Author:

Jean-Claude Horiot

Abstract

Radiotherapy was born in 1896, a few weeks after the discovery of X-rays. Its action against cancers was almost immediately investigated. Progress slowly arose from the production of more penetrating beams and better understanding of biological actions, Radiation physics, radiation biology and clinical research steps which allowed X-rays, gamma-rays and a few other beams to promote radiotherapy as one of the best tools to cure cancers will be summarized from the end of the nineteenth century to nowadays. Herewith the first part of the history: From the discovery of X-rays and Radium to the era of megavoltage beams (1895-1960).

THE ERA OF ORTHOVOLTAGE X-RAYS AND RADIUM SOURCES.

The discovery of X-rays and birth of radiotherapy

^{[4][31] [32]} It is a common statement to claim that the history of radiotherapy, the use of radiation to treat cancers, started with the discovery of X-rays by Wilhelm Conrad Roentgen in 1895 . It is true that what happened on the 8th of November 1895 was a spark of intelligence going to revolutionize sciences and profoundly influenced the behavior of humanity. So, it deserves to have a closer look at it.

On the dusk of that memorable day, Wilhelm Conrad Roentgen, a professor of physics at Wurzburg (Germany) worked alone in his laboratory on the properties of the tube of Hittorf-Crookes. This glass bulb with a partial vacuum, contained two metal electrodes the cathode and the anode, one at either end. When a high voltage was applied between the electrodes, “cathode rays” were ejected from the cathode. Their nature, still unknown in 1895, was understood by J.J. Thompson two years later, in 1897, as being negatively charged particles named later electrons.

Let’s go back to the evening’s darkness of Roentgen’s lab while he was investigating the conduction of electricity in gases at low pressures. The Hittorf-Crookes tube was carefully wrapped within a thick black paper envelope. When electricity was applied, no light could filtrate out of it. However, some luminescence came out from a platino-cyanate paper inadvertently left at some distance. Earlier in the afternoon, Roentgen would not have noticed it. A few hours later, someone else might not have observed it at all. However, Roentgen, fascinated, repeated the experiment, reproducing each time the same fluorescence of the distant paper. He concluded that an invisible beam could only arise from the tube, going through the glass and black paper. Roentgen called his wife Bertha to make sure he was not the victim of a hallucination! Then, after checking that these mysterious beams were not stopped by thin layers of wood and metal, he realized the first radiography, his hand on a photographic plate and the tube above. One can imagine his enthusiasm when developing the paper and seeing his bones appearing gradually like those of the skeleton of a ghost! He baptized X-rays these invisible beams and presented his discovery on December 28th1895 at the meeting of the Wurzburg Medical Physics Society.

From there on, a sequence of events occurred in the whole world with an incredible speed. During the week of January 5 to 13, 1896, newspapers announced this fantastic discovery in their headlines, the “Neue Freie Press” in Vienna, the “Standard” in London, the “Frankfurter Zeitung” in Germany, the “New York Times” in the USA and “Le Matin” in France. During the same month of January, the Roentgen experiments were reproduced almost everywhere Hittorf-Crookes tubes were available. The first French publication on this topic was issued on January 20th, 1896, by Henri Poincaré, Toussaint Barthélémy and Paul Oudin at the session of the Académie des Sciences: Une photographie des os de la main obtenue à l’aide des X-Strahlen de Mr le Professeur Roentgen.

A burst of applications of X-rays exploded in the following decade: Radiology was born and immediately developed and used for medical diagnosis in almost every disease involving lungs and bones where accurate pathological changes could be observed with a never seen before accuracy (especially for tuberculosis and traumatology), Teaching of the new discipline appeared as soon as 1897, e.g. in the Hôpital Tenon at Paris by Antoine Béclère. The first international meeting (1er Congrès International d’Electrologie et de Radiologie Médicales) was held in Paris in July 1900.

Finally, Wilhelm Conrad Roentgen won the 1901 first Nobel prize of Physics, undoubtedly for one of the most important discoveries for the sake of humanity.

How and when did arise the idea, which at first glance does not seem obvious, to use these strange X-rays against cancer?

