Cancer, Radiation Therapy

Prior to the advent of the x-ray and radioactive isotopes, cancers were treated by removing them surgically. Many cancers grew undetected because imaging techniques had not yet been developed. The Roentgen ray, later referred to as the x-ray and named for the German physicist and discoverer Wilhelm Conrad Roentgen in the late nineteenth century, would change both the diagnosis and treatment of cancer. (See X-Rays in Diagnostic Medicine.)

Skin damage arising from careless use of x-rays led to early ideas for the therapeutic use of radiation on human tissue, though its ionizing effect was not understood at the time. Today scientists understand that some cancer cells are more susceptible to damage from ionizing electromagnetic radiation than are ordinary cells. The therapeutic use of x-rays began in 1896 when Emil Grubbe used x-radiation to treat a patient with breast cancer.

In 1902, Guido Holtzknecht created a chromo-radiometer, which could record and measure the radiation dose administered to a patient, paving the way for systematic use of radiation therapy. One of the first applications of x-ray therapy was to treat ringworm infection. If enough radiation was applied to kill the fungus, hair on the skin fell out, but if too much was applied, the hair did not grow back and the skin was burned. Thus the nemesis of treatment was defined: the narrow margin between enough and too much. By the 1920s, however, x-ray machines were routinely used in hospitals for clinical treatment.

The French physicist, Henri Becquerel is credited with the discovery of natural radioactivity when he observed that uranium salts produced images on nearby photographic plates. Other radioactive elements, first polonium and then radium, were discovered by French chemists Marie and Pierre Curie. Perhaps the first medical application of radium occurred when Marie’s husband Pierre burned his arm with it. The Curies lent radium to Paris physicians, and one early documented case in 1907 described the removal of a child’s facial angioma using a crossfire technique.

The first x-ray therapy was administered using radon gas in tubes. The challenge was then and continued to be the manipulation of a ray (which is straight) into a body that has contours, many layers, and organs of different densities and sensitivities. The objective was to obtain adequate tissue depth with rays without destruction of surrounding cells.

In 1913, the first external beam machine used a cathode, or ‘‘Coolidge,’’ tube for treating superficial tumors. It was referred to as an orthovoltage applicator and was very slow. Although these machines were extremely limited, they introduced a new genre of technology to medicine known as x- ray therapy, later called radiation therapy. In the 1930s, the use of so-called radium bombs (telecurietherapy) led to refined treatment times, shielding to avoid exposure of healthy tissue, and prescribed doses of radiation. However, results at that time were only palliative.

The Van de Graaff generator, built in 1931, was able to build up a high electrostatic charge and thus high voltages (up to 1 million volts). A medical Van de Graaff, in which electrically accelerated particles were used to bombard atoms and produce radiation, was first used in a clinical setting in 1937. Throughout the 1940s, radiation treatment with the Van de Graaff allowed a very narrow, targeted beam, higher energy (about 2 megavolts), and less treatment time than with gas tubes. But as with most other cancer treatments of the 1940s, these efforts were still palliative and only temporarily relieved pain or reduced the size of a tumor.

The first circular electron accelerator, named the betatron, was built in 1940 by Donald Kerst and Robert Seber. Originally designed for research in atomic physics in the U.S., the betatron was soon adopted for clinical use. Its first clinical application was by Konrad Gund in 1942 in Germany during World War II, and it was first used by Kerst in the U.S. in 1948. Both directly produced electrons, and x-rays produced by accelerators were an ideal source for therapy and a considerable improvement over the energy that could be achieved with gas and vacuum tubes (higher energy rays have better penetration properties).

The betatron energy range of 13-45 megavolts, with 25 megavolts being optimal for therapy, made the device suitable. Linear electron accelerators were developed simultaneously by D.W. Fry in England and William Hansen in the U.S. The first patient to be treated in London with a linear accelerator was in 1953.

Until the new specialty of radiation oncology was recognized in the 1960s in the U.S., diagnostic radiologists administered radiation therapy. Subsequently, the European Society for Therapeutic Radiation and Oncology as well as many other organizations of these specialists have formed worldwide.

In the early 1950s, a group of Canadian scientists isolated a highly radioactive cobalt-60 isotope from a nuclear reactor. This provided a source of gamma rays, popularly and misleadingly referred to as a ‘‘cobalt bomb,’’ which could be directed at patients. The Cobalt 60 machine emitted gamma rays of 1.25 megavolts at a distance of 50 to 60 centimeters, and could penetrate deep tissues. Because of the danger of exposure to these rays, buildings in which the machines were located were required to have walls of very thick lead. Many of the original cobalt gamma ray systems have been replaced with linear accelerators.

In 1975, the development of proton beam radiation allowed for higher doses of radiation to target tissues while sparing adjacent cells. Since that time much of the progress in radiation therapy has been through the application of other technologies. Refinements have included more stable machines, radiation at higher rates, modifications to the treatment table, mobility of various machines, higher energy outputs, and collimators (a device to direct the beam). Energy is now described in millions rather than thousands of electron volts.

Most machines treat patients in the range of 10 to 25 megavolts or 18 to 20 megavolt photons. The new collimator takes the place of lead positioning blocks that were previously limited in shape and size. One system consists of 25 moving parts that can shape the direction of the treatment to conform to the target tumor.

Miniaturization of technology has allowed for as many as 120 motors to fit in the head of certain machines to deliver radiation to the patient. The newest system of external beam radiation is IMRT (intensity modulated radiation therapy), which links the treatment planning system to the linear accelerator and the multileaf collimator. IMRT has reduced the amount of radiation to surrounding tissues and provided high-resolution images of the patient’s anatomy.

By the 1990s, highly sophisticated imaging technology with the use of computed tomography (CT) scans, magnetic resonance imaging (MRI), and ultrasound facilitated more accurate treatment planning for radiation oncology. Radionuclides delivered to bone tissue can identify malignant tissues in a bone scan. More recently, the use of positron emission tomography (PET) has enabled physicians to image metabolic processes and to track tumor metastases from lung and bone tumors.

Another form of radiation therapy, brachytherapy, uses application of a source to tissues a short distance away. Typical sites are the lung, where high doses of radiation are given over a two-week period through a catheter placed in the lung, and the cervix, where cesium-137 is placed in the vagina for a few hours. Radioactive iodine and palladium are used to treat prostate cancer by placing or implanting ‘‘seeds’’ (tiny titanium cylinders containing the radioactive isotope) in the gland, and radioactive palladium is also used in implants for tumors of the tongue. This is known as implant therapy.

One tumor site that posed the most difficult problems for both external beam radiation therapy and implant technology was the brain because it is covered by bone. The Gamma Knife, developed in 1968 by Lars Leskall and Borge Larsson in Sweden, is an instrument that delivers a concentrated radiation dose from Cobalt-60 sources. It fires 201 beams of radiation into the skull that intersect at the target site. No single beam is powerful enough to harm surrounding tissue, but the cumulative effect of this precision tool destroys the tumor.