LO Hemato 5.

2 Dapots
 Role of radiation treatment
1. Radiation biophysical mechanism, radiation induced cell death, and ability of cellular repair
Radiation biophysics  The study of the effects of radiation on cells, tissues, biomolecules, and living
organisms
Mechanism : DNA can only be damaged when the cells are undertaking the replication process, so the
majority of normal cells that take longer to replicate are less affected than the cancerous cells
How does the ionizing radiation kills cells and damage DNA? When the cells are ionized, free radicals
and reactive oxygen species (ROS) form. Free radicals are simply atoms, molecules, or ions with
unpaired electrons, and ROS is a subset of free radicals that involve oxygen. These agents are very
chemically reactive due to their free electron. Due to this high reactivity, free radicals and ROS are likely
to attack the covalent bonds of the DNA and other cells they encounter, and these reactions typically
occur in chains. Enough injury in the cell will result in apoptosis, or programmed cell death. At the
same time, if enough DNA is damaged, the cells will be unable to replicate. Thus, when the radiation
targets the tumor cells, the affected cells will die or be unable to proliferate, effectively reducing or
eliminating the cancer.
Cellular resistance to radiation : Though radiation therapy has often resulted in remission of cancer,
recurrence is fairly common. Recent research has found that this might be due to cancer stem cells
producing higher level of antioxidant proteins than other cancer cells. The antioxidants capture and
disarm ROS before they cause too much damage. Thus, even though it seems that most of the cancer
cells have been killed, some cancer stem cells remain and proliferate over time due to the antioxidant
defense against ionizing radiation
Secondary cancer induced by radiation therapy (radiation-induced cancers) : Though radiation is a
widely accepted treatment, it can potentially have a counterproductive effect due to the effect of
radiation on healthy cells. The radiation works to kill cells it encounters, which is a positive result if the
encountered cell is cancerous. However, there remains the risk that the radiation will affect other
surrounding cells that are healthy. Radiation exposure of vital healthy tissues near the tumor could
induce a secondary cancer near the first.
Types of radiation :
 Photon radiation
Most common to treat cancer, using a beam of high-energy protons (so it can penetrate deeply)
from a radioactive such as cobalt or cesium by linear accelerator machine
 Particle radiation
Using electron, proton, neutron, alpha, and beta particle beams in low energy level so it can’t
really penetrate deeply (effective for tumors and lymph nodes that are near the body surface).
Proton beams are believed to emit their energy to tissue at the end of their path, without causing
great damage to the tissues they previously travelled through.
Neutron beams are often used in cancer of the head, neck and prostate, however is not usually
the first line choice of therapy as it is difficult to target the beam and surrounding tissues can
easily be affected.
2. Radiosensitivity, redioresistance, and cellular response
 Radiosensitivity  The relative susceptibility of cells, tissues, organs, or organisms to the harmful
effects of ionizing radiation
Sel akan lebih radiosensitive pada proliferation phase (S  G1  G2  M phase) dan akan semakin
radiosensitive pada sel yg quickly dividing such as tumor cells. But the tumor cells are not always
more radiosensitive than the normal one because tumor cell can be hypoxic karena free radicals yg
diproduksi radiotherapy biasanya berasal dari ionizing oxygen.
It has meanwhile been shown that the most sensitive cells are those that are undifferentiated (non-
specialized type), well nourished, dividing quickly and highly active metabolically. Amongst the body
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cells, the most sensitive are spermatogonia and erythroblasts, epidermal stem cells, gastrointestinal
stem cells.[3] The least sensitive are nerve cells and muscle fibers.

 Radioresistance  The level of ionizing radiation that organisms are able to withstand.
 Cellular response
 Every cells have their own threshold of irradiation to get the effect of radiotherapy.
 DNA damage ada 2, yaitu yg double dan single-stranded DNA damage. Sel akan meresponse
kerusakan tersebut dengan melakukan DNA repair. Double-stranded DNA breaks are much
more difficult to repair and can lead to chromosomal abnormalities and genetic deletions  Cell
death. Sedangkan single-stranded DNA breaks biasanya harus accumulated dulu baru dia akan
die or reproduce more slowly.
3. Dosimetry
 Study and measurement of radiation dose
 The calculation of the absorbed dose in tissue resulting from exposure to ionizing radiation
 Dose is reported in units of gray (Gy) for mass, and dose equivalent is reported in units of sieverts
(Sv) for biological tissue, where 1 Gy or 1 Sv is equal to 1 joule per kilogram. By definition, 1 Gy = 100
rads and 1 Sv = 100 rems
 The average background dose for a human being is about 350 milli-rems per year, resulting mostly
from cosmic radiation and natural isotopes in the earth.
 Radiation dose limits :
 Radiation workers
 5.0 rems for whole body
 15.0 rems for lens of the eye
 50.0 rems for skin or an extremity
 Mild, in an occupational setting
The yearly dose limits for a minor working in a restricted area are 10% of the doses for an adult
radiation worker. This is 0.5 rems (or 500 milli-rems) for a whole body dose.
 Occupational dose for an embryo or fetus
The dose to an embryo or fetus, resulting from the mother’s occupational exposure, shall not
exceed 0.5 rems (or 500 milli-rems) during the 9-month period of pregnancy.
 Members of the public
The dose to individual members of the public from the licensed operation does not exceed 0.1
rem (or 100 milli-rems) in a year.
4. Clinical use, whether for curative intent or palliative intent
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5. Methods of delivery and penetration
2 types of radiation therapy :
 External  Delivered outside the body, directing high-energy radiation beams at the area being
targeted within the body using various different radiotherapy machines.
Types :
 Intensity-Modulated Radiotherapy (IMRT)
The radiotherapy beams allowing different doses to be given to different parts of the area
needing treatment. This gives us control of the radiation enabling us to avoid or minimise
exposure to surrounding healthy tissue. This is particularly effective when dealing with
cancers that are close to vital organs or structures within the body. IMRT can be used to treat
any part of the body
 Stereotactic Body Radiotherapy (SBRT)
A type of therapy where a few very high doses of radiation are delivered to relatively small,
well-defined tumours. SBRT is used to treat small, isolated tumours that lie outside the brain.
SBRT treatment allows multiple radiation beams to be directed at any part of the body from
any direction to deliver a high radiation dose to the tumour and, at the same time, limit
damage to healthy tissue. Many doctors refer to SBRT systems by their brand names such as
CyberKnife (a sophisticated robotic external beam radiotherapy system).
 Image-Guided Radiotherapy (IGRT)
Radiotherapy beams allowing different doses to be given to different parts of the area needing
treatment. This gives us control of the radiation enabling us to avoid or minimise exposure to
surrounding healthy tissue. This is particularly effective when dealing with cancers that are
close to vital organs or structures within the body. IMRT can be used to treat any part of the
body
 Intra-Operative Radiotherapy (IORT)
 Electron Therapy or Electron Beam Therapy
Type of external beam radiotherapy that uses electrons instead of photons (photons are the
most commonly used type of radiation therapy). Electrons do not penetrate the body as
deeply as photons and are therefore used to treat more superficial (closer to the skin) areas,
this spares the deeper tissues not requiring treatment.
Proton Therapy or Proton Beam Therapy is a type of external beam therapy that uses protons
to deliver radiation dose to the body. Because of how protons react with the tissues of the
body it can be directed at a tumour potentially at a more precise depth than photons.

