J. Green, D. Cutajar, S. Guatelli, & Rosenfeld, A.B.

Optimisation of eye plaque dosimetry using Monte Carlo method

Cancer of the eye is a rare and challenging disease

Uveal melanoma is the most prevalent of ocular malignancies in adults

Australia holds one of the highest rates of incidence worldwide

In 2006 – 99 new cases in NSW1

Projected outcomes set to rise to 100 cases per year in the new decade1

Intraocular melanoma: Iris with nodular melanoma (left) and large choroidal melanoma (right)2

Survival is generally poor

Reported 25% five-year mortality3

Metastasis is the main cause of death

Almost 50% of patients will lose vision or the eye due to the disease and/or the treatment

Ocular melanoma is typically treated by resection of the surgical mass or for progressed large tumours, via enucleation (removal of the eye)

Phototherapy

Stereotactic radiosurgery

Radiotherapy:

- Proton Therapy

- Episcleral eye plaque brachytherapy is the preferred treatment method

Surgical insertion (suturing) of a radioactive plaque to the sclera, close to the tumour

Good results in terms of tumour control as well as improved vision retention

I-125 is the most widely used isotope in eye brachytherapy4

Survival rates for patients treated with I-125 plaque brachytherapy are high and compare favourably to those of external beam radiotherapy and enculeation

Ru-106 is preferred for treatment of small tumours -90% tumour control rate5

I-125- 15mm ROPES plaque

Ru-106- Bebig applicators

TLDs

Extrapolation Chambers

Film

Fibre Optic Scintillators

I-125 Brachytherapy Source

AAPM Task Group No. 43 (TG43) Report6

Air Kerma Strength, Geometry, Radial Dose and

Anisotropy Functions

Ru-106 Brachytherapy Source

NIST traceable calibration protocol for dose rate calculation in Ru-106 eye plaque brachytherapy

BEBIG supply the 11 point “Protocol of Measurements”7

- depth-dose curve of 11 points from 0.6mm, then 1 – 10mm from the centre of the plaque surface

- 33 dose rate points

Plaque Simulator (BEBIG GmbH, Berlin, Germany)

Interactive 3D simulation of desired treatment plan

A variety of sources and plaque types are available

Integrates 3D CT information of the eye

Allows the selection of any seed configuration and activity, providing depth dose and isodose curves

TG43 Protocol- the quality of the radial dose function fit for calculating dose data is reduced for values of r ≤0.5cm8

- non-physical fluctuations and significant inaccuracy for values of r ≤ 0.25cm8

- single Amersham Health model 6711 source data for radii between 0.5cm and 7cm

Bebig Protocol of Measurements- measuring 1mm away from the surface of the source decreases resolution

Steep dose gradients

Surrounding critical structures

TPS inaccuracy around border of eye9

Variations in seed activity

Detector size

Three-dimensional semiconductor detectors such as the Medipix2 have been used successfully to provide high spatial resolution X-ray imaging

Radiography, neutronography, and micro-tomography

Single-particle-counting pixel detector with a high detection efficiency and an unlimited dynamic range

256 x 256 sensitive silicon pixel array

real time intensity read-out

Three-dimensional dosimetric images of the dose distribution from a 15mm ROPES plaque loaded with I-125 seeds and the Ru-106 CCD plaque obtained using the Medipix2 detector placed below the plaque within a tissue equivalent phantom of eye matching dimensions10

The CMRP have developed dosimetry software, EyeCan, based on TG43 data, which provides:

- Analytical calculation of the Medipix 2 output- Cross sectional dose colour map- Depth dose distribution- Isodose map

We need to validate the dosimetry using Geant4

Monte Carlo methods of dosimetry: - handle complex geometry of the brachytherapy

sources - can achieve even distribution of radioactivity from

the source

Both I-125 and Ru-106 Monte Carlo dosimetry have been performed with good results

new experimental methods such as the Medipix2 developed at CMRP, necessitate Monte Carlo methods to verify dosimetry

Geant4.9.3 Monte Carlo Toolkit for dose optimisation?

