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 Linac’s 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 > 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 (>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.

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.