Umamaheswar Duvvuri Gregory/.
Kubicek
Radiation oncology plays an important role in the treat-
ment of head and neck cancers, both in the adjuvant and
the definitive setting. Radiation is an important modality
and has a large influence in terms of both survival and
toxicity for patients. The field of radiation oncology is
rapidly evolving, and head and neck oncologists should
be aware of some of the important and changing fea-
tures of this field to ensure that the patients they refer
are treated appropriately. The goals of this chapter are
to review the fundamental basis of radiation oncology
(radiobiology), to describe some of the everyday aspects
of radiation therapy delivery and toxicity, and finally to
describe some of the new innovations in the field of radi-
ation oncology.
RADIOBIOLOGY
Radiobiology describes the effects of ionizing radiation on
the cellular level. Ionizing radiation induces cell death via
DNA damage. DNA damage occurs when radiation inter-
acts directly with the DNA strand or, more commonly,
when the radiation interacts with a water molecule with
secondary DNA damage. When ionizing radiation hits a
water molecule, it forms free radicals; these free radicals
are very unstable and, if formed in the vicinity of the DNA
strand, are able to inflict damage.
DNA damage does not always lead to cell death; the cell
has the capability of repairing radiation-induced damage
to DNA. The rate and capability for repair are different for
different types of cells. In general, more rapidly growing
cells are more susceptible to damage from radiation (the
process of cell division makes the DNA more susceptible
to damage and also DNA damage is declared during DNA
division). This is why the mucosa of the oral cavity (which
is always dividing and being replaced) is very sensitive to
the effects of radiation. In general, normal tissues have
greater capacity for DNA repair than cancer tissues; one
1682
of the rationales for fractionation of radiation is to allow
repair of normal tissues during fractions.
The more radiation damage that is inflicted upon a
population of cells, the more cell death; the initial radia-
tion dose causes damage to the cell population but does
not necessarily cause cell death. As the radiation damage
accumulates, cell death starts to occur. A simplistic way to
view this is to imagine that both strands of the DNA must
be damaged before the cell is irreversibly killed; the initial
dose of radiation is most likely to damage a number of sin-
gle strands and occasionally both strands in a single cell.
As radiation dose continues, it becomes more likely that
double-strand damage occurs in more cells and thus causes
cell death. During the initial (single strand) DNA damage,
there is potential for the cell to repair the single-strand
break and undo the radiation damage. The differential
ability for DNA repair has led to the terms •radiosensitive•
and '"radioresistant." Although the exact terms are very
subjective, the basic principle is that some types of cells
and tumors have very little repair ability and die rapidly
from even low doses of radiation. On the other side are
•radioresistant• tumors; such tumors have ability to repair
DNA, which makes them less likely to undergo cell death
from radiation damage. Some typical radiosensitive tumors
include lymphomas, while radioresistant tumors include
sarcomas and melanomas. In Figure 110.1 we have three
cell populations; cell population A would be radiosensitive
(note the lack of a shoulder region and the immediate lin-
ear decline in surviving cells; such a curve is seen in blood
cells that lack any repair mechanisms). Population C has
a wide shoulder representing a radioresistant cell popula-
tion; the initial portion of the curve is where cell repair is
occurring preventing death from the radiation.
In addition to the capacity for DNA repair, another
component that affects radiation sensitivity (and the slope
of the cell death curve) is oxygenation. Under hypoxic
conditions, it is thought that the free radicals, which are
 Chapter 110: Principles of Radiation Oncology 1683

