Radiotherapy
Abstract
Radiotherapy refers to the use of high-energy X-rays or charged particles to treat lesions that are radiosensitive. It is typically used as an adjuvant therapy once pathology is determined for lesions of the brain or spine. Different types of radiotherapy are associated with different courses of treatment. The type of treatment used is determined by radiation oncologists. Regardless of the type of treatment, nurses and other health care providers assist patients in their treatment journey, and they must be aware of the possible effects and complications the patients might encounter along the way.
Keywords: brachytherapy, CyberKnife, external beam radiotherapy, Gamma Knife, radiation oncology, radiobiology, stereotactic radiosurgery
16.1 Radiation Therapy
Surgery is the first step of treatment for many patients with benign tumors or vascular lesions and for all patients with malignant tumors. In most cases, however, surgery alone is not enough—adjuvant therapy is also indicated. The term radiation therapy refers to the use of high-energy X-rays or charged particles to treat benign and malignant tumors and certain functional conditions. It is often performed after surgery or in patients whose tumors are unresectable or can only be partially resected. Radiation therapy can also serve as the primary treatment for radiosensitive lesions or for lesions located in an eloquent area of the brain.
Ionizing radiation disrupts atomic structures by ejecting orbiting electrons. These electrons break chemical bonds and ultimately effect biological change.
If radiation has sufficient energy, it ejects one or more electrons from the atom or molecule in a process known as ionization. When radiation therapy is used as sole or adjuvant treatment, it is ionizing radiation
The idea to apply ionizing radiation in cancer treatment was realized soon after the discovery of X-rays
Radiation is thought to kill tumor cells by inducing lethal DNA damage
Ionizing radiation is composed of electromagnetic radiation (e.g., X-rays and γ-rays) and particulate radiation (e.g., electrons, protons, neutrons, and α-particles)
Radiation can be produced by megavoltage machines and by radionuclides. Megavoltage machines, used for external beam radiotherapy (EBRT), include linear accelerators, cobalt-60 machines, and cyclotrons, which produce protons or neutrons. Radionuclides are natural radioactive sources that emit radiation in the form of particles or γ-rays, and they emit energy characteristic of that particular radionuclide. Types of therapy that use radionuclides include brachytherapy and radiopharmaceutical therapy (Box 16.1 Measurement of Radioactivity).
Radiation oncology is the medical specialty that uses ionizing radiation to eradicate malignancies as well as to treat some benign diseases.
A treatment regimen is centered around a dose of radiation high enough to cure or control the tumor/disease but not so high as to seriously damage normal surrounding tissue
The tissue tolerance dose is the amount of radiation that normal tissue can withstand while continuing to function.
Box 16.1 Measurement of Radioactivity
The unit of measurement for radioactivity is the gray (Gy)
RAD is an older term that may still be used. It stands for radiation absorbed dose and is synonymous with centigray (cGy)
1 Gy =100 cGy = 100 RAD
Activity of radioactive sources is measured in curies (Ci) or becquerel (Bq)
16.1.1 Principles of Radiobiology
Radiobiology is the study of events that occur after ionizing radiation is absorbed by a living organism.
Radiation works at cellular level by breaking chemical bonds, eventually leading to tissue change
Probability of cell death is higher if critical sites, such as DNA, are damaged by radiation
Both normal and cancerous cells are susceptible to the effects of radiation
Rapidly dividing cells are the most radiosensitive cells
The “Five Rs” of radiobiology—Repair, Redistribution, Reoxygenation, Repopulation, and Radiosensitivity—play a major role in a patient’s response to radiation therapy and in tumor growth fraction and cell loss factor (Box 16.2 The “Five Rs” of Radiobiology). Different types of radiation therapy may be indicated depending on the disease and the patient. In this chapter, we discuss various types of radiotherapy, addressing the indications, standard dosing, and typical patient response for each.
