Title: Plaque Brachytherapy: An Inspiration to Radiation Oncology
1Plaque Brachytherapy An Inspiration to Radiation
Oncology
- Jenna Ebeling
- University of Wisconsin-La Crosse
- Gundersen Lutheran
2The Basics of Eye Anatomy
- The eyes are made up of many different structures
which all work together giving us the ability to
see. - Three tunics (outermost to innermost)
- 1. Outer fibrous layer
- 2. Middle layer
- Also known as the uvea
- Consists of the choroid, ciliary body, and iris
- The iris, which is an extension of the choroid,
is made up of radioresistent melanocytes. - 3. Sensory layer
- Consists of the retina, fovea, optic disc, and
optic nerve.
3Ocular Anatomy
The eye contains many intricate structures each
with their own unique function.
4The Macula
- Tumor location in the eye can be represented in
relation to the macula, a posterior eye landmark
in the retina providing us with our focused
central vision. - A study done by the University of Massachusetts
found that in both eyes the macula was the most
common location of choroidal and ciliary tumors,
with frequency decreasing moving proximally to
the ciliary body.
5The Macula
Providing us with our central vision, the macula
sits in the center of the retina creating sharp
and distinct images. Within the macula, a small
nodule known as the fovea, is the area in which
our greatest vision is formed.
6Ocular Melanoma
- In adults, ocular melanoma poses the greatest
risk to ones life of all ocular malignancies. - Choroidal melanoma is the most common primary
ocular malignancy in adults. - Arises from melanocytes in the uveal track.
- Ocular melanoma is extremely rare, especially
when compared to skin melanoma. - Only 6 to 7 cases per million per year in the
United States.
7The Past
- Prior to 1980 enucleation was the standard
treatment modality for ocular melanoma. - Resulted in
- Poor cosmetic results
- Complete loss of vision in affected eye
- Decreased patients self esteem
- Increased risk of metastasis due
- to tumor seeding
8The Present
- Radiotherapy has revolutionized the treatment of
ocular melanoma and has made enucleation very
controversial. - Results in
- Greater cosmetic outcomes
- Restoration of vision in affected eye
- Increase in patients self esteem
-
9Epidemiology
- Often diagnosed around 55 years of age.
- Caucasians have a higher incidence when compared
to African Americans and Hispanics.
10Etiology and Risk Factors
- Having blue eyes
- Why? Those with light irises have more dense and
active melanocytes within their choroid and
consequently are at a higher risk of developing
choroidal melanoma. - Excessive sun exposure
- Sun exposure at young ages
- Severe eye burns
- History of snow blindness
- Dysplastic nevus syndrome
- Chromosomal abnormalities
- Family history seems to have no correlation
11Symptoms
- When a tumor begins to obstruct critical
structures the following symptoms may occur - light flashes
- blurry vision
- spots in vision
- a loss of peripheral vision
- The greatest visual disturbances occur when the
tumor extends near or into the macula. Then, the
following symptoms may occur - far-sightedness
- loss of vision
- discrepancies in colors
12Detection
- Choroidal melanoma is often diagnosed late due to
its hidden location within the eye. - In addition, the choroid is out of our general
vision range making symptoms almost unapparent
until the tumor has grown to a significant size.
- Ophthalmologists find ciliary body melanoma the
most difficult to diagnose.
13Detection
- The best screening method is by means of an
annual dilated retinal eye examination after the
age 40. - Ophthalmologists examine blood vessels on the
outside of the eye as well as visualizing the
inside of the eye. - Fluorscein angiography and idocyanine green
angiography are supplemental methods to visualize
the blood vessels within the retina and to get a
better picture of the tumor. - Ophthalmologists often see a brown mass, and less
commonly a yellow or non-pigmented mass. - Often diagnosed around 4.5mm
- The ability to detect smaller lesions is
improving. - A diagnosis if often confirmed with ultrasound
and a biopsy is typically not needed.
