Download Intensity-modulated radiation therapy in head and neck cancers: An

CLINICAL REVIEW
Mark K. Wax, MD, Section Editor
INTENSITY-MODULATED RADIATION THERAPY IN HEAD AND
NECK CANCERS: AN UPDATE*
Nancy Lee, MD,1 Dev R. Puri, MD,1 Angel I. Blanco, MD,2 K. S. Clifford Chao, MD2
1
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue,
New York, New York 10021. E-mail: [email protected]
2
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Accepted 1 August 2005
Published online 15 December 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20332
Abstract:
Intensity-modulated radiation therapy (IMRT), an
advent of three-dimensional conformal radiotherapy (3D CRT),
has excited the profession of radiation oncology more than any
other new invention since the introduction of the linear accelerator. Approximately 1000 articles have been published on this
topic to date, more than 200 of which focus on head and neck
cancer. IMRT is based on computer-optimized treatment planning and a computer-controlled treatment delivery system. The
computer-driven technology generates dose distributions that
sharply conform to the tumor target while minimizing the dose
delivered to the surrounding normal tissues. The high dose volume that tailors to the 3D configuration of the tumor along with
the ability to spare the nearby normal tissues allows the option of
tumor dose escalation.
The head and neck region is an ideal target for this new
technology for several reasons. First, IMRT offers the potential
for improved tumor control through delivery of high doses to the
target volume. Second, because of sharp dose gradients, IMRT
results in the relative sparing of normal structures, such as the
Correspondence to: N. Lee
C
V
2005 Wiley Periodicals, Inc.
*Several text portions of the Abstract, Clinical Results, Nasopharynx,
Oropharynx, Paranasal Sinus, and Thyroid sections and the entire
Conclusion were previously published in Am J Clin Oncol 28: 415–423,
2005, and are republished here with permission of the publisher,
Lippincott Williams & Wilkins. The current study was initially published
online 15 December 2005 without referencing or acknowledging this
earlier source.
Intensity-Modulated Radiation Therapy
parotid glands, in the head and neck region. Third, organ motion
is virtually absent in the head and neck region so, with proper
immobilization, treatment can be accurately delivered. Although
this is a relatively new technology, single-institution retrospective
studies show better dosimetric profiles compared with conventional radiation techniques, as well as excellent clinical
results. Salivary gland sparing using IMRT has also resulted in
reduced incidence and severity of xerostomia, and this has
been tested in a randomized trial against conventional radiotherapy for early-stage nasopharyngeal cancer. The results do
confirm that IMRT does decrease xerostomia compared with
C
conventional radiotherapy. V
2005 Wiley Periodicals, Inc.
Head Neck 29: 387-400, 2007
Keywords: IMRT; head cancer; radiation; cancer
Intensity-modulated
radiation therapy (IMRT)
has the ability to deliver high doses of radiation to
the tumor target with very high precision while
minimizing the dose received by the surrounding
normal tissues.1–3 IMRT is based on computeroptimized treatment planning and a computercontrolled treatment delivery system. In complicated anatomic sites such as the head and neck,
true IMRT requires inverse planning. (Please see
‘‘Treatment Planning’’ for details.) Imagine a
broad radiation beam that is further subdivided
into a number of smaller pencil beams. The inten-
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387
sities of these neighboring pencil beams differ
from one another, and they ultimately combine together to conform to the shape of the tumor target.
Simplistically, one can think of IMRT as putting
together a three-dimensional (3D) jigsaw puzzle,
where this puzzle, which consists of tumor and
surrounding normal tissue, by the summation of
these different intensity pencil beams.
Several advantages can be seen with IMRT for
head and neck cancer. The high dose volume that
conforms to the 3D configuration of the tumor and
the sparing of the nearby normal tissue allow for
tumor dose escalation. Because of the tolerance of
the normal tissues that surround the tumor target, a maximum feasible dose is delivered with
conventional radiotherapy, usually between 65
and 70 Gy. At this dose, a high frequency of local
relapse can be seen, probably because of the radioresistance of subpopulations of tumor clonogens.