c:
0

~
C\
c:
'S:
·~
Ill

Dll~t:
Figure 110.2 Unear accelerator.
FiguN 110.1 Three cell populations showing different levels of
sensi\ivity to radiation. Cell population A would be radiosensitive
(note the lack of a shoulder region and the immediate linear de-
dine in surviving cells, such a curve is seen in blood cells that lack linear accelerator (Fig. 110.2). lhe patient lies on the treat-
any repair mechanisrN). Population C has a wide shoulder repre- ment table, and the linear accelerator rotates around the
senting a radioresistant cell population; the initial ponion of the
curve is where cell repair is ocxurring preventing death from the patient to deliver the radiation. In order to ensure that the
radiation. patient is not moving while the radiation is being deliv-
ered. an immobilization device is used; for HNC this typi-
cally consists of the thermoplastic head mask (Fig. 110.3).
responsible for DNA damage, can be scavenged by the Radiation is desaibed in terms of dose; the common
hypoxia-induced acidic environment and that oxygen itself convention for dose is the gray (Gy). lhe definition of a
may play a role in continuing the cascade of the free radi- Gy is the amount of enetgy dose absomed per unit mass
cal formation. laige tumoa tend to grow faster than their ( 1 Gy =1 J/kg}. Le8s often used is rads, 1 rad is equal to 0.01
blood supply, leading to hypoxic areas in the center of Gy. 1he typical total dose for treatment of HNC is 60 to
large tumoiS. lhis phenomenon is thought to contribute 66 Gy for adjuvant radiation and 70 to 74 Gy for defini-
to the relatively poor control rates for lcuge head and neck tive radiation. By comparison. doses for lymphoma would
canceu treated with ionizing radiation. be 30 to 40 Gy, and the dose for a computed tomography
(Cf) scan is 0.1 to 0.2 Gy.
lhe total dose of radiation is divided into smaller doses
DOSE AND DELIVERY
called fractions. The dose for a fraction of radiation is usu-
1he most commonly used form of radiation is photons, ally between 1.8 and 2.0 Gy, although there can be a wide
but other particles can also be used, including electrom, range (e.g., the dose for radioswger:y in the treatment of
protons, neutrom, and carbon iom. Electrom are widely
available but not as commonly used as photom. Electrons
have a short depth of penetration; this allows for good
dose to the surface and minimal dose to deeper levels (e.g.,
6 MV electrom will deposit 90% of their energy 2 an into
tissue). Because of the dose distribution. electrons are a
ver:y good treatment option for the treatment of skin can-
ceu. Protons and carbon ions are other forms of radiation
and are less frequently used. Protons, neutrons, and car-
bon ions (referred to as heavy particle radiation) are not
produced by normal radiation oncology linear accelera-
toD and require special (and ver:y expensive) acceleratOIS
to produce this type of radiation (see below for a more
detailed description of proton radiation oncology).
It should be noted that all twes of radiation work via
the same basic mechanisms although some of the logis-
tics of delivery are different For photon radiation (usually
just desaibed as radiation), the radiation is produced by a Figure 110.3 Thermoplastic head mask use~d for Immobilization.
1684 Section VII: Head and Neck Surgery
trigeminal neuralgia can be as high as 80 Gy in a single
fraction). The purpose of delivering the total dose of radia-
tion as a number of smaller fractions is to take advantage
of normal tissue repair of DNA damage. For the most part,
normal tissues have a much greater ability for DNA repair
than do cancer cells. Thus, if damage is incurred to both
normal tissues and cancer cells, the normal tissues will
repair themselves while the cancer cells will die (this is not
completely accurate as there is still a lot of normal tissue
damage as discussed later).
The interplay between dose and fraction is sometimes
referred to as "radiobiologically equivalent dose. n Several
mathematical models exist to convert from one dose and
fractionation to another dose at a different fractionation
(e.g., in terms of spinal cord tolerance, at 3 Gy per frac-
tion, the maximum dose is 30 Gy, whereas at 2.0 Gy per
fraction. the maximum dose is 45 Gy). The differential
in repair between normal and cancer cells is magnified
as radiation is delivered over a long period of time. This
allows for improvement of the toxicity profile and mini-
mizes toxicity to normal tissues.
FRACTIONATION AND TREATMENT
TIME
The most common fractionation pattern is to deliver
the radiation every day (Monday through Friday) and is
