp increase or peak in dose deposition at the end of
particle range is called the Bragg peak.

10. Proton dose distribution
 Low entrance dose (plateau)
 Maximum dose at depth
(Bragg peak)
 Rapid distal dose fall-off
Photons Protons

11. The Bragg peak of a monoenergetic proton beam is too narrow to cover the extent of
most target volumes.
In order to provide wider depth coverage, the Bragg peak can be spread out by superim-
position of several beams of different energies.
Called as spread-out Bragg peak (SOBP).
SOBP
Active modulation Passive modulation
Problems with Bragg peak

12. SOBP
 Active modulation
 Passive modulation

13. SOBP
Active modulation Passive modulation
 A beam of particles of fixed
energy is attenuated by range
shifters of variable thickness
 Collimators & compensators
are used
 Treatment planning is simple
 Disadv.- significant dose is
delivered along the entrance
path
 A tightly focused pencil beam
is deflected by 2 magnetic
dipoles to allow scanning of
the beam over t/t field
 Energy of the incoming beam
is varied during t/t
 Dose distribution can be
tailored to any irregular tm
 Treatment planning is
complex

14.  A safety margin is added
for the movement
 Increased nuclear
fragments (including
neutrons) are produced
by nuclear interactions
with beam modifiers
 Extremely sensitive to
movements of the target
 Integral dose is
minimized.

15. RBE
RBE OF PROTONS IS 1.1
In clinical practice, RBE of 1.1 is generally used (Same as photons but with better physical
properties)
However, RBE changes as there is change in LET (LET increases when energy decreases
towards the end of the range)
There is rapid rise in RBE during last several mm3 of the proton range producing
an RBE value of 1.3.
 Actual RBE corrected dose may exceed physical dose by 25% at the end of the
spectrum
Relative biologic efficiency is
a ratio of doses from two
beams to produce the same
effect

16. Conception of proton therapy
-1946 Harvard physicist Robert Wilson :
 Protons can be used clinically
 Maximum radiation dose can be placed
into the tumor
 Proton therapy provides sparing of
healthy tissues
 Early proton: for research only
 1990: First hospital based proton
therapy facility was opened at the Loma
Linda University Medical Center
(LLUMC) in California.

17. Proton therapy
 1954: First treatment of
pituitary tumors
 1958 : First use of protons as
a neurosurgical tool
 1990: First hospital based
proton therapy facility was
opened at the Loma Linda
University Medical Center
(LLUMC) in California.

18. Proton Therapy : An Emerging
Modality
42 centers in operation worldwide.
26centers are under construction (To be started by
2014-2016)
96537 patients have been treated till date
**www.ptcog.web.psi.ch

19. BASIC PHYSICS
 The Existence of proton was first demonstrated by
Ernest Rutherford in 1919
 Proton is the nucleus of hydrogen atom
 It has a positive charge of 1.6 x 1019 c
 Its mass is 1.6x10-27 kg(1840 times of electron)
 It is the most stable particle in universe with half
life of >1032 years

20. Proton Interactions
It interacts with electrons and atomic nuclei in the
medium through coulomb force
a. Inelastic collisions
b. Elastic scattering
Protons scatter through smaller angles so they have
sharper lateral distribution than photons

21. Mass Stopping Power
 It is more with low atomic number materials and
low with high atomic number materials
 High Z materials= Scattering
 Low Z materials= Absorption of energy and slowing
down Protons

22. Unit of dose delivered
 Dose delivered with particles are prescribed in Gray
equivalents(GyE)
 Cobalt Gray equivalents(CGE) often used with protons
 These units are equal to measured physical dose in
Gray times the specific RBE of the beam used
 For protons absorbed dose is multiplied by 1.1 to
express the biologic effective proton dose

23. Components of proton beam therapy
 Proton accelerator
 Beam transport
system
 Gantry
 Treatment delivery
system

24. GENERATION OF PROTON
 Protons are produced from hydrogen gas
1. Either obtained from electrolysis of deionized
water
or
2. commercially available high-purity hydrogen
gas.
 Application of a high-voltage electric current to the
hydrogen gas strips the electrons off the hydrogen
atoms, leaving positively charged protons.

25. Proton Accelerators
 Linear Accelerator
 Cyclotron
 Synchrotron
 High gradient Eletrostatic Accelerator
 Laser Plasma particle Accelerator

26. Cyclotron
Two short metallic cylinders, called Dees
Placed between poles of direct magnetic field
An alternating potential is applied between Dees.
Frequency is adjusted of alternating potential to accelerate the particle as it passes
from one Dee to another.
With each pass, the energy of the particle and the radius of the orbit increases.

