Proton Therapy Flashcards
(98 cards)
1
Q
What is the rationale for proton therapy?
A
No exit dose past the target volume (most important).
Reduce morbidity - including integral dose and second malignancy (important for paediatric).
Dose escalation - can increase curative treatment options (motivation for adult treatments).
2
Q
What does the proton depth dose curve look like?
A
Surface dose to just before the peak, the dose is approximately constant, the dose curves up to a point at the peak, after the peak there is a sharp fall off to zero dose.
Photon depth dose has additional dose outside of the target at depth and superficially.
3
Q
What is the peak of the proton depth dose called?
A
Bragg peak
4
Q
What is a major technique called that delivers protons?
A
Pencil beam scanning
5
Q
What are the 3 proton interaction types?
A
Coulomb interactions with (orbital) electrons - (stopping)
Coulomb interactions with nuclei - (scattering)
In-/Non-elastic collisions with nuclei - (halo)
6
Q
Describe the process of coulomb interactions with electrons.
A
Secondary electron(s) released. Proton loses energy and slows down. As the proton slows down, the rate of energy deposition increases. Probability of further Coulomb interactions increased which produces the Bragg peak. The range is defined by the initial energy of the beam.
7
Q
What is the stopping power for a proton beam?
A
S = - dE/dx
Stopping power, S, is the rate of change of energy over distance
8
Q
What is the mass stopping power for protons?
A
S/ρ = -(1/ρ)(dE/dx)
where ρ is mass density
and S/ρ is mass stopping power
9
Q
What is the Bethe-Bloch equation (protons)?
A
S/ρ ∝ 1/v^2 * Z/A * z^2 Where: v = velocity of incident proton z = atomic number of incident proton Z = atomic number of target nucleus A = atomic number of target nucleus
10
Q
What does CSDA stand for, and what does it mean? (protons)
A
Continusous Slowing Down Approximation.
The approximation states that the rate of energy loss at each point along the track is assumed to be equal to the total stopping power. Energy loss fluctuations are neglected. This assumes energy deposition is a smooth process instead of a discrete process when the proton interacts with particles in the medium. This makes energy loss a statistical process; not each proton stops at the same range. This results in a finite slope of the distal edge of the Bragg peak.
The CSDA range is a close approximation to the average path length as it slows to rest calcuated by the CSDA.
The range is the integral of the reciprocal of the total stopping power wrt energy.
11
Q
What determines the range of a proton beam?
A
The initial energy.
12
Q
What is the total energy of a proton?
A
E = rest mass energy + kinetic energy
E = mc^2
E = γm(0)c^2
Where γ is the Lorentz factor
13
Q
What is the equation for the Lorentz factor? (proton)
A
γ = 1 / √(1 – v^2/c^2)
14
Q
What is the proton rest mass?
A
m(0) = 1.67 E-27 kg
= 9.38.28 MeV/c^2
(1 MeV = 1.602 E-13 J)
15
Q
What is the equation for the proton velocity?
A
v = = √[ c^2 – (m(0)^2 c^6) / E^2 ]
16
Q
What does the proton velocity vs. Energy curve look like?
A
As energy increases, velocity increases.
The graph is a curve (almost logarithmic increase).
17
Q
Describe proton coulomb interactions with nuclei.
A
Proton direction is changed.
This produces a lateral spread of the beam with a Gaussian profile.
18
Q
Describe proton inelastic/non-elastic interactions with nuclei.
A
Nuclear fragments may be released.
The original proton cannot generally be identified.
This produces the halo.
19
Q
What are the provisions from the DoH regarding proton therapy?
A
They have facilitated the setting up of a clinical reference panel to approve referrals of appropriate NHS patients to proton therapy centres outside of the UK in a fair and equitable manner.
Furthermore, they have developed a business case for at least one modern proton treatment facility in England.
20
Q
What is the National Proton Therapy Service?
A
Two NHS proton developments: The Christie (due to open Aug 2018), UCLH (due to open 2020).
Each centre aims to treat approx. 750 patients per year.
This will stop the overseas referring for proton therapy eventually as the 2 year ramp up for each centre occurs.