Because IMRT can conform to the irregularly
shaped tumor target and spare the nearby normal
tissues, dose escalation to the tumor target can
potentially overcome these radioresistant clonogens. In addition, on a daily basis, because IMRT
has the ability to delivery to the gross tumor volume (GTV) a higher dose per fraction than the
surrounding subclinical regions as well as the normal tissues, a more effective biological dose can
been seen. As a result of all the preceding, an
improved therapeutic ratio can be seen.3,4
However, several important issues regarding
IMRT must not be overlooked. IMRT, when compared with conventional treatment, results in a
greater target dose inhomogeneity. Oftentimes, it
can be a challenge to minimize unwanted ‘‘hot
spots’’ within the GTV and even within the normal
tissues. These ‘‘hot spots’’ can lead to a higher likelihood of posttreatment complications, depending
on their location.5 To date, no excessive late toxicity has been reported, although longer follow-up
of patients treated with IMRT is still required to
ensure there are no unwarranted complications.
Therefore, IMRT really requires greater expertise
on the parts of both the physician and the physicists to ensure that these ‘‘hot spots’’ within a
given plan are minimized.6
As we enter the era of highly conformal radiotherapy, radiation oncologists are now faced with
another issue. What exactly needs to be included
in the treatment volume? This especially applies
to head and neck cancer. Because IMRT has a
very sharp dose fall-off gradient between the gross
tumor target and surrounding normal tissue,
adequate target volume delineation is absolutely
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essential. Inadequate coverage in the treatment
volume can result in tumor recurrence. The treatment planning system will not treat areas not
drawn on the CT slices, and the algorithm will
even ‘‘work hard’’ to spare regions that are not
contoured. Precise GTV delineation depends on a
very thorough physical examination and adequate
imaging studies such as MRI, especially near the
skull base region. Significant inter-physician variability can exist in producing target volumes and
radiation treatment plans for conformal radiotherapy. One study comparing target volumes
delineated by three diagnostic radiologists and
eight radiation oncologists showed up to a threefold variation in volumes outlined by different
clinicians.7 To minimize such variability, it is
strongly encouraged that GTV delineation be
done in a multidisciplinary fashion, including a
team consisting of a radiation oncologist, a neuroradiologist, and, whenever necessary, a head and
neck surgeon, particularly in the postoperative
setting.8 When such a team is not available, fusion
of the diagnostic MRI, CT, and/or positron emisssion tomography (PET)/CT scans with the treatment planning CT should be implemented to further assist the radiation oncologist in GTV delineation (Figure 1).
The definition of the subclinical microscopic
region also known as the clinical target volume
(CTV) is another difficulty that the radiation oncologists face in IMRT treatment planning. The
question often lies in what exactly the physician
should outline on the treatment planning CT
scans to ensure that all the areas of potential
microscopic spread are adequately included. Recently, several articles examining the precise definition of the lymphatics of the head and neck
region have been published.9,10 These nodal atlas
guidelines are helpful to the radiation oncologists
in delineating CTV during treatment planning.
Efforts by experts from the Radiation Therapy
Oncology Group (RTOG), European Organization
for the Research and Treatment of Cancer
(EORTC), and the Danish Head and Neck Cancer
(DAHANCA) cooperative groups have drawn up a
consensus guideline for the N0 nonsurgically violated neck.11 This atlas also can be found on the
RTOG website. However, these atlases, whether
anatomy based or imaging based, are limited
because their primary focus is on the delineation
of the lymph node regions for the normal neck.