27.  Fixed energy machine
 Many cyclotron have an energy limit of only upto 70 Mev which
suits them only for treating superficial tumors (orbital tumors)
 In order to treat all common tumors in human body,
cyclotronshave to be able to deliver a beam with energy upto
about 230 Mev (range 32 cm)
 Cyclotrons can produce a large proton beam current of up to
300nA and thus deliver proton therapy at a high dose rate
 Energy Degraders
Modify Range and intensity of beam
 Energy selection system (ESS)
consist of energy slits, bending magnets, and focusing
magnets, is then used to eliminate protons with excessive energy
or deviations in angular direction.

28. Disadvantage of cyclotron
 Inability to change the energy of extracted particles
directly
 Energy degradation by material in the beam path leads
to an increase in energy spread and beam emittance
and reduces the efficiency of the system
 More shielding is required because of secondary
radiation

29. SYNCROTRON
 Produce proton beams of selectable energy, thereby
eliminating the need for the energy degrader and
energy selection devices
 Beam currents are typically much lower than with
cyclotrons, thus limiting the maximum dose rates that
can be used for patient treatment, especially for larger
field sizes
The maximum dose rate available from a commercially
available synchrotron based proton delivery system for
25×25 cm2 field has been specified at 0.8Gy per
minute.

30. Proton pulse exiting a pre-accelerator, with energy typically upto 7 MeV is injected
into ring shaped accelerator.
Each complete circuit of the proton pulse through the accelerator increases the
proton energy.
 When the desired energy is reached, the proton pulse is extracted from the
applicator.

31. Beam line/ transport system
 The proton beam has to be transported to the treatment room(s) via the beam
transport system.
 Consists of bending and focusing magnets and beam profile monitors to
check and modify beam quality as it is transported through the beam
transport system.
 Gantries are usually large because of 2 reasons
-protons with therapeutic energies can
only be bent with large radii and
-Beam monitoring and beam shaping
devices have to be positioned inside
the treatment head affecting the size
of the nozzle
• Nozzle has a snout for mounting
and positioning of field specific
aperture and compensator
One of the gantries at the Northeast Proton Therapy Center

33. SCATTERING BEAM TECHNIQUE

34. Beam delivery system
 The proton beam exiting the transport system is a
pencil-shaped beam with minimal energy and
direction spread.
 Narrow Bragg peak, not suitable for practical size of
tumors
Pencil beam is modified either by
1.Scattering Beam Technique
2.Scanning Beam Technique

35. Scattering beam technique
 Small fields: single scattering foil (made out of Lead)
 Larger field sizes: double-scattering system (bi-
material: High and low z material) to ensure a
uniform, flat lateral dose profile
 Modulator wheel: variable thickness absorbers in
circular rotating tracks that result in a temporal
variation of the beam energy

36.  It aims to produce a dose distribution with a flat
lateral profile.
 The depth-dose curve with a plateau of adequate
width is produced by summing a number of Bragg
peaks.
 Range modulation wheels consisting of variable
thicknesses of acrylic glass or graphite steps are
traditionally used for this purpose.
 The width and thickness of the modulation wheels are
calibrated to achieve SOBP.
 The width of SOBP is controlled by turning the beam
off when a prescribed width is reached.

37. RANGE MODULATOR WHEEL

38. Scanning beam
technique
Double scattering technique

39. Scanning beam technique
 An alternative to the use of a broad beam is to generate
a narrow mono-energetic "pencil" beam and to scan it
magnetically across the target
• Typically the beam is scanned in a zigzag pattern in the
x-y plane perpendicular to the beam direction
• As the pencil beam exits the transport system, it is
magnetically steered in the lateral directions to deliver
dose to a large treatment field

40. SCANNING BEAM TECHNIQUE

41. SCANNING BEAM TECHNIQUE

42. Scanning beam technique
 The proton beam intensity may be modulated as the
beam is moved across the field, resulting in the
modulated scanning beam technique or IMPT.
 Current implementation of IMPT uses so called spot
scanning technique, in which the beam spot is moved
to a location within the target and the prescribed dose
is delivered to the spot, before it is moved to the next
spot to deliver its prescribed dose.

43. Advantage of scanning
 In contrast to broad beam technique, arbitrary shapes
of uniform high dose regions can be achieved with a
single beam
 No first and second scatterers, less nuclear
interactions and therefore the neutron contamination
is smaller
 Great flexibility, which can be fully utilized in
intensity-modulated proton therapy (IMPT)
 Disadvantage: Technically difficult and more
sensitive to organ motion than passive scattering

44. Treatment planning
Treatment planning for proton therapy requires a volumetric
patient CT scan dataset.
The CT HU numbers are converted to proton stopping power
values for calculating the proton range required for the
treatment field.
Uncertainties in the conversion of CT numbers to proton
stopping power in proton dose calculation translate into
range calculation uncertainties and errors.
Marking the intended SOBP with a distal margin beyond the
target and a proximal margin before the target in the range
calculation of each treatment field.
Other consideration in determining the margins include
target motion, daily set up errors, beam delivery
uncertainties and uncertainties in the anatomy and
physiologic changes in the patient.

