Transcript Practice of Radiation Therapy

Practice of Radiation
Therapy
Practice of Radiation Therapy
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There are multiple means of modifying the
way in which radiation therapy is delivered
in order to enhance the effect of the
radiation on the tumor relative to normal
tissues.
Practice of Radiation Therapy
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Ways of enhancing effect on tumor
• Hypoxic cell sensitizers
• Halogenated Pyrimadines
• Radioprotective agents
• Alternate types of radiation (high LET)
• Hyperthermia (heat)
• Intraoperative radiation therapy
• Radioactive implants (brachytherapy)
• Intensity modulated teletherapy.
Hypoxic Cell Sensitizers
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Drugs which are electronphyllic
Scavenge Electrons to increase Free
Radical formation
Represented by misonidozole and its
relatives ( used to treated Giardiasis)
These drugs have long tissue halflives and diffuse into tissue further
than oxygen
Hypoxic Cell Sensitizers
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Theoretically will increase sensitivity
of tumor tissues relative to normal
tissues
Difficult in some cases to reach levels
of efficacy in patients without toxicity
Hypoxic Cell Sensitizers
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Some chemotherapy agents, esp
platinum drugs are also sensitizers
Act by interfering with DNA synthesis
in S phase.
Some evidence that hypoxic cells are
more sensitive.
More of a synergistic action with
radiation than an interaction.
Hypoxic Cell Sensitizers
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Vasoactive drugs such as
nicotinomide can be used in
conjunction with oxygen to prevent
or overcome transient ischemia.
Used in some experimental trials
with and without hyperfractionation
Hypoxic Cell Cytotoxins
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Drug or cytotoxic agents which
selectively attack and kill hypoxic
cells with or without radiation.
• Improve the kill by getting to radiation
resistant cells.
• Tirapazamine is the first drug of this
type used to specifically treat hypoxic
cancer cells.
Halogenated Pyrimidines
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Halogenated chemical similar in
nature to thymidine, a DNA
precursor.
• Incooperation into the DNA results in
the DNA being more susceptible to
radiation.
• Works best if tumor surrounded by
noncycling cells
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There is no preference for tumor uptake.
Halogenated Pyrimidines
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Must be present for several
generations
Will increase sensitivity of cycling
normal cell populations.
The iodinated form of the chemical
works better than the brominated
one.
• Produces less solar sensitization.
Radioprotectants
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Sulfhydryl compounds
• Hydrogen atom donors to aid repair
• Free radical scavengers
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Only FDA approved version is Amiphostine
(WR2721)
• Confers substantial protection at clinically
relevant doses.
• Penetrates normal cells faster than tumor cells.
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Preferential protection of normal cells if timed
correctly.
Alternate (high LET) radiations
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Neutrons
• High LET increases killing of hypoxic
cells
• Relatively penetrating
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On an order similar to
60Co
• No fractionation effect
• Normal cells as susceptible as tumor
• Requires complex and expensive
installation for clinical use.
Protons
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Exhibit a Bragg-Gray absorption curve.
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Dose is sharply peaked at end of path
Thus much high LET at end of path
Good killing of hypoxic cells. Little OER
Spares the superficial tissues
Requires large and expensive clinical
installation. Used at a few centers
• Requires cyclotron and dose spreading filters.
Electrons
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Not a high LET particle
• Very small mass
• Easily Scattered
• Quickly absorbed
• At end of path length LET may reach 3.0
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Widely used in clinical medicine to
treat superficial tumor.
• Available from many medical Linac’s
• Sharp dose drop off spares deep tissues
Heavy Ions
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Helium and larger nucleus’
Very High energy particles
• Argon nucleus at 700 MeV
• Required because of very High LET
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Very narrow Bragg-Gray peak at end
Not used in clinical medicine.
Hyperthermia
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Tissue temperatures above 39o C
Interest began with anecdotal
evidence that high fevers were
antitumor under the right conditions
Local heating can produce effect in
tumor. Whole body heat not required
Hyperthermia
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Synergistic effects with radiation
• S phase cells are most sensitive to heat
• Cell killing is not oxygen dependent
• More effective at low pH > hypoxic cells
• Kills nutritionally deprived cells
• Damages tumor vasculature
• Poor tumor vasculature = increased
heat in tumor
• Heat inhibits DNA repair
Hyperthermia
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Very difficult to measure the dose of
heat being given accurately.
• Tumor vasculature uneven
• Measurement may alter deposition
• Vascularization may change during dose
• Local heating difficult to do evenly
• Systemic or regional heating is toxic
Hyperthermia
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Thermotolerance
• Repeated dosing at high temp (>41o C)
results in decreased effect.
• Ditto for long term heating at low dose
• Hyperthermic effect is a product of
temperature and time
• Effective heating can only be done
about once weekly vrs radiation daily.
Intraoperative Irradiation
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Local irradiation with soft x-rays or
electrons at surgery after tumor
removed.
Single shot technique
Usually used to “clean up” a surgical
bed
Dose is quite large for a single dose
• May be as High as 20 Gy.
Brachytherapy
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Implantation of radioactive source
directly into a tumor.
Widely used in clinical medicine
Tumor receives large dose
Normal tissues protected by inverse
square effect.
• Dose margin as small as 5 mm
Brachytherapy
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Advantages
• Single or few treatments
• Multiple isotopes to choose from
• Most of effect is usually from beta
particles
• Total dose delivered faster than
teletherapy.
• Simple for patient
Brachytherapy
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Disadvantages
• Requires operator to handle large
activities of radioactive materials
• Better effect with large #’s of implants
increases operator dose.
• Dose calculation difficult
• Sources may move and/or be lost
• Changes in tumor size may increase
normal tissue dose or reduce tumor
dose.
Multifield or Intensity Modulated
Teletherapy
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Much of radiation therapy still done
with external Mega voltage beams.
Get superficial sparing
• Due to scatter buildup effect.
• But dose deep to tumor can be high.
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Using multiple fields which intersect
at tumor spares normal tissues
• Can be used to shape dose deposition
profile.
Multifield or Intensity Modulated
Teletherapy
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Use of special filtering system allows
the effective energy of the beam to
vary across the surface of the beam
• Allows more accurate shaping of dose
volume.
• Requires computer planning
• Requires specialized equipment and
more time
• Up to 200 “portals” may be used.