Distortion of the normal head and neck anatomy
can occur when there is surgical violation or when
there is gross disease involvement of adjacent tis-
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FIGURE 1. CT delineation of tumor volume with correlating MR
images. Gross tumor volume (GTV), light blue; planning target
volume (PTV) for GTV, yellow; subclinical regional, red; right
parotid gland, dark blue; left parotid gland, orange. Reprinted
with permission from Puri DR, et al. Intensity-modulated radiation therapy in head and neck cancers. Dosimetric advantages
and update of clinical results. Am J Clin Oncol 2005; 28(4):
415–423, Lippincott Williams & Wilkins. [Color figure can be
viewed in the online issue, which is available at www.interscience.
wiley.com.]
sues such as muscles. The radiation oncologist
should use his or her discretion and clinical judgment when drawing the CTV and consider drawing the CTV volume with guidance from standard
conventional radiation treatment portals that
include a substantial margin around the GTV plus
a margin for potential direct routes of microscopic
spread and apparently uninvolved lymph nodes.
This practice has been successful in preventing
subsequent marginal tumor recurrences.8
TREATMENT PLANNING (SOFTWARE)
Different methods of beam intensity modulation
have been used historically in an attempt to
decrease the dose to the normal tissue surrounding the tumor target. One of the simplest forms of
beam modulation is using wedge filter to variably
attenuate the radiation beam. Another example is
using field-in-field technique to deliver multiple
levels of intensity. Such simple forms of beam
modulation can be designed with forward plan-
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ning (FP), in which the planning begins with the
planner defining the beam directions and shapes,
beam weights, wedges, blocks, margins, and so on,
followed by the dose calculation, and then the
display and evaluation of the dose distributions.12
When the level of complexity of FP increases,
some would define this as IMRT.13
However, to fully use the potential of IMRT in
head and neck cancer because of the complex
anatomy compared with other sites within
the human body, inverse planning (IP) is required.2,14,15 IP starts with clinical objectives that
are specified mathematically, and a computer
optimization algorithm is used to automatically
determine beam parameters (namely, smaller
beam weights called pencil beam weights) that
will lead to the desired dose distribution. It is
based on user-predefined criteria for dose distributions to the tumor, subclinical disease region,
and the surrounding normal tissues. The computerized optimization algorithm subdivides each of
the radiation beams into a series of pencil beams,
and by varying the intensity of each of these
beams, a final composite 3D dose distribution will
be generated that tailors to the tumor target.
Therefore, in IP-IMRT, the techniques are significantly more complex than many other traditional
forms of radiotherapy, including a very sophisticated FP. Many different in-house and commercial
IP treatment planning software programs are
available throughout the world. It is beyond the
scope of this review to describe the pros and cons
of each treatment plan. In general, they are all
comparable.
TREATMENT DELIVERY (HARDWARE)
The multileaf collimator (MLC) is the most common hardware used in IMRT delivery. Many different IMRT delivery systems are available.16
Again, it is beyond the scope of this review to
describe the similarities or differences between
them. One can conclude that, in general, they are
all comparable to one another. An example of the
more commonly used delivery system is called
the ‘‘step-and-shoot’’ delivery system in which the
intensity-modulated beams are carried out by
superimposing many small pencil beams using the
MLC. The MLC steps to a predesigned configuration and then it shoots the pencil beams. The MLC
then steps to a different configuration and then
shoots another series of pencil beams. This is why
it is called the ‘‘step-and-shoot’’ method of delivery.
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389
QUALITY ASSURANCE
As we enter the era of such high precision in planning and delivery of radiation therapy, quality
assurance (QA) is absolutely crucial. Each type
of treatment planning and delivery system is
slightly different from another as stated previously.1,16,17 Therefore, QA can be very different
from one IMRT system to another IMRT system.
QA is an ongoing and evolving subject as we gain
more and more experience in IMRT. The manufacturers are continuously improving the performance of their linear accelerators in IMRT delivery.
In general, QA consists of two broad categories:
machine-related QA versus patient-related QA.
An example of a machine-related QA is checking
the linear accelerator’s hardware MLC leaf position accuracy. Periodic checks on the leaf positions
and movement to the designated positions across
a field, including off-center positions, should be
done as part of the QA program in a given center.