45.  In contrast to x-ray planning, the PTV for proton
therapy is specific for each treatment field.
 Lateral margins are identical to traditional definitions,
but the distal and proximal margins along the beam
axis are calculated to account for proton specific
uncertainties.

46. BEAM SPECIFIC PTV
Accounted for three types of uncertainties
 Geometrical miss of the CTV due to lateral set up
error
 Range uncertainties accounted by giving proximal and
distal margin
 Range error caused due to tissue heterogeneity

47. STEPS FOR BEAM SPECIFIC PTV

48. Pencil-beam algorithms are used for proton therapy dose calculations
which model proton interaction and scattering in various heterogeneous
media of the beam path, including the nozzle, range compensators, and the
patient.
Monte Carlo calculations has been used to study the accuracy of such dose
calculation algorithms which indicates errors near surfaces of media
differing significantly in density and composition, such as air cavity and
bones

49. Advantages: Proton Therapy
 Reduction in integral dose to normal tissues
:Reduced toxicities
 Dose escalation to tumors – increased local
control
 Treat tumors close to critical organs –eye,
spinal cord

50. Clinical situations: Proton therapy
 Pediatric malignancies:
 Craniospinal Axis Irradiation: Medulloblastoma
 Craniopharyngioma
 Prostate cancers
 Skull base tumors
 Paranasal sinus tumors, Lymphomas, Lung Cancers
 GI Malignancy: HCC, Pancreatic cancers

51. When Should We Use Protons?
 Better organ sparing (Skull base tumors)
 Better local control needed (Ca Prostate)
 Late morbidity (Pediatric malignancies)
 Complex geometry (Ocular melanoma)
 Large target volume (Childhood Medulloblastoma)
Zietman, Goiten, Tepper JCO 2010

52. UVEAL MELANOMA

53. Paediatric tumours

54. The Exit dose from photon
therapy exposes the thyroid,
heart, lung, gut, and gonads to
functional and neoplastic risks
that can be avoided with
proton therapy.
Medulloblastoma : A case scenario
for ideal PBT

55. Medulloblastoma: Late Toxicity

56. SKULL BASED CHORDOMAS

57. CARCINOMA PROSTATE

58. NSCLC

59. SECOND MALIGNANCY
Due to higher integral dose produced by neutron scatter

60. SECOND MALIGNANCY
 Harvard Cyclotron Laboratory
 Matched 503 HCL proton patients with 1591 SEER patients
 Median follow up: 7.7 years (protons) and 6.1 years
(photon)
 Second malignancy rates
 6.4% of proton patients (32 patients)
 12.8% of photon patients (203 patients)
 Photons are associated with a higher second
malignancy risk: Hazard Ratio 2.73, 95% CI 1.87 to 3.98,
p< 0.0001
Chung et al. ASTRO 2008

61. COST EFFECTIVENESS

64. PROBLEMS WITH PROTON THERAPY
Patient related
 Patient set up
 Organ motion
 Patient movement
Physics related
 CT number conversion
 Dosimetry
Machine related
Cumbersome
Cost

65. CONCLUSIONS
 Currently, proton therapy is a rare medical resource
 best used in situations where outcomes with
commonly available radiation strategies present
opportunities for improvement in the therapeutic ratio
via improvements in dose distributions

66.  At this stage in the development of proton therapy,
there are no clear class solutions to treatment
planning.
 In addition, the full potential for dose distribution
improvements with protons has not been realized
because of uncertainties in both treatment-planning
algorithms and delivery modes.

67.  Strategies for motion management and quality
assurance are not fully developed.
 Finally, the clinical impact of some patterns of dose
distribution improvements achievable with proton
therapy may require time, careful trial design, and
special assessments to define.

68. THANK YOU

69. Difference Between scattering and scanning
beam technique
SCATTERING SCANNING
 Use of patient specific beam
modifying devices
 Dual scattering generates
neutrons which increases
integral radiation dose to the
patient
 Dual scattering can not do
IMPT. However multiple
fields can do but because of
switching of compensators
and aperatures in each field ,
the treatment time increases
 No use of beam modifying
devices, making it a greener
option
 Without scattering material,
produces fewer neutrons
 Scanning makes IMPT
possible. With scanning, dose
distribution can be varied
voxel by voxel

70. SCATTERING SCANNING
 Scattering is more forgiving
for tumour and organ motion
because of the smearing
effect of the broadened beam
 Simple
 Scattering decreases the
penetrating power of the
proton beam
 Enhanced ability of proton
scanning to paint dose more
conformally, voxel by voxel,
increases the chance of target
misses due to organ motion
 Complex
 For any given accelerator,
scanning penetrates deeper
than scattering. So scanning
can treat deeper tumours