Box 16.2 The “Five Rs” of Radiobiology
Repair (of sublethal damage): Time period required for healthy cells to repair
Redistribution: Process of waiting for surviving tumor cells to enter more sensitive phases of the cell cycle, so that future radiation doses can kill them
Reoxygenation (of tumor cells): Occurs in tumor cells, but not in normal tissue. Tumor cells are generally hypoxic, but tumor cells with high intracellular oxygen concentration are more susceptible to radiation. During fractionated radiation treatment, oxygenated tumor cells are killed by early doses. The oxygen freed by this process can then diffuse to the radiation-resistant cells, oxygenating them and making them easier to kill at the next round of treatment
Repopulation (of normal tissue): Repopulation of stem cells and mature cells by surviving stem cells is a key factor in regaining tissue function after treatment
Radiosensitivity: Sensitivity or susceptibility of different cell types to X-rays or other sources of ionizing radiation
16.2 Types of Radiotherapy
16.2.1 External Beam Radiation Therapy
External beam radiotherapy delivers radiation from a distance to a defined target.
Can be administered postoperatively or as an alternative to surgery
May be given concurrently with chemotherapy
Indicated in most types of malignancies
Involves daily treatment over the course of several weeks to deliver radiation to the affected area
Specific indications for radiotherapy in the central nervous system (CNS) are discussed later in this chapter
External Beam Radiotherapy Techniques Used in the Central Nervous System
Craniospinal irradiation (CSI)
Irradiates the entire subarachnoid space
Technically challenging
Frequently used in management of pediatric patients with tumors of the CNS
Whole brain irradiation (WBI)
Irradiates the entire brain
Partial brain irradiation
Radiation directed at the primary tumor site and edema, plus an additional margin determined by protocol or by the treating physician
Most commonly used in adult patients with tumors of the CNS
Different techniques are used to plan the treatment course for tumors of the CNS. Modern computer technology has made three-dimensional (3D) treatment planning possible.
Conformal radiotherapy (CRT)
Also known as 3D-CRT
Refers to the use of a patient’s 3D geometry to select beam directions, determine doses, design beam apertures, evaluate plans, and verify effectiveness of treatment
Intensity-modulated radiation therapy (IMRT)
Uses the same technology as in CRT, but creates beams of varying intensities, compared with the uniform doses contained in each 3D-CRT beam
Both 3D-CRT and IMRT are intended to apply a lethal dose of radiation to the tumor while sparing normal surrounding tissue. These methods are used to treat most tumors of the CNS
16.2.2 Fractionation
Fractionation of treatment takes the total required dose of radiation and separates it into a number of equal daily treatments. Fractionation can reduce both acute side effects and late reactions to radiation.
Spares normal tissue, as cells can repair and repopulate between doses of radiation
May increase cancer cell damage due to reoxygenation of tumor cells between cycles. Reoxygenated tumor cells are more responsive to radiation treatment than hypoxic tumor cells
Time between doses allows for reassortment of tumor cells into more radiosensitive cell cycles
High-dose fractionation administered in a short period of time is likely to produce severe acute side effects, which may jeopardize completion of the radiation treatment
Conventional fractionation usually involves one treatment per day, 5 days per week, at a dose of 1.8 to 2.2 Gy/fraction
Hyperfractionation is a type of treatment designed to reduce late side effects. Patients undergoing hyperfractionation usually receive two treatments per day, roughly 6 hours apart
Accelerated fractionation, also called hypofractionation, decreases overall treatment time but can increase acute effects both to tumor tissue and normal tissue
16.2.3 Stereotactic Radiosurgery
The word stereotactic refers to precise localization of a specific target point based on 3D coordinates derived either from imaging or from external devices. Stereotactic radiosurgery (SRS) is a treatment strategy in which narrow beams of radiation are focused on a precise target and deliver a high dose of localized radiation to that target (Box 16.3 Stereotactic Radiosurgery).
