CHAPTER 3

Basics of Radiation Therapy

Ryan K. Funk, MD*, Abigail L. Stockham, MD,
Nadia N. Issa Laack, MD, MS

INTRODUCTION of radiation. This section describes types of radia-

William Roentgen received the first Nobel Prize tion, radiation sources of radiation, and how radi-
in physics for his discovery of radiographs in ation is deposited in tissue.
1895. It was quickly recognized that radiographs
had the potential to cause damage to living tis-
sues, and within 1 year, radiographs were used TYPES OF RADIATION
in the treatment of breast cancer. Early radiation Radiation is defined as the emission and propaga-
treatments were groundbreaking in their time, tion of energy through space or matter. For the
but the techniques were crude by modern stan- purposes of therapy, radiation can be divided
dards. For example, early dose measurements into electromagnetic (EM) radiation and particle
were based on daily changes in skin color. This radiation. EM and particle radiation can be gener-
crude measure of dose to the skin correlates ated using accelerators (eg, linear accelerators
roughly with dose to underlying tumors, but the [linacs], cyclotrons, or synchrotrons) or by radioac-
dose to produce skin erythema varies between tive materials undergoing decay.
patients. Furthermore, early radiation treatment
modalities delivered relatively high surface doses Electromagnetic Radiation
(ie, skin dose) compared with dose to deeper EM radiation is a form of energy propagation
areas, where most tumors are found. In addition, where photons with both particle and wavelike
radiobiology, the study of the biologic effects of properties travel at the speed of light.1 EM waves
radiation on living tissues, was in its infancy, and carry energy and transfer their energy upon inter-
early predictions regarding normal and tumor action with matter. The energy associated with
response to radiation were unreliable. The inter- EM radiation is proportional to frequency and
vening century has resulted in discoveries by phy- inversely proportional to wavelength. Thus, EM
sicians and radiobiologists that have improved waves with shorter wavelengths have more
the understanding of radiobiology. Technological energy. Examples of EM radiation (from lowest
advances, facilitated by radiation physicists, engi- to highest energy) include radio waves, micro-
neers, and physicians, have resulted in tech- waves, infrared, visible light, UV, and radiographs
niques that allow for greater precision in (Fig. 3.1). EM radiation can be further divided into
radiation dose calculation and treatment deliv- ionizing and nonionizing radiation. EM radiation
ery. This chapter reviews the basic underpinnings at or below the UV spectrum is nonionizing,
of radiation therapy and practical aspects of whereas radiographs are ionizing. Ionizing EM
modern radiotherapy. Potential side effects has enough energy to remove tightly bound elec-
from radiotherapy are explored in depth in a trons from an atom or molecule. The release of
separate chapter. bound electrons leads to the generation of ions
and free radicals. Within living cells, ions and
free radicals interact with cellular machinery and
BASIC PHYSICS cause DNA damage, which can ultimately lead
A basic understanding of the physical properties to cell death. Radiotherapy uses ionizing radiation
governing radiation therapy aids in a clinician’s in order to cause damage to tumor cells. The pho-
appreciation of the characteristics of radiation tons used for therapeutic radiation generally have
that lead to therapeutic and deleterious effects wavelengths of 10 11 to 10 13 m (see Fig. 3.1).1

Department of Radiation Oncology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
* Corresponding author.
E-mail address: [email protected] 39
40 Section I Oncology and Hematology Principles for the Cardiologist

Fig. 3.1 The EM spectrum. The energy per photon increases as frequency increases and wavelength decreases.
High-frequency, short-wavelength (eg, high energy) radiation is used for radiotherapy. (From Franck P, Henderson
PW, Rothaus KO. Basics of lasers: history, physics, and clinical applications. Clin Plast Surg 2016;43(3):505–13; with
permission.)

Particle Radiation therapeutic radiographs. A radiograph tube has

Particle radiation refers to energy carried by fast- an anode and a cathode. A voltage applied across
moving electrons, protons, neutrons, or other the tube releases electrons from the cathode.
atomic nuclei (ie, carbon). Beams of these particles These electrons are directed at the cathode and
are generated using linear accelerators (electrons) the interaction between the electrons and the
or cyclotrons/synchrotrons (protons, neutrons) cathode generates radiographs. The maximum
and then directed at the target. As the particles energy of the resulting photons is equal to the
interact with matter, they deposit energy in a voltage applied across the radiograph tube.
pattern specific to the particle and the composi- Radiograph tubes are able to generate kilovolt-
tion of the target medium. age beams but not higher-energy megavoltage
beams.

SOURCES OF RADIATION Accelerators

Radioactive Decay Megavoltage photon and electron beams and
Radioactive decay is another important source of particle beams are generated by various accelera-
therapeutic radiation. Radioactivity is a phenome- tors including linear accelerators (for electrons
non whereby radiation (in the form of EM radia- and photons), cyclotrons (heavy particles), and
tion, particle radiation, or both) is generated by synchrotrons (heavy particles). A full discussion
the transition of an unstable, high-energy atomic of how these machines work is beyond the scope
nucleus to a more stable, lower-energy state.1 of this chapter but a detailed description can be
The rate of decay can be communicated in terms found in Khan, chapter 26.1 As linear accelerators
of the half-life, which is defined as the time it takes are the most commonly used accelerators for
for half of the radioactive particles to undergo radiotherapy, a brief description of their function
decay. The half-life for each specific isotope is is provided.
constant. Radioactive isotopes may emit several Linear accelerators (Fig. 3.4) use EM fields to
types of radiation, but, for therapeutic purposes, accelerate a beam of electrons. The accelerated
the most relevant are a particles (helium nuclei), electrons can be used directly for treatment or
b particles (electrons), and g rays (photons). can be used to generate radiographs that are
Radioactive decay continues to provide the then used for treatment. Most modern radio-
source of radiation for most brachytherapy treat- therapy units can treat using either electrons or
ments and for units using cobalt-60 as a source radiographs. Electrons gain energy as they accel-
(Gamma Knife machines [Elekta AB, Stockholm, erate. Once the beam is accelerated to the treat-
Sweden] and older external beam radiotherapy ment energy, electromagnets then direct the
machines) (Fig. 3.2). Because they constantly electron beam into the treatment head of the
decay, radioactive sources must be periodically machine and toward the patient. At this point,
replaced. the beam is only about a millimeter in cross sec-
tion. Because therapeutic areas, or targets, are
Radiograph Tubes much larger than the size of the small beam, steps
Radiograph tubes (Fig. 3.3) are used to are taken in the treatment head to spread the
generate diagnostic radiographs and low-energy beam out to cover a larger area (generally up to
 Chapter 3 Basics of Radiation Therapy 41

Fig. 3.2 Gamma Knife radiosur-

gery unit. A Gamma Knife radio-
surgery unit is used to deliver
high doses of radiation to small
areas in the brain (see SBRT dis-
cussion in this chapter). Radioac-
tive decay of cobalt-60 provides
the radiation for this type of
treatment. Radiation from the co-
balt sources is shielded, or
blocked, when the device is not
delivering treatment. The shield-
ing moves to open small channels
for the delivery of multiple small
radiation beams that are focused
on a small area. The small area
of high dose is focused on the tu-
mor (or other treated abnormal-
ity). The surrounding brain tissue
receives much less dose. Cobalt
has a half-life of 5.27 years.
Without replacement of the co-
balt sources, the dose delivered
per unit time will drop by half, and the treatment time needed to deliver a specific dose will double every
5.27 years. (Copyright ª Mayo Foundation for Medical Education and Research. All rights reserved.)

