Intro
Radiotherapy is the basic therapeutic modality of oncology. The use of radiotherapy was the
start of oncology in the late 1800’s.
This preparatory will present to you some basic concepts of radiophysics and radiobiology
that you need to understand, before you attend the clinical radiotherapy lecture.
1. We will begin with a historical expose 'of early discoveries, how it all began more than 100
years ago.
2. Then we will look at what kind of radiation that is used in the clinic.
3. We shall dwell on some key concepts in radiation biology and how radiation affects
the human body and our cells.
These are the facts you need to learn and be able to address in the tentamina.
Pictures marked with the target symbol are of special importance.
It all began with the discovery of X-rays. An important research area for physicists in the late
1800s was to examine electrical discharges in tubes with different gas filling. In November
1895 Wilhelm Conrad Röntgen discovered a hitherto unknown, invisible and penetrating
radiation which he named X-rays. Already at Christmas the same year he published a work on
the rays and their properties. He illustrated his work with a photo of his wife's hand exposed
to X-rays. This caused a huge stir in the medical world when the medical community quickly
realized the potential to be able to look into the human body.
Just four months after Röntgen’s discovery, the discovery of radioactivity by Henri Becquerel
came in spring 1896. Becquerel later gave his name to the unit of radioactive decay (Bq).
Alongside came purification of polonium and radium by the Curie spouses. Radium was also
quickly adapted to treatment of tumours.
Needles and tubes containing radium salts were applied in tumour tissue, on its surface or in
body cavities. Already in 1899 the first patient was treated for a squamous cell carcinoma of
the skin by this method.
Here we see the electromagnetic spectrum. EM radiation is electrical and magnetic waves that
can transport energy quanta from one place to another.
In tumor therapy exclusively ionizing radiation is used. It is a common term for the highenergy radiation emitted by radionuclides or created artificially by the deceleration of high
energy electrons. Ionizing radiation may also be delivered by particles.
The definition of ionizing radiation is:
High photon or particle energies that can provide sufficient energy of the radiation to release
an electron from an atom or molecule.
The ionizing radiation can be divided into electromagnetic radiation and particle radiation.
The electromagnetic radiation is divided into gamma rays and X-rays.
Particle radiation can be uncharged when using neutrons.
There are also charged light particles like electrons or positrons and heavy charged particles
like protons, alpha particles and light ions.
The radiation interacts with electrons in atomic shells, excites or knocks out electrons from
the shell, resulting in electrically charged atoms and ions.
When photons interact with matter it will result in a cascade of electrons that will eventually
build up into a cloud of electrons and positrons. Depending on the energy of the photons the
build-up distance (x0) will be shorter or longer.
Different types of radiation will attenuate in different ways. If you want to treat a tumor on
the skin surface, electrons can be a better choice than photons since they will start to interact
with the tissue at a smaller depth. If you want to spare the skin the use of photons of a higher
energy would be preferable, since they will start to interact deeper into the tissue. The protons
deposit their energy in a sharp peak (Bragg peak). Protons are used in situations where
avoidance of normal tissue is critical f.ex. in child tumors or for brain targets.
This is an example of a dose plan, showing how the dose is distributed in the tissue when
treating a vertebral body with a single photon field from the dorsal direction.
This shows the dose distribution of an electron field coming in from the ventral direction.
Mostly electrons are used to treat more superficial targets since the electrons attenuate more
rapidly and reach more shallow areas, whereas photons usually are used for deeper located
areas.
The impact on larger composite oxygen containing particles as molecules, gives rise to socalled (ROS) radical oxygen species, with a free orbital electron. These are very reactive
particles that quickly react with other atoms or molecules and break chemical bonds. Water is
the most common source of free radicals.
O=ionization
n
There are two main modes of action:
Direct Impact by dense ionizing particles that provide a large biological effect in tissue with
severe DNA damage and double strand breaks as a result (High LET= linear energy transfer).
Indirect effects are interactions with water molecules that give rise to free radicals and usually
results in less severe DNA damage. This is the most common mechanism of photon and
electron radiation.
In conclusion, we see the physical effects on the tissues after microseconds, the chemical
effects after seconds and it will continue for days to years. Radiation-induced cancer takes 1520 years to develop and is rare.
How will radiation affect DNA? Damage to DNA is often the most crucial and most serious
lesion for the cell, even though serious damage may also occur to the membrane or other
structures.
When radiation damages the DNA it is mostly repaired and the damage and the event passes,
the cell survives, or there is an incorrect or incomplete repair which may lead to cancer or cell
death. If no repair occurs it is likely that the cell will die. This risk is higher in dividing cells.
The SI unit for absorbed dose is Gray (fr Radio biologist Louis Harold Gray, Cambridge)
It measures the absorbed dose. 1 Gy = 1 Joule / kg.
It is not the amount of energy that kills. It is the fact that the radiation is micro-focused and
the energy quanta are energetic enough to break chemical bonds and cause ionization.
Ionizing radiation hardly results in any heat generation in the tissue.
What happens if one irradiates the whole body with a certain dose? If you give less than 0.25
Gy, you notice no clinical reaction. Doses up to 1 Gy may cause minor changes in the blood
count. 1-2 Gy result in transient reduction of platelets and white blood cells, 2-4 Gy may
result in a serious impact on the blood picture after some weeks. It also may result in nausea,
hair loss, bleeding and risk of death. Doses above 4 Gy will result in death in <2 months for
more than 50%.
Normal tissues have varying tolerance to radiation. These are very sensitive tissues depending
on a high mitotic rate or sensitivity due to protection mechanisms (apoptosis in germ/cell).
Less sensitive tissues are often composed of non-dividing cells.
Critical organs are organs that often are located close to tumour sites that are irradiated to
high doses. These organs need special attention to avoid unnecessary exposure that may result
in serious damage and function loss.
Here we see two breast ca patients. These patients received the same dose, ie 50 Gy to the left
breast. Still, the skin reaction and the biological effect of this dose are different. This is
because we have different capacities to repair the damage.
All patient receive the same dose for a certain diagnose and disease stage. Due to the different
repair capacity the biological effect of this dose will vary. A few patients may even get a too
“low dose” biologically. Extreme variations are uncommon; most patients have a reaction that
lies between these extremes. As we respond differently to solar radiation, we also vary in
sensitivity to ionizing radiation.
3% of all radiation treatment with curative intent must be stopped prematurely due to
pronounced normal tissue reactions, due to different repair capabilities and different
sensitivity.
It would be most important to be able to determine the individual radio sensitivity of each
patient thereby personalize the dose and adapt to the repair capacity of each patient.
This is not yet possible, but is not unreasonably far away in the future.