Manufacturers are continuously trying to improve the leaf position accuracy with build-in
redundant and independent sensors to check the
leaf position accuracy. Patient-related QA includes the ability to reproduce the treatment on a
daily basis. Frequent verification films are done to
ensure this accuracy. Immobilization not only of
the head and neck but also of the shoulders can
further improve setup accuracy (Figure 2). Last,
intensity patterns of a given treatment can also
be verified by checking the pattern against the
patient’s bony anatomy. Point dose and isodose
curve verifications can be done using phantom
(mimics a real patient) plans.18
CLINICAL RESULTS
At The University of Texas M. D. Anderson Cancer Center and Memorial Sloan-Kettering Cancer
Center (MSKCC), we now routinely use IMRT for
most of our patients with head and neck cancer.
Our interest in the approach is supported by a
growing body of clinical experience showing that
IMRT is feasible, well tolerated, and effective in
the head and neck region. Chao et al19 reported
an outstanding 3-year locoregional control rate
among 126 patients with head and neck cancer
treated at Washington University in St. Louis.
What makes these data all the more impressive is
that 90% were stage III and IV tumors. Lee et al8
studied 150 patients with head and neck cancer
who underwent IMRT at UCSF. The 3-year local
freedom from progression rate was 95% in
patients who underwent definitive radiotherapy
and, importantly, no marginal failures occurred.
Zhen et al20 at the University of Nebraska
reported in abstract form an analysis of patterns
of failure in 188 patients treated with IMRT for
head and neck cancer. With a median follow-up of
17 months, 6% had locoregional recurrences
develop and 12% had distant metastases develop.
They conclude that, with short follow-up, IMRT
offers excellent local control, with distant disease
remaining the predominant site for treatment
failure.55 Most recently, the University of Iowa reported their experience of treating 151 patients
with head and neck cancer with IMRT. The 2-year
local progression-free rate was 94%, with a
median follow-up of 18 months.21
NASOPHARYNX
FIGURE 2. Thermoplastic mask system extending from vertex
of scalp to shoulder aids in immobilization of the patient.
Reprinted with permission from Puri DR, et al. Intensity-modulated radiation therapy in head and neck cancers. Dosimetric
advantages and update of clinical results. Am J Clin Oncol
2005; 28(4): 415–423, Lippincott Williams & Wilkins. [Color figure can be viewed in the online issue, which is available at
www.interscience.wiley.com.]
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Intensity-Modulated Radiation Therapy
Because of the proximity to numerous critical
normal organs near the nasopharynx such as the
brain stem, IMRT is especially ideal in its attempt
to deliver an adequate dose to the gross tumor
while sparing these surrounding normal tissues.
IMRT plans involving the nasopharynx require
contouring the gross disease, including the tumor
and nodal GTV. The CTV involves bilateral coverage of neck levels I through V and the retropharyngeal nodes, which should be delineated up to
the base of skull.22,23 Level I nodes can be spared
when the neck is N0. Besides important at-risk
nodal regions, the CTV should also include the
entire nasopharynx, clivus, base of skull, ptery-
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April 2007
FIGURE 3. Clinical target volume (CTV) delineation for a
T2bN0M0 nasopharyngeal carcinoma receiving definitive intensity-modulated radiation therapy (IMRT). Gross tumor volume
(GTV), light blue; planning target volume 2 (PTV2), red; right
parotid gland, dark blue; left parotid gland, orange. Reprinted
with permission from Puri DR, et al. Intensity-modulated radiation therapy in head and neck cancers. Dosimetric advantages
and update of clinical results. Am J Clin Oncol 2005; 28(4):
415–423, Lippincott Williams & Wilkins. [Color figure can be
viewed in the online issue, which is available at www.interscience.
wiley.com.]
goid fossa, parapharyngeal space, inferior sphenoid sinus, and posterior third of the nasal cavity and maxillary sinuses (Figure 3).55 A margin
around the GTV, as well as the CTV, should be
added to account for patient motion and setup
errors. This is the planning target volume (PTV).
