Technical advancements in the treatment of cancer using External beam Radiation
Human beings as other living things are made up of a very large number of cells, which are the basic units of life. During a lifetime, many of the cells that make up the body age and die. These cells must be replaced so that the body can continue functioning optimally. There are several safeguards built into the cell division process to assure that cells do not divide unless they have completed the replication process correctly and that the environmental conditions in which the cells exist are favorable for cell division. Cancer cells divide without appropriate external signals; they do not exhibit contact inhibition and can divide without receiving the 'all clear' signals. Cancer cells do not conform to the “cell division rules”. The abnormal behaviors demonstrated by cancer cells are the result of a series of mutations in key regulatory genes. Cancer cells reproduce faster than normal cells in the body.
Radiation therapy is one of the many tools used to combat cancers. Radiation treatments utilize high-energy ionizing radiation like x-rays to kill cancer cells. Radiation can be used alone or in conjunction with other treatments (e.g. chemotherapy and surgery) to cure or stabilize cancer. Radiation therapy targets these rapidly dividing cells. The radiation reacts with water and oxygen in the cells and this reaction damages the DNA or genetic material in the cell that controls cell growth. Normal cells can repair themselves and continue growing. But since cancer cells can't repair themselves as easily, they die. Although normal cells are also affected, they repair themselves more effectively.
The greatest challenge for radiation therapy or any cancer therapy is to attain the highest probability of cure with the least morbidity and toxicity. The simplest way in theory to increase this therapeutic ratio with radiation is to encompass all cancer cells with sufficient doses of radiation during each radiation dose fractionation, while simultaneously sparing surrounding normal tissues.
One of the key technical problems faced in the treatment of cancer is the early detection of the disease. Often, cancer is detected in its later stages, when it has compromised the function of one or more vital organ systems and is widespread throughout the body. In practice, however, the abilities to both identify the cancer cells and target them with radiation have been limited. The latest developments in the computer technology have stimulated the innovative technical approaches to cancer detections and treatments. These computer advancements have fueled parallel advances in imaging technologies utilizing the computer’s processing speed, accuracy, storage capacity, data transmission speed and security.
Computed Tomography (CT), for example, has undergone rapid developments in recent years to the extent that many thin slices of higher quality images can now be acquired within a short period of time covering a larger volume. Presently, 64-slice CT is the top of the line in diagnostic imaging. Magnetic Resonance Imaging (MRI) can be used to diagnose cancers that cannot be achieved by CT. There are numerous advantages of MRI over CT that include; no radiation exposure, excellent soft tissue contrast, no artifacts due to radiodense structures, patency of blood vessels can be easily determined, and IV contrast is much safer. Both CT and MRI are anatomical based imaging modalities. Positron Emission Tomography (PET), which is physiological based imaging modality, is also another available imaging technology capable of detecting cancer cells that cannot be detected by CT. There is now a combined PET-CT technology that can fuse both the CT and PET images to allow both the anatomical and physiological definitions of the targeted region. As a result of these technical developments, the tumors can be differentiated and staged with increased accuracy. The improvements in imaging have in turn allowed a higher level of complexity to be incorporated into radiotherapy-computerized treatment planning systems. Because of these changes, the delivery of radiotherapy evolved from therapy designed based primarily on plain (two dimensional) x-ray images and manual hand based radiation dose calculations to three-dimensional x-ray based images incorporating increasingly complex computer algorithms.
There are two options that can be chosen to deliver radiation therapy treatments. One option is the use of external beam radiation therapy which utilizes the medical linear accelerator or teletherapy (radio-active cobalt) machines which generate high energy X-rays or electrons, protons and other heavy particles. The other option is the use of radio-active isotopes implanted directly in contact with the tumor commonly referred to as brachytherapy. The choice of the treatment modality may depend on the stage of the disease, geometrical complexity of the treatment region, the decision by the patient and or a host of many other factors.
Intensity Modulated Radiation Therapy (IMRT) is the latest and most exciting development in the field of radiation therapy utilizing medical linear accelerators. It is an extension of the three-dimensional conformal treatment methodology (3DCRT). It completely alters the way radiation therapy is planned and delivered, enabling tumors to be treated in areas that were previously difficult to reach. This technology allows for higher radiation dose delivered to the tumor at the same time sparing the normal organs located within the proximity of the tumor.
The CT, PET or Magnetic Resonance (MR) images are transmitted to a radiation therapy treatment-planning computer system through the computer network. Another option is the submission of the images via CD but the images must be in a standard DICOM format. The radiation therapy computer has medical linear accelerator’s data modeled and stored in it. It is therefore capable of predicting with greater accuracy, the dose that the linear accelerator can deliver under any given conditions. With the images stored in the computer, the radiation oncologist outlines the tumor volume and other critical normal structures surrounding it and places desired radiation dose constraints to the identified normal organs.
