Organ-sparing radiotherapy in head and neck cancer

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P ractic e
g u i d e l in e s
Organ-sparing radiotherapy in head
and neck cancer
A u tho rs
P. Dirix, S. Nuyts
Key wo rds
Head and neck cancer, radiotherapy, IMRT, organs at risk
Summary
Intensification of radiotherapy (RT) treatment
for locally advanced head and neck cancer
(HNC) through the use of altered fractionation
schedules and/or concomitant chemotherapy has
resulted in significantly improved loco-regional
control and survival rates. However, these
improvements in outcome come at the cost of
increased acute, and perhaps also late, toxicity.
It is to be expected that technological advances
Introduction
Several groups have evaluated the major contributing
factors to quality of life after RT for head and neck
cancer.1,2 It has been shown that both late xerostomia and swallowing disorders are the main causes
of decreased quality of life.2,3 These discomforts are
the focus of this review. Some specific OAR such
as the lens, the optic nerve and the chiasm (in sinonasal cancer) or temporal lobes (in nasopharyngeal
cancer) will not be addressed.
Salivary glands
Since irreparable damage is caused to the salivary
glands which are included in the radiation fields, a
permanent dry mouth or xerostomia is one of the
most common complications of conventional radiotherapy for head and neck cancer.4 About 60 – 65%
of the total salivary volume is produced by the parotid glands. Therefore, most attention has been directed to developing parotid-sparing techniques.5,6 It
is generally accepted that a significant reduction of
xerostomia can be achieved by maintaining a mean
parotid dose lower than 26 to 30 Gy as a planning
criterion.4 However, since lower doses (10 – 15 Gy)
can also induce serious loss of function, the mean
dose should probably be kept as low as possible.7 If
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such as intensity-modulated radiotherapy (IMRT)
will further improve the therapeutic index of RT
in HNC by limiting toxicity and possibly increasing local control. The organ-sparing potential of
IMRT and other highly conformal radiotherapy
techniques relies heavily on the appropriate
selection and accurate delineation of the critical organs at risk (OAR), with the application of
rigorous restrictions during planning.
(BJMO 2008;vol 2;4:212-5)
patients are carefully selected, parotid-sparing does
not result in higher recurrence rates.8,9
Since the submandibular glands are responsible for
most of the saliva production during stimulation,
they could also play an important part in radiationinduced xerostomia.4 Saarilathi et al were the first to
demonstrate that sparing of the contralateral submandibular gland (mean dose < 25 Gy) is feasible
with IMRT and results in prevention of xerostomia.
Recently a group from the university of Michigan
suggested a mean dose threshold of 39 Gy for submandibular gland sparing.10,11 Although data on
possible thresholds are currently lacking, the mean
dose to the oral cavity, representing the RT effect on
the minor salivary glands, may also be important in
the prevention of xerostomia.4
Swallowing structures
Swallowing dysfunction during or after radiotherapy
is correlated with compromised quality of life, anxiety and depression. It can also lead to life-threatening
complications such as aspiration pneumonia.12 Dysphagia is more and more recognized as being the doselimiting toxicity of concomitant chemoradiotherapy
for head and neck cancer.13 It is to be expected that
limiting the dose to the critical swallowing struc-
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Table 1. Delineation guidelines for the swallowing structures.
OAR
Superior border
Inferior border
Anterior border
Posterior border
Superior pharyngeal
constrictor muscle
caudal tip of the
pterygoid plates
(hamulus)
upper edge of
hyoid bone
cervical vertebra
or pre-vertebral
muscles
Middle pharyngeal
constrictor muscle
upper edge of
hyoid bone
lower edge of
hyoid bone
widest diameter of
rhinopharynx, base
of tongue, hyoid
bone and larynx
Inferior pharyngeal
constrictor muscle
lower edge of
hyoid bone
lower edge of
cricoid cartilage
Base of tongue
below soft palate
(uvula)
upper edge of
hyoid bone
Supraglottic larynx
(lumen excluded)
top of the
upper edge
piriform sinus and of the cricoid
aryepiglottic fold cartilage
Glottic larynx
(lumen excluded)
at the level of the cricoid cartilage
Upper esophageal
sphincter including
cricopharyngeus muscle
lower edge of
cricoid cartilage
Esophagus
upper edge of
trachea
anterior tip of the
thyroid cartilage
cornu of the thyroid
cartilage
upper edge of
trachea
subglottic larynx
cervical vertebra
first 2cm
trachea
cervical vertebra
tures will reduce the incidence of dysphagia.12 However, several questions regarding to which swallowing
structures are essential and what volume and dose restrictions should be applied, remain to be answered.