referred to as "conventional• or standard fractionation.
Hypofractionation is delivering less than one fraction per
day (typically done in radiosurgery where the fraction is
given every other day). Hyperfractionation is delivering
more than one fraction per day. While there is repair of
normal tissue DNA between radiation fractions, there is
also (hopefully to a lesser extent) repair of cancer DNA and
potential growth of the cancer itself. In order to decrease
this risk, there have been several studies that have investi-
gated the potential advantages of hyperfractionation.
The most well-known study is RlOG 90-03 (1). In this
study, patients with stage III and N HNC where random-
ized to conventional radiation (standard arm), hyperfrac-
tionation with twice daily treatments, hyperfractionation
with twice daily treatments with a planned 2-week break
during the radiation, and accelerated hyperfractionation or
concomitant boost (which consists of daily radiation until
the final 12 treatments at which time radiation is given
twice daily). The results of this study showed an improve-
ment in local control in the hyperfractionation and acceler-
ated hyperfractionation arms (survival had a trend toward
improvement, but did not reach statistical significance).
Several other studies have shown similar results including
DHANCA where patients were randomized to five versus
six treatments per week. and local control was found to be
improved with the six fraction regimen (5 year local con-
trol 70% vs. 60%) (2).
It should be noted that while tumor control appears to
be improved with a reduction in treatment time, there is
also an increase in acute toxicity (the normal tissues now
have less ability to repair). However, the studies have not
found a significant increase in late toxicity.
While hyperfractionation appears to be one method
to improve outcome, chemotherapy is another.
Chemotherapy has been shown to improve outcome ver-
sus radiation alone in both the definitive and the adjuvant
setting. Brizel et al. (3) found that concomitant chemo-
therapy delivered with hyperfractionation provided bet-
ter locoregional control than hyperfractionated radiation
alone (70% vs. 44%). Brizel et al. (4) performed a math-
ematical analysis of the data obtained from RI'OG 90-03
to determine what the impact of chemotherapy was on the
radiobiologically equivalent dose. They determined that
a 1% increase in radiobiologically equivalent dose lead
to a 1.1% increase in locoregional control. Similarly, the
addition of chemotherapy effectively increased the total
radiobiologically equivalent dose by about 10 Gy. The
authors concluded that this increase in effective radiation
dose could not be safely achieved by simply increasing the
amount of radiation delivered to the patient.
RI'OG 0129 (5) set out to examine if chemotherapy (cis-
platin 100 mg/m2 every 3 weeks) plus hyperfractionated
radiation (concomitant boost) was better than the same
chemotherapy plus standard (once daily) radiation. The
study did not find a difference between the two arms, and
given the increase in acute toxicity and logistical difficulties
with hyperfractionation, most institutions use once daily
treatments for locally advanced HNC treated with chemo-
radiotherapy.
In summary, based on the lmown benefits of chemo-
therapy and the negative RI'OG 0129 study, hyperfraction-
ation is typically only used for patients who cannot get
chemotherapy and have to be treated with radiation alone.
The overriding principle for the benefits of hyperfrac-
tionation is that a reduction in overall treatment time
corresponds to an improvement in tumor control. The
opposite is also true; when the overall treatment time is
extended, tumor control decreases (6-9). RTOG (6) looked
at the importance of treatment time in HNC radiation and
found that local failure increased when the total treatment
time (from surgery to completion of radiation) exceeded
11 weeks. This is why treatment breaks should be avoided
unless absolutely necessary.
RADIATION ONCOLOGY PLANNING
The first step in radiation oncology planning is consulta-
tion with a radiation oncologist to examine the patient and
discuss the risks and benefits of therapy. After this, a radia-
tion planning cr scan is performed. This is similar to a
diagnostic cr scan except that the cr scan is performed
with the patient in the same position as they will be when
receiving the daily radiation treatments. In order to reduce
setup error between and during treatments, patients will
have a plastic mask made that conforms to their facial
 Chapter 110: Principles of Radiation Oncology 1685