At least, for two reasons: Firstly, Ultra-violet light was known since 1801 when the German scientist Johann Wilhelm Ritter discovered that invisible light existed beyond the optical region of the electromagnetic spectrum. In fact, at the turn of the century, physics pioneers understood that there was something common in the range of invisible beams that we later characterized by their wavelengths: shorter than visible light (10 to 400 nm) for UV, e.g. much longer than x-rays and gamma rays. In other words, all these beams are made of photons with increasing energy as their wavelength gets shorter, thus with increasing depth of penetration within matter. UV were already used in the last decade of the nineteenth century to treat superficial dermatological diseases and already known to induce skin inflammatory reactions identical to sunburns. Niels Ryberg Finsen, a Danish physician first reported the curative power of ultraviolet rays, called photo or light therapy, especially for lupus vulgaris and got the 1903 Nobel Prize of Physiology or Medicine.

Secondly, the radiology pioneers soon observed more severe acute inflammatory reactions than with ultraviolet therapy, when using X-rays without any protection (especially on their hands). Freund and Shiff (Vienna 1896) reported epilation in patients treated for dermatitis. Radioscopy was becoming widely used in rooms insufficiently darkened and the first radiologists were often modifying patient’s positions with their naked hands without switching off X-rays! Improved Crookes tubes designed to produce more energetic beams speeded up the understanding of the detrimental acute effects of the “not so wonderful” X-rays. Much worst late effects were still to come…

Anyhow, the use of the X-rays against cancer, was almost contemporary to the diagnostic applications, although less often and to a smaller scale. It is somewhat difficult to assess who was the first medical doctor to treat a cancer patient with X-rays. Probably several did it in 1896 on both sides of the Atlantic. However, the first written report was made by Emil Grubbe from Chicago who treated a patient with a recurrent breast cancer. In fact, he was a medical student also involved in the making of Crookes vacuum tubes for physicists. As soon as the discovery of X-rays was claimed, he modified the tube to produce more x-rays (which would also be slightly more energetic). Experimenting these new tubes, he at once noticed hand burns on himself and proposed to “burn out” a recurrent breast carcinoma with the agreement of his mentors. The date of the first session is known: January 29, 1896. One month only after the announcement of the discovery of Roentgen! Emil Grubbe was wise (or lucky?) enough to deliver the first radiotherapy in 17 sessions, probably more because of the low X-ray output of his Crookes tube than for aiming at a better and safer use of X-rays! Nevertheless, by doing so, not only was he the first radiation oncologist but also the innocent inventor of the concept of fractionated radiotherapy. The history concluded to the “success” of this treatment. Let’s not argument the high probability of a subsequent failure and only celebrate the birth of radiotherapy!

The same year 1896, Victor Despeignes, a French parasitologist from Lyon, treated a patient with an advanced gastric cancer. He suspected that parasites or bacteria could be responsible for such cancers and wanted to investigate the action of X-rays to consolidate his theory. Treatment started on July 4 with two daily sessions of half an hour each, the Crookes tube being directed towards the palpable mass. The duration of the session was the only “dosimetry” parameter available! Not the source to skin distance nor the field size! After eight days, Despeignes observed a significant improvement of the patient’s condition and a measurable reduction of the tumor mass. Unfortunately, despite that, the patient died on July 24. Despeignes concluded: “Although I did not cure my patient, the treatment brought some hope when there was no longer anymore. I wonder whether with a less advanced and less aggressive disease, this new treatment modality would lead to a longer survival and maybe, even to a cure.” What a sharp prediction!

Then, every year brought additional data, with a more accurate description of patients, cancer types, improvement of X-rays producing equipment and early attempts of measurement of delivered skin dosages. Herewith a non-exhaustive choice of these early publications:

In 1897, Oudin, Barthélémy and Darier (France) described the early normal skin and visceral reactions of the first irradiated patients. Gocht (Germany) reported improvements after irradiation of inoperable breast cancers.

In 1900, Steinbeck and Sjögren published several cases of cure of skin cancers with a photography before and after treatment. Was it only apparently complete tumor regression with a rather short follow-up? Anyhow, let’s imagine the legitimate enthusiasm of these pioneers, experimenting with an innovative treatment modality resulting in an unsurpassed efficacy!