One can have a PTV for the GTV, a PTV for the CTV
at the highest risk of microscopic spread for the
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gross tumor, and a PTV for another CTV at a lower
risk of microscopic spread from the gross tumor.
At MSKCC, the implementation of IMRT for
our nasopharyngeal cases has resulted in significant improvements compared with traditional and
3D-conformal radiotherapy (CRT) plans. First,
there is better coverage of the retropharynx, base
of skull, and medial aspects of the nodal volumes.24
At UCSF, Xia et al25 compared IMRT treatment
plans with conventional treatment plans for a case
of locally advanced NPC. They concluded that
IMRT provides improved tumor target coverage
with significantly better sparing of sensitive normal tissue structures in the treatment of locally
advanced NPC.55 Kam et al26 from Hong Kong performed a dosimetric analysis comparing IMRT
with two-dimensional radiation therapy (RT) and
3D-CRT treatment plans. Three patients with different stages, including T1N0, T2bN2, and T4N2,
were compared. In all stages, IMRT was noted to
have significant dosimetric advantages. In earlystage disease, it provided better parotid gland
and temporomandibular joint sparing. In locally
advanced disease, it offered better tumor coverage
and normal organ sparing and permitted room for
dose escalation. Phase III evidence now shows
the advantage of IMRT in terms of improvement
of xerostomia compared with conventional radiotherapy.27
The dosimetric advantages seen with IMRT
for nasopharyngeal cancers have also translated
into excellent clinical outcomes.22,28 The most
mature data on local control using IMRT in locally
advanced nasopharyngeal cancer comes from UCSF
(Table 1; references 29 and 30). With a median
follow-up of 31 months, the 4-year local progression-free rate was 97%, whereas the 4-year regional progression-free rate was 98%.22 Bucci
et al28 have recently updated the UCSF experience
and included more patients (n ¼ 118).55 Excellent
locoregional control rates continue to hold up.
Other important studies have recently emerged
from Hong Kong and are also detailed in Table 1.55
An ongoing RTOG phase II trial using IMRT
with or without chemotherapy for all localized
nasopharyngeal cancer is currently accruing patients. The protocol is an important one, because
it tests whether the ability to achieve excellent
control rates in patients with nasopharyngeal
cancer treated with IMRT can be reproduced in a
multi-institutional setting.55
The reirradiation of nasopharyngeal cancer is
a more risky proposition. It is more feasible with
IMRT than conventional techniques for multiple
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Table 1. Results from series treating NPC with IMRT 6 chemotherapy.
Study
22
Lee et al
(United States)
Kwong et al29
(Hong Kong)
Kam et al30
(Hong Kong)
Median
follow-up (mo)
Time
point (y)
Local
control
Regional
control
Distant
metastasis-free
rate
Overall survival
N
Characteristics
67
All stages
31
4
97%
98%
66%
73%
33
T1N0–N1, M0
24
3
100%
92%
100%
100%
64
All stages
29
3
92%
98%
79%
90%
Abbreviations: NPC, nasopharyngeal cancer; IMRT, intensity-modulated radiation therapy.
Reprinted with permission from Puri DR, et al. Intensity-modulated radiation therapy in head and neck cancers. Dosimetric advantages and update of
clinical results. Am J Clin Oncol 2005; 28(4): 415–423, Lippincott Williams & Wilkins.
reasons stated previously. Lu et al31 have recently
reported on the experience with reirradiation
using IMRT for recurrent nasopharyngeal cancer.