anatomy (Fig. 110.3 ). Because of the special positioning

(including the mask), a diagnostic cr scan cannot be used
as a substitute for a radiation planning scan (although the TARGET DOSES
information from a diagnostic cr scan can certainly be
used to help in planning). Sometimes a positron emission
tomography (PET) scan can be done at the same time as Target Dose Range Description
radiation planning (see section on PET scans). High risk 70-74 Gross disease plus small margin
After the radiation planning scan has been performed, Intermediate 60~6 In adjuvant setting, tumor bed
the radiation oncologist will begin planning the radiation risk and resected but involved
beams. This process has evolved over time (see below) but lymph node basins. In
adjuvant or definitive setting,
in all cases involves distinguishing normal structures from
lymph node basins at high risk
areas that are targeted for radiation. Several terms are com- for failure
monly used to describe this process (Table 110.1 ). Gross Low risk 50-54 In adjuvant and definitive
tumor volume (G1V) represents the areas of actual tumor; setting, uninvolved lymph
this can be defined either radiographically (cr, PET, MRI) node basins at low risk for
failure
or clinically. In patients who have had surgery, there
should not be a GIV since there is no longer any gross dis-
ease. Clinical tumor volume (C1V) defines areas that are
After the radiation oncologist has distinguished the
at risk for harboring microscopic disease (such as lymph
different target volumes, there is some time required for
node basins); there can be discrepancy between different
the radiation planning (mapping out the number and
physicians in deciding the CIV volumes (e.g., does the con-
direction of the radiation beams) done by a dosimetrist
tralateral neck need to be covered in a patient with tonsil
and physicist. This can take anywhere between 10 minutes
cancer). Planning tumor volume (PIV) is a small expan-
and 3 days depending on the complexity of the plan.
sion on the CIV or GIV to account for errors in daily setup.
When the radiation plan has been completed, the radia-
A typical PIV expansion is 0.3 to 1.0 em. At our institu-
tion oncologist will evaluate the plan to make sure that
tion, we use daily imaging verification to reduce random
the target volumes (GIV; crv, PIV; etc.) are adequately
setup error and are able to use a smaller PIV margin (3 to
covered by radiation dose while simultaneously sparing
5 mm). Organ at risk (OAR) is defined as normal tissue
the normal structures (OARs). There are general guidelines
that is not involved with cancer and needs to be protected
for how much radiation dose a normal structure can tol-
from radiation (examples include the spinal cord, parotid
erate (Table 110.3). In order to evaluate a radiation plan
glands, mandible, etc.). Depending on the degree of risk,
and determine if it is safe for normal structures (OARs),
different areas will receive different doses of radiation. For
a dose volume histogram (DVH) is constructed. A DVH
example, the gross disease (G1V) will typically receive 70 to
plots percent volume of a structure versus the radiation
74 Gy; areas of low risk (uninvolved lymph node basins)
dose. Oftentimes in order to cover the tumor, it is neces-
are treated to 50 to 54 Gy, while intermediate risk regions
sary to deliver radiation doses beyond tolerance to some
receive 60 to 66 Gy (Table 110.2).
normal tissue; this can lead to some of the long-term tox-
icities of radiation (discussed later). In the DVH shown
in Figure 110.4 (patient with left base of tongue cancer),
we see that the right parotid is being spared, because of
the location of the tumor; the left parotid, being too dose
ORADIATION TERMS to the tumor, will receive dose that will likely make the

Term Definition
Hyperfractionati on Delivery of more than one fraction of
radiation a day
NORMAL STRUCTURE DOSE
Hypofracti on ation Delivery of less than one fraction of TOLERANCE
radiation a day
Gross tumor volume Gross disease as defined by radiology Structura Dose Limit Toxicity
and physical exam
Clinical tumor volume Areas at high risk for microscopic tumor Spinal cord 45 Gy (point dose) Paralysis
involvement Mandible 70Gy Osteoradionecrosis
Planning tumor volume Treatment field, which includes margin Parotids 25 Gy (50% of gland) Xerostomia
for setup error and other uncertainty Pharyngeal con- 55 Gy (50%) Swallowing
Organ at risk Normal structure (such as spinal cord) stri ctor muscles d iffi cu lti es
that must be protected to some Optic chiasm 54Gy Blindness
extent from radiation Lens 10 Gy Cataracts
1686 Section VII: Head and Neck Surgery