By 1903, several publications were made on both parts of the Atlantic to document the use of X-rays in a variety of malignant diseases, skin, breast, larynx cancers, and already some deep-seated cancers such as esophagus, stomach and rectum. Other malignancies included sarcoma and leukaemia. In July 1903, William Allen Pusey, MD, Professor of Dermatology at the University of Illinois, and Eugene Wilson Caldwell, an engineer and Director of the Gibbs X-ray Laboratory University and Bellevue Hospital in New York, published the first textbook of radiology and radiotherapy, The Practical Application of the Roentgen Rays in Therapeutics and Diagnosis. The poor penetration of these X-rays beams was probably insufficient to obtain cure. However, W.A. Pusey expressed a remarkable prediction: X-rays used after surgery might prevent recurrence. Moreover, he was the first to use the wording of “prophylactic use” of X-rays.31

The discovery of Radioactivity and birth of Curietherapy (Brachytherapy)

^[4][31] At this point of our historical review, we should consider another major discovery of great relevance to the use of radiation in the treatment of cancers: Natural radioactivity was discovered by Henri Becquerel in 1896, followed by the discovery of radioactive elements, radium and polonium by Marie Sklodowska-Curie and Pierre Curie in 1898, for which the three scientists were jointly awarded the 1903 Nobel Prize.

These achievements were a direct consequence of Roentgen’s discovery. Becquerel had been studying phosphorescence for a long time. He was present on January 20th 1896, at the session of the French Academy of Sciences mentioned earlier. He immediately suspected that phosphorescent materials could also emit X-rays when exposed to a bright sunlight. So was he astonished on March 1 while observing that uranium salts would also emit radiation in complete darkness! Natural radioactivity was clearly proven by May 1896, when other experiments involving non-phosphorescent uranium salts showed that radiation were emitted without any need for excitation by an external energy source.

In 1897, Marie Sklodowska-Curie, after completion of an outstanding training in physics, chemistry and mathematics, was looking for a research topic for her Ph.D. thesis. She decided to further study the so-called “-rayons de Becquerel-” in various minerals. In July 1898, she and her husband Pierre Curie published a paper describing a new radioactive element they named "Polonium", in honor of her native country. In December 1898, they were able to separate another element from uranium: which they named "Radium”. Natural radioactivity was proven, opening an avenue for a novel cancer treatment firstly named curietherapy with legitimacy. Marie Curie was awarded a second Nobel prize, that one of Chemistry, in 1911. At that time, Radium applications (in various containers, tubes and needles) had been already used successfully to treat both superficial cancers (skin, breast) and even deep-seated cancers in accessible anatomical cancer locations (mainly gynecological).

Radiobiology and radiation physics

History tells us that X-rays were directly tested in humans without being investigated in animals or even in cells cultures. This process may look inappropriate to us, but we should understand that our present experimental designs arose from the adverse effects met by the pioneers of X-rays on themselves and on their first patients. Moreover, at this time, there was no active treatment against cancer but surgery and the probability for the discovery of another powerful treatment was low. Thus, greater was the excitement of human experiments. Fortunately, two major scientific approaches soon emerged at the beginning of the 20th century: Radiation Biology and Radiation Physics. They remained the best companions guiding all progress of therapeutic radiation research.

In 1906, Jean-Alban Bergonié (a biophysicist, ^[14]) and Louis Tribondeau (a pathologist), from the University of Bordeaux, France, formulated a principle stating that the sensitivity of cells to radiation was directly proportional to their reproductive activity and inversely proportional to their degree of differentiation. These laboratory experiments allowed to understand why cancer cells, usually dividing faster than normal cells are more sensitive to radiation exposure. At about the same time, Claudius Regaud, (a histologist from the Faculty of Medicine in Lyon) conducted detailed histological studies on the effects of radiation on spermatogenesis, demonstrating the differential sensitivity of various cell types within the testis, the greater effects taking place on spermatogonia, leading to sterilization while spermatozoids appeared unaffected. Radiobiology was predicting the extreme sensitivity of seminoma and the risks of incidental irradiation of testis and ovary. In 1912, Claudius Regaud was heading in Paris the Institut du Radium that became the Institut Curie, the first French cancer center. His experiments led to the concept of therapeutic ratio: The difference between the sensitivity of cancer cells and that of surrounding normal tissue will become the basis to optimize the radiotherapy parameters (irradiated volume, dose, time, number of fractions) aiming at achieving a significant death rate of cancer cells consistent with an acceptable normal tissue damage. Radiotherapy, from the early days to the present time, will remain the final product of this compromise. Regaud also established the biological basis of fractionated radiotherapy and is considered by many as the “father” of modern radiotherapy although that discipline did not yet formally exist and was just part of Radiology.

