Use of radiation to treat cancer
Early Day Developments 1895-1950
The Discovery of X-Rays 1895
When approaching the topic of the introduction to radiotherapy, it is important to address the foundations of radiation and the discovery of radioactive sources. The first evidence of ionising radiation happened in 1895 with Wilhelm Rontgen. This was the discovery of X-rays and came about while Rontgen was experimenting with cathode tubes in which he applied a current to different vacuum tubes. He discovered that when he covered one of the tubes with black cardboard, it blocked the light, but other rays seemed to penetrate through and interact with a barium solution over a metre away. He concluded that light could not have been interacting with the barium solution and it must have been X-rays. Rontgen initially came up with the term X-ray as it was something mysterious and unexplained, but the name has stayed the same ever since.
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Medical Applications of X-Rays 1896
During early experiments with X-rays, it was noticed that prolonged exposure caused the inflammation and damage of the skin. This was studied by Leopold Freund and Eduard Schiff who realised there could be medical application with this side effect. At the same time Emil Grubbe experimented using X-rays to treat cancer. Emil Grubbe was able to teach other physicists how to use X-rays but his downfall was within his prolonged exposure to X-rays. Unfortunately due to Grubbe’s repeated exposure to X-rays, he required over 90 operations for cancerous burns emphasising the danger of exposure to X-rays.
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However, Victor Despeignes attempted a more rigorous use of x-rays on a patient with stomach cancer. This consisted of a week long treatment when the cancer was exposed to X-rays and in Despeigne's paper he stated that there was a reduction in the size of the tumour and in the pain the patient was facing. This seemed like a step forward in the world of radiotherapy but ultimately the patient was also taking other medicines at the time so there was no conclusive evidence that the shrinking of the tumour was caused by the X-rays.
Finsen Lamps 1896
Following on from the development of X-rays, Niels Finsen was able to build on these foundations. He initially had a strong interest in the medical application of light on human skin. This is linked to X-rays of course as we know that light and X-rays are both forms of electromagnetic radiation. However, light is non-ionising radiation whereas X-rays are ionising. In 1896 Finsen published a paper on the use of concentrated light medically which included the use of ultraviolet light. Finsen’s first evidence of the medical qualities of ultraviolet light was when he treated a patient with lupus vulgaris. This disease is caused by bacteria which also causes tuberculosis in the lungs. The symptoms of Finsen’s patient included lesions on the neck and face. Furthermore Finsen’s patient had tried surgery and other medication before the ultraviolet light therapy, but the surgery was not efficient at improving the patient’s condition. However the ultraviolet therapy improved his condition just after 4 days. Although this was a very small sample size, Finsen was convinced that this improvement was caused by the ultra violet light as he ensured the light was focused precisely onto the patient's lesions for periods at a time.
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Discovery of Radioactive Materials 1896
In 1896 Henri Becquerel discovered that uranium salts also emit X-rays naturally without the need for cathode rays. However, this discovery was glossed over by his work colleagues and they were much more focused on Rontgen’s X-rays and their applications. However, Marie Curie developed our understandings from Becquerel’s observations by conducting further experiments. This consisted of testing different materials to see if they also emit X-rays. Marie found that thorium also emitted the same x-rays as uranium salts.
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Marie Curie found that the intensity of X-rays did not depend on the material being used but solely on the quantity of the material. Furthermore, she found that the physical properties of the material being used also did not make a difference in the intensity. For example, when Marie experimented with dark uranium powder and a transparent yellow crystal, they both had the same intensity of X-rays emitted. Therefore, Marie was able to conclude that the arrangement of uranium atoms in the lattice was irrelevant but the emission of x-rays must have been linked to the internal components of the atom. This was a huge discovery by Marie Curie and was the first step in to understanding the fundamental physics behind radioactive materials.
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Although at this point what Marie Curie was witnessing was purely observational, she was not able to explain the process behind this phenomenon. Uranium nuclei in this instance were undergoing a process called spontaneous radioactive decay. This is where a uranium isotopes such as uranium 238 are unstable and go through a decay process to become more stable. The uranium 238 nucleus splits into a thorium 234 nucleus and releases an alpha particle which is a helium 4+ ion. Additionally large amounts of energy in the form of gamma rays and X-rays are released which explains Marie Curie’s observation.
