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Title: 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.
6
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.

10
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

11
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

12
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.

13
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.

14
Choroidal Melanoma vs. Iris Melanoma
Iris Melanoma- brown observable pigmentation
Choroidal Melanoma- hidden pigmentation
15
Diagnosis Confirmation
Ultrasound is not only a tool used to confirm
diagnosis, but also used define a tumors
dimensions, extension, and retinal involvement.
16
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.

17
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

18
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

19
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.

20
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.

21
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.

23
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.

24
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.)
25
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

26
Characteristics of Radioisotopes Used for
Episcleral Brachytherapy
27
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.

28
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.

29
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.

31
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.

32
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.

33
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

37
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.

38
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.
40
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.

41
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