The biological action of X-rays was easier to analyze than to solve the technical problems linked to the measurement of the delivered dose or to improve of the quality of the X-ray beams. Histopathology was already available to the biologists while accurate dosimetry and more energetic X-ray tubes (Kilovoltage X-rays), took several decades to be developed. For a long time, the X-Rays tube only allowed superficial therapy (10 to 150 kV). The “so-called deep orthovoltage therapy (200 to 300 kV)” became only accessible in a few large institutes in the late thirties.

Over four decades (1900-1940), advancements in X-ray tube technology and dosimetry slowly improved the precision and effectiveness of orthovoltage treatments. In 1913, the Coolidge tube, was developed, allowing for more controlled and higher energy X-ray production. Single fields directed to tumor location, most often without sufficient margins, were used to treat superficial tumors. Skin reactions of increasing intensity (erythema, dry desquamation, moist desquamation,) were the first commonly used as a “clinical dosimetry” to evaluate the maximum acceptable skin dose tolerance and the right time to stop treatment. Converging oblique, tangential, and parallel opposed fields were then more often used for deeper tumor locations. Such techniques speeded up the need to precisely evaluate the dose distribution to tumor and normal tissues.

The units of radiation dose

No need to explain why the first reliable scientific unit for measuring dose was named “The Roentgen”! Wilhelm Roentgen who died in 1923, had not the chance to witness this celebration, this unit being introduced in 1928. The Roentgen measures the ionization of air by X-rays or gamma rays, more precisely this unit is the amount which will produce, under normal conditions of pressure, temperature, and humidity, in 1 kg (2.2 lbs) of air, an amount of positive or negative ionization equal to 2.58 × 10−4 coulomb. Hence it was a unit of exposed dose. The unit of Radiation Absorbed Dose, the Rad was only introduced in 1953 representing the amount of energy deposited in tissue. One rad is equivalent to the absorption of 100 ergs of radiation energy per gram of tissue. In 1975, the Rad was renamed Gray to be consistent with the International System of Units (SI) in which the Radian was the unit of measure of the angle. Louis Harold Gray (1905-1965) was a British physicist and biologist who developed the Bragg–Gray equation, the basis for the cavity ionization method of measuring gamma-ray energy absorption by materials. One Gray (Gy) is equivalent to 100 rads. It measures the energy deposited by ionizing radiation in a kilogram of tissue.

A specific unit was needed to be defined to characterize the biological effect of radiations of different type in the human tissues: The Rem (Roentgen Equivalent Man) introduced in 1940, is a unit of equivalent dose, calculated by multiplying the absorbed dose (in rads) by a quality factor specific to the type of radiation. After conversion of the Rem in the International System, 100 Rems became equivalent to one Sievert (Sy), the international unit used for radiation protection rules.

Towards the maturity of orthovoltage radiotherapy

^[6] The first treatment plans based upon depth dose curves appeared in the early twenties in a few research teams benefiting of the presence of a new physics expert called to a brilliant future: The radiation physicist. These isodose curves were not customized to the anatomy of each patient and rather used as a catalog of dose distributions per field size and X-rays energy provided by the manufacture of the X-rays unit. Of course, the true distribution of absorbed dose was approximative. The quality of treatment was largely due to the experience of the radiologist. Some of them specialized in specific tumor areas, obtained outstanding results that could rarely be duplicated elsewhere since the recipe of success stood more in the experience of the person than in the technical description of treatment. Examples of such “artist pioneers” exist in nearly every country contributing to the development of the era of orthovoltage radiotherapy. Let’s mention in France Antoine Béclère, Henri Coutard, Claudius Regaud, and Antoine Lacassagne. A bit later I had a chance to meet with one of them, François Baclesse, from the Institut Curie, a rare survivor of the orthovoltage era, who was among the first to report large series or curative radiotherapy of breast and head and neck cancers. Baclesse proposed extremely sophisticated techniques to treat complex volumes such as breast and peripheral lymphatics with multiple portals and oblique fields trying to go across the risks of skin overdosage and tumor underdosage without the help of individually customized dosimetry.

In summary, Orthovoltage radiotherapy brought a major contribution to demonstrate the potential of X-rays to the management of cancers. It has been particularly effective in treating non-melanoma skin cancers and a variety of rather superficial cancers especially in the head and neck and facial areas. It also allowed to treat and sometimes to cure extremely radiosensitive pathologies such as testis seminomas even with nodal metastases and Hodgkin’s disease of limited extension and favorable histology. Although it could not yet challenge surgery to treat deep seated tumors, it was clear that future research for producing more powerful beams was the right direction to follow.

