Current RT Developments - Proton Therapy

Question 1

What are the advantages of using Proton therapy over conventional photons?

Answer 1

1) No exit dose past target - spares healthy tissue beyond target
2) Reduced morbidity - reduced integral dose and second malignancies, especially for pediatric patients where longer timescales (longer life left) given rise to a greater risk of induced cancer; also less risk of treatment effecting natural development
3) dose escalation - can increase curative treatment options - “major motivation in adult indications”

Question 2

Describe the bragg peak and the Spread Out Bragg Peak (SOBP).

Answer 2

When high energy/velocity charged particles enter the patient, their high velocity means there is a lower probability of interactions with the patient mass. As they penetrate deeper into the patient, interactions inevitably occur reducing the energy of the particles which in turn increases the probability of interaction and further energy loss.

Once the particles have slowed significantly they are highly likely to interact and lose their energy to the surrounding mass; therefore, most of the energy from the particles is deposited at the end of their path through the patient. This results in a peak of energy deposited with no further energy deposited in the patient beyond this point.

The SOBP occurs when particles of different initial energies are used/are incident on the patient. Each individual particle thus has a different maximum depth it will penetrate and therefore the bragg peak will occur at varying depths. if these energies are chosen so that the bragg peaks are adjacent to each other, this results in a range/spread of peaks.

Question 3

What are the interaction types for a proton?

Answer 3

1) Coulomb interactions with electrons
2) Coulomb interactions with nuclei
3) in/Non elastic collisions with nuclei

Question 4

For Pencil beam scanning systems, what are the typical deliverable energies?

Answer 4

70-230MeV (4-35cm deep in water).

Question 5

What is range straggling?

Answer 5

Energy loss is a statistical process with each proton stopping at a slightly different range, hence range is ‘straggled’.

Question 6

What is LET and what is it used for?

Answer 6

Linear Energy Transfer is the energy deposited per unit distance. It is used as a measure of beam quality. For multiple protons, the average is taken.

Question 7

When a proton undergoes a Coulomb interaction with a nucleus, what happens to the proton?

Answer 7

It deposits some of its energy to the nuclei and changes direction with reduced velocity. The resultant spread of protons is gaussian in nature.

Question 8

Describe a proton in-elastic interaction with a nucleus?

Answer 8

1) Nuclear fragments may be released
2) Original proton cannot be generally identified
3) produces a halo

Analytical modeling - lateral spread is a Gaussian function.

Question 9

What are the characteristics of cyclotrons?

Answer 9

single energy
stable beam energy
high intensity beam produced
not good for very high energies
not good for heavier particles

Question 10

What are the characteristics of synchrotrons?

Answer 10

Variable energy output
Pulsed beam
Can deliver at high energies and with heavier particles compared to cyclotrons.

Question 11

What are the two types of proton treatment delivery?

Answer 11

Scattering and scanning.

Question 12

Describe a proton delivery scattering system.

Answer 12

Monoenergetic protons are incident on a range modulator wheel (energy spreading); the output from this enters 2 scattering foils (lateral spreading); the output from this enters a perspex compensator to fine-tune the beam shape before the beam enters a brass collimator.

Note, the collimator and the compensator have to be custom made for each field; therefore time, resources, disposal/recyling needs to be considered.

Question 13

Describe a proton delivery scanning system.

Answer 13

Monoenergetic protons are incident on an energy selection device (possibly a range modulator wheel); the output then traverses two pairs of orthogonal magnets acting as steering magnets to facilitate scanning of the pencil beam over the target, effectively dose painting the target.

Question 14

What are the advantages and disadvantages of a scattering proton delivery system?

Answer 14

Advantages are:
dose is delivered to the entire target simultaneously (good for moving targets)

Disadvantages are:
Longitudinal length of SOBP is fixed; extra dose ust be delivered proximal to the target

Field-specific hardware needed:

1) additional source of neutron dose
2) manufacture, manual handling, storage, recycling, radiation protection implications
3) more difficult to adapt treatments

Question 15

What are the advantages and disadvantages of a scanning proton delivery system?

Answer 15

Advantages are:
Improved ability to conform to target
No field-specific hardware required

Disadvantages:
Treating moving targets may be difficult due to interplay effects
Lateral edge of field is less sharp for shallow targets

Question 16

How are targets less than 4cm from the patient surface treated with Proton Beam Therapy?