14Choroidal Melanoma vs. Iris Melanoma
Iris Melanoma- brown observable pigmentation
Choroidal Melanoma- hidden pigmentation
15Diagnosis Confirmation
Ultrasound is not only a tool used to confirm
diagnosis, but also used define a tumors
dimensions, extension, and retinal involvement.
16Aggressive Presentations
- Due to the eyes poor lymphatic system, lymph
node involvement is rare. - May happen if tumor invades and extends through
the sclera. - Critical structures within the eye may be damaged
due to direct invasion by the tumor. - Because ocular melanoma is often diagnosed in an
advanced stage, metastasis is common. - Treatment should begin promptly after diagnosis
to improve local control.
17Treatment Options
- -The size, stage, mitotic activity,
location, and a patients overall health must be
considered when deciding which treatment is most
appropriate.. - Epsiscleral plaque brachytherapy
- Charged particle therapy
- Transpupillary thermotherapy
- Cryotherapy
- Ultrasonic hyperthermia
- Stereotactic radiation therapy
- Stereotactic radiosurgery
- Enuculation
- Cobalt-60
- Gamma Knife
- Denotes radiotherapy treatment
18Enucleation
- Enucleation is often necessary when
- Treatment will significantly impair ones vision
- The tumor involves the sclera or iris
- Intraocular pressure is too high
- Greater than 30 of the eye consists of tumor
- The tumor has exceeded 15 mm in diameter
19Plaque Brachytherapy Guidance
- COMS (Collaborative Ocular Melanoma Study) found
enucleation and plaque brachytherapy to be very
comparable, showing similar mortality rates. - The ABS (American Brachytherapy Society) guides
plaque brachytherapy for choroidal melanoma. - Plaque brachytherapy procedures should only be
done by experts in a specialized hospital due to
the complexity of the surgery. - All surgeries in discretion to recommendations on
patient selection, dose prescription, plaque
design, isotope selection, and techniques. - The American Joint Committee on Cancer provides
ocular melanoma TNM staging. - Staging is not often used.
20Staging Uveal Melanoma
- TNM Staging of Uveal Melanoma
- T1lt10mm greatest dimension, lt3mm thickness
- T1alt8mm greatest dimension, lt2mm thickness
- T1bgt8 to 10mm greatest dimension, gt2-3mm
thickness - T210-15mm greatest dimension, 3-5mm thickness
- T3gt15mm greatest dimension, gt5mm thickness
- T4Extraocular extension
- N1 All sties, regional
- M Metastasis
- ABS recommends T1 lesions to be watched for
growth prior to treatment and T2 lesions to begin
treatment as soon as possible.
21Plaque Brachytherapy Patient Specifications
- Plaque brachytherapy has shown significant and
dramatic results in patients who have growing
medium tumors and whose vision can still be
restored. - Recommendations
- Actively dividing malignancy
- Overall good visual outcomes and local control
- Absence of invasion outside of the sclera, ring
melanomas, and a tumor involving the vast
majority of the ciliary body - Often overruled when tumors are in close
proximity to the optic disc and fovea.
22Plaque Composition and Design
- Just as every persons eye is unique, so are an
individual eye plaques.
- Eye plaques are shaped like a dome and made out
of gold. There are six different sizes of gold
cases available.
- Radioactive seeds are uniquely placed on the
inside of the gold surface or silastic carrier.
23Customization
- The ophthalmologist makes note of the tumors
measured dimensions and confirms the dimensions
with ultrasonography. - A fundus diagram is obtained by CT or MRI
diagramming the eyes base - When combined with a three dimensional image of
the eye the tumor can be precisely located.
24Fundus Diagram
The fundus diagram of the eye is a map of the eye
used to locate the tumor in respect to critical
structures (retina, choroid, sclera, optic disc,
blood vessels, etc.)
25Plaque Radionuclides
- Cobalt-60
- Disadvantages high doses to critical structures
and personnel. - Being replaced by newer and more safe
radionuclide's - Ruthenium 106-rhodium 106
- Replaced Co-60 plaques
- Beta emitter
- Greatest dose fall off
- Radon-222
- In 1920s were directly inserted into the tumor.