A diagram to show spontaneous uranium decay
The Discovery of Radium 1898
​However Marie and Pierre Curie are more famously known for the discovery of the element radium. This was discovered during a period when Marie and Pierre were focussed on experimenting with different radioactive materials and assessing each of their radioactive activities. They found that there was a high level of radioactive activity from compounds containing bismuth and barium. The compound that Marie and Pierre were most interested in was pitchblende ore. Marie Curie found that every time she was able to isolate bismuth away from the compound, the activity of the remaining substance was greater. By repeating this process Curie was able to obtain a substance over 300 times more active than uranium. They determined that this substance was a new element which Marie called polonium after her country of origin, Poland. Furthermore after this discovery Marie continued the investigation into pitchblende ore and discovered another highly radioactive element which they named radium. Radium was characterised by its high level of activity and its property of luminescing in the dark. This was a huge discovery and was instrumental in the immediate future of radiotherapy.
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Marie and Pierre Currie pictured in their lab where they discovered radium
Radium Therapy 1901
There was huge speculation very soon after the discovery of radium that radioactive compounds could have medical uses in the same way as x-rays. Henri Becquerel was particularly instrumental at verifying this theory. This was when he placed a tube of radium into his pocket for a few hours, then a few weeks after the exposure, Becquerel noticed a burn on his skin near where the radium was being kept. This inflammation was more severe than what was seen with x-rays but nevertheless there was a strong correlation between them. Henri-Alexandre Danlos who was physician tested radium’s efficiency in a hospital environment and was successfully able to treat cases of lupus. However, it is important to keep in mind that the process of obtaining radium was highly time consuming and hence the supply of radium was very low. Therefore trials of radium therapy progressed at a much slower rate than treatments with X-rays.
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Throughout the following years more research was done into the effectiveness of radium in treating different medical conditions. It was found that radium treatments fell into two categories depending on the form the radium was in. The two types included radium emanation and radium salts.
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Radium Baths 1903
Development of treatments with radium did progress slowly over the years since it’s discovery. One discovery which is important to mention is Thomson’s discovery of radioactivity in water within different natural wells. This emphasised the fact that radium was found naturally underground and was present in small quantities in some of the water people have been drinking. Further analysis into many of the natural baths across the world found that they also contain traces of radium. This initiated the idea that patients could create their own radium baths at home using radium salts. This was used to help cure arthritis and gout but there was no strong evidence to this being effective. In fact radium baths are still available for people to go in today. Although the dose of radiation is low, the time allowed in the bath is still restricted so the dose of radiation is not dangerous. Below is a picture of the Roman Baths located in Bath where radium has been found:
Radioactive sources were detected in natural baths like this Roman bath in Bath.
Coolidge X-Ray Tubes 1913
It is important to address the development in X-ray tubes by Coolidge. Coolidge’s development of the X-ray tube allowed higher energy X-ray’s to be produced allowing cancer’s deeper within the body to be treated due to the X-ray’s being able to penetrate more soft tissue. Coolidge built on the strong foundations from Rontgen’s X-ray tube but he stated that tungsten should be used as the filament and the anode of the tube. Furthermore, Rontgen’s X-ray tube relied upon ionised gas within the tube for the electrons to reach the anode. However, Coolidge’s tube contained no ionised gas particles but instead had a vacuum. This improved greatly the output and performance of X-rays. This X-ray tube with a few minor variations is still used in medicine today.
A diagram to show how X-Rays are produced in Coolidge tubes.
Radiation Safety 1920's
It was during the early 1920’s when scientists realised that how the radiation is administered affects the outcome of the patient’s treatment. Initial treatments involved a long exposure time to the ionising rays which was found to be much less effective than regular smaller doses of radiation. This was discovered by Henri Coutard in 1922 and was instrumental in the course of radiation treatment. Even modern day treatments are based around the Coutard method when deciding how often to administer a radiation dose.