Answer 16

Use of a range shifter which is a perspex block in the beam path to reduce the energy (and therefore depth penetration) of the proton beam.

Note, additional scatter due to this block and more likely to scatter at lower energies; therefore, spot size is increased at shallower depths - therefore distance between range shifter and patient surface needs minimizing to reduce the impact of the increased spot divergence. Could use bolus on patient surface instead of range shifter.

Question 17

Name a method used to calibrate a map of HU to relative proton stopping power.

Answer 17

Stoichiometric method.

Question 18

How do you get dosimetry for a patient proton treatment plan?

Answer 18

Imaging with photons, treating with protons.
Phantom with varying known mass densities is CT scanned, from these known materials and densities, proton stopping power is derived. This is then used in TPS.

Note: in theory, stopping power changes with energy but in reality this change is negligable.

Question 19

What are the main points to consider when commissioning a Proton Beam System (PBS)?

Answer 19

1) Depth dose profiles
2) Quantifying dose
3) Lateral profiles
4) Divergence of: a) individual spots and b) the steering system

All these are characterized by commissioning measurements.

Question 20

What type of chamber would you use in PBS commissioning?

Answer 20

A parallel plate such as a PTW bragg peak chamber with a 8cm diameter. Note diameter of chamber must be&raquo_space; than field size
(i.e. spot size).

Question 21

What is Integrated Depth Dose (IDD)?

Answer 21

The charge in a parallel plate chamber is collected over a large chamber area.

Question 22

How are IDDs acquired?

Answer 22

A parallel plate chamber is used to acquire the IDD profiles along the axis of the beam over the whole length of the bragg peak for a variety of incident energies that are used clinically. These allow the bragg peak to be characterised for each energy.

Note, due to range straggling, the bragg peak will broaden as depth (i.e. incident energy) increases.

Question 23

Why are IDDs not able to determine absolute dose?

Answer 23

They miss the ionisation outside of the diameter of the chamber (caused by scatter due to nuclear interactions).

Question 24

What is an MU?

Answer 24

As photons or charged particles pass through an ionisation chamber, they ionise the gas in the chamber. The chamber collects and counts the deposited charge.

An MU corresponds to a defined amount of charge collected at the chamber. As the energy of the ionising particle is directly related to the charge deposited, therefore the number of particles per MU depends on the energy of the ionising particle.

Question 25

What is a typical reference depth for PBS commissioning?

Answer 25

2cm

Question 26

What is the process for quantifying dose in PBS commissioning?

Answer 26

Measuring output 1) Use a small, e.g. roos 1.56 diameter, chamber 2) use a larger reference field (e.g. 10x10cm) 3) acquire data in a water tank at a reference depth of 2cm; a 'grid' of spots must be delivered at this depth across the whole 10x10 field; this will give a value for Gy mm2/MU. Note a grid of spots must be delivered to ensure charged particle equilibrium (for each spot, adjacent scatter from nuclear interactions will balance that lost). This will give a dose area per MU at the specific incident energy of the proton, as the absolute dose will be a function of this energy. The process must be carried out for all energies to be used clinically and the TPS should be updated accordingly.

Question 27

Outline the parameters that are configured during PB therapy planning.

Answer 27

Those chosen by the operator/planner: 1) Technique 2) Objectives 3) Beam angles 4) Beam modifiers (e.g. range shifters) Those chosen by the optimiser: 5) spot positions 6) spot weights - to build up the SOBP

Question 28

Define SFO and MFO.

Answer 28

SFO (Single Field Optimisation) and MFO (Multi Field Optimisation). These are how spots are put together to get dose spread.

Question 29

What are the advantages and issues regarding MFO for PB therapy planning?

Answer 29

1) MFO allows greater control over dose distribution (only the combined dose is required to be uniform, not each field as in SFO) 2) This gives the optimiser greater flexibility when optimising the plan Issues are: 1) assessing if the optimiser has arrived at a safe solution 2) assessing how sensitive the plan is to uncertainty e.g. in H&N. if the CT to HU conversion is in error, this translates to a range error, therefore a greater dose to the spinal cord may be delivered; therefore even though the quality of the distribution is good, there may be a range error.

Question 30

What is an established PB range uncertainty from literature?