40 cm  40 cm in modern radiotherapy units).2 If of radiographs. These radiographs pass through

the patient is to be treated with photons, a metal a flattening filter to ensure relatively homogenous
target is placed in the beam path (Fig. 3.5A). Elec- dose to the center of the field compared with ob-
trons strike the target and, secondary to physical jects further from the center. For treatment with
characteristics of radiation, result in generation electrons, the radiograph target is removed

Fig. 3.3 Radiograph tube. An electron beam travels from the cathode and hits the target on the anode resulting in
the generation of radiographs. In this figure, a spinning anode is used to dissipate heat. (Courtesy of Dr Matt Skalski,
Los Angeles, CA.)
42 Section I Oncology and Hematology Principles for the Cardiologist

Fig. 3.4 Modern linear accelerator. (A) A linear accelerator and treatment table. This model can generate megavolt-
age images for patient position verification using radiographs from the treatment head. The detector for megavolt-
age imaging is the retractable panel positioned under the head of the treatment table. (B) The gantry can rotate
360 to provide treatment from any angle. This model has the ability to generate kilovoltage images for patient po-
sition verification. The kilovoltage radiograph tube and detector are set at 90 to the treatment beam. Kilovoltage
imaging allows for higher contrast images compared with magavoltage images. Please refer to the section on IGRT
in this chapter for further details. (Courtesy of Varian Medical Systems, Palo Alto, CA; with permission.)

from the beam path and the electron beam is beam of the appropriate size and shape for treat-
spread out using a beam spoiler (Fig. 3.5B). After ment. Further discussion of treatment field
the flattening filter or scattering foil, the beam is shaping can be found later in the Intensity-
collimated using metal blocks to generate a Modulated Radiation Therapy section.

Fig. 3.5 Components of a treatment head. (A) Radiograph treatment mode. The electron beam hits the radiograph
target and generates radiographs. The primary collimator shapes the beam to the desired size. The flattening filter
improves dose homogeneity. The ion chamber measures dose. The secondary collimator shapes the beam further.
Further modifications to the beam profile can be made by adding wedges or blocks (discussed in the Specific Mo-
dalities section of this chapter). (B) Treatment head components for electron treatment. The scattering foil converts
the narrow electron beam into a broad beam. The ion chamber measures dose. Collimation, or beam shaping, is
achieved with the secondary collimator and the electron applicator. (From Zeman EM, Schreiber EC, Tepper JE. Ba-
sics of Radiation Therapy. In: Niederhuber JE, Armitage JO, Doroshow JH, et al, editors. Abeloff’s Clinical
Oncology. Fifth edition; 2014. p. 396; with permission.)
 Chapter 3 Basics of Radiation Therapy 43

RADIATION INTERACTIONS IN THE BODY the body is important. Depth dose curves are
Radiation-induced Cellular Damage used to graphically represent energy deposition
Radiation is thought to act primarily at cellular as radiation hits the surface of an object and
and molecular levels. Ionizing radiation traverses then travels through that object (ie, the patient).
the entirety of a cell and has the potential to The specific pattern of dose deposition depends
interact with all of the cellular contents. However, on the type of radiation, the initial energy of the
the consequences of radiation on cellular func- beam, and the composition of the interposing
tions appear to be mediated primarily by matter. In general, higher energy beams are
radiation-induced DNA damage. Direct damage more deeply penetrating, which means that these
occurs as the result of interaction between the beams are often used for treating deep-seated tu-
incident radiation and the DNA molecule to mors. The following sections describe dose depo-
cause single- or double-strand breaks. Indirect sition for commonly used radiation beams.
damage occurs when ionizing radiation interacts
with water molecules to generate hydroxyl ions. Orthovoltage Photon Beams
These ions, in turn, interact with DNA to cause Orthovoltage and megavoltage refer to the en-
strand breaks. Large particles (protons, a parti- ergy of the photons or particles used in a treat-
cles) primarily cause direct damage, whereas ment beam. Orthovoltage photon beams have
photons and electrons primarily act via indirect peak energies in the range of 10 to 400 kV poten-
damage.3 tial (kVp) with most modern commercial units
operating in the 50- to 150-kVp range.4 The sur-
Dose Deposition face dose for orthovoltage photons is nearly
The amount of DNA damage caused by a partic- 100% of maximum with very rapid dose falloff
ular beam is proportional to the dose; therefore, (Fig. 3.6). For example, the relative dose of a
an understanding of how dose is distributed in 50-kVp radiograph beam at 2-, 10-, and 20-mm

Fig. 3.6 Percentage depth dose curves for kilovoltage radiograph beams with energies of 50 to 280 kVp. The dose
at the surface is nearly 100% for beam energies in the kilovoltage range. Half value layer (HVL) refers to the thickness
of a material to attenuate half of the beam energy. Al, Aluminum; Cu, Copper. (From Hill R, Healy B, Holloway L,
et al. Advances in kilovoltage x-ray beam dosimetry. Phys Med Biol 2014;59(6):R185. http://dx.doi.org/10.1088/
0031-9155/59/6/R183. ª Institute of Physics and Engineering in Medicine. Reproduced by permission of IOP Pub-
lishing. All rights reserved.)
44 Section I Oncology and Hematology Principles for the Cardiologist

depth is approximately 98%, 73%, and 49% of proton beam has an initial plateau that sharply in-
maximum, respectively. The relative dose for a creases at the end of the proton range and then
280-kVp radiograph beam at 2-, 10-, and 20-mm falls off rapidly. The sharp increase in dose depo-
depth is approximately 99%, 93%, and 82%, sition is referred to as the Bragg peak. The width
respectively, and drops to 50% by 5-cm depth.4 of the Bragg peak from a monoenergetic beam is
Before the invention of higher-energy treatment too narrow to cover most clinical targets so multi-
machines, orthovoltage machines were used to ple beams of decreasing energy are used to pro-
treat even deep-seated tumors. In the modern vide a wider area of high dose. The summation of
era, however, orthovoltage beams are used these beams is referred to as a spread-out Bragg
almost exclusively to treat skin cancers.5 peak7 (SOBP; Fig. 3.8). The width of the SOBP is
designed to cover the proximal and distal ends of
Megavoltage Photon Beams the target.
Megavoltage photons (typically with energies of 4–
20 MV) are more penetrating than orthovoltage
photon beams and reach their maximum doses at RADIATION TREATMENT PLANNING AND
varying depths depending on the energy6 DELIVERY
(Fig. 3.7). Megavoltage photons deliver a lower Radiation treatment relies heavily on technologies
relative dose to the surface than electrons or low- that allow for accurate planning and delivery of
energy photons and are thus commonly referred the desired dose. This section reviews various
to as “skin-sparing.” Modern teletherapy machines common planning and treatment methods used
(ie, linacs) operate in the megavoltage range. by the radiation oncologist.