If the dose gradient (i.e., the degree to which beams are focused on the target and spare surrounding tissues) is very steep at the edges of target, a single dose can cause tumor necrosis
Fractionated SRS refers to stereotactically guided high-dose radiation administered to a precisely defined target over the course of two to five separate treatment sessions
There are many different modalities for SRS, including Gamma Knife (Elekta Instruments, Inc., Crawley, UK), LINAC-based SRS, CyberKnife (Accuray, Sunnyvale, CA), and proton beam SRS.
Types of lesions/disorders
Arteriovenous malformation
Benign or malignant tumor
Brain metastasis
Trigeminal neuralgia
Vestibular schwannoma
Indications
Adjuvant to surgery or EBRT
Alternative to surgery
Primary management in selected patients
Recurrent lesions
Subtotal resection of lesions
Key requirements for optimal stereotactic irradiation
Accurate radiation delivery
Exclusion of sensitive structures
High conformity of lesion
Sharply defined target
Small target/volume
Gamma Knife
The Gamma Knife system is a machine that contains 192 sources of cobalt-60 radiation (Video 16.1)
Radiation sources are oriented in such a way that all beams converge at a single point, referred to as the isocenter
Target accuracy is between 0.1 and 1 mm
A rigid head frame is used to limit motion during treatment. This frame, which is essential for treatment, means that Gamma Knife treatment is limited to targets in the head or upper cervical spine
Frame-based methodologies such as Gamma Knife are the gold standard for SRS
LINAC-Based Stereotactic Radiosurgery
Similar to Gamma Knife, but multiple noncoplanar arcs of radiation are used instead of cobalt sources
Multiple arcs of radiation intersect at the isocenter, resulting in high doses at the beam convergence with the surrounding normal tissue receiving only a minimal dose
CyberKnife
Device that uses an image-guided robotic system with a mobile linear accelerator
Uses the skeletal structure of the body as a reference frame for targeting, instead of a rigid head frame
Proton Beam Therapy
This type of therapy involves the use of protons instead of X-rays to target tumors. These charged particles (i.e., protons) cause the most ionization at energy-dependent depth
Almost no exit dose; therefore, a smaller volume of normal tissue is exposed
This is a very expensive technology and is currently only available at a limited number of centers
16.2.4 Internal Radiation
Internal radiation, or brachytherapy, involves surgical implantation of a radioactive source in or beside a tumor.
Implanted during surgery or through a device (i.e., a catheter)
Delivers a large dose of radiation to the tumor volume, with rapid fall-off in surrounding tissues
Source works by releasing low-dose radiation for duration of the life of the isotope
The isotope most commonly used in internal radiation procedures is iodine-125
Interest in brachytherapy has waned with the advent of IMRT, 3D-CRT, and SRS, as these treatment options offer greater radiobiological and dosimetric advantages compared with brachytherapy
Studies have failed to demonstrate the efficacy of brachytherapy in the treatment of malignant gliomas
16.3 Indications for Radiation Therapy in the Central Nervous System
Radiation therapy may be used to treat both benign and malignant conditions of the CNS; see also Chapter 7: Tumors.
Tumors of the brain, supporting structures, and spine vary widely from benign to malignant
Primary and metastatic tumors arising from or affecting these structures are of great interest to radiation oncologists, due to their sensitivity to radiation therapy (▶ Table 22.1)
Even tumors that are pathologically benign may be life threatening due to their location or effect on surrounding structures. See Box 7.3: Benign Tumors in Chapter 7: Tumors
Normal tissue in the CNS is often incapable of regeneration, which may make complete surgical resection or high doses of radiation unsafe
Tumors of the spinal cord may be treated differently than tumors of the brain due to the increased dose tolerance of the spinal cord and its location
Malignant tumors | Benign tumors | Functional disorders |
Astrocytoma: grades I–IV Oligodendroglioma Oligoastrocytoma Ependymoma Medulloblastoma Primitive neuroectodermal tumor Chordoma/chondrosarcoma Primary CNS lymphoma Hemangiopericytoma (solitary fibrous tumor) Pineal region tumor Metastatic tumor | Meningioma Pituitary adenoma Arteriovenous malformation Cranial nerve and spinal cord schwannoma Neurofibromatosis Craniopharyngioma Glomus jugulare Paraganglioma Hypothalamic hamartoma | Trigeminal neuralgia |
Abbreviation: CNS, central nervous system. | ||
16.3.1 Dosing
Most primary adult tumors are treated with partial brain irradiation using conventional fractionated EBRT (e.g., IMRT, 3D-CRT).