Answer 30

2.7% - 4.6% +1.2mm

Question 31

What are the clinical sources of range uncertainty?

Answer 31

1) CT calibration and artifacts (unrelated to patient setup, systematic) 2) Beam paths traverse inhomogeneous regions (patient setup, patient motion, gas/liquid filled cavities, etc) 3) Patient anatomy changes (weight gain/loss, tumour regression, etc)

Question 32

What are the potential consequences of range uncertainty in PB therapy for brain tumours?

Answer 32

1) dose to cord may increase and may exceed tolerance, leading to patient paralysis below the affected part of the cord 2) underdosing of the PTV and increase in radiation to the surrounding, healthy, tissue. This could lead to the cancer not being cured as well as cognitive impairment for the patient ( i.e. a sub-optimal outcome).

Question 33

What is more sensitive to inhomogeneties, photon or proton therapy? What are the potential issues faced?

Answer 33

Proton Therapy!!! 1) Moving targets 2) beams passing/grazing inhomogeneous regions 3) cavities (air or liquid filling) 4) Dense targets in low density surroundings (e.g. Lung)

Question 34

How many fields does a typical PB therapy plan have? Roughly how many spots per field?

Answer 34

1-5 fields, each field has several 1000 spots.

Question 35

What makes a plan robust?

Answer 35

The ability to remain within tolerance whatever the possible error scenarios.

Question 36

What could the planner do to avoid/minimise issues with uncertainties?

Answer 36

1) avoid having beam directions where an OAR is directly behind the target 2) use lateral beams (avoids range uncertainty issues) - avoids brain stem, eyes, optic chiasm, etc 3) use additional/patched fields (e.g. 2 lat and one sup) 4) use beam specific PTVs 5) robust optimisation by disregarding the PTV and using the CTV instead with uncertainties being given/entered into the TPS so the optimiser can take them into account. The optimiser thus finds plans satisfying the objectives for a nominal plan + plans with a number of error scenarios Note: robustness is a tradeoff with plan quality!

Question 37

Define robustness (in terms of planning).

Answer 37

A plan is robust to specified objectives under specified conditions, i.e. a plan cannot be 'globally' robust!

Question 38

Is an independent check of treatment plans mandatory in the UK?

Answer 38

Yes, specified in Towards Safer Radiotherapy (2008), i.e. guidance.

Question 39

Outline the typical procedure for PB physical plan verification.

Answer 39

1) deliver each field at gantry angle 0 to a 2D array in water or a water equivalent material 2) measure photon fluence for comparison to TPS calculation 3) measure @ 2-3 depths covering the range required clinically 4) compare absolute dose vs TPS

Question 40

List some advantages of using Monte Carlo for software plan verification.

Answer 40

1) independent validation of spot weights 2) independent validation of Bragg Peak range 3) improved dose calculation w.r.t. inhomogeneities 4) full modeling of nuclear interactions

Question 41

What is the Relative Biological Effect (RBE)?

Answer 41

RBE = Dphoton/Dion With Isoeffect being defined as achieving the same biological effect (i.e. RBE * Dion gives the same biological effect as Dphoton).

Question 42

What does Relative Biological Effect (RBE) depend on?

Answer 42

Some factors are: 1) Photon energy/LET 2) Tissue type 3) Endpoint (cell survival, toxicity, etc) 4) Tissue oxygenation (hypoxic cells more radio-sensitive)

Question 43

What general Relative Biological Effect (RBE) value is used clinically?

Answer 43

RBE = 1.1 (conservative value).

Question 44

What are the two methods of calculating LET?

Answer 44

1) Track average LET 2) Dose average LET Measuring LET directly is impossible/difficult. Therefore, Monte Carlo or analytical methods are used.

Question 45

What is the summary of experiences of planning and delivering PB therapy at the Christie?

Answer 45

1) wide range of cases have been treated, each involved adapting the planning approach to suit each individual case but following common principles 2) becoming clearer on what is and is not possible with PBT in terms of both dose escalation and OAR sparing 3) multi-modality imaging is essential 4) close management with consultants has been extremely beneficial in terms of workflow and mutual learning. 5) No in-vitro dosimetry performed as no exit dose 6) Verification takes longer than with photon treatments 7) proton therapy more sensitive to changes in anatomy and setup errors than photon treatments, therefore tend to do more imaging than with photon treatments.