Megavoltage Electron Beams Types of Radiation Treatment Delivery

Electrons used for radiotherapy typically have en- Various terms used in describing radiation therapy
ergies of 6 to 25 MeV. They reach their maximum delivery are summarized in Table 3.1. Telether-
dose at 1 to 3 cm within the target and have a rela- apy, or external beam radiation (EBRT), refers to
tively rapid dose falloff thereafter6 (see Fig. 3.7). the delivery of radiation from a source external
Because of their rapid falloff, electrons can be to the patient. EBRT is the most common form
used to treat relatively superficial targets (such of radiation therapy delivery. Photons, electrons,
as internal mammary lymph nodes) with relative protons, and neutrons can be used for EBRT.
sparing of the deeper tissues compared with Most modern EBRT machines are isocentric. Iso-
megavoltage photons. centric machines rotate around a point, called
the isocenter, and the center of the radiation
Proton Beams beam is at the isocenter (Fig. 3.9). An isocentric
The depth of maximum dose deposition for pro- setup allows for precise calculations when deter-
tons depends on the initial energy of the proton mining the relationship between patient position
beam. The depth dose curve for a monoenergetic and treatment machine position.

Fig. 3.7 Percentage depth-dose

curves for megavoltage radio-
graph and mega-electron voltage
beams. Photon beams (6 MV and
18 MV) deliver less dose at the
surface (depth 0 cm) compared
with electron beams. Electron
beam penetration increases with
increasing energy from 6 MeV to
20 MeV, but these beams drop
off much more rapidly than
MV photon beams. Penetration
of radiograph beams also in-
crease as the energy increases
from 6 MeV to 18 MV. Note
the change in x-axis scale
compared with the correspond-
ing orthovoltage figure. (From
Brengues M, Liu D, Korn R, et al.
Method for validating radiobiological samples using a linear accelerator. EPJ Tech Instrum 2014;1(1):4; with
permission.)
 Chapter 3 Basics of Radiation Therapy 45

Fig. 3.8 Depth-dose curves for

proton beams. Depth-dose curves
for a SOBP (red), the constituent
pristine proton beams of
decreasing energy (blue), and a
10-MV photon beam (black). The
SOBP is a summation of the dose
from the constituent pristine
proton beams. The SOBP in this
example could treat a target area
spanning approximately 5- to
15-cm depth. The surface dose
(depth 0 mm) is higher for SOBP
than for the 10-MV photon beam
or the individual constituent
beams. (From Levin WP, Kooy H,
Loeffler JS, DeLaney TF. Proton
beam therapy. Br J Cancer
2005;93(8):850; with permission.)

Beams from the treatment machine are colli- standard conditions, and then these standard
mated, or shaped, to match the shape of the measurements are used to inform dose calcula-
target volume. Early radiotherapy machines had tions in patients. The absorbed dose (commonly
relatively rudimentary collimators, or collimation referred to as simply “dose”) is measured in units
was achieved by creating custom high-density of gray. A dose of 1 Gy is defined as the absorption
cut-out blocks that were either attached to the of 1 J of energy per kilogram of matter. Historically,
treatment machine or placed on the patient. dose was reported in units of rads (radiation
Modern treatment machines have multiple colli- absorbed dose). One rad is equivalent to 1 cGy
mators that can move during treatment to better (one-hundredth of a gray, cGy).
shape the dose. Further specifics of EBRT delivery
are discussed later in the chapter.
Brachytherapy refers to delivery of radiation RELATIVE BIOLOGICAL EFFECTIVENESS
from sources placed inside or very near the patient. Different types of radiation have different biologic
The primary advantage of brachytherapy is that ra- effects. As a consequence, equivalent absorbed
diation exposure from a point source decreases doses of different types of radiation may have
proportional to the inverse square law. That is, different biologic effects. Relative biologic effec-
exposure is proportional to 1/r2 at a distance r tiveness (RBE) is defined as the ratio of doses of
from the source. Thus, high doses can be delivered standard (Ds) and test (Dr) radiation to provide
to the tumor with nearby organs receiving much equivalent biologic effect (RBE 5 Ds/Dr). The
lower dose. For example, if dose is prescribed to selected biologic effect may be cell killing, muta-
1 cm from a single source, then the dose at 2 cm tion, or another biologic endpoint. Historically,
will be 25% of the prescribed dose. For more com- the standard radiation was 250-kVp radiographs,
plex brachytherapy treatments using multiple although sometimes the RBE comparison is
sources, the dose falloff is not as steep as for a sin- made with cobalt-60 g rays.1 Relative to 250-kVp
gle source, but the falloff typically surpasses what radiographs, the RBE of protons (RBE 5 1.1)
can be achieved with external treatments. and neutrons (RBE 5 1–2) is higher, whereas the
RBE of megavoltage photons (RBE 5 0.85) is
lower.8 Doses for proton therapies are often re-
RADIATION TREATMENT PARAMETERS ported in units of “cobalt Gray equivalent”
Dose (CGE) in order to make the comparison between
Early radiation oncologists used the skin on their proton and megavoltage photon plans simpler.9
arms to estimate dose. The dose required to pro-
duce a pink, sunburnlike reaction was called the Dose Prescription
“erythema dose” and was considered an appro- Before the development of volumetric
priate daily dose. Modern dose is measured under radiation planning, targets were delineated on
46 Section I Oncology and Hematology Principles for the Cardiologist

TABLE 3.1
Terms describing methods of radiation therapy
Modality Brief Description Examples
Brachytherapy The placement of sealed radioactive
sources into or immediately
adjacent to tumors.
LDR The use of low-activity sources for Permanent: Prostate seed implant
brachytherapy. The implant may Temporary: Cervical cancer
be permanent or temporary. (historical in United States as most
Patients are hospitalized for the centers now use HDR)
duration of temporary implants
(usually 24–96 h).
HDR The use of high-activity sources for Cervical cancer (most centers in
brachytherapy. A device called an United States)
afterloader is used to advance the Accelerated partial breast
radioactive source into the patient irradiation (APBI) using balloon-
to deliver dose. After the specified based or multichannel based
dose is delivered, the afterloader brachytherapy
retracts the radioactive source.
The treatment takes minutes to
deliver.
Intracavitary Isotopes are placed into a natural or APBI using balloon- or multichannel-
artificial body cavity. based brachytherapy
Interstitial Isotopes are embedded directly in Prostate seed implant
the tumor.
Teletherapy (EBRT) Treatment using an external source
of radiation.
Conventional Delivery of daily doses of Conventionally fractionated lung,
fractionation w1.8–2 Gy. The total dose is breast, or esophageal cancer
typically delivered over 4–8 wk. treatment
IGRT The use of imaging in the treatment
room to verify patient position.
Hypofractionation Delivery of doses >2 Gy per day. Hypofractionated whole breast
May be delivered on consecutive radiotherapy
days, every other day or weekly.
Hyperfractionation The total dose is divided into smaller Early-stage small-cell lung cancer
doses and treatments are given
more than once per day.
SBRT The use of high doses per fraction Early-stage (node negative) non–
(usually 6–24 Gy per fraction). small-cell lung cancer
SBRT uses advanced
immobilization, image-guidance,
and treatment planning to
minimize dose to nearby normal
tissues.
SRS SBRT directed at the central nervous Limited brain metastases
system. May be delivered as a
single fraction or multiple
fractions.