 Superficial Radiotherapy
Radiotherapy is the use of low energy X-ray’s to treat cancer and other conditions that occur
either on or close to the skin surface.
 Internal
Internal radiotherapy involves having radioactive material placed inside the body. These can be
either radioactive implants (such as metal wires, seeds, or tubes placed inside the body, within or
close to a tumour) or radioactive liquids (given either as a drink, capsule or injection)
Brachytherapy (internal implants) is when radioactive material is inserted directly into and around
the affected area. A relatively high dose of radiation is given to the tumour \ target area whilst
healthy surrounding tissue only gets a very small amount of radiation. In some types of cancer
these implants may be left in the body permanently. This type of therapy is usually given on an
outpatient basis but can sometimes involve staying in hospital for a few days until the radioactive
source has been removed.
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 Radioisotope or Radionuclide Therapy
Delivers radiation directly into the cancer cells via a capsule, drink or injection into a vein.
Cancer cells specifically absorb the radioactive substance more than normal, healthy cells
which means they receive a higher dose of radiation. The radioactive part of the liquid is
called an isotope. It may be attached to another substance, which is designed to take the
isotope into the tumour. There are different types of radioisotope used for different types of
cancers e.g. phosphorous, radium, strontium and iodine. For this type of treatment, it may be
necessary to stay in hospital for a few days until most of the radioactivity has disappeared
from your body. Please note these can be used for non-cancerous therapies also.
 SIRT (Radio-embolisation)
A special type of internal radiotherapy that uses high doses of radiation to target liver
tumours inside the body. It delivers much higher doses of radiation over much longer periods
of time than would be possible with external beam radiation and works by delivering
microspheres to the liver which lodge themselves in the very small blood vessels in and
around the liver tumours giving off high doses of radiation. This radiation will affect only a
small area, meaning the liver tumour is directly targeted while doing little damage to the
surrounding healthy liver. The radiation effect on the tumour lasts for about two weeks, after
which only 3% of the initial useful radiation remains. After one month it has all gone, but the
effects of the radiotherapy on the cancer last much longer.
6. Conventional radiation, LINEC, gamma knife, cyberknife
 Conventional radiation
Radiation therapy is used to shrink or destroy tumours using high-energy X-rays. Conventional (also
called fractionated) radiation therapy delivers a part (fraction) of the complete radiation dose over
several sessions. By delivering a fraction of the total radiation dose at one time, any radiation
damage to normal cells can be repaired between treatments. In this way, the healthy cells are
protected from permanent injury or death. During the first consultation, a treatment plan will be
drawn up. The treatment will take place everyday for several weeks to deliver the complete radiation
dose.

You may need conventional radiation therapy if you have a:

 Metastatic cancer (cancer that has spread to another part of your body)
 Prostate cancer
 Lung cancer
 Liver cancer
 Kidney cancer
 Gynaecological cancer (cancer of the female reproductive system)
 Colorectal cancer

 LINAC
 Gamma knife
 Cyberknife
7. Side effects of radiation treatment
https://en.wikipedia.org/wiki/Radiation_therapy
 Acute side effects (during treatment)
 Nausea and vomiting
 Damage to the epithelial surfaces
 Mouth, throat, and stomach sores
 Intestinal discomfort
LO Hemato 5.2 Dapots
 Swelling
 Infertility
 Long-term side effects (months or years following treatment)
 Fibrosis
 Epilation
 Dryness
 Lymphedema
 Cancer
 Cardiovascular disease
 Cognitive decline
 Radiation enteropathy
 Radiation-induced polyneuropathy
 Cumulative (after re-treatment)
 Effects on reproduction
 Effects on pituitary system
 Drug development trials (phase I, phase II, phase III, meta-analysis)