History of Radiation Therapy
The field of Radiation Therapy (currently referred to as Radiation Oncology) was born not long after the discovery of x-rays in 1895 by the German physicist Wilhelm Roentgen.
Wilhelm Roentgen (1845-1923)
While performing experiments on electricity, Roentgen noted that an energy “ray” was produced which passed through most objects, including his own body. He also noted that these rays, which he named “x-rays”, could be used to produce images of bones. In fact, one of the first known x-ray images ever produced was of his wife Bertha’s left hand.
X-ray image of Bertha Roentgen’s Left Hand. November 8th, 1895
In an amazing feat of industriousness, Roentgen characterized and validated his findings in a technical report within 6 weeks. His paper, entitled Uber Eine Neue Art von Strahlen (On a New Kind of Ray) was presented on December 28th to the Wurzburg Physical-Medical Society.
His first public presentation describing his ground-breaking findings followed on January 23rd, 1896. He concluded that lecture by taking an x-ray image of the hand of a volunteer from the audience!
News of Roentgen’s remarkable discovery traveled rapidly around the world. In recognition of his ground-breaking research, he was awarded the first Nobel Prize in Physics in 1901.
Newspaper Coverage of 1901 Nobel Prize Awards
Not long thereafter, a Polish-émigré working at the Sorbonne in Paris named Marie Sklodowska (together with her husband Pierre Curie) isolated the first known radioactive elements which she named Polonium (after her homeland of Poland) and Radium.
Marie Sklodowska Curie (1867-1934)
Radioactive elements emit a natural form of x-rays known as Gamma Rays. In recognition of their work, the Curies received the Nobel Prize in Physics in 1903 (although as a woman she was not allowed to address the audience).
Pierre Curie (1859-1906)
Marie Curie subsequently went on to receive a second Nobel Prize in 1911 for her work on the chemistry of Radium. (Of note, she was not only a double Nobel prize recipient but was also the mother of a Nobel Prize winner. Her daughter Irene received the 1935 Nobel Prize in Chemistry for her own work on radioactivity).
Irene Curie (1897-1956)
The potential role of x-rays (produced artificially by a machine or naturally by a radioactive element) as both a diagnostic and therapeutic tool was realized remarkably quickly. In fact, the first diagnostic x-ray was in fact taken within 2 months of Roentgen’s discovery.
First American diagnostic x-ray (Dartmouth, February 1896)
Interestingly enough, the therapeutic potential of x-rays was demonstrated even earlier. After noting peeling of his hands exposed to x-rays, a medical student in Chicago named Emil Grubbe convinced one of his professors to allow him to irradiate a cancer patient, a woman named Rose Lee, suffering from locally advanced breast cancer. By doing so, Grubbe became the World’s first Radiation Oncologist.
Emil Grubbe (1875-1960)
No longer responding to medical treatments, Ms. Lee benefited greatly from Grubbe’s intervention, demonstrating the potential value of x-ray treatments. In a few short years, patients throughout the United States and Europe were undergoing Radiotherapy.
At first, Radiotherapy was delivered primarily in a limited number of treatments. A Professor at the Radium Institute in Paris name Claude Regaud, however, recognized that treatment may be better tolerated and more effective if delivered more slowly with modest doses per day over several weeks.
Claude Regaud (1870-1940)
This approach, known as fractionation, is one of the most important underlying principles in Radiation Therapy. To this day, fractionation lies at the heart of many treatment programs currently used in Radiation Oncology.
The early French Radiation Oncologist Henri Coutard pioneered the use of fractionated Radiotherapy in a wide variety of tumors. Of note, he reported impressive results using this approach in patients with locally advanced laryngeal (voice box) cancers. His seminal 1934 report of the outcome of these patients is still quoted today.
Henri Coutard (1876-1950)
Despite their promise, an important limitation of the early x-ray machines was their inability to produce high energy, deeply penetrating beams. It was thus difficult to treat deep-seated tumors without excessive skin reactions.
Early Radiation Therapy Machine
Many early advocates of Radiation Therapy thus relied instead on the placement of radioactive sources in close proximity or even within the tumor, a technique known as brachytherapy [Brachytherapy]. In many tumors, for example cervical and uterine cancers, brachytherapy became the mainstay of treatment (as it so remains to this day).
Breast Brachytherapy (1920s)
Following World War II, England became the primary focus for Radiotherapy research. Founded by Ralston Patterson, the Holt Radium Hospital was quickly recognized as a world renowned center for radiation treatment and research.
Ralston Patterson (1897-1981)
Through his careful clinical observations, Patterson established the optimal treatment approaches for a wide variety of tumors undergoing external beam radiotherapy. Together with the noted Physicist Herbert Parker, Patterson developed the basic principles underlying brachytherapy prescription, the so-called “Patterson-Parker Rules”.
