Proton beam therapy uses protons to treat cancer. It can reduce the dose to healthy tissues compared to photon therapy by depositing most of the energy at a specific depth. Proton therapy has potential applications in tumors near critical structures where dose escalation may improve outcomes. However, more evidence from controlled trials is still needed to demonstrate comparative effectiveness versus other radiation therapies.

1. PROTON BEAM THERAPY
Dr Nanditha Kishore

2. Rationale
Basic Physics
Technology
Potential Applications
Present Evidence
 Toxicity
Comparative Effectiveness

3. RATIONALE
 To Reduce dose to non target regions
 Dose escalation
 To Reduce probable second malignancies
 Better constraints to Organ at Risk

4. 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 consists of 3 Quarks(two up and one
down)
 It is the most stable particle in universe
with half life of >1032 years

5. 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

6. 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

7. BRAGG PEAK and SOBP

10. RBE
RBE OF
PROTON
S IS 1.1

11. Evolving Technology
 Generation of protons
 Proton accelerators
 Beam transport
 Beam Delivery systems
 Treatment planning

12.  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.

13. Proton Accelerators
 Linear Accelerator
 Cyclotron
 Synchrotron
 High gradient Eletrostatic Accelerator
 Laser Plasma particleAccelerator

14. Cyclotron
 It is a fixed energy machine which produces
continuous beam of monoenergitic (250Mev
Range) protons.
 Cyclotrons can produce a large proton beam
current of up to 300 nA and thus deliver
proton therapy at a high dose rate.

15. Cyclotron

16.  Energy Degradators
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.

17. Synchrotron
 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.

19.  Shielding requirements are less
 The pulsed nature of the beam introduces
additional complexity in certain treatment
delivery scenarios, such as gated treatment
of mobile targets and intensity-modulated
proton therapy (IMPT).

20. Beam transport system
 The proton beam, whether exiting the ESS or
a synchrotron-based system is transported
to the treatment room(s) via the beam
transport system.
 Maintenance of beam focusing, centering,
spot size, and divergence throughout the
beam transport system is critical to
maintaining a high-quality proton beam for
treatment delivery.

22. Beam delivery system
 The proton beam exiting the transport
system is a pencil-shaped beam with minimal
energy and direction spread.
 The beam has a small spot size in its lateral
direction and a narrow Bragg peak dose in its
depth direction.
 This dose distribution is not suitable for
practical size of tumors.

23. Pencil beam is modified either by
1.Scattering BeamTechnique
2.Scanning BeamTechnique

24. Scattering beam technique
 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.

26. Scanning beam technique
 As the pencil beam exits the transport
system, it is magnetically steered in the
lateral directions to deliver dose to a large
treatment field.
 The proton beam intensity may be
modulated as the beam is moved across the
field, resulting in the modulated scanning
beam technique or IMPT

27. Treatment planning
 Treatment planning for proton therapy requires
a volumetric patient CT scan dataset
 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.
 The concept of PTV does not strictly apply to
proton therapy.

28.  Pencil-beam algorithms are used for proton
therapy dose calculations
 They model proton interaction and scattering
in various heterogeneous media of the beam
path, including the nozzle, range
compensators, and the patient.

29. Potential Applications
 Many publications have reported significant
differences in dose distribution
 Reduction in the volume of non targeted
receiving low- to medium-range radiation
doses.
 In some cases, there is also a reduction in the
volume of non targeted tissue receiving
moderate- to high-dose irradiation.

30.  With currently available double-scattered
proton delivery modes the target dose
homogeneity and conformality index can
sometimes, but not always, be inferior to that
of IMRT.
 Each case within each tumor type is different
so accurate comparitive plans are essential.

31. Skull base sarcomas
 Skull-base sarcomas frequently are not
amenable to complete resection
 Require very high radiation doses for disease
control.
 Proton therapy can achieve dose
distributions that often permit the delivery of
potentially curative doses of radiation to the
tumor
Weber DC, Bogner J,Verwey J, et al.. Int J RadiatOncol Biol
Phys 2005;63:373–384.

33.  The major advantage is the sharp gradient
between the target and brainstem achievable
with the proton plan.
 The maximum and mean relative doses to the
brainstem are 71% and 42% with IMRT
compared to 59% and 11% with protons,
respectively.
 In addition, there is a substantial reduction in
low-dose exposure to non targeted tissue, which
might result in more acute tolerance of
treatment or fewer late neurocognitive sequelae.

