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Practice of Radiation Therapy

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Title: Practice of Radiation Therapy


1
Practice of Radiation Therapy
2
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.

3
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.

4
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

5
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

6
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.

7
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

8
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.

9
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.

10
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.

11
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.

12
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.

13
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.

14
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

15
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.

16
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

17
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

18
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

19
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.

20
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.

21
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

22
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

23
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.

24
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.

25
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.
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