General guidelines call for doses of 50 to 54 Gy for benign/low-grade lesions of the CNS and 60 Gy for malignant primary lesions of the CNS
Dosage to the optic nerves, optic chiasm, brainstem, and spinal cord is a limiting factor as injury can occur after high doses. More sophisticated technologies and novel fractionation may be indicated
Prior CNS surgery or radiation therapy, comorbidities, advanced age, smoking history, and tumor location may be contraindications for radiation therapy, given they may increase the risk for radiation-induced injury
The decision to treat a specific tumor is based on many factors, including the following:
Patient’s age
Patient’s medical history
Tumor pathology and location
Extent of tumor resection
Physician judgment (▶ Table 22.2)
Radiation dose constraints are based on many factors, including the following:
Patient’s history
Tumor pathology and location
Physician’s judgment (▶ Table 22.3)
Patients may receive a combination of both EBRT and SRS
Type of lesion/tumor | Radiation treatment recommendations |
Glioblastoma multiforme | EBRT up to 60 Gy, concurrent with chemotherapy using temozolomide (Temodar) |
Anaplastic astrocytoma | EBRT to 60 Gy, concurrent with chemotherapy |
Anaplastic oligodendroglioma | EBRT to 60 Gy, either sequential to (standard) or concurrent with chemotherapy |
Low-grade astrocytoma | EBRT to 54 Gy vs. observation if GTR of tumor |
Oligodendroglioma | EBRT vs. chemotherapy vs. observation |
Pituitary adenoma | Nonfunctioning: observation vs. SRS or EBRT up to 45–50 Gy Functioning (secretory): observation vs. medical management vs. SRS or EBRT |
Meningioma | Grade I: Observation vs. SRS to residual Grade II or anaplastic: EBRT or SRS to residual Inoperable: EBRT or SRS alone Recurrence: EBRT or SRS as salvage |
Ependymoma (including anaplastic) | If GTR: radiotherapy up to 54–60 Gy Subtotal resection with positive CSF culture: CSI up to 36 Gy, with additional dose to gross disease up to 54–60 Gy, if needed Recurrence: EBRT if no prior radiotherapy; SRS for salvage |
Metastases | WBI up to 30–37.5 Gy vs. SRS alone for fewer than four metastatic lesions Spine: EBRT up to 30–45 Gy Recurrence: SRS as salvage vs. repeat WBI |
Arteriovenous malformation | SRS as adjuvant therapy (or when surgical resection/embolization are not possible) |
Vestibular schwannoma | SRS for small lesions, adjuvantly for residual tumor or recurrence |
Primary CNS lymphoma | Chemotherapy vs. WBI up to 45 Gy (radiotherapy is rarely undertaken due to potential neurotoxicity, but may be used in cases of recurrence) |
Medulloblastoma | Standard risk: reduced-dose CSI concurrent with chemotherapy up to 23.4 Gy with additional dose to posterior fossa to 54 Gy, if needed High risk: CSI up to 36–39 Gy with posterior fossa and metastases boosted to 54 Gy, plus chemotherapy |
Abbreviations: CNS, central nervous system; CSF, cerebrospinal fluid; CSI, craniospinal irradiation; EBRT, external beam radiotherapy; GTR, gross total resection; Gy, gray; SRS, stereotactic radiosurgery; WBI, whole brain irradiation. | |
Site | Maximum tolerance dose |
Whole brain | 60 Gy |
Partial brain | 60–70 Gy |
Brainstem | 54 Gy |
Spinal cord | 45–55 Gy |
Optic chiasm | 50–54 Gy |
Retina | 45 Gy |
Optic lens | 10 Gy |
Abbreviation: Gy, gray. | |
16.4 Preparation for Treatment
Whether the patient is undergoing intracranial or extracranial radiation treatment, the patient must undergo treatment simulation. The treatment planning session usually takes place a few days before the start of therapy, unless radiation must occur in an emergent manner. With some SRS techniques (e.g., Gamma Knife), planning and treatment occur on the same day.