Orthovoltage X-rays survived during a few decades in radiotherapy departments after the availability of megavoltage beams. They remained useful to treat metastatic sites when there were not enough megavoltage units. They were also maintained for a while to treat some benign conditions, angioma, keloids, painful arthrosis of vertebrae and joints in elderly patients. These indications then almost disappeared because of the unacceptable (although rare) risk of radiation-induced cancers.

Superficial X rays (40 to 100 Kv) could still be convenient today to treat superficial radiosensitive skin cancers of the facial area. Unfortunately, these specific X-Ray units, with their dosimetry accessories and tools (e.g. small size collimation cones) are no longer manufactured leading to the extinction of the practice and know-how. Surgical reconstructive techniques have replaced radiotherapy not always to the best!

Two specific indication of low-voltage (50-60 Kv) X-rays survived and will be developed later: The intracavitary radiotherapy of small rectal cancers, commonly called contact radiotherapy. The intraoperative radiotherapy of early breast cancers.

The era of Radium brachytherapy

^{[4][31] [32] [35]} The use of Radium, contained in needles or tubes, inserted in natural cavities or directly implanted in tissues, revealed an extraordinary ability to destroy malignant and normal tissues as well in the immediate vicinity of the radioactive sources, thus delivering much lower doses at some distance according to the inverse square law. Unfortunately, it also showed that the accumulation of small doses was hazardous for those who settled the radioactive material in place. It was soon understood that these risks were strongly dependent from the distance. Enough Radium killed any tumor or normal cells within a few days at the contact of the sources. Named Curietherapy in France, radium applications were called brachytherapy in England and USA, which is more pertinent to characterize such action at a short distance. The sneaky detrimental effect at a longer distance soon appeared with time to the medical staff exposed during a frequent use of radium: skin erythema, burns, dermatitis, fingers skin atrophy, ulcers, necrosis, and after several years, radiation induced leukemias and other malignancies due to the accumulations of rather low doses of whole-body irradiation during several years without adequate radiation protection. Hence Radium had to be stored in thick lead containers and manipulated with tools at the largest distance consistent with the type of application, either in uterine and vaginal applicators or inserted in tissues.

Accurate dosimetry of radioactive sources was difficult because of the steep fall-off of dose with distance. The amount of radium contained in 2 cm tubes (10 to 20 mg on average) or in needles of various lengths (2 to 5 cm containing 2 to 10 mg on average) was a rather stable reference because of the 1620 years period (half time) of Radium, providing these containers were not leaking! A so-called dosimetry consisted of the total weight of radium multiplied by the time of application (e.g. 50 mg x 50 hours = 2500 mgh, mg per hour application). An even stranger calculation was that of “millicuries détruits (mcd)” during the application. Initially defined for radon, it expresses the amount of radiation emitted until total disintegration by a source de 1 mCi (milliCurie). This amount being the same as that one emitted in 133 hours by a radium source of 1 mg (or mCi) de Ra: Hence the number of mcd (=133 mgh) was used to quantify a Radium application.

By the end of the 1930s, gynecological brachytherapy systems, techniques and rules were designed in four major European cancers centers in Paris, Stockholm, Munich and Manchester, with some variations of equipment, contents, number and lengths of Radium sources, number and timing of insertions.

For several decades these estimates linked to the amount of radium left in place for a given time remained used. A significant progress in gynecological applications was made at Manchester with the “Manchester system” based upon the dose received a two specific points (on each side), point A located laterally at 2 cm from the lowest uterine source tube and point B, at 5cm. The dose prescribed to these points came from physics measurements made experimentally. They remained used all over the world even when individual dosimetry became available.

Computer dosimetry of brachytherapy appeared only in the mid-sixties allowing an individual dose distribution linked to the patient’s anatomy and true position of the radioactive sources in the patient. Nevertheless, the experience of the operators had allowed increasing successes of brachytherapy during the first half of the twentieth century: High cures rates were reached with acceptable side effects whenever the treated cancer could receive an adequate dose of radiation (even when it could not be accurately measured!). Intracavitary brachytherapy became a reference for radical local cure in early cancer of cervix, vagina, endometrium used alone or in combination with surgery and/or deep orthovoltage X-rays. Of course, the first cancer cures obtained by brachytherapy since several decades for skin cancers and accessible head and neck cancers especially in the oral cavity, were confirmed and increased with longer experience and specific rules for optimize and secure radioactive applications. A second life will be offered to brachytherapy with the discovery of radium substitutes, cesium 137 and iridium 192 during the second part of the twentieth century and the development of remote-controlled afterloading equipment (see later).

