Practice of Radiation Therapy

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Practice of Radiation Therapy
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Practice of Radiation Therapy

• 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.

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Practice of Radiation Therapy

• 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.

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Hypoxic Cell Sensitizers

• 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 half-lives and
  diffuse into tissue further than oxygen

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Hypoxic Cell Sensitizers

• Theoretically will increase sensitivity of tumor
  tissues relative to normal tissues
• Difficult in some cases to reach levels of
  efficacy in patients without toxicity

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Hypoxic Cell Sensitizers

• 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.

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Hypoxic Cell Sensitizers

• 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

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Hypoxic Cell Cytotoxins

• 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.

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Halogenated Pyrimidines

• 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
• There is no preference for tumor uptake.

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Halogenated Pyrimidines

• 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.

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Radioprotectants

• Sulfhydryl compounds
• Hydrogen atom donors to aid repair
• Free radical scavengers
• Only FDA approved version is Amiphostine (WR2721)
• Confers substantial protection at clinically
  relevant doses.
• Penetrates normal cells faster than tumor cells.
• Preferential protection of normal cells if timed
  correctly.

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Alternate (high LET) radiations

• Neutrons
• High LET increases killing of hypoxic cells
• Relatively penetrating
• On an order similar to 60Co
• No fractionation effect
• Normal cells as susceptible as tumor
• Requires complex and expensive installation for
  clinical use.

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Protons

• Exhibit a Bragg-Gray absorption curve.
• 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.

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Electrons

• Not a high LET particle
• Very small mass
• Easily Scattered
• Quickly absorbed
• At end of path length LET may reach 3.0
• Widely used in clinical medicine to treat
  superficial tumor.
• Available from many medical Linacs
• Sharp dose drop off spares deep tissues

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Heavy Ions

• Helium and larger nucleus
• Very High energy particles
• Argon nucleus at 700 MeV
• Required because of very High LET
• Very narrow Bragg-Gray peak at end
• Not used in clinical medicine.

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Hyperthermia

• 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

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Hyperthermia

• Synergistic effects with radiation
• S phase cells are most sensitive to heat
• Cell killing is not oxygen dependent
• More effective at low pH gt hypoxic cells
• Kills nutritionally deprived cells
• Damages tumor vasculature
• Poor tumor vasculature increased heat in tumor
• Heat inhibits DNA repair

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Hyperthermia

• 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

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Hyperthermia

• Thermotolerance
• Repeated dosing at high temp (gt41o 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.

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Intraoperative Irradiation

• 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.

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Brachytherapy

• 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

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Brachytherapy

• Advantages
• Single or few treatments
• Multiple isotope to choose from
• Most of effect is usually from beta particles
• Total dose delivered faster than teletherapy.
• Simple for patient

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Brachytherapy

• 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.

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Multifield or Intensity Modulated Teletherapy

• 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.
• Using multiple fields which intersect at tumor
  spares normal tissues
• Can be used to shape dose deposition profile.

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Multifield or Intensity Modulated Teletherapy

• 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.