Radiation therapy refers to the use of ionizing radiation for the treatment of disease. It is most commonly deployed for the treatment of cancers, but has definite applications for other serious, yet non-malignant, conditions as well. When used in curative approaches, radiation therapy can be the primary treatment modality for some forms of cancer, but in others—such as mesothelioma treatments—its efficacy will derive from its use as part of a multimodal treatment protocol.
Radiation is the term we use to describe the energy that is emitted from a body, such as an atom, as it moves from a state of higher energy to a state of lower energy. There are two basic forms of radiation: ionizing radiation, where the radiation can alter the atomic structure of an atom or a molecule through a process called ionization, and non-ionizing radiation, where the radiation can cause an excitation in the atomic matter, but cannot actually alter its structure. In scientific terms, ionization is the physical process of converting an atom or molecule into an ion by adding or removing charged particles such as electrons or other ions. As we said above, radiation therapy refers to the use of ionizing radiation for the treatment of disease.
The therapeutic use of radiation therapy is based on its ability to damage the DNA structure of irradiated cells. The ionization—either directly or indirectly—creates instabilities in DNA’s constituent atoms, undermining its structural integrity. The damaged DNA then hinders a cell’s ability to effectively reproduce and, therefore, slows the growth of the tumor. In those cells that are able to reproduce, each successive generation is created with damaged DNA, which further slows the growth of the tumor, until—hopefully—the tumor completely disappears.
Ionizing radiation is dangerous to all kinds of cells, so its use must be strictly managed and great care must be taken to prevent the side effects associated with radiation exposure. Medical science has developed a number of useful strategies in its ability to effectively apply radiation therapy for treatment purposes while minimizing the side effects from exposure.
Due to its unique morphology and behavior pattern, mesothelioma is not typically amenable to the primary use of radiation therapy. Currently, there are no known cures for mesothelioma, but treatment with radiation is effective at relieving symptoms. Unlike other forms of cancer that may present as an individual tumor (or tumors), mesothelioma presents as a diffuse spread of multiple small tumors throughout a surface area. The malignancy appears as a “sheath-like” structure over the affected surfaces, which means there is not a single focal point to irradiate. For curative, primary modality radiation to be effective for mesothelioma, it would have to cover the entire cancerous field and it would need to be delivered in very high doses for the treatment to be effective. This is a problem for at least two very important reasons: because radiation can be harmful to human tissues, physicians need to closely control the doses that are used for treatment, so the need for very high doses functions as a negative indicator for the use of radiation therapy in this context. The second, equally important reason refers to the radiosensitivity of the organs in and around the pleural cavity: the lungs, heart and kidneys are all sensitive to damage from ionizing radiation, so the wide coverage that would be needed to treat the entire tumor would likely irradiate these vital organs as well.
However, this does not mean that radiation therapy has been banished from mesothelioma treatment. In fact, mesothelioma cells are fairly radiosensitive, so the targeted use of the therapy can have important benefits for patient treatment. The primary therapeutic function that radiation therapy currently serves in the treatment of pleural mesothelioma, which affects the lining of the lungs, is control over the logo-regional spread of the disease after surgery. In this context, radiation is used to prevent tumor seeding at instrumentation sites, such as points of surgical excision, the placement of drainage catheters or other points of medical intervention. Mesothelioma has a tendency to invade these areas after surgery, so radiation is used to irradiate the marginal tissue structures that remain, which hopefully kills whatever occult or otherwise microscopic cells are left in the these areas and prevents the further spread of the disease. When radiation is successfully used in this way, it has clear benefits for patient quality of life, prognosis and survival time.
The efficacy of radiation for loco-regional control of disease spread has been investigated after pleurectomy-decortication (PD) and after extrapleural pneumonectomy (EPP). Some of this data suggests that while pleurectomy-decortication + radiation gives better local control than simply pleurectomy-decortication alone, the use of EPP + radiation seems even more effective for stopping the spread of the disease after surgery than EPP or PD alone, or PD + radiation. In fact, some studies have shown that in patients who undergo extrapleural pneumonectomy followed by radiation, the major cause of death comes from metastatic spread of the cancer to distant body sites—not from the local entrapment of the lungs and pleural cavity that is the traditional manner in which mesothelioma causes death.
Researchers are still investigating the conclusive reasons for the greater efficacy of EPP + radiation over PD + radiation, but some of the current thinking identifies the ability to use higher dose administrations due to the complete removal of the lung as a possible reason for this enhanced effectiveness. Once the lung is out of place, physicians can deliver higher amounts of radiation to the areas making up the excision margins, while still blocking these higher doses from irradiating the spine and other regional organs. Much more research still needs to be conducted to study the boundaries of these techniques, but the positive results achieved by the use of radiation to control local spread of the disease likely means that its use in the multimodality treatment of the disease is assured.