Just to mention it, a rare, exceptional and hazardous equipment: The Radium bomb. In fact, it was initially designed for intracavitary brachytherapy and nicknamed bomb because it was looking like a hand grenade. The first one was made at Memorial Hospital in New-York in 1917: a 4 cm ball lead and copper containing 1000 curies of Radon. Rather uncomfortable for transvaginal brachytherapy, it was modified to become a teleradiotherapy radioactive device used also in Paris and Stockholm, the later up until 1965! Needless to say that radiation protection was a big problem. The rapid success of “Cobalt bombs” led to the abandon of the few “Radium bombs” to an imaginary museum of the history of radiotherapy, of course without their radioactive content! Some Telecesium 137 units were built in the late fifties. I saw one still in use at the University of Cairo in the late seventies!

THE ERA OF MEGAVOLTAGE RADIOTHERAPY (FROM 1951 UNTIL NOW)

Early attempts: 1939-1951

^[32] Gamma-rays from Cobalt 60 and high energy X-rays beams (Megavoltage beams) produced by linear accelerators only became widely available at the beginning of the second part of the twentieth century. Nevertheless, the use of external radiotherapy had gradually progressed to became the second-best tool after surgery. However, despite more efficient X-ray beams (up to 200-250 KV), able to deliver tumoricidal doses to most early and moderately advanced superficial cancers, the acute skin effects were often of high intensity although reversible, while late effects on skin, connective tissue and bones could hamper the cosmetic results and alter the quality of life (atrophy, telangiectasia, ulcers, severe fibrosis, fractures). Herewith a few milestones to illustrate these facts at the turn of the mid of the past century:

1939 is a landmark for modern teleradiotherapy: High voltage generators were developed by Robert Van de Graaff and John D. Trump (the uncle of Donald!) with megavoltage levels of 1-2 MV. The first megavoltage x-ray cancer treatment took place in Boston on 1 March 1937. Forty-three generators of this kind were in use clinically until 1969. One was used at the Royal Marsden Hospital London from 1951 in 1961.

In 1944. the first operational european supervoltage X-rays unit (about 1 MeV) was installed at St Bartholomew’s hospital, London.

From 1960 to about 1975, a few betatrons (circular accelerators of electrons) from a few Mev to 45 Mev (the last one by Siemens) were produced. During my training at the MD Anderson Hospital in Houston, I had a personal experience with the Brown Boveri betatron. It produced X-rays and electron beams of continuously adjustable energy from 5 to 35 Mev and was also equipped with a 125-kv diagnostic x-ray unit for controlling beam localization. Fixed-field, pendulum, rotational, and tangential therapy may be carried out.

All the above equipment tools were progressively abandoned with the emergence of lower cost megavoltage units of two different types: Telecobaltotherapy and linear accelerators.

Telecobaltotherapy: The main tool worldwide at the beginning of the era of megavoltage radiotherapy (1951-1980s)

