PROTON BEAM THERAPY

Dr Nanditha Kishore

Rationale

Basic Physics

Technology

Potential Applications

Present Evidence

Toxicity

Comparative Effectiveness

RATIONALE

To Reduce dose to non target regions

Dose escalation

To Reduce probable second malignancies

Better constraints to Organ at Risk

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

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

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

BRAGG PEAK and SOBP

RBE

RBE OF PROTON

S IS 1.1

Evolving Technology

Generation of protons

Proton accelerators

Beam transport

Beam Delivery systems

Treatment planning

Protons are produced from hydrogen gas 1.Either obtained from electrolysis of deionized water

or2. 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.

Proton Accelerators

Linear Accelerator

Cyclotron

Synchrotron

High gradient Eletrostatic Accelerator

Laser Plasma particle Accelerator

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.

Cyclotron

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.

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.

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).

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.

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.

Pencil beam is modified either by

1.Scattering Beam Technique

2.Scanning Beam Technique

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.

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

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.

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.

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.

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.

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 Radiat Oncol BiolPhys 2005;63:373–384.

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.

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

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

Mock U, Georg D, Bogner J, et al. Int J RadiatOncol 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

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.

Beltran C, Roca M, Merchant TE. Int J Radiat Oncol BiolPhys 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%

LTHippocampus

50% 61% 16%

LT COCHLEA 16% 7% 0

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

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 Radiat Oncol Biol

Phys 2007;68:646–649.

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

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 RELATIVECARDIAC DOSE

72% 57% 37%

V4 AND V20 79% & 54% 76% AND 26% 40 & 26%

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.

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 BiolPhys 2006;65:1087–1096.

Prostate Cancer

Prostate cancer results with IMRT are generally excellent, but dose-escalation trials are significantly associated with the incidence of gastrointestinal toxicity.

Dosimetry studies show that the low to moderate doses delivered to the rectum with proton therapy are less than with IMRT

Rectal wall V30, V40, and V50 :29%, 23%, and 17% with IMRT

Rectal wall V30, V40, and V50 : 18%, 16%, and 14% with proton therapy, r

Vargas C, Fryer A, Mahajan C, et al. Dose-volume comparison of proton therapy and intensity-modulated radiotherapy for prostate

cancer. Int J Radiat Oncol Biol Phys 2008;70:744–751.

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

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

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.

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

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.

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

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