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Radiation Therapy Explained: Uses, Mechanisms and Complications
1. Radiation therapy
• Since the discovery of
x-rays radiation therapy
for the treatment of
various types of cancers
• Radiotherapy involves
nuclear medicine which
is employing
radioactive materials
for diagnosis and
treatment of cases.
• It is a well known fact
that ionizing radiation
kills cells
2. • Radio sensitivity refers to the susceptibility of the
cells or tissue to the killing effect of absorbed
radiation.
• Radio responsive is the degree to which a normal or
neoplastic tissue visibility changes during or after
radiotherapy.
• Radio curability in veterinary medicine is a two year
patient survival after radiotherapy without further
progress of the neoplasm and subsequent
metastases.
3. • The nuclides which have the same atomic
number but different mass number are the
radioisotopes i.e. isotopes of a given atom
have same number of protons but differ in
number of neutrons.
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• Naturally occurring or artificially produced by
irradiation of stable nuclides by subatomic particles
such as neutrons in a nuclear reactor.
• The unstable nuclides of heavy elements such as
cobalt, cesium etc are unstable and undergo the
process of spontaneous decay to form stable
nuclides by the process of radioactive decay and
emit radiations which include alpha or beta rays or
gamma rays also sometimes.
5. Mechanism of action of Radiation
• These are explained by direct or target theory
and indirect theory
• Direct: Radiant energy acts by a direct hit on
the target molecules within the cell causes
ionization and ejection of the orbital
electrons. This causes damage to the cell.
• DNA molecule is the most important target of
radiation in the cell, especially its linkages and
bonds.
6. The main effects on the DNA molecule
is
• Genetic damage: Occurs in the germ cells, response is
observed in the next generation.
• Production of Cancer: the derangement of Nucleic acid result
in abnormal metabolic activity producing a malignant disease.
• Cell death: Due to radiation damage to the DNA the
multiplication of cells is affected causing cell death and it very
well explains the theory behind death of cancerous cells by
ionizing radiation.
7. Indirect theory
• Production of free hot radicals such as
peroxides within the cell occurs that damage
the specific target.
• Water molecule is split into H+ and OH- and
other unstable particles such as HO2 and H2O2.
These radicals are very unstable and produce
a crucial biological change in the cell which
leads to cell death.
8. Tissue tolerance to radiotherapy
• Amount of energy transferred: The rate at which energy is
transferred from ionizing radiations to the expose tissue is
called as linear energy transfer (LET)
• Oxygenation of tissues: Due to high proliferation potential of
a tumor, tissue amount is unable to receive required
circulation. Thus many cells are hypoxic and also radio
resistant.
• Radiation therapy is more effective in oxygenated cells. So it
is always attempted to increase the oxygenation of tissues
which is attempted by the use of high pressure oxygen tanks,
blood substitutes that carry increased oxygen, hypoxic cell
radiosensitizer drugs such as misonidazole and metronidazole
, and hypoxic cytotoxins (tissue poisons), such as
tirapazamine.
• Oxygen is a potent radiosensitizer, increasing the
effectiveness of a given dose of radiation by forming DNA-
damaging free radicals.
• The radio sensitivity is directly proportional to the mitotic
activity of the cell and indirectly proportional to their level of
specialization.
9. Normal tissue response
• Normal tissue response to radiations is the main
limiting factor of radiation therapy.
• Tumoricidal doses of radiation to treat any neoplasm
should be done with minimal normal tissue
complication.
• Different types of neoplasm require different lethal
dose i.e. the dose of radiation at which in vivo lethal
effects of radiation can bring about 80- 90% of
regression.
• The therapeutic ratio i.e. the ratio of normal tissue
tolerance dose to the neoplasm lethal dose.
10. • The sensitive neoplasm have therapeutic ratio higher
for e.g. squamous cell carcinoma. The resistant
neoplasms like fibrosarcoma only 34% regression
occur. Mast cell neoplasm is an e.g. of moderately
sensitive neoplasm where the therapeutic ratio is 1
and only about 54% regression is brought about in
the neoplasm.