However, Co-60 eventually replaced radon seeds
and the direct application approach. - Palladium-103
- Lower dose to personnel
- Currently being researched
- Iodine-125
- Replaced Co-60 Plaques due to greater shielding
ability - Can treat more deeply when compared to
Ruthenium106-rhodium 106 - Currently the most commonly used radioisotope in
US and Canada - Gold-198
- Thallium-182
26Characteristics of Radioisotopes Used for
Episcleral Brachytherapy
27Plaque Fabrication
- Multiple tumor characteristics are analyzed
before picking the desired radioisotope and
plaque size. - Plaques can fit tumors as large as 12mm in
thickness and can be made as large as 20mm in
diameter. - Shapes include
- Circular
- Irregularly shaped (oval or kidney shaped)
- Notched near optic disk.
- All are dome shaped so the plaque is not in
direct contact with sclera. - Gold casing
- Blocks about 99 of radiation from plaques
periphery and towards personnel. - Directly glued radioactive seeds
- Insert silastic insert with either pre determined
seed arrangement or with wells so seed
arrangement can be manipulated. - Seed strength is double checked with a well
chamber prior to seed loading.
28Plaque Brachytherapy Planning and Dose
Distribution
- Extensive and complex planning
- Planning includes
- Obtaining accurate tumor information from
measurements and diagrams - Deciding the dose rate and cumulative dose to be
delivered to the tumor - Choosing the appropriate radioactive seed
arrangement and plaque type - Compiling a dose volume histogram
- Uniform or non-uniform seed loading
- The TG-43 method of calculating dose accounts
anisotropy, attenuation, and backscatter from the
gold shield and the attenuation from the silastic
insert. - ABS (does not take into account above parameters
and uses COMS calculation guidelines) recommends
85Gy to tumors peak and 85Gy isodose line to
cover entire tumor. - TG-43 discovered that the COMS calculation method
overestimated about 30 percent in the true dose
delivered. - ABS recommends .60 and 1.05Gy per hour in three
to seven days for I-125. - Dose and dose rate ultimately decided upon by
radiation oncologist for local control.
29Critical Structures
- To locally control uveal melanoma, a dose greater
than the tolerance of critical structures must be
used. - Critical structures include
- Retina
- optic nerve
- Lens
- Eyelid
- Lashes
- Lacrimal glands
30Surgical Procedure Guidelines
- Inpatient or Outpatient
- General or local anesthesia
- Dummy plaque can be used prior to plaque
placement to verify its location. - Extraocular muscles may have to be
- removed and the eyeball rotated to place
- the plaque.
- Ophthalmologist sews cap onto the sclera.
- MRI or ultrasonography can be used to validate
the plaques location.
31Surgical Procedure Guidelines
- Plaque kept on the eye for 4-5 days and is
monitored carefully (especially outpatients). - After desired amount of radioactivity has been
delivered to the tumor the plaque is removed
under local anesthesia and the seeds are counted.
- Because of human error and slight misalignments
of the plaque during surgery, doses to the tumor
and critical structures must again be
recalculated to obtain the true doses delivered.
32Complications and Side Effects
- Great variation which is dependent on tumors
size, extension, and location to critical
structures within the eye, specifically the fovea
and optic disc - Extension into the optic disk can lead to
retinopathy and papillopathy - Tumors whose location was at least five
millimeters away from the optic disk and fovea
showed improved long term vision conservation - Most significant effects are retinopathy and
optic neuropathy where non-proliferative
retinopathy can cause permanent loss of vision if
it is not treated. - Over half of all patients treated with plaque
therapy reported declining vision after ten years
according to Shields. - Transpupillary thermotherapy (TTT), a procedure
that uses a laser to deliver heat to tumors
through the pupil, has been used in combination
with plaque brachytherapy to improve the visual
complications from plaque therapy alone.