2-dimensional films (2D), and the dose was often Fractionation

prescribed to the isocenter. Modern EBRT plans Most EBRT treatments require that total dose be
are typically designed using 3-dimensional (3D) divided into fractions that are delivered daily.
imaging, and dose is prescribed to the planning Normal cells typically have greater capacity for ra-
treatment volume (PTV) as described below. diation damage repair compared with tumor cells.
 Chapter 3 Basics of Radiation Therapy 47

Fig. 3.9 Isocenter of a gantry-

based radiotherapy machine. The
gantry, collimator, and table all
rotate around a single point, called
the isocenter. The center of treat-
ment beam is at isocenter. The
use of an isocenter allows for reli-
able and reproducible movement
of treatment machine with respect
to the patient. (From Bourland
JD. Radiation oncology physics.
In: Gunderson LL, Tepper JS, edi-
tors. Clinical radiation oncology.
3rd edition. Philadelphia: Saun-
ders; 2012. p. 98; with permission.)

Fractionation, or delivery of radiotherapy over radiation. A more complete discussion of side ef-
several different sessions, allows normal tissues fects will be addressed in a separate chapter. In
to recover between fractions to a greater degree brief, tumor and normal tissue response to ther-
than tumor cells. In general, fraction size (quantity apy and the likelihood of acute and late side ef-
of radiation delivered in a single treatment) corre- fects depend on the total dose, the dose per
lates with late toxicity, whereas acute toxicity is fraction, and the time elapsed for treatment.
more dependent on total dose. However, smaller The development of side effects is also depen-
fraction size also lowers the therapeutic effect on dent on patient-specific factors, such as prior in-
the tumor. Conventional fractionation typically re- sults to the irradiated tissue (eg, surgery or
fers to daily doses of 180 to 200 cGy, although pe- radiation), modifiable behavioral factors such as
diatric and lymphoma patients may be treated smoking, and nonmodifiable factors such as un-
with lower daily doses (w150 cGy). These doses derlying genetics. The dose-and–fractionation
were selected to try to balance tumor killing and schedule prescribed by the radiation oncologist
normal tissue sparing. Subsequent studies have attempts to maximize the therapeutic ratio
since shown that hypofractionation with daily (Fig. 3.10), that is, the ratio between the likeli-
doses of greater than 250 cGy per day are effec- hood of controlling the cancer and the likelihood
tive and without increased toxicity in certain clin- of causing side effects.
ical scenarios. Stereotactic body radiotherapy
(SBRT) (also called stereotactic ablative body radi-
ation, SABR) treats small, critically located targets PRACTICAL ASPECTS OF RADIATION
through high-dose-per-fraction treatments using THERAPY PLANNING AND DELIVERY
advanced immobilization and treatment planning Simulation
techniques to allow large quantities of radiation to Most patients will undergo a radiation planning
reach the tumors. A very steep dose-gradient session, called a simulation, days or weeks before
outside the target results in a much lower dose initiating radiation therapy. The purpose of the
to surrounding normal tissues. Palliative regimens simulation is multifold. First, it allows the radiation
are often hypofractionated, delivering large quan- oncologist to generate a reproducible setup so
tities of radiation over a small number of treat- that the patient is in the same position each day
ments, because late effects are unlikely to for treatment. Immobilization devices, often
develop within the patient’s lifetime. made of thermoplastics, vacuum-evacuated
Extensive effort has been dedicated to identi- bags, or quick-setting foam, are used to ensure
fying and quantifying normal tissue tolerance to reproducibility. Uncertainty in patient position
48 Section I Oncology and Hematology Principles for the Cardiologist

Fig. 3.10 Therapeutic ratio. The

probability of tumor control (red)
and normal tissue toxicity (blue)
can be plotted as a function of radi-
ation dose. The radiation oncolo-
gist seeks to deliver a plan that
delivers a high likelihood of cure
while minimizing the probability of
normal tissue toxicity. In this
example, the selected radiation
dose (dashed line) provides a high
probability of tumor control and
low probability of normal tissue
toxicity. Increasing the dose would
increase the probability of tumor
control at the expense of higher toxicity. Note that the curve shown is idealized and may not represent the clinical
reality. (From Citrin DE, Mitchell JB. Altering the response to radiation: sensitizers and protectors. Semin Oncol
2014;41(6):848–59; with permission.)

leads to uncertainty in the delivered dose, and the if prior therapy (surgery or chemotherapy) has
simulation is one effort to minimize this uncer- eradicated gross disease. The clinical target vol-
tainty. The simulation also allows imaging of the ume (CTV) identifies a target volume that accounts
area to be treated. These images are used to for microscopic disease spread. The shape and
identify the target volumes and normal tissues size of the CTV depend on the clinical features of
and for planning and dose calculations. Modern a particular disease entity but are often concerned
radiotherapy planning systems use tissue- with addressing adjacent draining nodal basins.
specific information from the computed tomo- The planning target volume (PTV) is usually a geo-
graphic (CT) scan to accurately calculate dose. metric expansion of the CTV to account for uncer-
Calculating dose without the tissue-specific infor- tainties in daily patient setup, organ and tumor
mation provided by CT can lead to differences be- motion, and radiation beam targeting. The size
tween the calculated dose and the actual dose of the PTV expansion depends on anticipated
delivered of up to 5% or more. setup uncertainties and the use of image guid-
ance. Predictable organ motion in certain parts
Target Volume Delineation of the body can be imaged dynamically in order
An integral part of modern radiation therapy treat- to assess tumor motion. For example, a 4-dimen-
ment planning is the identification of target sional CT (3 dimensions of space and the fourth
(Fig. 3.11) and normal tissue volumes (Fig. 3.12). dimension of time) may be obtained during plan-
Most modern treatment-planning systems use ning for targets in or near the lungs so as to assess
CT imaging for target volume delineation, treat- movement during breathing. This dataset pro-
ment planning, and dose calculation. Previously, vides information on the position of the tumor
target volumes were delineated on 2D images, and normal tissues during different phases of the
and calculations were based on patient anatomy respiratory cycle. These data can be used to
as measured at the time of simulation. MRI and expand the CTV to an internal target volume,
ultrasound can also be used for treatment planning which is then expanded to the PTV. If different
purposes, but dose calculations are generally car- areas of the patient are to be treated to different
ried out using a CT dataset. doses, then PTVs (and corresponding CTVs) for
Several factors influence the final volume to be each dose level will be delineated.
treated. These factors include the size and loca-
tion/tissue affected by the primary tumor and Normal Tissues
any visibly involved lymph nodes, the pattern of Normal tissues are also contoured on the simula-
disease progression for a particular disease tion CT (see Fig. 3.12). In the thorax, the most
type, tissue movement (eg, breathing motion, commonly delineated, or contoured, normal tis-
bladder/stomach distension), anticipated random sues include the heart, lungs, spinal cord, and
errors in daily patient setup, and known uncer- esophagus. If the patient is undergoing SBRT,
tainties in radiation beam targeting. the proximal bronchial tree, great vessels, and
The gross tumor volume (GTV) refers to visible chest wall may also be contoured. Contouring
tumor on imaging studies. The GTV may be absent normal structures allows the treatment software
 Chapter 3 Basics of Radiation Therapy 49

Fig. 3.11 Target volume delineation. Representative gross tumor volume (GTV) and clinical tumor volume (CTV)
contours for esophageal cancer (A) GTV (red) and CTV (yellow) for a distal esophageal cancer. The CTV encompases
potential microscopic submucosal and lymphatic spread. (B) Examples of contours encompassing specific nodal re-
gions. The CTV (yellow) encompasses at-risk nodal volumes (blue and purple) at each level. The volumes included
vary based on the location of the primary tumor and any grossly involved nodes. The CTV will be expanded to ac-
count for setup and treatment delivery uncertainty to create the planning treatment volume. The CTV-to-PTV expan-
sion is typically between 5-10 mm in all directions depending on the equipment being used. (From Wu AJ, Bosch
WR, Chang DT, et al. Expert consensus contouring guidelines for intensity modulated radiation therapy in esopha-
geal and gastroesophageal junction cancer. Int J Radiat Oncol Biol Phys 2015;92(4):914–6; with permission.)

