Dosimetry for Eye Plaque Brachytherapy: Beyond COMS to the Future with Image-Guidance

Mark J. Rivard, Ph.D.

Professor and Chief Medical Physicist Tufts Medical Center Boston, Massachusetts, USA

Disclosure

Research support provided by:
1. GE Healthcare / Oncura, Inc. 2. IsoRay Medical, Inc.
Opinions contained are solely those of the presenter, not meant to be interpreted as societal guidance. Specific commercial equipment, instruments, and materials are described to fully describe the necessary procedures. Such identification does not imply recommendation or endorsement by the presenter nor imply that the identified material or equipment is necessarily the best available for these purposes.

Learning Objectives

background on eye plaque brachytherapy
COMS protocol clinical results current dosimetry methods
dosimetry advances and AAPM TG-129
better spatial resolution improved dose calculation accuracy practical implementation using MBDCA methods
imaging advances beyond COMS and TG-129 future plans
Pertinent Societal Recommendations

ABS 2003 (Nag et al.)

plaque size (margin based on US) prescription dose and point implant duration radionuclide choice
AAPM 2004 (Rivard et al.)
updated TG-43 dose calculation method dose interpolation/extrapolation methods (2007 supplement)
AAPM 2008 (Butler et al.)
source strength assay practice, quantities, actions
AAPM 2012 (Chiu-Tsao et al.)
clinical physics practice guidelines specific to eye plaques draft report currently under review

ABS 2003 Recommendations

plaque coordinate system
outer sclera is 1.4 mm from middle source center origin positioned 1.0 mm deeper on central axis (inner sclera)
lesion height > 2.5 mm, basal diameter > 10 mm
height measured from inner scleral surface via ultrasound (US) plaque size (2-3 mm lesion margin)
prescription dose and point recommendations
radionuclide choice (low energy sources: 103Pd, 125I, 131Cs) minimum tumor dose 85 Gy dose rate 0.60-1.05 Gy/h implant duration 3-7 days
Background: Eye Plaque Brachytherapy
formation of Collaborative Ocular Melanoma Study (COMS)
multi-institutional, prospective, randomized, phase III, clinical trial sponsored by U.S. NIH National Eye Institute
1st COMS study with EBRT, 4 Gy in 5 Fx (20 Gy total)
apical height > 10 mm, basal dimension > 16 mm no survival improvements over enucleation

COMS-style Eye Plaques

Silastic Inserts

Pd-keV model 200

I-125 Cs-keV 30 keV model 6711 model CS-1 Rev2
Monte Carlo source characterization
Simulated Eye Plaque Loading
Eye Plaque Construction / Sterilization
eye plaque Bx (222Rn) first reported 81 years ago
R. Foster Moore, Brit. J. Ophthalmology 14, 145-156 (1930)
2nd COMS study with 100 Gy 125I temporary brachytherapy
apical height d, 2.5 mm < d < 10 mm, basal dimension < 16 mm tumor classification considered medium 1985-2004 accrual period (~1,300 patients) minimum tumor dose of 100 Gy (85 Gy pre-TG-43 formalism)
enucleation survival benefits equal to brachytherapy
study stopped early due to ethics of randomization Category 1 clinical results demonstrated Bx efficacy
2004 AAPM TG-43U1 Brachytherapy Dosimetry Formalism (2D)

D r, S K D r,

SK gL(r) GL(r,) F(r,)

GL r, GL r0 ,0

g L r F r,
S to water in waterrat point g F r,P(r, dose rate
air kerma strength dose rate constant radial dose function geometry function (line source approximation) 2D anisotropy function
Brachytherapy Dose Calculation Geometry
Rivard et al., Med. Phys. 31, 633-674 (2004)

Low-Energy Brachytherapy Sources
Laser Welded Ends (0.1 mm wall)
Inorganic Substrate w/Cs-131 Attached Gold X-Ray Marker (0.25 mm diameter) Titanium Case (0.05 mm wall)

0.8 mm

4.1 mm 4.0 mm 4.5 mm 4.5 mm

IsoRay model CS-1 Rev2

Dosimetry Parameter Data Trail
Example Dosimetry Parameter Dataset
prefer AAPM-recommended datasets otherwise rely on published literature and manufacturer
Source Dosimetry Data Entry
Default Source Coordinates / Orientations
Incorrect Source Orientation

Grid Size Adjustment

Variable Grid Resolution

10 mm Eye Plaque (2D)

12 mm Eye Plaque (2D)

14 mm Eye Plaque (2D)

16 mm Eye Plaque (2D)

18 mm Eye Plaque (2D)

20 mm Eye Plaque (2D)