Along with the therapeutic benefits identified above, radiation can also used for palliative purposes. A number of studies have shown that radiation is quite effective in reducing the pain and the severity of other common symptoms associated with advanced pleural mesothelioma.
Radiation doses are expressed in grays (Gy), a unit of measure that refers to the amount of energy absorbed by a body. When developing a radiation treatment plan, a radiation oncologist will make a detailed analysis of the patient’s individual presentation, including the type of cancer involved and the location in which the cancer has arisen. This analysis will directly inform the oncologist’s decision regarding the amount of radiation to be delivered because different types of cancers require different dose amounts to be effective. For example, solid tumors require higher radiation doses than lymphomas do, so a radiation oncologist may specify a radiation plan of 60Gy for the former case, but only 30Gy for the latter one.
Radiotherapy, like chemotherapy, is not given during a single session, but is delivered over time. When the radiation oncologist determines the total dose that will be delivered, he or she will also determine the amount of radiation for each individual administration, along with the total number of administrations. This is known as fractionation and it is done to maximize the efficacy of the treatment, while minimizing the occurrence of side effects. The smaller doses should still keep the cancer in check, but they give healthy cells time to recover from the radiation.
The typical fractionated doses that are delivered in American hospitals range from 1.8Gy to about 2.5Gy. The number of administrations is then based on a simple equation where the total dose to be delivered is divided by the fractional amount of each administration. In many cases, extra fractions or a higher radiation amount during some fractions—both kinds of adjustments are known as a boost dose—may be given at the end of treatment to attempt a more complete eradication of the tumor tissue.
When radiation is used for pain management for mesothelioma patients, doses above 40Gy are most effective at controlling symptoms. Similar doses are used when radiation is deployed for therapeutic purposes. Many of the studies investigating radiation followed by EPP have utilized dose levels between 45Gy – 54Gy.
Radiation therapy can be delivered from outside the body, where it will be “beamed” at a specific location or it can be delivered internally, where the radioactive material is ingested or injected. Radiation delivered externally is known as external beam radiotherapy (XBRT), while internally-delivered radiation is known as either sealed source radiotherapy (brachytherapy) or unsealed source radiotherapy. External beam radiotherapy is the standard technique that is used for mesothelioma treatment. XBRT delivers the radiation from a number of different angles to maximize the coverage of the tumor, while also attempting to minimize the effects of the radiation on adjacent tissues. The motivation for this strategy is that a number of precisely-placed and finely-controlled beams will be more effective and easier to control than will a single beam, with a wider scope.
There are a number of techniques available for external beam radiotherapy. Conventional external beam radiotherapy (2DXRT) is the name of the traditional XBRT process where the planning and structure delineation for the radiation is conducted through x-ray. While this is a common procedure, the poor soft tissue resolution of x-ray can complicate this treatment’s deployment because physicians are unable to know which tissues are likely to be irradiated. This is especially a problem for mesothelioma treatment because the adjacent tissue structures are particularly radiosensitive and the areas in which the tumor infiltrates are often complex biological structures themselves.
However, a number of recent advancements in radiotherapy have dramatically improved the precision, and treatment efficacy, of XBRT. These innovations have benefited all forms of cancer therapy, but mesothelioma treatment has especially benefited from them.
In place of x-ray, CT or MRI can now be used to map the interior structures of the target areas and to better delineate the malignancy from adjacent tissues. This is known as virtual simulation and it has enabled greater accuracy in the planning of treatment and the placement of the beams. Additional therapeutic benefits have come from the introduction of techniques that control the actual delivery of the radiation. 3-Dimensional Conformal Radiation (3DCRT) is a procedure that allows the radiation beam to be shaped according to the structural pattern of the tumor. 3DCRT can also be used to vary the radiation dose that is delivered to specific parts of the malignancy. Intensity-Modulated Radiation Therapy (IMRT) is an advancement on 3DCRT that allows even more accurate delivery of radiation, as well more fine-grained control of the dose delivered. IMRT enables the radiation oncologist to conform the radiation beams to tumors that are actually wrapped around other structures.
Both 3DRCT and IMRT have been used for mesothelioma treatment, although the available data doesn’t lend itself to a conclusion of choosing one over the other. IMRT is a more complex procedure, but it allows a better conformance between the beam and the target tumor. However, the real world effects of this added precision are still being investigated, so the choice between the procedures is more likely to be based on a particular institution’s investment in either technology than it is an affirmative set of research studies.