The ultimate goal of this research and the collaborative research of CMRP, is to provide eye plaque quality assurance in a clinical setting in four refined steps:

1. Treatment planning based on three-dimensional (3D) imaging

2. Customised eye plaque preparation according to treatment plan

3. Dose calculation using TG43 and Monte Carlo derived data

4. 3D dosimetric imaging with Medipix2 for quality assurance of the treatment plan and dose verification

i

Imaging Plaque selection TPS(TG43/MC) QA (Medipix2)

Monte Carlo simulation of eye plaque brachytherapy sources using GEANT4 to obtain comprehensive dose data for TPS optimisation

Simulation 1:I-125 single Amersham 6711 seed

Simulation 2:Ru-106 Bebig CCD plaque

Monte Carlo simulation techniques were used to model a single Amersham Health model 6711 I-125 seed in water using the Geant4.9.3 Monte Carlo toolkit

Obtain TG43 parameters

Cylindrical geometry

Source encapsulated within a titanium shell

Fattened endcaps as opposed to curved (Williamson et al. 1988)11

Set of concentric cylinders with an inner silver rod

Eye diameter = 24mm

Radial distances ranging from 1mm – 25mm

Sets of 25 concentric toroids

Positioned every 1mm at an angle, θ, from the centre of the source (assuming radial symmetry), every five degrees

Geant4 visualisation of Monte Carlo simulation of model 6711 seed showing inner silver core (magenta), air gap (blue) and titanium shell (silver), and set of 50 concentric scoring toroids (red) positioned 1mm apart

To measure at zero degrees,scoring toroids were replaced with solid cylinders of varying radius and thickness to score the dose over the 25mm range

Larger radius cylinders used for 1cm and greater distances

Geant4 visualisation of Monte Carlo simulation of single 6711 seed with scoring tubes (red) positioned every 1mm on the

source central axis

Random energy based on spectra

I-125 is a low energy photon emitter

Half-life of 59.4 days6

G4EMLOW.6.9 low-energy data set

Range Cuts - 1μm

Photon energy (keV)

Photons per disintegration

27.2 0.405

27.47 0.756

30.98 0.202

31.88 0.043

35.45 0.067

Cylindrical Geometry considered for random particle generation

Random Coordinate: - side of cylinder - two endcaps

Generate random coordinate between zero and 2AE + AS

The y coordinate was defined by rcosθ and the x coordinate by rsinθ

Geant4 visualisation of Monte Carlo simulation of model 6711 seed

The results of the I-125 simulation were used to calculate the TG43 dosimetric parameters and were in good agreement with the published data

Radial dose functions over the scoring range fell within 3% with a maximum deviation from the TG43 data of only 2.8% (occurring 1mm away from the source on the plaque central axis)

Anisotropy functions were obtained within 5% uncertainty for all polar angles

Monte Carlo derived radial dose function demonstrating the depth-dose delivered on the central axis compared with TG43 data

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TG43

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r = 0.5 (TG43)r = 1cm (TG43)r = 2cm (TG43)Poly. (r = 0.5cm (MC))Poly. (r = 1cm (MC))Poly. (r = 2cm (MC))

Monte Carlo anisotropy functions compared with tabulated data provided by the TG43 protocol

Upturn in dose from 90 to 70 degrees about the source for small values of r

Lower anisotropy functions at small values of theta

Attenuation and geometry effects seed endcaps12

Seed geometry assumed by MC code did not have curved endcaps nor did it consider generating from beneath the silver surface of the inner rod

Results verify the suitability of Geant4 based dosimetry methods for I-125 eye brachytherapy dose optimization

The BEBIG CCD Ru-106 plaque was modelled using the Geant4.9.3 toolkit

BEBIG Ru-106 CCD plaque

Two Monte Carlo simulations to obtain:

1. depth dose data on the central axis for calibration

2. dose rate array spanning the entire volume of the eye for future input into treatment planning software

Plaque Geometry:- Rim diameter = 17.9mm- Height = 4.3mm- Radius of curvature =12mm

Silver spherical cap :- Inner radius = 12.1mm- Inner height = 4.3mm- Two eyelets excluded- 0.1mm added to radius to

account for silver window

Calibration simulation performed using a series of scoring cylinders (G4Tubs) 0.5mm thick and 0.2mm in radius

positioned at 90 degrees, 1mm from the centre of the plaque

Total of 25 cylinders, positioned 1mm apart along plaque central axis to provide comparison data with the BEBIG “Protocol of Measurements”

Sets of 25 concentric scoring rings were positioned at a variable distance along the central axis of the plaque

Rings were 0.2mm thick and of radius ranging from 1mm –25mm

When combined with the central axis calibration data, a total of 650 sampled regions encompassed the eye

Ruthenium-106 decays by beta emission via Rhodium-106

Max energy - 39.4keV

Rhodium-106 half life - only 30seconds

Main electron contribution from the decay of Rh-106

Photon contamination contribution from Rh-106 is significant

Rh-106 beta energy emission:- max 3.54MeV - average 1.41MeV

*Decay data for Ru-106 from the National Nuclear Data Center (2001) was obtained from Appendix A of the ICRU Report 72 (2004) (see Tables 4 & 5)13

Spherical cap uniformly coated with Ru-106 Particles may be emitted from any point on

surface Surface area is proportional to h

Random Height:- random height, z generated between zero and h- consider series of rings located at any point, z- ring radius determined by height in plaque

Random Coordinate:- generated at any point x,y on ring- determine radius of ring

Geant4 visualisation of Monte Carlo simulation of Ru-106 plaque showing silver curved surface

Geant4 simulation successfully generated particles from a uniform distribution of Ru-106 on the surface of the plaque

Scoring over wide range was possible

650 dose point array obtained

Monte Carlo uncertainty within 10% for small distances

Improved statistics required for large distances

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Monte Carlo derived Ru-106 CCD plaque central axis depth dose compared with central axis dose generated from the Plaque Simulator

Monte Carlo results differed considerably from TPS generated depth dose data

Greatest deviation occurring at very close distances to the plaque surface

A significantly higher dose at small distances (r ≤1cm) in comparison with the TPS results, likely due to:

- source thickness- depth of particle generation

Simulation generated particles from the surface of an infinitesimally thin layer of silver 0.1mm beneath the plaque surface (Bebig)

Astrahan (2003) determined that the radioactivity of the plaque is a distribution through 0.2mm of the silver

Indicates a 0.6 – 0.75mm thick gap between where the radioactive part begins and the edge of the plaque itself

Cross et al. (2001)14 performed Monte Carlo dosimetry of various Ru-106 plaque types and compared the results with experimental measurements performed in Soares et al. (2001)15

Findings:- planar source results within 10%- curved plaque results differed by about 30%

Conclusions:- while limited, experimental approach is more accurate- likely to be a result of differences in source geometry definitions and specifications

Producing unifrom distribution of activity on complex curved surface

Replicating the complicated energy spectrum of Ru-106

Results emphasise the importance of experimental 2D and 3D dosimetric imaging of Ru-106 plaques with devices such as the Medipix2 used in the recent experimental work at the CMRP

Geant4 is a useful tool for dosimetry of plaque brachytherapy sources used in the treatment of ocular melanoma

The dose point array obtained for the 6711 seed can be input into the dose planning software for dose optimisation and the quality assurance of eye plaque brachytherapy treatment

Ru-106 results highlight the complexity of eye brachytherapy source dosimetry, consistent with current literature

Revised source models and scoring –‘babushka’

3D dose imaging and reconstruction of Ru-106 using Medipx2

Monte Carlo modeling of Medipix2 with eye plaque and brachytherapy sources

Monte Carlo modeling of 15mm ROPES plaque

Effect on surrounding critical structures using Geant4

“And so we say ‘Hooray for eyes! Hooray, hooray,

hooray . . . for eyes!”