16.4.1 Simulation
Patients undergoing EBRT require treatment simulation. This establishes a reproducible treatment position upon which daily radiation treatments will be modeled. This is a necessary part of any radiation treatment to ensure the accurate dose is delivered to the intended target.
The ability to reproduce the position at each treatment session is critical to ensure the tumor receives the maximum radiation dose and normal surrounding tissue suffers only minimal damage
A thermoplastic mask is fabricated for each patient for customized immobilization
Imaging studies such as computed tomography and, in some cases, magnetic resonance imaging (MRI) are performed to better define tumor volume and normal surrounding critical structures
Simulation of radiation therapy for the spinal cord is similar. However, rather than the mask used in patients receiving cranial radiation, patients receiving spinal cord radiation receive permanent marks (i.e., tattoos) on the skin to ensure consistent positioning for treatment
16.4.2 Simulation for Steriotactic Radiosurgery
It depends on the type of SRS
CyberKnife simulation is similar to the simulation described earlier for EBRT. It involves a meticulous stereotactic planning process, rigorous quality assurance, and supervision of simulated radiation delivery
Patients undergoing Gamma Knife and CyberKnife procedures generally require collaborative treatment planning from radiation oncologists, neurosurgeons, and radiation physicists
16.4.3 Potential Side Effects
Radiation treatment is a form of local therapy, so side effects are generally confined to the treatment region.
Acute side effects usually do not manifest until after 2 to 3 weeks of treatment
Patients are monitored for side effects during treatment, and those side effects are managed as they occur in an effort to keep the patient comfortable, to reduce complications, and to help prevent prolonged treatment breaks
Patients may experience emotional reactions to diagnosis and therapy, including fear, depression, and anxiety. Education, counseling, and medication should be offered as indicated to ameliorate these emotions
Early Side Effects
Acute Alopecia
Alopecia is hair loss that occurs approximately 3 to 4 weeks into conventional therapy. It occurs as the result of radiosensitivity of the hair follicles and glands
May occur after doses as low as 5 Gy and is usually temporary
Doses of 45 Gy or greater may cause permanent hair loss or delayed regrowth
Alopecia occurs regionally in the path of the radiation beam
Hair loss over the entire scalp occurs after WBI
Acute Radiation Myelopathy
May occur after radiation to the spinal cord; involves transient demyelination of the myelin-producing oligodendroglial cells in the targeted spinal cord segment
May occur as transient phenomenon
Acute myelopathy is clinically manifested by momentary electric shock–like sensations and numbness from the neck down to the extremities when the neck is flexed (i.e., Lhermitte’s sign)
Early delayed myelopathy usually occurs 1 to 6 months after cessation of radiotherapy, and often resolves within 6 to 12 months
Cerebral Edema
Most commonly occurs when large doses of radiation are delivered to the brain
Incidence of cerebral edema increases with higher doses per fraction (between 1.8 and 2.0 Gy is generally a well-tolerated dose)
Potential for cerebral edema increases if patients are weaned off steroids too rapidly after surgery (Box 16.4 Clinical Alert: Treatment-Related Toxicities)
Symptoms include headache, nausea, vomiting, and decreased neurologic function
Box 16.4 Clinical Alert: Treatment-Related Toxicities
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