to calculate the dose any target or normal tissue prescription dose) and contains any normal tissue
of interest receives. Radiation planning and deliv- constraints that the plan should meet. Radiation
ery techniques can then be used to maximize dosimetrists use treatment planning software to
target coverage while respecting normal tissue design a treatment plan that meets the goals
tolerances. specified in the prescription document. The soft-
ware or the dosimetrist selects beam arrange-
Treatment Planning ments that are likely to result in target coverage
Once target volumes and normal tissues are iden- while minimizing normal tissue dose. Iterative ad-
tified, the radiation oncologist prepares a pre- justments are made until an acceptable dose dis-
scription document that identifies the desired tribution is obtained. The final plan finds a balance
dose and fractionation schedule. The document between optimal target coverage and normal tis-
states the desired coverage to the treatment vol- sue sparing to maximize the likelihood of tumor
umes (eg, 95% of the PTV will receive 95% of the control and minimize the likelihood of side effects.
50 Section I Oncology and Hematology Principles for the Cardiologist

Fig. 3.12 Normal tissue contours.

Normal tissue contours allow the
planning system to calculate dose
to the specified tissues. IVC, infe-
rior vena cava. (Courtesy of Radia-
tion Therapy Oncology Group,
Philadelphia, PA; with permission.)

Creating an optimal plan requires knowledge of the time of treatment. These methods compare
how dose (quantity and volume) affects various positional data from the simulation to the treat-
tissues. Some organs are highly sensitive to the ment position data. After correct positioning
actual maximum dose, such as the spinal cord. and verification, treatment begins. During treat-
Other organs, such as the lungs, are more sensi- ment, the patient is encouraged to remain as
tive to the volume of tissue irradiated. Balancing motionless as possible. There is typically no
the need to deliver effective radiation therapy detectable sensation as the radiation is delivered.
doses to the treatment target and known accept-
able radiation limits (referred to as constraints) re-
sults in the challenge of a dosimetrist (or SPECIFIC MODALITIES
treatment planner) and a physician in balancing Photon Radiotherapy
the benefits of minimizing heart dose perhaps at Photons are by far the most used modality for
the expense of higher lung dose and vice versa. EBRT. Advances in treatment technique now
The treating radiation oncologist asks for allow for very conformal delivery of radiation.
coverage that is likely to balance risks to each of Because many cardiac sequelae may occur de-
these organs and minimize overall risk. Physicians cades after treatment, also discussed are
review the plan to confirm that it is clinically outdated methods of treatment delivery.
appropriate and ask for adjustments to the plan Although primitive by modern standards,
as needed. Medical physicists then perform qual- megavoltage machines of 1 MV were available
ity assurance measures to confirm that the actual as early as the 1930s. Cobalt machines (1.3 MV)
delivered dose distribution will match the calcu- and megavoltage linear accelerators (4–18 MV)
lated dose distribution. became available in the 1950s. Initially, treatment
field design was based on the physical examina-
Treatment Delivery tion and clinical judgment. As machines increased
Treatments are delivered with the patient in the in sophistication, 2D radiographic images were
same position as at the simulation. As noted used to define treatment volumes. Knowledge
above, there are uncertainties regarding organ of bony anatomy with respect to soft tissue coun-
motion, patient setup, and radiation beam deliv- terparts was used to identify appropriate target
ery that are accounted for by the PTV margin. volumes. Dose calculations were initially done by
The PTV margin takes into account the method hand based on measurements taken under con-
of localization to be used to verify correct position trol conditions. Radiation beams could be deliv-
at the time of treatment. In the modern era, many ered from multiple angles to maximize dose to
patients undergo daily imaging using radio- the target, but without 3D data (provided by a
graphs, a CT scan, or mounted cameras that eval- CT scan), the dose calculations were inexact.
uate the external surface contour of the patient at Limited dose shaping could be accomplished by
 Chapter 3 Basics of Radiation Therapy 51

placing high-density material of various shapes in leaf moves into the beam path, it attenuates, or
the beam path. Specific configurations (for blocks dose in that area. The individual MLCs
example, a wedge) were available that would pro- can be positioned independently to generate a
vide a calculable change to the dose profile under custom shape that blocks dose to areas outside
standard conditions. of the intended target volume. Once the beams
are arranged, dose is calculated and the dosimet-
Three-Dimensional Conformal Radiotherapy rist makes adjustments as needed to obtain the
3D conformal radiation therapy (3D-CRT) gained desired dose distribution. This method of planning
popularity in the 1990s as improvements in (as with 2D planning) is called forward planning
computing and imaging allowed for dose calcula- because the beams are arranged first and then
tions on 3D image sets (see https://www.astro. the dose distribution is calculated.
org/rtevolution/player.html). After delineation of
target volumes and normal tissues on the CT simu- Intensity-Modulated Radiation Therapy
lation images, multiple radiation beams are ar- IMRT is an advanced method of treatment plan-
ranged to maximize target coverage while ning and delivery. In contrast to 3D-CRT, IMRT
avoiding normal tissues (Fig. 3.13, left panel). uses inverse planning, meaning that target and
Wedges can be used (as in 2D treatment) to normal tissue constraints describing the desired
conform the shape of the distal edge of the dose distribution are transferred to the planning
beam to provide more uniform target coverage. software, which then uses algorithms to generate
In addition, multileaf collimators (MLCs) in the beam arrangements that best meet the objectives
treatment machine can be used to closely conform specified. IMRT algorithms generate beams that
the edges of the beam to the shape of the target are dynamically modulated during treatment de-
or to avoid critical normal tissues. MLCs are banks livery using moving MLCs. The dynamic modula-
of closely spaced, mobile “leaves” made of high- tion of the beam allows for much tighter
density, high-atomic number material. Because conformality around the target volume and better
of the high atomic number, when an individual sparing of nearby normal tissues (see Fig. 3.13,

Fig. 3.13 Comparative radiotherapy plans. Axial (top) and coronal (bottom) images of 3D CRT (left), intensity modu-
lated radiotherapy (IMRT, middle), and proton radiotherapy (right) plans for a patient with esophageal cancer. The
target PTV is shown with a yellow line, and the CTV is shown with a purple line. Dose is shown in color wash (see the
color key along the left side of each image; high dose is at the top of the key and low dose is at the bottom of the
key). The IMRT and proton plans conform more tightly to the PTV than the 3D CRT plan. The IMRT plan has much
more low-dose spread than the proton plan. (From Ling TC, Slater JM, Nookala P, et al. Analysis of intensity-
modulated radiation therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) for reducing perioperative
cardiopulmonary complications in esophageal cancer patients. Cancers (Basel) 2014;6(4):2356–68.)
52 Section I Oncology and Hematology Principles for the Cardiologist