1
""
. Left Esophagus
.. Parotid

"'
f ..
J Right
!
~
10
Parotid
..!
g ••

JO

••

Figure 110A Dose volume histogram. This plots the pel"C8nt volume of a structure (y-axis) versus
the radiation dose (x-axls). In 1hls DVH we see 1hat the right parotid Is 1'801i1lv!ng less radiation 1han
the left parotid.

parotid nonfunctional (as seen in Thble 110.3, the dose
limit for parotid glands is 25 Gy at 50% of the orgarli
in Figure 110.4 we see 1hat right parotid is getting about
25 Gy to 50% of the organ whereas the left parotid iJ getting
25 Gy to greater than 70% of the otgan).
A typical time from consult to the start of radiation is
a week to 2 weeks; this can be longer if a dental ezttaction
is required or if patients are not compliant with appoint-
ments. As discussed above, overall treatment time is a very
important metric in HNC outcomes; this is why it is valu-
able to have the consultation with the radiation oncologist
within the fint week of surgery for patients who may need
adjuvant radiation. This allows everything to be set up and
ready to start without undue delay.
The radiation therapy is typically delivered once daily
(see above for discussion on fractionation). A typical treat-
ment time is 5 to 10 minutes, and the entire session will be
completed in about half an hour (time from in the door to
out the door). The radiation oncologist will see the patient
at a minimum of once per week; oftentimes there will also
be weekly appointments with nursing and dietary staff as
well. A typical course of radiation is 7 weeks for a definitive
case and 6 weeks for adjuvant.
More details on the indications for adjuvant radiation
are available in individual chapters, but in general, radiation
is recommended in the adjuvant setting for positive lymph
nodes, laJge tumor size (r3 orT4), pe:rineural invasion (PNI),
and positive swgical m;ugins. Chemotherapy is added to
radiation in the setting of positive InaJgins and emacapsular
extension (ECE) of a lymph node (see Table 110.4).
RADIA110N DELIVERY
As computer technology continues to improve so does the
delivery of radiation. Radiation delively has evolved over
time and continues to improve The most basic system for
radiation delivery is 2D (two dimensional) and involves
planning the radiation from plain x-ray films. For 2D radia-
tion delivery, a radiation planning cr scan would not be
used. In 3D (three-dimensional) radiation delivery, an extra
dimension is added to 2D planning; this incorporates imag-
ing data from the cr scan used for radiation planning. 3D
planning has the advantage of being able to accurately cal-
culate doses to normal structures. The next step in radiation
oncology evolution is intensity-modulated radiation ther-
apy (IMRI'). IMRI' imprCM!S upon 3D radiation planning
INDICA110NS FOR RADIA110N AND
CHEMORADIA110N
Recommendations for adjuvant radiation
+margins
+ lymph nodes (N+)
Large tumor size (T3, T4)
Perineural invasion
Recommendations for adjuvant chemoradfatfon
Extracapsular extension
+margins
 Chapter 110: Principles of Radiation Oncology 1687

