Definition/Introduction
Radiation therapy is the use of directed x-rays or subatomic particles primarily for cancer management in both curative and palliative settings. Radiation therapy can be delivered either externally or internally. External beam radiation, also known as teletherapy, is most common and involves a radioactive source outside of the patient, with the energy focused and shaped to the target of interest. Brachytherapy, in contrast, refers to the practice of placing naturally occurring radioactive sources that decay over time and produce high doses of radiation in a focal area. Examples include intracavitary procedures (such as tandem and ovoid placement for cervical cancer), interstitial radioactive seed placement (commonly used for prostate cancer), or placement overlying a cutaneous tumor.
Treatment was traditionally administered using naturally occurring radioactive elements that emit photons during decay. However, in the modern era, these are typically generated by machines called linear accelerators, which accelerate a stream of electrons toward a target, producing photons resulting from the atomic interactions occurring within that target. These photons are directed toward the patient through a mobile gantry, and motorized collimators are used to shape the radiation beam as it exits the gantry head.
Physical and Biological Principles of Radiation
The most common form of ionizing radiation used in clinical practice is the photon. However, electrons are also commonly used for increasing the radiation dose to the skin when needed. More exotic particles, such as protons, carbon ions, or neutrons, can be used for certain diagnoses or tumor locations but are available only at specialized centers. Each type of radiation possesses unique physical characteristics that dictate the interactions it will undergo as it travels through the patient’s body. This, in turn, determines how and where the dose is deposited in the tissue, and knowledge of these patterns can be manipulated to limit the dose to normal structures and thereby improve the therapeutic window.
The therapeutic window in radiation also relies on differences in DNA interactions between cancer cells and normal cells. Double-stranded DNA breaks induced by radiation result in a mitotic catastrophe, in which cell division is fatally interrupted; mitotic catastrophe is the main form of cell death induced by ionizing radiation.[1] Hence, the radiosensitivity of a cell line depends on its rate of cell division. In general, poorly differentiated tumor cells are more radiosensitive because a greater proportion of their cell population is dividing at any given time. This also applies to rapidly dividing normal tissue cells such as those of the gastrointestinal mucosa and explains why reactions such as mucositis and diarrhea can be common. The reliance of radiation effect on the cell cycle phase underlies one of the four basic tenets of radiation biology that dictate the success of a particular regimen: the redistribution of cells within the cell cycle, repair of DNA damage, repopulation of cells, and reoxygenation of hypoxic areas within the tumor.[2]
Radiation exploits cancer cells because these cells often have impaired DNA repair mechanisms, whereas normal cells can rapidly repair double-stranded breaks. Therefore, a fractionated approach, ie, splitting the total radiation dose over multiple daily treatments, is typically used, such that DNA damage in normal cells is repaired between treatments, while damage to cancer cells accumulates over time, causing preferential cancer cell death. Both the dose per fraction and the total dose affect tumor and normal tissue response. In general, the lower the daily dose of radiation, the less likely it is to cause toxicity, but only specific cell lines (such as myeloma or lymphoma) are susceptible to these relatively low daily doses. Therefore, a balance needs to be achieved between daily doses low enough to spare normal tissue but high enough to cause cancer cell death. For many cancers, a dose of 180 to 200 cGy per day is used.[3]
Issues of Concern
Radiation Field Design
Target delineation is a crucial skill in creating radiation fields. Traditionally, bony anatomical landmarks were used to create ports, resulting in large volumes of normal tissue being radiated to target the high-risk areas within. This limited the maximum doses achievable with acceptable toxicity. Since many histologies require high doses of radiation for effective cell killing, this approach reduced radiation’s potential to cure cancer. Over time, however, the ability to deliver more conformal treatments has dramatically improved, with the advent of CT-based target delineation, dynamic multi-leaf collimators that can reshape the field while radiation is delivered from multiple angles, and computer-generated inverse radiation planning (intensity-modulated radiation therapy [IMRT]) to create complex radiation dose distributions that target the tumor while sparing normal tissue.