21
Q
Name 5 indications for paediatric referral for proton therapy. (as per Final Business Case 2015)
A
Any from: •Very Young Age •Rhabdomysarcoma Orbit •Rhabdomysarcoma Parameningeal/Paraspinal •Rhabdomyosarcoma Pelvis •Ewings •PPNET (extra osseus) •NGGCTs (Germinoma) focal RT •Nasopharyngeal (H&N) •Chordoma/Chondrosarcoma •Osteosarcoma •Adult Type Sarcoma (Bone/ST) •Ependymoma •LGG •Optic Pathway Glioma •Craniopharyngioma •Meningioma (excluding G3) •Esthesioneuroblastoma •Pituitary Gland Tumours •Juvenile Angiofibroma •*Retinoblastoma •*Medullo (PNET) •*Hodgkins •*Selected Neuroblastoma •*Selected Wilms Tumour
Where * are UK service expansion criteria
22
Q
Name 3 TYA indications for referall for proton therapy.
TYA = Teenage; Young Adult
A
Any from: •TYA satisfies OP paediatric criteria •TYA satisfies OP adult criteria •*TYA satisfies UK paediatric criteria •*TYA satisfies UK adult criteria •*Lymphoma (selected) •*Breast Cancer (selected) •*Ano-Rectal Cancer •*Seminoma •*Gynae Cancers (selected)
Where * are UK service expansion criteria
23
Q
Name 3 Adult indications for referral for proton therapy.
A
Any from: •Chordoma BoS •Chondrosarcoma BoS •Para Spinal/Spinal Sarcoma •*Meningioma •*Orbital/Skull Base NOS •*CSI - Curative •*Skull base H&N e.g. Paranasal
Where * are UK service expansion criteria
24
Q
Name 3 trials for referral for proton therapy.
A
Any from: •*Lung Ca St3 •*Recurrent Ano-Rectal •*Oesophageal Ca/Nasopharynx •*Nasopharynx Ca •*Mediastinal rare - Thymoma •*Gynae - Ca Cx nodal, Adv Vaginal •*Selected Hodgkins/Non-Hodgkins
Where * are UK service expansion criteria
25
What are the drawbacks of having multiple rooms in a proton centre?
If there are multiple rooms, the accelerator can only provide a beam to a single room at a time, thus limiting the number of rooms that can be served by an accelerator.
If the cyclotron breaks, or anything connecting it to the rooms, it is likely that more patients will be affected due to the likely higher throughput.
Due to the timing of beam provision to rooms, careful planning of patient timing is required.
26
How does a cyclotron work?
A uniform magnetic field is applied perpendicular to an electric field. The electric field is applied across two dees (semi circles). Electrons are injected in the centre of the dees. The electric field is reversed just as the electron finishes the half circle, causing an acceleration across the gap. With the increased speed, the electrons move in a larger circle, so the electric field switches with constant frequency. This process is repeated many times, resulting in an electron exiting the port at high speed.
27
Name the 4 key points of a cyclotron.
Single energy.
Stable beam energy.
Continuous beam.
High intensity.
28
Name the 2 key points of a synchrotron.
Variable output energy.
| Beam has a dead time.
29
How does a synchrotron work?
The particle beam travel around a fixed closed-loop path. A magnetic field is created through use of electromagnetics. The magnetic field which bends the particle beam increases with time during the accelerating process (synchronized with the kinetic energy of the beam). This increase in magnetic field strength allows a constant trajectory of the particle as its momentum is increased. This accelerates the beam until the particles reach almost the speed of light.
In addition the frequency of the accelerating electric field is increased in synchrony with the orbital frequency of the charged particle.
30
What are the components of a synchrotron?
Schematic of a weak-focusing electron or proton synchrotron includes:
(1) injector, (2) injection system, (3) vacuum chamber, (4)
electromagnet sector, (5) straight section, (6) accelerating device.
The magnetic field is perpendicular to the plane of the figure of an aerial view.
31
Name the 2 types of proton delivery technologies.
Scattering System
| Pencil Beam Scanning System
32
Name the components in a scattering system.
Range Modulator Wheel - this does the energy spreading.
Typically 2 scattering foils (double scattering) - this provides lateral scattering.