By the 1960s, the epicenter of Radiation Oncology began to shift to the United States, primarily due to the immigration of many noted European radiotherapists. An exciting development was the introduction of high energy (megavoltage) treatment machines, known as linear accelerators or linacs. Such machines were capable of producing high energy, deeply penetrating beams, allowing for the very first time treatment of tumors deep inside the body without excessive damage to the overlying skin and other normal tissues.
Modern Linear Accelerator
A prototype linac was developed by Henry Kaplan and his colleagues at Stanford University. The first patient treated using this machine was a child with retinoblastoma (a cancer of the eye). Treatment was highly successful for more than 40 years later, this patient remained free of disease with good vision.
First patient treated on a megavoltage linear accelerator
Subsequently, many noteworthy Radiation Oncologists made enormous contributions to the field of Oncology. Malcolm Bagshaw, also of Stanford University, demonstrated the curative potential of Radiation Therapy in prostate cancer. Today, based in part on his ground breaking work, radiotherapy is recognized as a mainstay in the treatment of prostate cancer.
Gilbert Fletcher of the MD Anderson Cancer Center established optimal treatment regimens in a wide variety of tumor sites including head and neck cancers and cervical cancer.
Samuel Hellman, the founding Chair of the Joint Center for Radiation Therapy (Harvard University), who trained UCSD Radiation Oncologists Dr. Arno Mundt and Dr. Kevin Murphy, was instrumental in establishing breast conserving therapy (the use of lumpectomy plus radiation instead of mastectomy) as the treatment of choice for women with breast cancer.
The 1960s saw the beginning of widespread proliferation of radiotherapy throughout the United States and Europe. This growth was due in part to the increasing availability of commercial linear accelerators and other equipment. Varian Medical Systems the current leader in Radiation Oncology technologies, began work on the first commercial linac in 1958.
By the early 1960s, both Stanford University and UCLA were treating with Varian machines. Over the years, other accelerator vendors including Siemens and Elekta introduced commercial linacs. Commercial linacs are currently used in Radiation Oncology centers across the globe.
In subsequent years, the field of Radiation Oncology has experienced multiple technologic revolutions. By the late 1980s, computer tomography (CT)-based treatment planning had become commonplace, allowing the development of 3-dimensional conformal radiotherapy (3DCRT). 3DCRT greatly improved the quality and delivery of radiotherapy by reducing dose to surrounding normal tissues.
The next major technologic development known as Intensity Modulated Radiation Therapy (IMRT), however, represents arguably the most important revolution in Radiation Oncology. Unlike conventional approaches, IMRT conforms the prescription dose to the shape of the target in 3 dimensions, thereby reducing the volume of normal tissues receiving high doses and thus the risk of potential side effects.
In head and neck patients, for example, IMRT focuses treatment on the tumor reducing exposure of the nearby salivary (parotid) glands. Head and Neck cancer patients treated with IMRT are thus less likely to develop dry mouth (xerostomia).
IMRT plan in a patient with a right-sided tonsil cancer
The high dose isodose lines curve in avoiding the right (pink) and left (light green) parotid (salivary) glands
IMRT also provides a means of safely escalating the prescription dose and even re-treating previously irradiated patients, potentially improving cure rates.
While initially available at only a limited number of academic centers, IMRT has been quickly adopted by the Radiation Oncology community in recent years. A survey in 2005 performed by Dr. Mundt and his colleagues found that nearly 75% of Radiation Oncologists in the United States were treating patients with IMRT.
This was all the more remarkable given that their earlier 2003 survey found that less than a third of radiotherapists were using IMRT.
IMRT Adoption in the United States (Mell et al., 2005)
IMRT is rapidly becoming standard practice in a wide number of tumors, particularly prostate and head/neck cancers. Interest has also grown in other sites, notably cervical cancer, brain tumors and breast cancer.
IMRT is commonly used at UCSD. UCSD physicians and physicists have considerable experience in its use. Dr. Mundt is the Editor of the first International IMRT textbook on IMRT entitled IMRT: A Clinical Perspective. This textbook brought together over 175 physicians and physicists interested in the clinical use of IMRT from 42 institutions in 9 countries (USA, Belgium, Canada, China, Japan, Germany, Great Britain, Switzerland and Spain).
Today, Radiation Therapy is in the midst of yet another important technologic revolution, namely Image-Guided Radiation Therapy (IGRT). While not truly new, IGRT is rapidly growing in popularity primarily due to the widespread adoption of new linear accelerators which function both as treatment and imaging machines. The Varian Trilogy machine used at UCSD for IGRT is shown below. The Trilogy is capable of producing high quality CT scans of the patient on the treatment table.
Machines, such as the Varian Trilogy, also have the ability to perform cone-beam CT scans of the patient while he or she is on the treatment table. This ability will someday allow treatment to be adapted to changes occurring in the tumor, hopefully translating into higher cure rates and lower rates of toxicity. Researchers at UCSD led by Steve Jiang, Ph.D., Director of Research in the Department of Radiation Oncology, are actively investigating the potential roles for IGRT in a wide number of tumor sites.