by using multiple radiation beams (referred to 8l!l beamlets)
from different directions, all of which can potentially have
different intensities of radiation. IMRT allows the radiation
dose to "bend' around normal struct\li'ea. In Figure 110.5
iJ a patient who had both a 3D and an IMRT plan. In the
3D plan, there is a beam from the right and a second beam
from the left; everything in the radiation field gets a fairly
high dose of radiation. In the IMRT plan, the dose iJ able
to be shaped and bent; this allows less the radiation dose
to the parotid glands to be drastically reduced. 1he conse-
quence of this iJ an increase in the low-dose region with
the IMRT plan as compared to the 3D plan (bottom row
of Fig. 110.5). IMRT involves a la!ge amount of planning.
While a 3D plan can be generated within an hout an IMRT
plan can take up to a week to plan. The main catalyst for
the evolution from 3D to IMRT iJ the multileaf collimator
(MLC), an attachment to the head of the linear accelerator
that allows the radiation beams to be modulated. MLQI are
relatively cheap and easy to implement. & a result, IMRT is
available essentially everywhere that radiation is available
(at least in the United States).
There are obvious advantages to IMRT; with reduction
in dose to normal structures, there is a reduction in the
likelihood oflate radiation-induced toxicity. As shown in
Figure 110.5, the radiation dose delivered to the parotid
glands iJ reduced; this will hopefully result in a reduction
of xerostomia Howevet;. IMRT also has some significant
(and perhaps underappreciated) disadvantages. First of
aiL IMRT takes significantly longer to plan and is much
more expensive than 3D. For patients with rapidly grow-
ing or bleeding tumors, it often makes sense to start with
a 3D plan, which can begin rapidly and then convert to
an IMRT plan to complete the radiation. Another disad-
vantage iJ the distribution of low-dose radiation. While
Figure 110.5 shows a dear reduction in the areas of high
radiation dose, we also see an increase in the low dose

Figure 110.5 IMRTversus 30 plan The left hand column Is a 30 plan (two opposed lateral beams).
The right hand Is the same patient with an IMRT plan. Notice that the top row Is the high-dose
region and It Is much more conformal In the IMRT plan. The bottom row Is the low-dose region and
Is much largc~r In the IMRT plan.
1688 Section VII: Head and Neck Surgery
of radiation. In IMRT there is a significantly higher vol-
ume of tissues getting a low dose of radiation. 1he volume
of low-dose radiation has some repercussions. There are
toxicities that are seen in IMRT that were not seen in 3D
planning; one of these side effects is nausea &om radia-
tion beams going through the brainstem. If the radiation
oncologist does not mark an area as an OAR. the computer
will not see it as being at risk. and this area will receive
higher doses of radiation in the computer's attempt to
spare areas that were marked as OARs. Another concern
of the low-dose volume in IMRT is that this might confer
a higher chance of a radiation-induced cancer. This risk is
mainly theoretical, although it should be noted that IMRT
has only been used in high volume recently and the aver-
age time to develop a radiation-induced cancer is 10 to
20 years. Figure 110.6 represents a typicaliMRT plan for a
base of tongue cancer.
Most of the date describing IMRT outcomes is retro-
spective. but there are some limited phase Ill data. The
published level I evidence consists of two randomized
Figura 110.6 Base ohongue IMRT plan.
prospective nials treating nasopharyngeal cancer {NPC).
Similar in design, each trial randomized locally advanced
NPC patients between conventional radiation and IMRT
along with conament chemotherapy. The results showed
that sali:vaiy gland (parotid) function was significantly
and dramatically improved in the IMRT arms in both stud-
ies. Kam et al. (10) found a reduction in observer-rated
xerostomia from 82.1% with conventional radiotherapy
to 39.3% with IMRT and also measured improvements
in measured parotid :flow rates. Similarly, Pow et al. {11)
found an improvement in stimulated saliva flow with
IMRT and also found that patients treated with IMRT had
an improvement in patient-reported quality oflife scores.
The primary end point for both studies was parotid func-
tion; neither ni.al was powered or intended to examine
the role of IMRT in disease control or overall survival.
Retrospective data in both nasopharyngeal (12-15) and
nonnasopharyngeal HNC (16-21) compare vecy favor-
ably to historical norms. It should be noted that the
essentially all of the phase 1II HNC data acquired thus far