Perspex Compensator.
Brass Collimator.
33
Name the components in a pencil beam scanning system.
```
Energy selection (the location of this differs for each system).
Steering magnets.
```
34
List the advantages/disadvantages of using a scattering system over a pencil beam scanning system.
Adv:
•Dose delivered to entire target simultaneously (good for moving targets)
Disadv:
•Longitudinal length of SOBP (spread out Bragg peak) is fixed (extra dose is required proximal to the target)
•Field specific hardware is needed (collimators, compensators.)
- This is an extra source of neutron dose
- Has implications for manufacture, storage, handling
- Harder to adapt treatments.
35
List the advantages/disadvantages of using a pencil beam scanning system over a scattering system.
Adv:
• Improved ability to conform to target
• No field specific hardware
Disadv:
•Potential for interplay effects causing difficulty in treating moving targets
•Lateral edge of field is less sharp for shallower targets
36
What is the typical energy range of a PBS system? What depth does this correspond to?
70-100 MeV.
| Depth of: 4.0-7.5 cm
37
What options are available to enable treatments at shallower depths?
```
Range shifter (block of material attached to nozzle which broadens the spot as it introduces extra scatter)
Bolus (block of material on patient)
```
38
What are the features of a range shifter?
Acts as a scatterer; spot size at shallow depths is increased and has greater divergence
Air gap between patient and range-shifter should be minimised to minimise the spot divergence
The lateral edge is less sharp than for a scattering system (where a collimator defines the egde).
39
Define VSAD.
Virtual Source Axis Distance:
The distance from isocenter to the apparent source of the proton beam. It may vary in x and y dependent on the design and position of the steering magnets.
40
What are the 2 types of steering available?
Divergent steering = finite VSAD
| Parallel steering = infinite VSAD
41
What is the purpose of the CT scan?
A kV CT scan enables target/organ delineation and dose calculation (after HU to SP calibration curve is applied)
42
What are the main interactions of photons with electrons, and at what energy range are they dominant?
Photoelectric: 10 - 25 keV
Compton scatter: 25 keV - 25 MeV
Pair production: > 25 MeV
43
What does HU map to for proton planning?
relative proton stopping power
| Stoichiometric method is usually used for the calibration curve
44
What is the main uncertainty in the dose planning of proton therapy?
The imaging and treatment delivery use different particles.
45
Which measurements are required to configure a beam model for a PBS system?
For all energy ranges:
Bragg peaks in water - characterises range as a function of energy and allows the dose per MU to be defined.
Lateral profiles in air - allows the beam optics to be characterised.
46
What is an IDD?
Integrated Depth Dose:
| A 1D version of a Bragg peak curve
47
How can the halo be estimated?
Monte Carlo dose calculations
or
Analysis of the difference of Bragg peaks in water using a large chamber with a smal field and a small chamber with a large field
48
What feature is desired from the choice of detector when measuring a Bragg peak?
Its ability to capture entire lateral profile of a single Bragg peak, including the halo. This is why a large chamber is used.
49
Which detector size would you choose for measuring the Bragg peaks in water?
Large chamber size for a small field (typically used as it can capture the entire lateral profile of a single Bragg peak, including the halo).
or
Small chamber size for a large field.
50
What CoP is used for protons?
IAEA TRS-398 CoP (designated primarly for scattered beams)
51
What is the reference beam for the proton CoP?
Co-60
52
What is the primary standard for the proton CoP?
Graphite calorimeter (at NPL)
53
What is the primary standard expected to be in the new NPL CoP for scanned beams?
Portable graphite calorimeter. It is designed to be able to be transported to the individual centres using proton beams. This is expected to be available in 2018.
54
Where are the monitor chambers located?
In the nozzle, before the range shifter.
55
What chamber is used to measured IDDs?
Traceable parallel plate chamber.
56
At which location does the reference point lie? What is the reasoning behind this location?
It is situated at the entrance region of the Bragg Peak, typically 2 cm deep.
It is chosen as it is a stable point, away from the surface, and available to all energies.
The charge from the monitor chamber is related to dose at the reference point.
57
How is matching achieved?
Adjusting the gain of the monitor chamber to best fit all energies.