Acute toxicity of the skin, mucosa, and salivary
glands was acceptable according to the RTOG criteria. Tumor necrosis was seen toward the end
of IMRT in 14 patients, or 28.6%. At a median
follow-up of 9 months, the locoregional control
rate was 100%. Although longer follow-up is necessary, the preliminary toxicity and local control
data for these recurrent cases are promising.55
OROPHARYNX
Radiation therapy, given either definitively or
postoperatively, has long been a component in
the management of primary oropharyngeal carcinoma. However, the patient often has permanent
xerostomia because of bilateral parotid gland irradiation. With conventional treatment, 60% to 75%
of patients are expected to have grade 2 or higher
xerostomia after radiation therapy for an oropharyngeal primary tumor.32 The permanent loss of
saliva can, in turn, have a negative impact on
nutrition, dentition, communication, emotional
well-being, and the risk of infection in the oral
cavity.33,34 As one might expect, therefore, parotidsparing IMRT has been shown to broadly improve
a patient’s quality of life.35–39,55
One possible concern in oropharyngeal cancer
is that efforts at parotid sparing may occur at the
expense of local control. However, this is not the
case to date. Eisbruch et al23 have shown that the
3-year locoregional control rate is 94% in 80
patients with oropharyngeal cancer. The median
follow-up in this cohort was 32 months, and 93%
of the patients had stage III or IV disease. With
slightly longer follow-up, Chao et al38 reported
a local control rate of 87% using IMRT in 74
patients with oropharyngeal cancer. In this study,
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46% of the patients had T3/T4 disease, and 76%
of the patients had locally advanced stage III/IV
disease. Multivariate analysis demonstrated that
primary tumor GTV and nodal GTV were independent risk factors determining loco-regional
control and disease-free survival for patients with
definitive oropharyngeal IMRT. It follows that
attempts at parotid sparing should not compromise tumor coverage.55 Different centers have
consistently shown excellent tumor control and
improved salivary function (Table 2; references
40–42). An example of a patient with oropharyngeal cancer treated with IMRT and chemotherapy
is shown in Figure 4.
A multi-institutional RTOG study, H-0022,
using IMRT for early-stage oropharyngeal cancer
has completed accrual, and the results are underway. The protocol is also an important one, because it tests the ability to test the feasibility and
transportability of IMRT from single institutions
to multi-institutions.
PARANASAL SINUS
Treatment of paranasal sinus (PNS) tumors with
conventional radiotherapy is typically associated
with poor outcomes43,44 and high toxicity rates,45
prompting the use of postoperative rather than
definitive radiotherapy in an effort to reduced
optic nerve injury. Because of the proximity of
the multiple nearby critical tissues, the use of
IMRT is of substantial clinical interest in the
treatment of PNS tumors.46 Several dose comparison studies have shown that IMRT can further decrease the dose delivered to the optic
chiasm, brain stem, optic nerves, and the orbits
while having the ability to fully cover the tumor
target.47 The difficulty in treating these tumors
lies in the definition of the target volume. In general, these tumors have already undergone surgi-
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Table 2. Results from series treating OPC with IMRT 6 chemotherapy.
Time
point (y)
Local
control
Locoregional
control
Disease-free
survival
Distant
metastasisfree survival
Overall
survival
Study
N
Characteristics
Median
follow-up (mo)
Chao et al38
(Mallinckrodt)
Garden et al40
(MDACC)
Huang et al41
(UCSF)
De Arruda et al42
(MSKCC)
74
93% stage III or IV
33
4
NR
87%
81%
90%
87%
80
T1–2, Tx
Nþ
T1–4
N0-3
Stage III and IV
17
2
NR
94%
NR
NR
NR
14
2
94%
89%
91%
NR
89%
18
2
97%
85%
NR
72%
100%
41
43
Abbreviations: OPC, oropharyngeal cancer; IMRT, intensity-modulated radiation therapy; NR, not reported; MDACC, M. D. Anderson Cancer Center;
UCSF, University of California San Francisco.