34. Paranasal Sinus Tumors
 They frequently extend into the orbit or
anterior cranial fossa adjacent to critical optic
structures
 With photon-based therapy, it is often
difficult to deliver adequate doses to the
entire tumor target without injury to at least
one of the critical optic structures.
 The physician must choose between
prioritizing tumor control and preserving
vision

36.  In this particular case, the major advantages
to the proton plan compared to the IMRT
plan are
1.Reduction in mean dose to chaism and
brain stem
2. Better Dose Homogenity

37.  Mock U, Georg D, Bogner J, et al. Int J Radiat
Oncol Biol Phys 2004;58:147–154
Parameter IMRT PROTON
D98%,D2%,
MEAN Dose
82%,118% & 109% 93%,112% AND 106%
Chaism dose 44Gy(RBE) 36Gy(RBE)
Brain stem 43GY 29Gy
Lt optic nerve 44GY 36Gy

38. Craniopharyngioma
 It is usually diagnosed in children and
adolescents.
 Its suprasellar location places the temporal
lobes, hippocampus, hypothalamus, optic
chiasm, and nerves at risk for radiation injury.
 Reductions in dose to nontargeted brain
tissues with proton therapy are likely to result
in reduced loss in neurocognitive and
auditory function.

40.  Beltran C, Roca M, MerchantTE. Int J Radiat Oncol Biol
Phys 2012;82(2)e281–e287
Parameter IMRT SRT PROTON
MEAN BRAIN
DOSE
9.2Gy 8.1Gy 3.2(Gy) RBE
RT
TEMPORAL
17% 20% 8%
LT
Hippocampus
50% 61% 16%
LT COCHLEA 16% 7% 0

41. Cranio spinal Irradiation
Craniospinal axis irradiation is required in
 Medulloblastomas
 Germ cell tumors
 Primitive neuroectodermal tumors (PNETs)
 Ependymomas.
Most patients with these tumors are young and
at risk for late effects of radiation

43.  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.
3DCRT compared with PROTON THERAPY
 The total-body :V10 37.2% and 28.7%
 total-body integral dose : 0.223 Gy-m3 and 0.185
Gy-m3
Krejcarek SC, Grant PE, Henson JW, et al.. Int J RadiatOncol Biol
Phys 2007;68:646–649.

44. Lymphomas
 Lymphomas frequently involve the
Mediastinum
 Typically require only a moderate dose of
radiation therapy in conjunction with
chemotherapy for disease control.
 Unfortunately, even low to moderate
radiation doses place the patient at risk for
late cardiac injury and second cancers,
particularly breast cancers

46. Hoppe BS, Flampouri S, Su Z, et al.Int J Radiat Oncol Biol
Phys 2012;83(1)260–267.
PARAMETER 3DCRT IMRT PROTON
MEAN RELATIVE
LUNG DOSE
48% 43% 27%
V4 &V20 59% & 25% 62% AND 10% 31% & 16%
MEAN RELATIVE
CARDIAC DOSE
72% 57% 37%
V4ANDV20 79% & 54% 76% AND 26% 40 & 26%

47. Lung Cancers
 Lung cancers typically are diagnosed at an
advanced stage and occur in patients with
underlying lung damage.
 Consequently, concern for protection of
unaffected lung tissue often mandates
compromise in the tumor dose.
 A smaller volume of non targeted lung tissue,
spinal cord, esophagus, and heart is exposed
to radiation with proton therapy.

49. The proton plan lowers the risk of
 Acute (potentially fatal) pneumonitis
 Acute esophagitis,
Has impact on the delivery of chemotherapy,
as well as the cardiac exposure, likely
correlating with greater chance of survival.
Chang JY, Zhang X,Wang X, et al. Int J Radiat Oncol Biol
Phys 2006;65:1087–1096.

50. Prostate Cancer
 Prostate cancer results with IMRT are
generally excellent, but dose-escalation
trials are significantly associated with the
incidence of gastrointestinal toxicity.
 Dosimetry studiesshow that the low to
moderate doses delivered to the rectum with
proton therapy are less than with IMRT

52.  Rectal wallV30,V40, andV50 :29%, 23%, and 17%
with IMRT
 Rectal wallV30,V40, andV50 : 18%, 16%, and 14%
with proton therapy, r
Vargas C, Fryer A, MahajanC, et al. Dose-volume comparison of proton
therapy and intensity-modulated radiotherapy for prostate
cancer. Int J RadiatOncol Biol Phys 2008;70:744–751.

53. CLINICAL EVIDENCE
TOXICITY
Comparison Of Clinical toxicity rates are
difficult due to
 Lack of controlled studies
 Small patient numbers
 Lack of appropriate comparitive groups
 Variable criteria for toxicity assessment

54. EFFICACY
 In most clinical situations, level 1 evidence of
comparative effectiveness is desirable
 It has been difficult to conduct randomized
controlled trials in proton therapy.
 Only small differences in RBE of proton therapy
compared to photon therapy.
 Therefore, the basic difference between protons
and photons is simply the difference in entrance
dose and exit dose to non target structures

55. ONGOING TRIALS
 Nikoghosyan AV, Karapanagiotou-Schenkel I,
Munter MW, et al. Randomised trial of proton
vs. carbon ion radiation therapy in patients
with chordoma of the skull base, clinical
phase III study HIT-1-Study. BMC
Cancer 2010;10:607.

56. 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

57.  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.

58.  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

59.  THANKYOU