33Prognosis
- Poor, has not changed significantly even with the
advent of newer treatment modalities. - According to the COMS group, after iodine-125
plaque brachytherapy or enuculation, metastasis
occurred most frequently in tumors whose height
was greater than 16mm. - Metastasis occurs 60 of the time to the liver
and 25 of the time to the lungs. - Chromosome mutations have shown the greatest hope
of a future method to predict metastasis. - Insulin-like growth factor, produced by the
liver, has also shown an increased probability of
liver metastasis. - Half of the patients end up dying within ten
years after diagnosis regardless of what
treatment method was undertaken. - Histologically, pure epithelioid cell uveal
melanoma is the most aggressive with a mortality
rate of 69 in five years.
34Follow-Up
- Follow-up diagnostic tests are frequently
required for many years after treatment - Follow up tests
- Test for liver function and liver metastasis
- Chest x-rays to detect lung metastasis
- Contrast loaded CT scans or MRI to better
visualize tumor extent.
35Tumor Response
- A study done at McGill University Health center
found that plaque therapy dramatically reduced
the tumor size by about 25 five years post
treatment. - Tumors located near the posterior of the eye
responded best to iodine-125 plaque therapy. - The recurrence rate after using plaque
brachytherapy and TTT are only 3 at eight years.
- In 458 patients who had small tumors, there was
only a 2 recurrence rate after five years after
using ruthenium-106 plaques.
36Emerging Modalities in Managing Ocular Melanoma
- Three emerging modalities introduced by plaque
brachytherapy in managing ocular melanoma
include - Proton therapy
- Linac-based stereotactic radiation therapy (SRT)
- Stereotactic radiosurgery (SRS)
- Variable of movement is of great concern when
treating with external beam radiation therapy
37Proton Therapy
- With rapid dose fall off in dose at the end of a
protons range, known as the bragg peak, the
isodose distribution is tightly bound to just the
tumor. - When a tumor is located near a critical
structure, like the retina and macula, proton
therapy is an advantageous treatment option. - However, tumors position during treatment
requires more attention due to tumor movement. - Eye must be tracked with x-ray images.
- The Massachusetts eye infirmary followed 2,069
patients treated with proton therapy and found
local tumor control in 95 percent of the patients
15 years after treatment.
38SRS and SRT
- SRS and SRT consequently irradiate a greater
amount of healthy tissue however, both have
successfully been implemented in intraocular
malignancy. - Must track the tumor
- One method of fixation is by the use of an LED
light and a video camera which attaches to a
stereotactic head frame. - Therapists watch real time video of patients eye
position, specifically the pupil. - Treatment time up to 40min long
- 50 to70Gy in five fractions that is typically
given over 10 days - More affordable and accessible treatment
alternative - Currently being researched
39University of Viennas Eye Tracking System
Prior to treatment the eye must be contoured to
its zero position using the pupil, iris, and
eye canthi.
The pupil is monitored during treatment by the
use of a small video camera and LED light which
are mounted onto the patients face mask.
40Conclusion
- Plaque brachytherapy began a transformation in
treating intraocular tumors with radiation
therapy. - Plaque brachytherapy has inspired and moved
researchers to further pursue radiation therapy
as a means to treat hidden and deadly tumors
within the eye. - There is now a hope and a future for individuals
with intraocular melanoma.
41References
1. Eatmon SL. Intraocular Tumors. Radiation
Therapist. 20071623-33. 2. Inquiry 4S13.
Radiation and life Web site.
http//www.science.mcmaster.ca/mciars/
Doug20Boreham/Website_July2/
inquiry_july2.htm. Accessed March 10, 2009. 3.
Facts about macular hole. National eye institute
Web site. http//www.nei.nih.gov/health/macu
larhole/index.asp. Accessed February 20,
2009. 4. Gragoudas ES, Lane AM, Shih HA, et
al. Management of uveal and conjuctival
melanoma. UpToDate. 2008. 5. Li W, Judge H,
Gragoudas E, et al. Patterns of tumor initiation
in choroidal melanoma. Cancer Research.
2000603757-3760. Accessed February 19, 2009. 6.
Posterior segment anatomy. Ocular anatomy Web
site. http//www.e- sunbear.com/anatomy_04.h
tml. Accessed March 10, 2009. 7. Gragoudas E,
Li W, Goitein M, et al. Evidence-based estimates
of outcomes in patients irradiated for
intraocular melanoma. Arch Opthalmol.