Artificial radioactive elements were the product of physics research allowed by the discovery of nuclear fission and development of the first nuclear reactors in the thirties. Second world war speeded up the process with the launch of the Manhattan project undertaken in 1942 to produce the first nuclear weapons. Uranium, bombarded with neutrons broke into separate fragments, opened the way for producing “artificial” radioactive isotopes with potential biomedical applications. In 1936, Sampson from Princeton University observed a long-lived isotope of cobalt-60 by irradiating stable cobalt-59 with neutrons. The half-life of this decay process is 5.27 years releasing two megavoltage photons are emitted with energies of 1.17 and 1.33 MeV. The challenges to manufacture and to use the first telecobaltotherapy involved a number of pre-requisites: Production and design of a powerful enough cobalt 60 source to treat a patient at a minimum 60 cm source-skin distance, the safe housing of the source which should be completely locked to an off position in order to protect the medical staff while settling the patient, and finally a collimator to direct the beam to the patient. Moreover, a heavy bunker had to be built to ensure full protection of the staff during treatment. Several teams competed in the race to treat the first cancer patient. Among them, Gilbert Hungerford Fletcher ^[10], a radiation oncologist and Leonard Grimmett a Physicist, both from the M.D. Anderson Hospital in Houston (MDAH), Texas, working in collaboration with the Oak Ridge Institute of Nuclear Studies and General Electric X-ray Corporation (Milwaukee, WI). I had the chance, some years later, to work with Gilbert Hungerford Fletcher and often heard than he and Grimmett were the inventors of the Cobalt machine. This may be true but a number of events precluded them to be the first to use it. Grimmett died in May 1951. The unit built by the General Electric X-ray Corporation of Milwaukee was displayed at a meeting of the American Roentgen Ray Society in 1951. Regulatory issues, dosimetry studies and bunker construction delayed its installation at the MDAH until September 1953. Meanwhile, a prototype commercial unit was designed by Donald T. Green of Eldorado Mining and Refining Limited and built by the Canadian Vickers company of Montreal, Canada. The “Eldorado A” became the first cobalt-60 teletherapy unit to be used on a cancer patient on 27 October 1951 in London, Ontario, Canada. Another unit was installed at the Los Angeles Tumor Institute, allowing to treat the first cancer patient in the United States with Cobalt-60 on April 23, 1952. Finally, the first treatment at the MDAH, Houston, Texas, took only place on 22 February 1954. Hence, despite of all his efforts, Gilbert Hungerford Fletcher was not the first to use clinically Cobalt 60. However, in the next decades, he would become one of the greatest masters of modern radiation oncology ^[10].

Cobalt machines remained commonly accessible on the market up to the end of the eighties as producing the best cost/ benefit ratio for external beam radiotherapy. From there on, only linear accelerators appeared consistent with the evolution of the high precision radiotherapy techniques leading to the gradual disappearance of Telecobalt 60 machines except in a few developing countries. However cobalt sources are still used in very specific devices such as the “cyberknife” for stereotactic radiotherapy (see later).

Linear accelerators (Linacs)

Linacs offered access to photon energies higher than those from cobalt-60 machines in a variety of equipment: Some provided only x-rays of low megavoltage range (e.g., 4 or 6 MV) perfectly fit for breast and head and neck tumors, while others produced both x-rays and electrons at various megavoltage energies (e.g., 6, 10 and 15,18 or 25 MV photons) and several electron energies (e.g.4, 6, 9, 12, 15, 18 and 22 MeV). Higher photon energies would only result in increasing exit doses and costs of bunkers to ensure radioprotection of medical staff. The larger sparing effect of superficial tissues and deeper penetration contributed to better distribution of dose to deep-seated tumors.

From 1970 to the 1990s, we had determined the best X-rays range to treat human cancers. The next question was how to improve its use? Optimal depth dose was obtained with 10-20 MV photon beams converging to the target. A moderate size department would cover most indications of radiotherapy with only two treatment units; a Cobalt machine or small linear 4 MV linac and one 10-20 MV linac for the deeper tumors.

From the 1990s, Progress in beam collimation offered a wider range from pencil beams allowing stereotactic applications to large portals for whole body irradiations. Multileaf collimators facilitated the specific coverage of complex target volumes (e.g. prostate) with minimal irradiation to close critical organs. The development of high precision radiotherapy techniques would not have been feasible without linacs.

A few words on the use of electron beams versus photon beams: the range of penetration of electron beams varying with their energy, made them of interest to irradiate superficial volumes while sparing deeper normal tissues (e.g. chest wall with lung sparing, or posterior cervical nodes while sparing spinal cord). A mix of photons and electron beams could also be used to lateralize some dose distributions (e.g. for parotid tumors).

Now, electron beams, although available on high energy linacs (4 to 18 Mev), are seldom used with a major exception: the intra-operative irradiation of early breast cancer, performed with specifically designed 9-12 Mev linacs (see later).

Modern techniques of intensity modulated radiotherapy (IMRT) and image guided (IGRT). offer now better ways to monitor dose distributions. We shall develop later these recent developments in Part II of this “short history of radiotherapy”.

Acknowledgements

These lines to the millions of unknown patients who accepted to receive the hazardous beams allowing us to write this (not always) successful story. I apologize to all those colleagues and friends who contributed actively to the development of radiation oncology and that I could not mention because of the limited space allocated for such a “short” story.

References

All references and iconographies are supplied at the end of Part II.