(Theo. LeSieg)

1. Cancer Institute NSW. (2009). Cancer in New South Wales: Incidence and Mortality 2007. NSW: Cancer Institute NSW.

2. Shields, C.L., & Shields, J.A. (2009). Ocular melanoma: Relatively rare butrequiring respect. Clinics in Dermatology, 27(1), 122 – 133.

3. Chang, A.E., Karnell, L.H., & Menck, H.R. (1998). The National Cancer Data Basereport on cutaneous and noncutaneous melanoma: A summary of 84,836 casesfrom the past decade. The American College of Surgeons Commission on Cancerand the American Cancer Society. Cancer, 83(8), 1664 – 1678.

4. Chan, M.F, Fung, A.Y.C., Hu, Y., Chui, C., Amols, H., Zaider, M., et al. (2001). Themeasurements of three-dimensional dose distribution of a ruthenium-106ophthalmological applicator using magnetic resonance imaging of BANGpolymer gels. Journal of Applied Clinical Medical Physics, 2(2), 85 – 89.

5. Eichmann, M., Flühs, D., & Spaan, B. (2009). Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators. Medical Physics, 36(10), 4634 – 4643.

6. Rivard, M.J., Coursey, B.M., DeWerd, L.A., Hanson, W.F., Huq, M.S., Ibbott, G.S.,et al. (2004). Update of AAPM Task Group No. 43 Report: A revised AAPMprotocol for brachytherapy dose calculations. Medical Physics, 31(3), 633 – 674.

7. Astrahan, M.A. (2003). A patch source model for treatment planning ofruthenium ophthalmic applicators. Medical Physics, 30(6), 1219 – 1228.

8. Taylor, R.E.P., & Rogers, D.W.O. (2008). More accurate fitting of I-125 and Pd-103 radial dose functions. Medical Physics, 35(9), 4242 – 4250.

9. Granero, D., Perez-Calatayud, J., Ballester, F., Casal, E., & de Frutos, J.M. (2004).Dosimetric studies of the 15 mm ROPES eye plaque. Medical Physics, 31(12),3330 – 3336.

10. Weaver, M., Green, J., Petasecca, M., Lerch, M.L.F., Cutajar, D., Franklin, D., et al.(2010). Three-dimensional dosimetry imaging technique of I-125 plaque for eyecancer treatment. Proceedings of the 11th International Workshop on RadiationImaging Detectors. Nuclear Instruments and Methods in Physics ResearchSection A: Accelerators, Spectrometers, Detectors and Associated Equipment,doi:10.1016/j.nima.2010.06.187

11. Williamson, J.F. (1988). Monte Carlo evaluation of specific dose constants in water for I-125 seeds. Medical Physics, 15(5), 686 – 694

12. Dolan, J., Li, Z., & Williamson, J.F. (2006). Monte Carlo and experimentaldosimetry of an 125I brachytherapy seed. Medical Physics, 33(12), 4675 – 4684.

13. ICRU (2004). Sources and their application in brachytherapy (Report 72).Journal of the ICRU, 4(2), 21 – 89.

14. Cross, W.G., Hokkanen, J., Mourtada, F., Sipila, P., Soares, C.G., &Vynckier, S. (2001). Calculation of beta-ray dose distributions fromophthalmic applicators and comparison with measurements in a modeleye. Medical Physics, 28(7), 1385 – 1396.

15. Soares, C.G., Vynckier, S., Järvinen, H., Cross, W.G., Sipila, P., Flühs, D., etal. (2001). Dosimetry of beta-ray ophthalmic applicators: Comparison ofdifferent measurement methods. Medical Physics, 28(7), 1373 – 1384.