Plaque Brachytherapy: An Inspiration to Radiation Oncology

1
Plaque Brachytherapy An Inspiration to Radiation
Oncology

• Jenna Ebeling
• University of Wisconsin-La Crosse
• Gundersen Lutheran

2
The 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.

3
Ocular Anatomy
The eye contains many intricate structures each
with their own unique function.
4
The 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.

5
The 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.
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Ocular 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.

7
The 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

8
The 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

9
Epidemiology

• Often diagnosed around 55 years of age.
• Caucasians have a higher incidence when compared
  to African Americans and Hispanics.

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Etiology 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

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Symptoms

• 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

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Detection

• 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.

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Detection

• 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.

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Choroidal Melanoma vs. Iris Melanoma
Iris Melanoma- brown observable pigmentation
Choroidal Melanoma- hidden pigmentation
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Diagnosis Confirmation
Ultrasound is not only a tool used to confirm
diagnosis, but also used define a tumors
dimensions, extension, and retinal involvement.
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Aggressive 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.

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Treatment 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

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Enucleation

• 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

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Plaque 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.

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Staging 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.

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Plaque 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.

22
Plaque 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.

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Customization

• 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.

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Fundus 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.)
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Plaque 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

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Characteristics of Radioisotopes Used for
Episcleral Brachytherapy
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Plaque 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.

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Plaque 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.

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Critical 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

30
Surgical 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.

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Surgical 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.

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Complications 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.

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Prognosis

• 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.

34
Follow-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.

35
Tumor 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.

36
Emerging 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

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Proton 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.

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SRS 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

39
University 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.
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Conclusion

• 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.

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