Traditional or even newer forms of conformal radiation therapy use one to six fixed different arrangements of high-energy radiation beams aimed at a target that has been identified by a radiation oncology physician and radiation oncology physicist. But IMRT uses inverse treatment planning, a computerized process that identifies the optimal treatment for each patient from millions of possibilities available. IMRT delivers up to 700 pencil-thin, three-dimensional beams of radiation that conform to the shape of the patient's tumor. Because IMRT pinpoints the tumor so well, it spares damage to healthy tissue and organs surrounding the tumor – even in cases where the tumor has wrapped itself around a vital organ. Consequently, the dose to the tumor can be escalated while the normal tissues are still spared from the damage. IMRT delivers very high doses of radiation with extremely high precision.
The computer-controlled linear accelerator generates high energy X-rays by using microwave energy to accelerate electrons to nearly the speed of light. As the electrons reach maximum speed, they collide with a metal target to release photons (or X-rays). The accelerator rotates around the patient to deliver the radiation treatments from nearly any angle. The linear accelerator is outfitted with an important accessory called a multi-leaf collimator. This device, which has computer-controlled mechanical "leaves" or "fingers," is used to shape the beam of radiation so that it conforms to the three-dimensional shape of the tumor.
The finally acceptable computerized treatment plan parameters are transmitted to the linear accelerator through a record and verify computer system where the plan undergoes numerous checks and tests before it is downloaded to the linear accelerator treatment console computer system and finally delivered to the patient.
Another form of technology geared towards “tracking, pointing and shooting” the radiation at the treatment target is the Cyber-Knife. This machine is made of robotic arms that are able to move in multiple dimensions. It has a laser system that tracks the movement of the target. It synchronizes the relative position of the target with that of the treatment plan and stops the radiation when it senses larger deviations beyond the pre-set tolerances. It is mostly suitable for aggressive tiny lesions located near very critical organs.
One major limitation of current linear accelerators is that the treatment plans are based on images acquired from other independent imaging modalities such as CT and MRI. Consequently longer period of time is required to link the complex processes together in a desirable manner before the treatment is begun. There is an active research on the development of an X-ray machine capable of acquiring the images, performing computerized treatment plan on a built in treatment planning computer as well as delivering IMRT treatments. An example of the technology that utilizes this impressive combination is Tomotherapy machine. Presently, tomotherapy machines are only available at Medical research institutions and their clinical impacts on treatment of cancer are yet to be evaluated.
In addition, greater awareness of the challenges to the accuracy of the treatment planning process, such as problems with the reproducibility of daily patient positioning and internal organ movements, have begun to be systematically addressed, ushering in an era of the so-called Four-Dimensional Radiotherapy and Adaptive Conventional Radiation Therapy. Image Guided Radiation Therapy (IGRT), is a technique that is used to fuse (register) the patient images acquired from the treatment planning computers with those acquired at the linear accelerator during the pre-treatment patient positioning set up. The sophisticated IGRT computer software linked to the linear accelerator computer control system calculates the difference in the location of the real time treatment target compared to the treatment planning target location and either instructs the linear accelerator (if equipped with this technology) to automatically shift the patient to match the reference images or the software outputs the required shift information so that the radiation therapists can manually move the patient. The IGRT therefore helps to increase the precision of radiation delivery to the targeted treatment region with less radiation delivered to the normal organs. This enables the radiation oncology physicians to escalate the treatment doses with reduced morbidity and hence better disease control. While the growth in radiation therapy technologies has been exciting, there are still many basic challenges that are far from being resolved. For example, it is still not possible to measure the exact radiation dose being delivered to an internal target organ. Presently, there are numerous relative surface dose measurement methods, which are calibrated to predict the doses delivered at different treatment depths. The accuracy of these methods are limited by many factors such as the internal patient temperatures, pressures, treatment energies, contour of the patient skin, point of placements with reference to the center of the treatment area, the actual location of the target at the time of radiation delivery etc. There is also no universal technique available to immobilize breast cancer patients with large and saggy breasts to assure their daily positioning reproducibility during treatment delivery. Similarly, treatment in the pelvis regions that requires prone positioning are challenging because of the difficulty in reproducing the radiation source to patient skin distances.
None-the-less, the latest technical developments in the treatment of cancer using external beam radiation therapy has been overwhelming. The future of external beam radiation therapy would still resonate between the developments of advanced imaging systems to link the treatment planning systems and the treatment delivery machines remotely. This would provide the transparency through the patient’s anatomy to allow the clinicians view the radiation dose cloud accumulation within the treatment target as the treatment proceeds.
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