Reprinted with permission from Puri DR, et al. Intensity-modulated radiation therapy in head and neck cancers. Dosimetric advantages and update of
clinical results. Am J Clin Oncol 2005; 28(4): 415–423, Lippincott Williams & Wilkins.
FIGURE 4. Intensity-modulated radiation therapy (IMRT) dose distribution for a T2N2b base of tongue cancer. (A) Axial. (B) Sagittal.
(C) Coronal. Planning target volume (PTV) for the gross tumor volume (GTV), (blue); encompassed by the 7000 cGy isodose line,
red. Ipsilateral subclinical region (orange); encompassed by the 5940 cGy isodose line, green. Contralateral subclinical region (yellow);
encompassed by the 5400 cGy isodose line, blue. [Color figure can be viewed in the online issue, which is available at www.interscience.
wiley.com.]
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FIGURE 5. T4N2bM0 squamous cell carcinoma of the left ethmoid and maxillary sinuses. The patient received induction chemotherapy
followed by left orbitomaxillectomy (A,B). At the time of referral for postoperative radiotherapy, recurrence was noted at the posterior margin of resection (B). The patient was referred for postoperative chemoradiotherapy and received a dose of 66 Gy in 30 fractions to the
areas of suspected gross recurrence. Target outlines and representative axial sections are shown (C). The corresponding dose volume
histograms are shown in (D). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
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HEAD & NECK—DOI 10.1002/hed
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FIGURE 5. (continued)
cal resection, typically with close or positive surgical margins. Therefore, one must ensure that
an adequate dose is delivered to the postoperative bed. When difficulty arises, the approach
should be to superimpose the preoperative scan
on the postoperative scan and then customize the
margins after discussing the case with the head
and neck surgeon and reviewing the pathology.
Whenever possible, it is encouraged that the
head and neck surgeon be present when the volumes are drawn. An example of a patient with sinus
cancer undergoing IMRT is shown in Figure 5.
Table 3. Grade 3 acute toxicity incidence from series treating TC with IMRT 6 chemotherapy.
Study
54
Ahamad et al
(MDACC)
Rosenbluth et al53
N
Characteristics
Pharyngitis/esophagitis
Skin
Mucositis
Laryngitis
24
All histologies
64%
29%
67%
NR
20
Nonanaplastic
15%
10%
35%
10%
Abbreviations: TC, thyroid cancer; IMRT, intensity-modulated radiation therapy; MDACC, M. D. Anderson Cancer Center; NR, not reported.
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An important feature of IMRT for sinonasal
cancer is the ability to prevent ‘‘dry eye syndrome,’’
a well-documented complication after conventional
radiotherapy.48 A dose response has been associated with this syndrome, because it is typically not
observed with doses less than 30 Gy but may
approach an incidence of 100% at doses exceeding
55 to 60 Gy. Clinically, dry eye symptoms usually
start approximately 1 month after radiation and
may include pain, itchiness, erythema, photophobia, foreign body sensation, and a hypersensitivity
to wind.55
A substantial amount of clinical experience
with treatment of PNS tumors has been collected
by Claus et al at the Ghent University Hospital in
Belgium. The original report in 2002 was updated
in 2003 by De Neve at a teaching course in Denmark.49,50 Between 1999 and 2002, 44 patients
received IMRT for ethmoid sinus, maxillary sinus,
or nasal cavity cancers. For most patients, the
PTV prescription dose was 70 Gy, with a maximum dose constraint of 60 Gy to the optic chiasm
and nerves with a 2-mm margin. Although followup is relatively short, importantly, it is sufficient
to detect the relatively acute dry-eye syndrome.
None of the patients in whom optic pathway sparing was attempted had severely dry eyes develop.
Locoregional control was noted to be excellent for
patients with T1–3 stage but poor in patients with
T4 stage disease. Further investigation is underway at multiple treatment centers to corroborate
this initial experience.
sity-modulated treatment plans for a case of anaplastic thyroid cancer. They concluded that inverse
treatment planning provided superior dose optimi-
THYROID
The role of radiation therapy for thyroid cancer
is mostly restricted to the postoperative setting.