11. Indications:
• Localized solid neoplasm that can not be excised
completely. It is usually not indicated in met
static neoplasm.
• When surgery has failed to treat neoplasm or is
expected to fail
• When regional or distant metastases has not
occurred.
• When radical surgery is unable to remove whole
of the lesion.
• To reduce the bulk of the neoplasm destined to
be removed after surgery
12. Multiple treatments are given over a
period of time called fractioned
therapy
•Fractionation allows normal cells time to recover, while
tumor cells are generally less efficient in repair between
fractions.
•Fractionation also allows tumor cells that were in a
relatively radio-resistant phase of the cell cycle during
one treatment to cycle into a sensitive phase of the cycle
before the next fraction is given.
•Similarly, tumor cells that were chronically or acutely
hypoxic (and therefore more radioresistant) may
reoxygenate between fractions, improving the tumor cell
kill.
13. •Radiotherapy is synergistic with chemotherapy. Radiation
therapy is combined often with surgery, chemotherapy,
hormone therapy, immunotherapy to decrease the dose
of radiation.
•To encourage more and more normal cell formation 4 R’s
of the radiotherapy is followed i.e. re oxygenation,
repopulation, redistribution and repair.
14. Shaped radiation beams are aimed from several
angles of exposure to intersect at the tumor,
providing a much larger absorbed dose there
than in the surrounding, healthy tissue.
Include a margin of normal tissue around the
tumor to allow for uncertainties in daily set-
up and internal tumor motion.
15. In animals it is usually 10 – 12 fractions of a radiation dose of 4-5
Gy each time usually three times per week. In man it is usually
1.8 – 2.0 Gy with a total dose of 60- 70 Gy over a period of 6-
7 weeks.
• Techniques
• Teletherapy: source of radiation is at a distance from the
lesion. Superficial x- ray therapy works in the energy range of
60- 100 KeV. For eg in small superficial lesion of skin.
16. • Deep x-ray therapy: energy range of 200- 300
KeV for eg small shallow lesion,
• Supervoltage therapy: linear accelerator (1 MeV
to 20 MeV) or cyclotron and through isotopic x-
ray machine with cobalt or cesium in a sealed
form eg. small deep lesions or substantial lesions
• Total body irradiation (TBI) is a radiation therapy
technique used to prepare the body to receive a
bone marrow transplant. .
17. Particulate beam therapy:
• Electro, neutron or proton :
• Antitumor effect independent of
tumor oxygen supply
• Direct energy transfer usually
causing double-stranded DNA +
breaks. +
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• Due to their relatively large mass,
protons and other charged particles
have little lateral side scatter in the
tissue; the beam does not broaden
much, stays focused on the tumor
shape, and delivers small dose side-
effects to surrounding tissue.
18. Brachytherapy
• The therapeutic use of
radioisotopes either
• Within the interstitium
(Interstitial Brachy therapy:
198
Au, 60CO etc) or
rice-sized transponder used in
• On the surface of a neoplasm treating prostate cancer
(Pliesotherapy: 90Sr) or
19. Systemically administered (systemic brachytherapy ;
131
I and 32P). Extensive lesions and specific malignant
conditions (leukaemia, thyroid cancer etc is treated
with systemic fluid isotope therapy)
20. Complications of Radiotherapy:
•The immediate complications are seen within minutes or
days after irradiation e.g., epilation , moist desquamation
of skin, skin erythema , chromosome aberration,
haematological depression etc, and in human beings it is
Damage to the epithelial surfaces, Mouth and throat
sores, Intestinal discomfort, Infertility, Swelling
22. Permanent xerostomia
Even though the dry mouth
(xerostomia) improves in most people
with time, it can be long lasting.
23. • latent complications which are seen after a long
time like over years e.g. leukemia, cancer, life span
shortening and lethal genes in coming generations’ .
• While treating a particular case for eg ophthalmic
neoplasm irradiation leads to conjunctivitis, keratitis,
cataract etc.
• In case of radiotherapy to the bone complications
may include fracture, septic osteoradionecrosis and
sarcoma formation.