Basics of Radiation Therapy
Summary of Key Points
Introduction and Historical Perspective
• X-rays were first discovered emanating from an energized Crooke’s tube by Wilhelm Roentgen in 1895. In 1896, Henri Becquerel discovered that some naturally occurring elements emitted ionizing radiation. The radioactive elements radium and polonium were isolated and characterized by the Curies in 1898.
• Within a year or two, ionizing radiation was in use worldwide for medical imaging and radiation therapy.
Radiation Physics
• Several types of ionizing radiation are used to treat patients; most are of the low linear energy transfer, less biologically potent varieties.
• Therapeutic x-rays (photons) and electrons are produced by linear accelerators but can also be produced by nuclear isotopes that undergo radioactive decay. These form the basis of external beam radiotherapy and brachytherapy, respectively.
• Ionizing radiation interacts with matter via several processes, the most important of which for clinical radiation therapy is Compton scattering.
• Megavoltage photons from linear accelerators have the desirable property of delivering their maximum dose at depth within the patient, thereby sparing the skin and, to some extent, other normal tissues.
The Radiobiology of Radiotherapy
• Ionization of biomolecules from the deposition of energy by photons or particles can occur directly and indirectly. The most important cellular target for radiation is DNA, with irreparable or “misrepaired” double-stranded breaks believed to be the lesions most responsible for cell killing.
• Irradiation elicits diverse cellular responses that include the sensing of DNA damage, mobilization of DNA repair proteins, repair (or attempted repair) of DNA damage, triggering of cell cycle checkpoints, and, for irreparable or mis-rejoined damage, cell death by one of several mechanisms (e.g., mitotic catastrophe, apoptosis, and senescence).
• The most commonly applied model of cell survival probability is the linear quadratic (α/β) model, with the surviving fraction of irradiated cells described by the equation 
. The α/β ratio is a convenient metric for describing cellular radiosensitivity and has been adapted to describe the response of irradiated tissues as a function of time, dose, and fractionation.
• DNA damage and repair were initially inferred by monitoring increases in cell survival or tissue tolerance with fractionation. These phenomena were termed sublethal and potentially lethal damage repair or recovery.
• Cells in different cell cycle phases possess different radiosensitivities; cells are most radiosensitive in the G2 and M phases of the cell cycle, and most resistant in the S phase, particularly the late S phase. Cells in the G1 phase are of intermediate radiosensitivity.
• Well-oxygenated cells are as much as three times more sensitive to radiation-induced cell killing than (severely) oxygen-deprived cells. Viable hypoxic cells that exist in many human tumors but that are mostly absent in normal tissues may be an impediment to tumor control. The elimination of such cells has been a long-standing clinical goal. Hypoxia may provide avenues for therapeutic gain through the use of hypoxia-directed therapies.
• Radiation sensitizers, particularly cytotoxic chemotherapy and, to a lesser extent, radiation protectors, aim to improve the therapeutic ratio.
Clinical Radiation Oncology
• Radiation therapy is used in more than half of all patients with cancer, either as an adjuvant or neoadjuvant treatment in combination with surgery; as a definitive treatment alone or in combination with chemotherapy; as an organ-sparing therapy; or to palliate symptoms.
• Fractionation of radiation and altered fractionation schedules, such as accelerated hyperfractionated radiation therapy, make use of differences in the responses of normal and malignant tissues to irradiation to achieve higher therapeutic ratios.
• Radiation produces early effects, such as mucositis, skin erythema, or desquamation, and late effects, such as fibrosis and carcinogenesis.
Planning and Delivery of Radiation Treatment
• Patient simulation uses multiple imaging approaches to identify cancerous and healthy regions within the patient and to select appropriate beams to deliver a dose to the tumor while minimizing the dose delivered to surrounding tissues.
• Three-dimensional conformal treatment planning and delivery has permitted escalation of doses and improved sparing of normal tissues.
• Intensity-modulated radiation therapy uses varying radiation beam intensities to precisely sculpt the dose distribution around the tumor to improve the therapeutic ratio.
• Image-guided radiation therapy uses real-time and/or daily imaging to ensure that the tumor is positioned such that the radiation beams are precisely delivered to the appropriate location within the patient.
Other Modalities in Radiation
• Brachytherapy delivers extremely high-dose radiation to tumor tissue with a much lower dose to surrounding normal tissues.
• Stereotactic radiosurgery and stereotactic body radiation therapy combine a high dose per fraction with highly conformal treatment delivery to increase the therapeutic ratio while reducing treatment time.
• Proton therapy has dose distribution advantages compared with photon therapy, and it may be used to deliver high doses of radiation to tumors in close proximity to sensitive normal structures.
1. For a typical radiation therapy x-ray beam, the dose will decay at what rate from absorption after it enters tissue and attains electronic equilibrium?
2. The oxygen enhancement ratio reflects which of the following?
A The differential rate of absorption of radiation by oxygen compared with nitrogen
B The rate at which oxygen is utilized by the tumor cells divided by the rate in normal tissues
C The relative enhancement of hypoxia-inducible factor–1 by oxygen compared with normal tissues
D The relative sensitivity of cells to radiation in an oxic versus hypoxic environment
3. If 4000 Gy of radiation is delivered to each of two areas in the body, the total dose given is:
4. Which of the following treatment modalities is not designed to primarily improve the radiation dose distribution in tissue?
1. Answer: B. X-ray beams in tissue are absorbed approximately exponentially as they are absorbed by the tissue through which they are traveling.
2. Answer: D. Oxygen enhances radiation cell kill compared with that in a hypoxic environment.
3. Answer: B. Radiation doses given to different areas do not add. They are independent events, and thus the dose given is still 4000 Gy to each site.
4. Answer: C. Radiation sensitization does not affect the dose-distribution pattern of radiation therapy.