22 mm Eye Plaque (2D)

Source Strength Calibrations

Medical Physics

Third-party brachytherapy source calibrations and physicist responsibilities: Report of the AAPM Low Energy Brachytherapy Source Calibration Working Group Compiling and clarifying recommendations established by previous AAPM Task Groups 40, 56, and 64 were among the working groups charges, which also included the role of third-party handlers to perform loading and assay of sources. This document presents working group findings on the responsibilities of the institutional medical physicist and a clarification of the existing AAPM recommendations in the assay of brachytherapy sources. The AAPM leaves it to the discretion of the institutional medical physicist whether the manufacturers or institutional physicists measured value should be used in performing dosimetry calculations.
2008 American Association of Physicists in Medicine Butler et al., Med. Phys. 35, 3860-3865 (2008)

Quantities to Assay

number to be assayed a
Butler et al., Med. Phys. 35, 3860-3865 (2008)
Actions Following the Assay
action by medical physicist

Source Calibrations at PSDL and Hospital

NIST WAFAC

Bx source

well chamber

Example Source Assay Worksheet

AAPM TG-32 (Report 21)

established U.S. source strength standard (SK) AAPM TG-32 (1987) is in agreement with:
NCRP Report 41 (1974) French Cmte on ionizing Radiat. Measurements (1983) British Cmte on Radiat. Units and Measurements (1984) ICRU Report 38 (1985) etc
SK (or RAKR) is the international standard apparent activity for brachytherapy source strength is unsafe and inexcusable (my emphasis)
NRC Information Notice 2009-17
The NRC has received reports of numerous medical events caused by errors in confusing the units of source strength in the specification of sourcesspecifically, units of air-kerma strength and apparent activity in units of millicurie (mCi).

(my emphasis)

27% overdose errors with I-125 78% overdose errors with Ir-192 manufacturers should not use mCi; use only air-kerma strength U.S. medical physicists should follow AAPM TG-32
AAPM TG-129 Recommendations
committee formed in 2006 chair = Sou-Tung Chiu-Tsao review eye plaque dosimetry literature evaluate influence of TG-43U1 on COMS dosimetry quantify material inhomogeneity influence on dosimetry QA recommendations of TPS and plaque use draft report under societal review, publication in 2012

Eye Plaque Dosimetry

Rivard, et al. Med Phys 38, 306-316 (2011)
Eye Plaque Brachytherapy Process
patient identified in multi-disciplinary tumor conference
known tumor progression, US-based dimensions, visual acuity
referral to Radiation Oncology
rule out metastatic disease (chest CT, bone scan) patient education (outpatient implants) pre-implant simulation (CT and/or MRI)

treatment planning

generalized approach with patient points image-based with DVHs

plaque preparation

source ordering, source receipt, assay, plaque assembly, sterilization

implant/explant endgame

plaque disassembly, source disposal, patient followup
Eye Plaque Quality Management Program
eye plaque brachytherapy quality depends on tasks preceding implant and during implantation initiate institution-specific task flowchart to:
create QMP with QA tests and Quality Controls (checklists) create quantitative quality metrics identify quality hurdles some tasks are beyond RadOnc+MedPhys control
evaluate utility of QMP and revise to quantitatively improve quality
scope: activities in Radiation Oncology
patient imaging (in Ophthalmology?) treatment planning source assay plaque assembly sterilization plaque positioning and explant (surgical suite?)
role of each activity on overall QUALITY

defined as achieving the goals of the Written Directive not limited to minimally-satisfying State/Federal regulations not based on general procedures lacking hospital-specific info requires stakeholders recognize quality is a component of care
Treatment Planning System: Plaque
spreadsheet-based calcs possible without imaging data TPS commissioning for high-strength low-energy seeds
compare dosimetry parameters to AAPM/RPC Source Registry compare plaque dose calculations to benchmarked results 1. Rivard et al., Brachytherapy 7, 327-335 (2008) 2. Melhus and Rivard, Med. Phys. 35, 3364-3371 (2008) 3. Thomson et al., Med. Phys. 35, 5530-5543 (2008) 4. Rivard et al., Med. Phys. 38, 306-316 (2011)
commission for seed positions, dose calculation, etc.