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The dangers of radiation therapy really came to light during this decade with the formation of the International Commission on Radiological Protection (ICRP) forming in 1928. This was necessary due to the care free use of radiation in decades before which caused many cases of the skin damaged caused by exposure to ionising radiation to develop into skin cancers. Furthermore prolonged exposure to radiation in radioluminescent watch factories caused deaths of factory workers. This sparked many investigations into the exposure of radiation leading to the formation of the ICRP. This caused the development in radiotherapy to take a step back as such to ensure safety protocols were there before further development could take place.
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Early radiation therapy safety suit consisted of gloves and an apron made of leather or rubber to shield some of the radiation exposure:
A diagram to show early developments to radiation safety equipment
The Roentgen Unit
One of the key advancements shortly after the formation of the ICRP was the development of the roentgen unit to quantify the dose of X-rays during treatments. The roentgen unit is defined as the electric charge freed by radiation in a volume of air divided by the mass of that air or as a statcoulomb per kilogram. This was very effective at standardising radiation measurement, but this unit could only quantify the ionisation in the air and not the absorption in materials such as human tissue.
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The mechanism behind the measurement of radiation involved an ionising chamber. This is where the X-rays are passed through a known volume and density of air contained within a chamber containing parallel plates. The X-rays ionise some molecules in the air and cause electrons to be produced to be released by the photoelectric effect, Compton effect and pair production. The high speed electrons then are attracted to the positively charge plate allowing a current to be measured hence electric charge over the mass of air can be calculated before administering the X-rays to patients.
This diagram shows how electrons are detected when the molecules in the air are ionised.
Orthovoltage 1930's
This era was also noted for the development of orthovoltage X-rays. Orthovoltage X-rays allow cancers 4-6 cm within human tissue to be treated effectively. The penetration at the time was considered quite deep as it allowed X-rays to penetrate through the patients skin without causing damage to the skin tissues. Therefore less cases of skin cancer were caused by this treatment as opposed to using X-rays generated by Coolidge tubes.
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The orthovoltage X-rays in this instance are produced with a linear accelerator (LINAC) which builds upon the foundations set by previous X-ray tubes. Electrons are first displaced from a heated filament in the process of thermionic emission. The electrons then interact with an electric field causing them to accelerate parallel to the electric field. After being accelerated by the electric field the electrons enter a waveguide allowing them to reach much higher energies and to a speed close to the speed of light. A bending magnet is then used to focus the beam of electrons and this can be incorporated with an energy selector to allow through electrons with the desired energy. This works when the electrons are higher than the desired energy then their radius around the bending magnet is greater and can be absorbed by a screen. When the electrons energy is too low it’s radius is lower than the desired energy and this electron can also be absorbed. Finally the electrons hit the tungsten anode and X-rays are produced using the same mechanisms as in previous X-ray technology. The orthovoltage X-rays produced had an energy range of 50-200 kV allowing a variable range to treat tumours of different depths.
This diagram shows the internal elements involved in generating these orthovoltage X-rays.
Development of Brachytherapy 1940's
In contrast to orthovoltage X-ray development, brachytherapy built upon the foundations of radium therapy. The overall idea is that a radioactive compound is inserted into a patient where the cancer is present for either a short or long period of time and then removed after the treatment concludes. The amount of time the radioactive source stays in your body depends on the severity of the cancer and how active the source is. For example, a source with a small half-life will spend less time within a patient due to it being highly radioactive whereas a larger half-life will enable the source to spend longer within a patient. This is described by the two strands of treatment, High Dose Rate (HDR) and Low Dose Rate (LDR). In High Dose Therapy, the source is only inserted into the patient for several minutes as opposed to LDR where the radioactive source stays in the patient for up to a few weeks.
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One of the key benefits of brachytherapy is the area irradiated is very localised around the radiation source. Due to this high precision, exposure to healthy tissues and cells is much lower than when using X-rays. The radioactive isotopes used are likely alpha or beta decaying which further emphasises the fact that the area irradiated by the source is small due to the alpha and beta particles having the property of poor penetration through human tissue. The key difference to note between radium therapy and brachytherapy is that in radium therapy the radium is left within the patient whereas in brachytherapy the radioactive source is removed after a period of time. Furthermore due to the development in the number of radioactive sources available, there are many different half-life to choose from as opposed to previously just using radium which was rare at the time of radium therapy.
The image shows the platinum tubes used during early brachytherapy. These tubes would contain radium and be inserted into regions which need to be treated.