middle panel). A potential downside to IMRT is Electron Radiotherapy

that it spreads low dose into a greater volume Electrons are typically used to treat superficial tar-
of normal tissue when compared with 3D-CRT. gets because dose from electrons falls off rapidly
Thus, normal tissues directly adjacent to the as the beam penetrates deeper into tissue. A
target volume are often spared from high doses common use of electron radiotherapy in the tho-
at the expense of spreading more low-dose radi- rax is in patients with breast cancer receiving
ation to normal tissues that are not directly adja- regional nodal irradiation. An election field can
cent to the target volume. be used for coverage of internal mammary lymph
nodes in conjunction with a photon plan to cover
Stereotactic Body Radiotherapy the axillary and supraclavicular nodes and the
SBRT refers to delivering large doses of highly remaining chest wall or breast. Electrons scatter
conformal radiation in few fractions. If the target laterally more than photons so care must be taken
is in the head, the term, “stereotactic radiosur- when designing adjacent photon and proton
gery (SRS)” is often used. The high doses used treatment fields so as to minimize hot spots where
in stereotactic treatments necessitate tech- the fields abut.
niques that minimize delivery uncertainties and
maximize dose falloff outside the target volume. Protons
Techniques to minimize delivery uncertainty Proton radiotherapy is available at a limited
include the use of advanced immobilization de- number of institutions. Construction and
vises such as a skull-anchored head-frame in treatment-related costs are generally higher
Gamma Knife or custom whole-body vacuum than for photon-based treatments, but significant
bags for linac-based treatments. In addition, advances have been made to make it viable for
advanced imaging may be used to verify the po- more centers to begin offering proton therapy.
sition of the patient at the time of treatment As noted above, treatment with protons and
(see IGRT in the next section). Because of the heavy ions takes advantage of the Bragg peak.
large fraction size, a steep dose gradient A monoenergetic proton beam enters a patient
between the target volume and nearby normal and delivers a low entrance dose of radiation.
tissue is needed to minimize normal tissue expo- Near the end of the proton range, the dose
sure (and the attendant side effects). The phys- deposited increases until it peaks at the Bragg
ics of radiation therapy are such that dose peak. Tissue distal to the Bragg peak receives
falloff is not as rapid for larger volumes minimal dose (see Fig. 3.13). Several beams of
compared with small volumes. Current tumor differing energies are used to create a SOBP so
size limits are approximately 4 cm in the brain10 as to cover the entire tumor (see Fig. 3.8). The
and 5 cm in the lung.11 SOBP allows for homogenous target coverage,
but it often increases entrance dose compared
Image-Guided Radiotherapy with photons. Because of the sharp dose gradient
Image-guided radiotherapy (IGRT) does not refer at the end of range, proton therapy treatments
to a particular treatment modality; rather, it refers tend to be more sensitive to small changes in pa-
to the use of in-room imaging at the time of treat- tient position or anatomy than a corresponding
ment to minimize positioning errors. Highly photon plan.
conformal techniques such as IMRT and SBRT Proton delivery systems can be broadly
require high levels of setup reproducibility to divided into either passive scatter systems or
ensure that the planned dose is delivered to the spot-scanning systems. Passive scatter systems
specified area. Recent decades have seen several generate a beam that is then passed through
advances in IGRT technology.12 Planar IGRT tech- materials that scatter the beam to create a
niques compare 2D radiographs obtained with broad beam that can be used to treat larger
the patient in treatment position with digitally fields. Custom compensators are then used to
reconstructed radiographs from the simulation shape the proton beam to conform to the lateral
imaging. Overlaying the radiograph from simula- and distal edges of the target volume. Spot-
tion with the radiograph from treatment allows scanning systems use electromagnets to direct
for accurate matching to bony anatomy. Volu- narrow proton beams to specific, precalculated
metric IGRT techniques provide 3D imaging that coordinates (spots). The dose is calculated by
can be compared with the simulation imaging to summing the dose from all of the discrete beam-
verify position. Volumetric IGRT imaging allows lets. In addition to conforming to the lateral
for soft tissue matching as well as bony matching. and distal edges of the target volume, spot-
Examples of volumetric IGRT include cone-beam scanning allows for conforming to the proximal
CT, CT on rails, and megavoltage CT imaging.12 surface of the target volume. Because of
 Chapter 3 Basics of Radiation Therapy 53

improved conformality, most new proton sys- is thought to be advantageous particularly

tems are using spot-scanning technology, when treating radioresistant tumor histologies
whereas older systems generally used passive- that are less responsive to photon-based
scatter techniques. radiotherapy.
As noted above, the RBE for protons is
generally taken to be 1.1, meaning that the bio- Brachytherapy
logic effect of proton radiation is about 10% Brachytherapy refers to temporary or permanent
higher than photons for the same amount of placement of radioactive sources into the body.
deposited energy. Thus, proton dose is typically Interstitial brachytherapy uses needles to intro-
reported in cobalt gray equivalents. In other duce radioactive sources into solid tumors or or-
words 60 CGE from a proton plan is thought gans. Intracavitary brachytherapy uses an
to be biologically equivalent to 60 Gy from a applicator to introduce radioactive sources into
photon treatment. Currently, most treatment natural (eg, vagina) or surgical (eg, lumpectomy)
systems assume a uniform RBE for proton dose body cavities.
deposition throughout the treatment field. Brachytherapy can be further classified as low-
Recent evidence suggests that the RBE may dose rate (LDR) or high-dose rate (HDR). In LDR
higher in the Bragg peak region of the treat- brachytherapy, radioactive sources of relatively
ment beam. Thus, the effective dose to the low activity are placed by the radiation oncologist
distal edge of the treatment field could be into the patient. Some LDR applications are tem-
higher than reported. An example where this porary, and the patient remains hospitalized for a
may be clinically meaningful to the cardio- few days until the applicator is removed. Other
oncologist is neoadjuvant proton therapy for applications, for example, prostate seed implants,
distal esophageal cancer. Most proton treat- are permanent. Isotopes used for permanent im-
ment plans use posterior beams that deliver plants typically have low energy, decay within
dose to the esophagus with a small margin months, and typically deliver negligible dose to
into the posterior surface of the abutting heart bystanders.
tissue. This margin is necessary to avoid under- HDR brachytherapy uses a high-intensity radio-
dosing the tumor. Because the proton beam active source on the end of a wire, which is con-
does not pass through the entire heart and tained in a computerized, shielded afterloader.
lungs as photons would, proton plans deliver Once the applicator and/or needles are posi-
much less dose to the heart and lungs than a tioned correctly and connected to guide-tubes,
traditional photon plan. However, because the staff leaves the room. A program remotely directs
distal edge of the proton beam is in the heart, the afterloader to extend the wire to position the
it is possible that the effective dose to that small HDR source at specified locations. The wire re-
portion of the heart is higher than would be mains extended until the specified dose is deliv-
calculated using a uniform RBE of 1.1. Active in- ered, and then the wire (with the source) retracts
vestigations should provide further information into the afterloader.
that may allow for a better understanding of Brachytherapy is often selected in areas with
this phenomenon. easy access for the placement of catheters or ap-
plicators (Fig. 3.14). Brachytherapy plans are
Heavy Ions capable of delivering highly conformal treatments
Therapeutic heavy ion particle accelerators are because the dose drops off quickly as a function
much less common than therapeutic proton ac- of distance from the radiation source. Structures
celerators. As of June 2015, there were 49 oper- immediately to the surface of the radiation source
ational proton facilities worldwide with an are expected to receive as much as 400% of the
additional 29 under construction. There were 8 prescribed dose. Because of difficulties in access-
carbon ion facilities with an additional 4 under ing the mediastinum and improvements in other
construction, and none of these were in the technologies, there has been a decrease in medi-
United States.13 Carbon and other heavy ions astinal brachytherapy, but future studies may lead
have a Bragg peak similar to that of protons, to a resurgence of this modality. Specific applica-
but the peak is steeper and the beam scatters tions of brachytherapy of interest to the cardio-
less in the lateral directions along the beam oncologist include intravascular brachytherapy to
path. These physical properties allow for prevent coronary in-stent restenosis,14 intravas-
greater dose conformality. In addition, heavy cular brachytherapy to prevent restenosis in pe-
ions deposit energy in a way that causes more ripheral artery occlusive disease after balloon
double-stranded DNA breaks than other dilatation,15 lung brachytherapy to prevent local
modalities of radiation delivery. This property recurrence,16 and esophageal brachytherapy.17
54 Section I Oncology and Hematology Principles for the Cardiologist