TPS Commissioning: Seeds

TPS acceptance testing upon receipt or upgrades
limited criteria and variable across vendors Plaque Simulator (not FDA-approved), Pinnacle, BrachyVision
dose calculations to a point using single-source dose superposition in liquid water without collimation/scatter first commission single-source dosimetry data document results
Patient Imaging: Ophthalmology US
courtesy of Sou-Tung Chiu-Tsao, 2005 AAPM
operating conditions of the US system
frequency window/level measurement tools

gathered data

basal dimensions lesion height X.XXX mm
data uncertainties? QA tolerances, actions, records? responsible party for QA? manufacturer or societal tolerance standardization? poorly constrained component for eye plaque quality
Patient Imaging: Radiation Oncology
infrequent CT acquisition (MRI more rare) patient positioning gathered data
critical structure visualization: lacrimal gland/lens/optic nerve lesion visualization: poor contrast and spatial resolution sensitivity to window/level (1 mm shifts) snapshot in time (mobile globe) no plaque present (no deformable registration)
clinical medical physicist responsible for QA develop imaging QA specific for eye plaque brachytherapy no manufacturer or societal tolerance standards new era of image-based treatment planning
quantitative metrics for construction accuracy
seed positioning within Silastic (for COMS plaques) Silastic:plaque coupling (source:eye distance) Silastic:plaque coupling (rotational symmetry variance) ripe area for research

quantitative metrics for sterilization
hospital Central Processing Department is responsible established procedures based on material composition test strips to validate sterilization performance verify test strip results preceding implant documentation of this verification: implant surgical note
Requirements for Written Directive
Written Directive: Quality
quantitative metrics for implant duration
time difference between implant:explant linear correlation of time with delivered dose regulations mandate +/-20% (medical event) what duration tolerance (dose tolerance) is acceptable?
quantitative metrics for plaque positioning
correct eye (OS/OD) is easy, how to specify location? correct plaque orientation? unknown correlation of positioning with delivered dose regulations vague on plaque positioning what positioning tolerance (dose tolerance) is acceptable?
Plan Check and Implant Audit
Where do we go from here?
Advanced Dosimetry Needs Advanced Imaging
An approach to using conventional brachytherapy software for clinical treatment planning of complex, Monte Carlo-based brachytherapy dose distributions
Mark Rivard,1 Chris Melhus,1 Domingo Granero,2 Jose Perez-Calatayud,2 Facundo Ballester3 1Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts 02111 2Radiation Oncology Department, La Fe University Hospital, Valencia, Spain 3Department of Atomic, Molecular, and Nuclear Physics, University of Valencia, Spain
Med. Phys. 36, 1968-1975 (2009)

Computed Tomography (CT)

Magnetic Resonance Imaging (MRI) T1
Magnetic Resonance Imaging (MRI) T2

Fundoscopy

requires dilated pupil/iris 1 mm localization accuracy direct incorporation into TPS FOV posterior to ora serrata ~20 min procedure

merged fundus images

Plaque SimulatorTM incorporated image

3D Ultrasound

probe frequency 10 MHz axial resolution 0.15 mm, lateral resolution 0.27 mm 25 mm focal point; 50 mm total image depth 7.5 s acquisition time; 6 s reconstruction time (vs. 5-10 min for A- and B-scans) reproducibility height: CV 0.7-3%, diameter: CV 0-10%
Optical Coherence Tomography (OCT)
>1500 A-scan images per second axial resolution m can identify tumors undetectable via conventional US FOV 20x30 (< 9 mm diameter & < 1 mm thickness) pointwise correlation with infrared, real-time fundus images most applicable for small choroidal lesions

Ultrasound B-scan

melanocytic nevus

Spectral Domain (SD) OCT unable to detect the lesion!
Enhanced Depth Imaging SD-OCT lesion: sharp highly-reflective band at Bruch/RPE/choriocapillaris layer

Color fundus photograph

lesion: highly reflective band, posterior shadowing
Heidelberg Retinal Tomography (HRT)
HRT = confocal laser scanning tomography
2D optical section images acquired in 32 ms @ 20 Hz
total acquisition time: 1.6 s
digitized in 256 x 256 individual height measurements
absolutely scaled for the individual eye reproducibility of m
FOV 10x10, 15x15, or 20x20

0.5 mm to 4.0 mm depth

3D image = 32 equally-spaced 2D optical section images pupil dilation (>1 mm) not required CV for area, volume, and depth ~ 5%
glaucomatous optic nerve head

topography

pseudo-3D

reflectance

Conventional Localization Method

Summary

eye plaque brachytherapy provides excellent clinical results in comparison to other treatment modalities multi-disciplinary procedure is manually intensive (like much of LDR brachytherapy) implant quality depends on successful completion of all tasks (where quality-sensitivity may be unknown) improved dosimetry knowledge improves implant quality areas for eye plaque brachytherapy quality research
US QA oversight loaded plaque assay plaque positioning imaging pre/post plaque implantation explant QA (of plaque and patient)

Acknowledgements

Nolan Gagne PhD student at Tufts Medical Center University Massachusetts Lowell