58
What equipment should be used for measuring beam profiles?
High resolution is desired:
Film (eg GaFChromic EBT3)
Scintillation screen
59
How are beam optics measured?
In air, at a range of distances from the nozzle.
60
How is the dose outside the chamber estimated?
Using Monte Carlo modelling.
61
What does the beam profile of a single beam optic look like?
Laterally: Gaussian
Longitudinally: Hyperbola
In practice the beam waist is often close to the isocentre and the focussing is weak.
62
How are beam profiles characterised?
Lateral profiles are measured for a minimum of 3 times, then a hyperbola is fitted.
63
Which ICRU report is relevant to proton therapy?
ICRU 78 - Prescribing, recording and reporting proton-beam therapy
64
Define 1 Gy
1 Gy = 1 J/kg
65
Name a planning system for proton beam planning.
```
Any from:
Commercial:
•Elekta - XiO
•Philips - Pinnacle3
•RaySearch Laboratories - RayStation
•Varian - Eclipse (v13.7 used at Christie)
```
In house TPS:
•Massachusetts General Hospital – Astroid
•Paul Scherrer Institut – PSIPlan
66
What is a serial organ, and name one?
If part of the organ dies, the whole organ losses function; typically the maximum dose to the OAR is limited, e.g: Spinal Cord (max dose typically 54Gy)
67
What is a parallel organ, and name one?
If part of the organ is damaged, the rest of the organ can continue to function; typically the volume receiving a certain dose is limited, e.g: kidneys.
68
What does the planning technique depend on?
* Anatomy of targets and OARs
* Type of cancer
* Delivery technology
* On-treatment imaging technology
* Treatment planning system features
* Department protocols
69
What is the purpose of a TPS in proton therapy?
* Determine the spot positions
| * Compute the optimal spot weightings
70
Name parameters configured during PB planning, and who it is done by?
* Technique - planner
* Objectives - planner
* Beam angles - planner
* Beam modifiers (range shifters, etc.) - planner
* Spot positions - computed by the optimiser
* Spot weights - computed by the optimiser
71
What are the basics of PBS plannign?
* Inverse planned
* PTV and OAR objectives
* Discrete beam angles (not arcs)
* Beams are not necessarily coplanar
* Typically 1-5 fields per plan (mean = 2.5)
72
Name the 2 types of PBS planning?
SFO & MFO
Single Field Optimisation (or SFUD: Single Field Uniform Dose)
Multi Field Optimisation (or IMPT: Intensity Modulated Proton Therapy
73
What are the advantages and disadvtanges of SFO and MFO for proton planning?
Both used clinically
MFO provides more control over combined dose distribution as a uniform dose for each field is not required; only the combined dose distribution is required to be uniform. (Cant give more sparing to an OAR)
MFO gives the optimiser more freedom to produce a combined dose in more ways, so sometimes we cannot be sure how it is achieving this - hence we have more confidence in SFO.
74
What is the difference between a photon PTV and proton PTV?
There are different uncertainties in the lateral direction, causing the van Herk formula to change and results in different growing margins.
75
Explain distal edge tracking for proton planning.
Distal spots are used for planning, and proximal spots are ignored, this results in a quicker delivery as the energy of the beam does not have to be changed.
However, concentrating the dose into fewer spots is riskier as it relies heavily upon accurate geometry (if slightly off, lots of dose will be deposited in wrong bit).
The TPS can be manipulated to provide distal edge tracking by increasing the number of MU required at each spot.
76
What is an error and an uncertainty?
Uncertainty is an estimate of what an error may be; a probability of an error magnitude.
Error is associated with a true value. It is not always known what an error may be, but each measurement has an error associated with it. The types of error are: Systematic (accuracy), random (precision), blunders (eg wrong units written).
77
What is the uncertainty called that is associated with the uncertainty of where a proton stops within a patient?
Range uncertainty. 2.7 - 4.6% + 1.2 mm
78
What are the clinical uncertainties associated with proton therapy?
CT calibration & artefacts: unrelated to patient setup, such as if calibration curve slightly off, the uncertainty of the LUT, etc - systematic
Beam paths passing through inhomogeneities: patient motion, patient setup, gas/liquid in cavities, etc.