20021201665- 1671. Accessed February 20,
2009. 8. Bell DJ, Wilson, MW. Choroidal
melanoma natural history and management
options. Cancer Control. 200411296-303.
Accessed February 19, 2009. 9. Shields CL,
Shields JA. Ocular melanoma relatively rare but
requiring respect. Clinics in Dermatology.
200927122-133. Accessed January 22, 2009. 10.
Wright, R. Robinson D. Linac-based stereotactic
radiotherapy in management of uveal
melanomas Web site. http//www.camrt.ca/english/ev
ents/AGC08- Presentations/Saturday/Wrig
ht_Robinson/800_Wright_Robinson.pdf. Accessed
April 4, 2009. 11. Parez CA, Halpein
EC, Brady LW, et al. Principles and Practices of
Radiation Oncology. 4. Philadelphia, PA
Lippincott Williams and Wilkins
2004. 12. Choroidal Melanoma. Eyecancernetwork
Web site. http//www.eyecancer.com/Patient
/Condition.aspx?nID62CategoryChoroidalTumorsC
onditionChoroidalMelanoma. Accessed
March 31, 2009.
42References
13. Ocular oncology. Bascom palmer eye institute
Web site. http//www.eyecancermd.org/treat
ment.htmlrpt. Accessed March 10, 2009. 14. Eye
Melanoma. MayoClinic.com tools for healthier
lives Web site. http//mayoclinic.com/healt
h/eye-melanoma/DS00707. Accessed January 27,
2009. 15. About choroidal
melanoma. COMS Web site.
http//www.jhu.edu/wctb/coms/general/about-mm/coms
1.htm. Accessed February 20, 2009.16. Nag
S, Quivey JM, Earle JD, et al. The American
brachytherapy society Recommendations for
brachytherapy of uveal melanomas. International
Journal in Radiation Oncology Biology
Physics. 200356544-555. 17. Definition of
fundus. MecicineNet Web site.
http//www.medterms.com/script/main/art.asp?articl
ekey3525. Accessed March 30, 2009. 18.
Evans MDC, Astrahan MA, Bate R. Tumor
localization using fundus view photography
for epsicleral plaque therapy. Medical Physics.
199320769-775. 19. Eye care. Bascom palmer eye
institute Web site. http//www.bpei.med.mia
mi.edu/site/disease/disease_anatomy.asp. Accessed
March 31, 2009.20.
Chiu-Tsao, Sou-Tung. Epsiscleral eye plaques for
treatment of intra-ocular malignancies
and benign diseases Web site.
http//www.aapm.org/meetings/05SS/program/eyeplaqu
e072005_chiu.pdf. Accessed March 30,
2009. 21. Diabetic retinopathy. Retinal Disorders
Web site. http//www.merck.com/
mmpe/sec09/ch106/ch106e.html. Accessed February
20, 2009. 22. Maumoud TA, Mansour M,
Deschênes J, et al. Iodine-125 radiotherapy for
choroidal melanoma. Annals of The New York
Academy of Sciences. 2008
113815-28.
43References
23. Damato B, Patel I, Campbell IR, et al. Local
tumor control after 106Ru brachytherapy of
choroidal melanoma. International Journal in
Radiation Oncology Biology Physics.
200563385-391. 24. Ocular melanoma and proton
therapy. OncoLink Web site.
http//www.oncolink.org/treatment/article.cfm?c9
s70id402p3. Accessed April 4,
2009. 25. Jaywant SM, Osei EK, Ladak S.
Stereotactic radiotherapy in the treatment of
ocular melanoma a noninvasive eye fixation
aid and tracking system. Applied
Clinical
Medical Physics. 20034156-161. 26. The national
association for proton therapy. Proton Therapy
Web site. http//www.proton-therapy.org/
. Accessed February 21, 2009. 27. Eye anatomy
illustrations. JirehDesign Web site.
http//jirehdesign.com/EyeIllustrations/eyeAnatomy
1.htm. Accessed March 10, 2009.