Fig. 3.14 HDR brachytherapy applicators. For HDR brachytherapy, an applicator is placed in the patient. The spe-
cific applicator chosen depends on the site to be treated and the anatomy of the patient/tumor. Once proper posi-
tioning is verified (typically with imaging), software is used to design a treatment plan. The applicators are
connected to the afterloader via catheters. The afterloader has a radioactive source on the end of a wire. The radio-
active source is shielded when it is inside the afterloader so that dose to the surrounding area is minimal. The wire is
advanced remotely by the computer system through the catheter(s) and into the applicator. Dose is determined by
the activity of the source and the time it stays at a precalculated position. Once the desired dose is delivered, the
wire retracts into the afterloader, and the applicator is removed from the patient. GYN, gynecologic. (From Wilkin-
son DA. High dose rate (HDR) brachytherapy quality assurance: a practical guide. Biomed Imaging Interv J
2006;2(2):e34.)

SPECIFIC DISEASE SITES effects of radiation. In addition, many of the

As noted above, sequela from radiation may chemotherapeutic agents used for these dis-
manifest years or even decades after exposure. eases are associated with cardiac and lung
Late complications are particularly relevant for toxicity in addition to the risk posed by radia-
patients who are treated at younger ages with tion. Some of the specifics regarding radiation
high likelihood of cure. In the thorax, patients in the management of these 2 diseases are dis-
with breast cancer or Hodgkin lymphoma (HL) cussed to better inform the cardio-oncologist
are at particular risk for late side effects. Radia- as to the potential late risks.
tion plays an important role in contributing to
the high cure rates seen in both of these dis- Breast Cancer
eases. However, the relative youth of many of Radiation therapy in the management of breast
these patients and the high probability for sur- cancer is typically given in the postoperative
vival signify a longer interval during which the setting. The volume of tissue irradiated and
patients might experience the deleterious the prescribed dose of radiation vary based
 Chapter 3 Basics of Radiation Therapy 55

on the type of surgery performed and the find- distanced from the treatment volume. Regardless
ings at the time of surgery. Surgery may of patient positioning, most treatment plans use
address the primary cancer with either a opposing tangential fields to cover the breast or
lumpectomy or a mastectomy (with or without chest wall (Fig. 3.16). These beams can be
reconstruction). Since the development of designed to also provide dose to the internal
sentinel lymph node biopsy (SLNB), nodal dis- mammary and low axillary nodal levels if indi-
ease is typically addressed with SLNB with a cated. The high axillary and supraclavicular nodal
completion axillary lymph node dissection for regions are typically targeted using 1 or 2 sepa-
select patients at high risk for further node rate beams. Alternative photon and/or electron
involvement. Patients with a large primary tu- beam arrangements have been studied and
mor or initially involved lymph nodes may may be beneficial in certain clinical situations.
receive neoadjuvant chemotherapy. Appro- Ultimately, the beam arrangement is chosen to
priate radiotherapy recommendations in the maximize target coverage while minimizing
setting of prior chemotherapy are the subject organ-at-risk dose.
of active investigation. Heart, particularly for left-sided breast can-
The target volume varies based on the stage, cers, and lung are the primary organs at risk
surgery, and risk factors for recurrence. Current considered during treatment planning for breast
guidelines recommend contouring target and cancer. A better understanding of late toxicity
normal tissues, but for many years, treatment has led to efforts to minimize dose to heart and
fields were generated using clinical landmarks lung. Management strategies that reduce heart
without formal contouring.18 Postlumpectomy dose include deep inspiration breath-hold
whole breast radiotherapy is the standard of care (Fig. 3.17), respiratory gating (the treatment ma-
for patients with early-stage, node-negative dis- chine delivers dose only when sensors on the pa-
ease. Survival and disease control outcomes for tient detect that the lungs are filled above a
patients with early-stage, node-negative disease certain threshold), prone positioning, partial
are similar between patients who undergo mas- breast irradiation for select patients, and the
tectomy alone or lumpectomy followed by adju- use of IMRT or proton therapy. In general, car-
vant radiation to the remaining ipsilateral breast diac sparing is more difficult to achieve for pa-
tissue.19 Younger patients with risk factors for local tients with left-sided tumors or who have
recurrence may have a higher dose (a boost) given indications for nodal irradiation.
to the lumpectomy cavity.20 For very early stage
disease, appropriately selected patients may Hodgkin Lymphoma
receive partial breast irradiation,21 that is, irradia- Treatment for HL has undergone significant ad-
tion of breast tissue adjacent to the lumpectomy vances in recent decades. A brief historical over-
cavity without targeting the remaining breast tis- view is provided because many patients are still
sue. Patients with node-positive disease, tumors alive following treatment that was given decades
greater than 5 cm, skin involvement, or pectoral ago. Treatment of HL was first described in 1902.
fascia invasion will often receive postmastectomy Initial responses to radiation therapy were impres-
radiation therapy directed to the chest wall and sive, but recurrences outside the treated field
draining lymph nodes (Fig. 3.15). If a lumpectomy were common, and the disease was thought to
is performed in a patient with nodal disease, the be incurable. In the 1950s, Vera Peters22
nodal volumes above are often targeted in addi- described long-term 5-, 10-, and 15-year survival
tion to the ipsilateral breast tissue. Conventionally in patients treated with radiation to the involved
fractionated breast radiotherapy is typically deliv- nodal volumes plus adjacent nodal volumes, so-
ered in 25 to 30 daily fractions (5–6 weeks) to a called extended-field radiotherapy. For several
dose of 50 to 60 Gy. Hypofractionated regimens decades, extended-field radiotherapy became
with equivalent cancer control and toxicity but the standard of care, but late toxicity after radia-
requiring only 3 weeks for delivery have recently tion led researchers to seek alternate treatment
gained wide acceptance for whole breast radio- methods. New chemotherapeutic agents became
therapy. Pending studies will determine whether available in the 1950s and 1960s, and in 1970, the
hypofractionation is appropriate when treating National Cancer Institute published evidence that
nodal volumes. multiagent chemotherapy could also provide
As with other sites, patients undergo immobi- long-term cures.23 Subsequent studies evolved
lization and simulation before treatment. Patients to use both chemotherapy and radiation in an
may be treated in the prone or supine position effort to maximize the benefit of each modality
with various devices used to position the breast and minimize toxicity. In the context of good
such that normal tissues can be reproducibly response to chemotherapy, significant evidence
56 Section I Oncology and Hematology Principles for the Cardiologist