are from 2D or 3D radiation planning but that the gen-
eral acceptance of IMRT technology has led to its inclu-
sion in RTOG trials; RTOG 0234 and 0522 are the first
major US cooperative group studies incorporating IMRT
into radiotherapy planning.
RADIATION TOXICITY
Radiation has multiple side effects and toxicities, some
of which occur during treatment (acute) and others that
occur months to years after therapy (late). If chemotherapy
is added to the radiation, there is a significant increase in
the rate of acute toxicities, although late toxicities appear
to be similar. There is a significant amount of variation
between patients and how the radiation is tolerated, but
some general remarks can be made. During radiation, the
first 2 weeks typically proceed without much difficulty
unless the first round of chemotherapy causes toxicity
such as nausea and vomiting or dehydration. After the sec-
ond week, the acute radiation steadily escalates; toxicities
include pain (sore mouth and sore throat) from mucositis,
taste changes, loss of facial hair (in treatment field) and
skin irritation,. thick mucus, and dry mouth. These toxici-
ties will typically escalate until they plateau around week
5 to 6 and remain constant through the remainder of the
therapy. The majority of patients state that pain is the most
difficult of the side effects and often requires narcotic med-
ications.
After the completion of radiation, the side effects slowly
subside. The first-week postradiation remains a difficult
time with modest improvement in pain and other side
effects; around the 2-week mark. patients begin to feel
some noticeable improvement in toxicity, and this contin-
ues for the next several weeks. Skin breakdown typically
heals in about 2 weeks, thick mucus resolves around week
3 to 4, and the pain improves but is often still present
until 8 to 12 weeks after radiation. Fatigue and ability to
return to work are dependent on a number of factors, but
in general most patients are able to return to work around
8 weeks after radiation.
In addition to the acute toxicities, there are a number
of late radiation associated side effects. One of the most
common side effects is xerostomia (dry mouth) from
damage to the salivary glands; this sometimes responds
to pilocarpine (Salagen), but oftentimes patient will need
to carry a bottle of water around and may have difficulty
swallowing dry meats and breads. Taste changes typically
resolve by 3 months after radiation although patients may
have some food items that never regain taste and develop
intolerance to spicy foods (which taste too spicy). Some
late side effects that develop months and even years after
the radiation include hypothyroidism, neck fibrosis,
carotid artery stenosis, osteoradionecrosis (the incidence
of which can be increased by dental work after radiation),
and dysphagia with concomitant aspiration. As seen in
Table 110.3, there are general dose guidelines for how
Chapter 110: Principles of Radiation Oncology 1689
much radiation certain tissues can tolerate. Radiation
tolerance doses are put together by a combination of
retrospective studies and animal studies and while this
data are tentative for obvious reasons cannot be easily
expanded upon.
In general, toxicity rates are poorly documented and
recorded; hence, a wide range of toxicity rates are reported
in the literature. Machtay reported on the toxicity with
chemotherapy and non-IMRT radiation in several RTOG
studies; 43% of patients had severe late toxicity. mostly
consisting of pharyngeal and laryngeal dysfunction (22).
Eisbruch and coworkers recently published their prospec-
tive data using IMRT to treat oropharyngeal tumors (23).
Swallowing function was assessed by two methods, vid-
eofluoroscopy and subjective symptom score assessment.
Videofluoroscopy demonstrated that on average, mild pre-
treatment dysphagia progressed to moderate dysphagia
after chemoradiotherapy. While many patients experienced
recovery of swallowing function, some patients never had
full recovery.
INNOVATIONS IN RADIATION
PLANNING
In addition to IMKT, there have been several other inno-
vations in radiation therapy, which have promise to
improve outcomes in HNC. Some of the recent innova-
tions in HNC radiation oncology have included incorpo-
ration of imaging such as PET scans, proton therapy, and
radiosurgery.
One major innovation to the treatment of HNC has
been PET scans. While the imaging aspect of PET scans is
described elsewhere, there is also an important role for PET
scans in radiation treatment planning. Geets et al. (24)
reported that the use of pretreatment FDG-PET in combi-
nation with pretreatment cr or MRI improves target defi-
nition in oropharyngeal cancer and results in more normal
tissue sparing. The same group also examined the role of
PET contouring in larynx cancer, by comparing standard