Patient anatomy changes from planning scan: tumour regression, weight loss, weight gain, etc.
79
What is the wiggle in the CT HU to stopping power curve?
This the attempt at finding the best fit as muscle, soft tissue, blood, etc. all have similar densities but the way that protons interact is very different. Therefore as there are many curves, the wiggly line is the best fit.
80
How does the range uncertainty affect protons?
If comparing a photon PDD to a proton PDD, and the particle passes through a lower density region, the photon curve changes as the dose at depth is increased, whereas the proton curve is shifted. Thus there is more positional difference than dose difference (ie the whole Bragg peak shifts for protons, where as the dose at depths for photons is just slightly increased).
81
What impact does range uncertainty have on SFO/MFO?
MFO has higher proximal dose: if geometrically off due to uncertainties, then can end up with a high dose to the OAR, so end up using SFO.
If the dose is overshot once, it will overshoot every fraction.
82
What type of uncertainty can deform the dose distribution, and how?
Lateral offsets: if two spots pass through different density material they will have different incident energies to compensate for those - ensuring the spots reach the same depth. If there is a lateral offset (such as incorrect patient setup), the energies that were selected to compensate for the bone/air/etc, will now reach a different depth than intended and will deform the intended dose distribution.
83
What effect does anatomy change have on the proton dose distribution?
Example: weight loss: less tissue between surface and target results in the dose overshooting the target as the distal range is still unchanged.
Similar effect for cavities filling with air.
84
Explain a possible way of coping with uncertainties for proton planning and delivery.
```
Beam directions (having more fields gives a more robust plan): avoid a direction where OAR is directly behind target, using a lateral edge avoids range uncertainties, additional/patched fields may help.
Target definitions: use beam specific PTVs - CTV to PTV expansion would depend on direction of beam and heterogeneities in beam path (as a uniform margin for growth of CTV to PTV does not ensure good coverage). If this is used, another method of reporting is required as each dose report for beam specific PTVs wouldbe different.
Robust optimisation: use the CTV for optimisation instead of a beam specific PTV, information on uncertainties is supplied to the optimiser which looks to meet objectives for an optimal plan and a number of different scenarios (but this is slower than non-robust planning; robustness is a tradeoff for plan quality).
```
85
At low energies, when using a range shifter, which has a broader spot size: PBS or scattered?
PBS
86
What does the proton lateral spot width depend upon?
Energy
87
What does a collimator do to shallow targets for protons?
Potentially sharpens the lateral edge.
88
What is the lateral shape of a proton spot?
Gaussian, with sigma = approx 3-8 mm.
89
In protons, which interactions result in a wide, low level halo that significantly affect the dose to the patient?
Nuclear interactions.
| Typically <0.1% of peak intensity, and >1000 spots per field
90
How are (proton) plans verified?
Independent dose calculation or measurement.
91
For proton PBS, how long can physical measurement for verification purposes take?
1-3 hours.
92
Why is MC useful for proton verification?
* Independent validation of spots weights (i.e. number of protons, or MU)
* Independent validation of Bragg peak range in CT
* Improved dose calculation around inhomogeneities
* Full modelling of nuclear interactions
93
What does RBE depend on?
Type of particle and energy.
| I.e: The biological effect of 1 Gy of photons is NOT equal to the biological effect of 1 Gy of protons.
94
What is the definition of RBE?
RBE = D(photon) / D(ion) |(isoeffect)
| the dose required by photons to give a specific effect divided by the dose required by an ion to give the same effect
95
What does RBE depend on?
Tissue type
Tissue oxygenation
Endpoint (Cell survival, toxicity, etc)
Proton energy/ Linear Energy Transfer
96
What is the RBE of photons
1.1 is used clinically; it is intentionally conservative.
97
How does LET change with the shape of a proton PDD?
Near the Bragg peak, more energy is deposited, so there is a higher LET at the end of the peak.
98
What are the future developments for proton therapy?
* Adaptive treatment
* Dual energy CT
* Proton imaging
* Extended indications list (clinical trials evidence)
* Moving targets (repainting, gating, scan path optimisation)