Fig. 3.15 Nodal contours for breast radiotherapy. Contours for the heart (red), chest wall (purple), levels 1 (yellow),
2 (pink), and 3 (blue) of the axilla, internal mammary (green), and supraclavicular (cyan) nodal volumes. The chest wall
would be a target in this patient with pT3 pN2. (Courtesy of Radiation Therapy Oncology Group, Philadelphia, PA;
with permission.)

now exists to support treating patients to lower- increases and overtakes the incidence of HL recur-
radiation doses24–27 and to smaller radiation vol- rence by 15 to 25 years after therapy.29
umes.28 Much of the data regarding late cardiac In the early era of combined modality therapy
effects after radiotherapy come from patients for HL, mediastinal disease was treated with
treated with large radiation fields to higher doses mantle field radiotherapy (Fig. 3.18). Mantle fields
than is currently used. For patients treated during were designed to cover the initial nodal sites of
that era, the incidence of HL recurrence plateaus disease with extension of the field to adjacent
after 5 years. However, the cumulative incidence nodal volumes (hence the term extended field
of second malignancies and cardiovascular events radiotherapy; EFRT). Bilateral neck, axilla, hilar,
 Chapter 3 Basics of Radiation Therapy 57

Fig. 3.16 Whole breast radiotherapy. This 43-year-old patient was diagnosed with T1 N0, ER1, PR1, Her2-negative
breast. She elected for breast conservation and received adjuvant whole breast radiation therapy with a 10-Gy boost
to the lumpectomy cavity. Selected contours (whole breast PTV [blue], lumpectomy cavity PTV [orange], and heart
[red]) and the whole breast tangent beams are shown on axial (upper left), coronal (lower left), and sagittal (lower
right) CT slices. A beams’ eye projection of the medial tangent field is shown in the upper right. Opposing tangent
beams are designed to cover the breast tissue while minimizing dose to the heart and lungs. A 1- to 2-cm sliver of
lung is included in the beam to provide adequate coverage to the PTV. Examination of the beams’ eye projection
shows the 3D relationship between the heart and the target volumes.

and mediastinal nodes were included in a standard IFRT treatment volumes included the entire
mantle field. Subsequent advances showed that involved field (eg, the entire mediastinum in the
smaller radiation fields were acceptable in the setting of initial mediastinal disease) without tar-
setting of improved chemotherapy. The first itera- geting fields that were note initially involved
tion of radiation volume reduction was from EFRT (Fig. 3.19). Smaller volumes, termed involved
(eg, mantle) to involved field radiotherapy (IFRT). site radiotherapy (ISRT), are now thought to be

Fig. 3.17 Deep inspiration breath-hold. Radiation treatment plans for a patient with left-sided breast cancer in free-
breathing (A) and deep inspiration breath-hold (DIBH) (B). The images are taken at the same patient level. In free-
breathing, the left ventricle and left coronary artery may be in the beam path. In DIBH, the heart moves inferior and
away from the left breast, allowing for better sparing of the heart without sacrificing target coverage. (From Beck RE,
Kim L, Yue NJ, et al. Treatment techniques to reduce cardiac irradiation for breast cancer patients treated with
breast-conserving surgery and radiation therapy: a review. Front Oncol 2014;4:327.)
58 Section I Oncology and Hematology Principles for the Cardiologist

Fig. 3.18 Mantle field radio-

therapy. The anterior mantle field
showing coverage of the medias-
tinum and bilateral neck, axilla,
and hilar regions. The patient
would have been treated with
both anterior and posterior mantle
fields to provide more uniform
dose. (From Koh ES, Tran TH, Hey-
darian M, et al. A comparison of
mantle versus involved-field radio-
therapy for Hodgkin’s lymphoma:
reduction in normal tissue dose
and second cancer risk. Radiat
Oncol 2007;2:13.)

Fig. 3.19 IFRT. Mediastinal IFRT

covering the mediastinum. The pa-
tient would have been treated with
both anterior and posterior medi-
astinal fields. (From Koh ES, Tran
TH, Heydarian M, et al. A compari-
son of mantle versus involved-field
radiotherapy for Hodgkin’s lym-
phoma: reduction in normal tissue
dose and second cancer risk.
Radiat Oncol 2007;2:13.)
 Chapter 3 Basics of Radiation Therapy 59

acceptable.30 ISRT volumes cover only the initial 7. Levin WP, Kooy H, Loeffler JS, et al. Proton beam
disease with a small margin (ie, only the involved therapy. Br J Cancer 2005;93(8):849–54.
mediastinum is treated instead of the entire medi- 8. Singh AD, Pelayes DE, Seregard S, et al.
astinum as was covered by IFRT). Ophthalmic radiation therapy: techniques and ap-
As of 2016, adult patients in the United States plications. Basel, Switzerland: Karger; 2013. p. 24–5.
with early-stage HL are often treated with 2 to 4 9. Paganetti H, Niemierko A, Ancukiewicz M, et al.
cycles of chemotherapy (for example, adriamycin, Relative biological effectiveness (RBE) values for
bleomycin, vinblastine, and dacarbazine) followed proton beam therapy. Int J Radiat Oncol Biol Phys
by 20- to 30-Gy ISRT. Pediatric patients are often 2002;53(2):407–21.
treated with chemotherapy (often a different 10. Nieder C, Grosu AL, Gaspar LE. Stereotactic radio-
regimen than that used for adults) followed by surgery (SRS) for brain metastases: a systematic re-
21-Gy ISRT. Indications for radiation therapy after view. Radiat Oncol 2014;9:155.
good response to chemotherapy in advanced- 11. Videtic GM, Chang JY, Chetty IJ, et al. ACR Appro-
stage HL include pediatric patients, partial priateness Criteria(R) early-stage non-small-cell
response to therapy, and initial bulky disease. lung cancer. Am J Clin Oncol 2014;37(2):201–7.
12. Verellen D, De Ridder M, Storme G. A (short) history
of image-guided radiotherapy. Radiother Oncol
SUMMARY 2008;86(1):4–13.
Radiation therapy continues to play an important 13. Kramer D. Carbon-ion cancer therapy shows prom-
role in curative and palliative cancer treatment. ise. Physics Today 2015;68(6):24–5.
The cardio-oncologist will encounter patients at 14. Oliver LN, Buttner PG, Hobson H, et al. A meta-
many phases in their cancer care from initial analysis of randomised controlled trials assessing
workup to decades after treatment. Modern drug-eluting stents and vascular brachytherapy in
radiotherapy benefits from advances in radiobi- the treatment of coronary artery in-stent restenosis.
ology and in treatment delivery that allow modern Int J Cardiol 2008;126(2):216–23.
treatments to better limit dose outside of the 15. Gorenoi V, Dintsios CM, Schonermark MP, et al.
intended target tissue while still delivering cura- Intravascular brachytherapy for peripheral vascular
tive doses to the tumor. The techniques discussed disease. GMS Health Technol Assess 2008;4:
above affect the acute, subacute, and delayed ef- Doc08.
fects of radiotherapy. A working knowledge of 16. Jones GC, Kehrer JD, Kahn J, et al. Primary treat-
current and historic radiotherapy principles, tech- ment options for high-risk/medically inoperable
niques, and effects will help the cardio-oncologist early stage NSCLC patients. Clin Lung Cancer
understand, anticipate, and treat various forms of 2015;16(6):413–30.
cardiovascular sequela of radiotherapy. 17. Gaspar LE, Winter K, Kocha WI, et al. A phase I/II
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