Because of the proximity of the tumor bed to the spinal cord, it has traditionally been very difficult to
deliver adequate doses to the PTV without risking
spinal cord damage. This risk is thought to occur at
doses greater than 45 Gy. Dosimetric studies done
on the use of IMRT in the treatment of thyroid cancer have shown improvements in target coverage
while reducing the spinal cord dose. Nutting et al51
compared IMRT with 3D-CRT and conventional
techniques. They noted that 3D-CRT reduced normal tissue irradiation compared with conventional
techniques but did not improve PTV or spinal cord
doses. This had to do with the anatomic relationship of the U-shaped PTV, which often surrounds
the spinal cord. Only IMRT improved the PTV coverage and reduced the spinal cord dose. In addition,
Posner et al52 compared conventional and inten-
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Intensity-Modulated Radiation Therapy
FIGURE 6. A patient with history of metastatic colon carcinoma
had a surveillance PET scan showing a T4N1bM0 Hürthle cell
carcinoma of the thyroid (A,B). The patient received surgical
resection. At the time of referral for postoperative radiotherapy,
gross nodal disease was evident in the left side of the neck
(level II). The patient received a dose of 66 Gy in 30 fractions
to the gross nodal disease, 60 Gy to the areas at highest risk
for sub-clinical disease in the thyroid bed, and 54 Gy to the remainder of the operative bed. Target outlines and representative
axial sections are shown (C). The corresponding dose volume
histograms (DVHs) are shown in (D). Note that, despite treatment of the bilateral supraclavicular regions and mediastinum,
the combined lung DVH was acceptable, with V20 below 30%.
[Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
HEAD & NECK—DOI 10.1002/hed
April 2007
zation, particularly with respect to the spinal cord
and CTV.55
At MSKCC, we routinely treat thyroid cancer
with IMRT. Our preliminary data show this to
be an effective, feasible, and well-tolerated treat-
ment, although longer follow-up is needed to
assess outcome and toxicity. Rosenbluth et al53
have recently looked at the MSKCC experience
with IMRT in 20 patients who were treated for
nonanaplastic thyroid cancer from July 2001 to
FIGURE 6. (continued)
Intensity-Modulated Radiation Therapy
HEAD & NECK—DOI 10.1002/hed
April 2007
397
FIGURE 6. (continued)
January 2004. Most of these patients had T4N1
disease. With two local failures, the 2-year local
progression-free rate was 85%. There were six
deaths, with a 2-year overall survival rate of 60%.
The worst acute mucositis and pharyngitis was
grade 3, with seven and three patients experiencing these symptoms, respectively. Only two patients had grade 3 acute skin toxicity, and two
had grade 3 acute laryngeal toxicity. No significant radiation-related late effects were reported.
Table 3 details the toxicity profiles of this experience, as well as that of Ahamad et al54 from M. D.
Anderson Cancer Center.55 An example of a
patient with thyroid cancer treated with IMRT is
shown in Figure 6.
398
Intensity-Modulated Radiation Therapy
CONCLUSION
IMRT is an obvious treatment approach for head
and neck cancer. Obtaining tight dose gradients
around gross and subclinical disease is desirable
in the vicinity of the spinal cord, parotid glands,
and brain stem. Although disease recurrence to
date has been reported to occur mostly in the infield high-dose volume, the theoretical concerns
regarding the sharp dose fall off of IMRT and
risks of irradiating normal tissue despite efforts
at immobilization are valid. Hopefully, in the
future, better anatomic and functional imaging,
refinement of image-guided radiation therapy,
and, perhaps most importantly, more experience
with the technology will allow for IMRT to pro-
HEAD & NECK—DOI 10.1002/hed
April 2007
duce further significant improvements in local
control, survival, and long-term toxicity profiles
in the head and neck region.55
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