The margin for error is now typically on the order of millimeters, allowing providers to drastically reduce the normal tissue volume radiated. But to take full advantage of modern machine capabilities, the prescribing radiation oncologist must be able to accurately delineate the gross disease and predict pathways of spread. Therefore, it is critical to use clinical and diagnostic information, along with CT-based planning images. Conceptually, a visible tumor is defined as the gross tumor volume. A clinical target volume is then generated to encompass areas at risk for microscopic spread, typically with a geometric expansion that is then anatomically modified to respect local boundaries. For example, a primary tumor with a gross tumor volume in the lung and spiculated borders may have a surrounding area of about 1 cm at risk for microscopic spread, forming the clinical target volume, but will not extend beyond the parenchyma. Therefore, a 1 cm expansion is drawn from the gross disease in all directions, but carved off the chest wall or bone. In radiation sites such as the lung, where internal motion can affect the target position, an internal target volume is generated to encompass the extent of that motion as identified on 4D CT, ensuring target coverage throughout treatment delivery, even as the target moves. Finally, a planning target volume is added to account for expected uncertainties in a daily setup, typically between 5 to 10 mm depending on the institution and type of immobilization.[4]
Given small margins for error, good immobilization is the foundation of quality radiation therapy. Great care is taken in the patient’s initial planning stages to ensure that the treatment position will be reproducible daily. A combination of small, permanent tattoos and semipermanent markers or paint is used to help align the patient accurately every day. Some form of position verification is used for each course: at least once every 5 fractions, but ideally daily, for targets expected to exhibit significant internal variation or treated with a high degree of conformality. Image verification may be bone or soft-tissue-based.
Logistics of Radiation Therapy
Fractionating radiation therapy means that a treatment course usually takes several weeks, but course length can be modified based on patient and disease requirements. Palliative regimens typically run anywhere from 1 to 10 fractions, with the choice depending on the type of tumor and goal of treatment, as well as logistics such as difficulty with travel for daily sessions. Conversely, curative courses of radiation are more standardized and typically take 6 to 8 weeks. Of note, however, hypofractionation (short course of high-dose radiation) is becoming an increasingly common technique where the goal of radiation is the ablation of a small area of targeted tissue rather than differential cell death within the target. This strategy is used to treat small targets with rapid dose falloff, sparing nearby critical structures. Examples of this strategy include stereotactic body radiotherapy for lung cancer (usually 3 to 5 treatments) and stereotactic radiosurgery for brain metastases (one fraction).[5]
Clinical Significance
Along with systemic therapy and surgical procedures, radiation forms part of the backbone of definitive oncologic care. Radiation is conceptually considered a loco-regional approach to cancer management, in contrast to surgery (generally a local strategy focused on removing gross disease) and systemic therapy (typically designed to control metastatic spread). The highest doses are delivered to gross disease, while more moderate doses are used for potential areas of spread near the primary tumor, as well as areas at risk for lymphatic spread regionally. Therefore, a thorough understanding of the anatomy of the affected region, as well as patterns of spread for particular histologies, is critical for the design of radiation fields.
Radiation therapy can also be used to palliate symptoms related to local tumor progression, such as pain, obstruction, bleeding, or compression. Short courses can be rapidly effective with low toxicity profiles and are therefore well-suited to the goals of hospice and palliative care, potentially improving quality of life even at the very end stages of illness. Several benign conditions such as heterotopic ossification, trigeminal neuralgia, and keloids can also be treated with radiation.
As technology rapidly advances, more and more applications and strategies in radiation are being explored, allowing for increased precision and better tolerability. However, while technology has evolved drastically, the heart of this field has remained the same for over 100 years. Since the discovery of x-rays and their effect on cancer, the goal of radiation has been maximizing tumor control while minimizing toxicity, seeking both cure and comfort for the cancer patient.
Nursing, Allied Health, and Interprofessional Team Interventions
All personnel involved in administering radiation therapy must possess knowledge of the anatomy of the area being treated, the physics of the treatment, and how to care for patients in the periprocedural realm. This includes radiation techs, oncology nurses, and, of course, the treating clinicians, with oncology specialists leading the way. As this field advances, it will undoubtedly require all interprofessional team members to be involved in patient care, openly share information, and for rising staff to play a significant role in both administering therapies and post-procedural care, leading to improved patient outcomes.
References
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Disclosure: Elizabeth Maani declares no relevant financial relationships with ineligible companies.
Disclosure: Christopher Maani declares no relevant financial relationships with ineligible companies.