imaging techniques and PET findings with the pathologic
specimens (25). They reported significantly smaller target
volumes when targets were drawn on FDG-PET as opposed
to cr scan. PET-based tumor volumes also showed better
correlation with pathologic findings compared with cr,
both for the primary tumor and the locoregional lymph
nodes (26). Long-term clinical data are emerging; favor-
able 3-year overall state and disease-free survival rates have
been shown in IMRT patients who all had PET-based con-
touring (27).
Proton therapy represents another possible evolution
in radiation oncology. Protons are fundamentally different
than photon radiation and are attractive because of its the-
oretical dose distribution in normal tissue. Photons lose
energy slowly as they travel through tissue; energy is depos-
ited in the tumor but is also in the normal tissue both in
front and in back of the tumor. Protons on the other hand
1690 Section VII: Head and Neck Surgery
have very low energy loss until they reach a certain depth at
which point all of the proton's energy is released at once.
Tissue distal to this point has almost no radiation dose.
This sudden peak in dose is known as the ·Bragg peak· and
can allow the proton beam to be targeted on the tumor
and has very little dose to normal structures on the other
side (very little exit dose). Theoretic plans have been cre-
ated testing conventional IMRTversus intensity-modulated
proton therapy, showing a significant advantage in tumor
coverage and normal tissue sparing with the intensity-
modulated proton therapy plans (28,29). It should be
emphasized that these were theoretic plans and not actual
treatments. Currently, most proton treatments are given
with conventional (3D; anteroposterior-posteroanterior,
lateral) proton beams.
Protons are currently only available in a limited num-
ber of centers, and experience and published results are
very limited, especially in the treatment of head and neck
cancer. The majority of reported results of proton therapy
in head and neck cancer involve rare and difficult to treat
tumors, such as chordomas and other skull-base tumors
(30). A small series from Lorna linda looked at 29 oropha-
ryngeal HNC patients treated with a proton boost (66% of
the radiation was delivered via photons); the study showed
good local control and toxicity (31) but larger and more
heterogeneous series are certainly needed.
Another radiation oncology innovation is radiosur-
gery. Radiosurgery is similar to IMRT in the delivery of the
photon radiation; the only difference between conven-
tional radiation and radiosurgery is in patient immobi-
lization and image verification techniques. Radiosurgery
requires very stringent immobilization and alignment
techniques; this allows for high doses of radiation to be
delivered in a highly conformal manner. There are mul-
tiple platforms that can be used for delivery of radiosur-
gery; some of the common devices include CyberKnife,
Gamma Knife. Trilogy, and TrueBeam. Although some
of the details differ. the basic performance for all of the
machines capable of radiosurgery is similar. Because of
the precise nature of radiosurgery, much higher doses
per fraction can be used, which allows for fewer over-
all fractions. For example. in the treatment of early-stage
lung cancer, 3 fractions of 20 Gy per fraction is a com-
mon radiosurgery schedule as compared to 35 fractions
of 2 Gy per fraction for nonradiosurgery HNC. Most
of the radiosurgery data in radiation oncology are in
the treatment of central nervous system (CNS) disease
(such as brain metastatic lesions) and in early-stage lung
cancer. However, there are growing data in the use of
radiosurgery in the treatment of head and neck cancer
(32). Radiosurgery in the HNC setting is most often in
recurrent HNC; the current approach at our institution
is to use radiosurgery (40 to 44 Gy in five fractions) for
patients with recurrent HNC that is not amenable to sur-
gical salvage. This is a growing field and will certainly
continue to evolve.
• Conventional fractionated irradiation therapy is
undertaken to allow normal tissue repair of DNA
damage between fractions while cancer cells die.
• Hyperfractionation (more than one fraction per
day) appears to improve outcome in patients treated
with radiation alone. However, it is also associ-
ated with increased acute toxicity, and the benefit
appears to be lost in patients treated with both radi-
ation and chemotherapy.
• Common indications for radiation include T3-T4
tumors, positive lymph nodes, and positive or dose
margins, PNI.
• Tumor control decreases when total treatment time
exceeds 11 weeks.
• Use of IMRT allows for the sparing of normal tissues
such as parotids, mandible. and pharyngeal con-
strictor muscles.
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