Based on a literature search, 8 relevant swallowing
structures for organ-sparing RT can be identified: (1)
superior pharyngeal constrictor muscle, (2) middle
pharyngeal constrictor muscle, (3) inferior pharyngeal
constrictor muscle, (4) base of the tongue, (5) supraglottic larynx, (6) glottic larynx, (7) upper esophageal
sphincter, including the cricopharyngeus muscle and
(8) the esophagus (Table 1). In most studies, the upper
and middle pharyngeal constrictor muscles as well as
the glottic and supraglottic larynx appear to be the
most critical OAR, and reducing their radiation doses
could lead to a clinical benefit.14-17
Auditory structures
Despite their apparent functional consequences,
radiotherapy-induced ear injuries remain underevaluated and under-reported. Up to 40% of patients
suffer from acute middle ear side-effects (e.g. otitis
media with effusion or transient conductive hearing
loss), while about one third of patients develop late
sensorineural hearing loss (SNHL) due to inner ear
(cochlea) damage.18 The use of concomitant chemotherapy (cisplatin), total RT dose and the tumor site
(nasopharynx) seem to be the most important factors
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posterior third of the tongue
associated with the risk of hearing impairment.18 Thus,
reducing the radiation dose to the auditory structures
should be attempted whenever possible. Researchers
from the university of Michigan conducted a prospective study of SNHL in which the function of the
cochlea ipsilateral to the tumor, which had received a
high dose, was compared to the contralateral cochlea,
which had received a low dose. They observed that
SNHL risk started at doses of 40 – 45 Gy.19 These
results are consistent with other prospective studies
that reported increased hearing loss risks associated
with doses in the range of 40 – 50 Gy.18
Mandible and temporo-mandibular joints
Osteoradionecrosis (ORN) of the mandibular bone
is a well-documented complication of conventional
radiotherapy in HNC.20 In general, bones are resistant to high radiation doses and will not sustain any
overt damage as long as the overlying soft tissue remains intact and the bone is not subjected to excessive stress or trauma. A retrospective analysis of 176
HNC patients treated with IMRT at the university
of Michigan revealed a 0% incidence of ORN, if a
maximal dose restrictions of 72 Gy was respected.21
Strict dental prophylactic care is probably the most
essential factor in the prevention of ORN.20,21
Irradiation of the temporo-mandibular joints (TMJ)
with high radiation doses can result in a slowly evol-
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Key messages for clinical practice
OAR
Dmax
Dmean
Volume restrictions
Spinal cord
45 Gy
-
-
Spinal cord extended
(5mm margin)
-
-
> 50 Gy to ≤ 1%
Brainstem
54 Gy
-
-
Brainstem extended
(1mm margin)
-
-
> 60 Gy to ≤ 1%
Parotid gland
1. mean dose to either gland (at least one) < 26 Gy or
2. at least 50% of either gland (at least one) < 30 Gy or
3. at least 20cc of combined volume of both glands < 20 Gy
Submandibular gland
no restrictions, reduce dose as much as possible
Oral cavity
-
< 40 Gy
-
Tongue
55 Gy
-
> 65 Gy to ≤ 1%
Pharyngeal constrictor muscles
no restrictions, reduce dose as much as possible
Larynx
-
< 45 Gy
< 50 Gy to 2/3 of volume
Esophagus
-
< 45 Gy
-
Inner ear (cochlea)
-
< 50 Gy
> 55 Gy to ≤ 5%
External and middle ear
-
< 50 Gy
-
Mandible
70 Gy
-
> 75 Gy to ≤ 1 cc
Temporo-mandibular joints
70 Gy
-
> 75 Gy to ≤ 1 cc
Brachial plexus
60 Gy
-
-
Brain (temporal lobes)
60 Gy
-
> 65 Gy to ≤ 1%
Overview of restrictions for critical organs at risk (OAR) in recent RTOG trials on head and neck radiotherapy
(adapted from www.rtog.org).
ving inability to open the mouth (trismus), with an incidence of 5 – 38% after conventional RT. Currently,
no reliable dose-response relationship exists, but most
problems are observed above a dose of 70 Gy.20
Brachial plexus
Concerns about the development of brachial plexopathy (mostly seen in patients irradiated for breast
or lung cancer) after radiotherapy for HNC have
prompted the radiation therapy oncology group
(RTOG) to include brachial plexus dose restrictions
ranging from 60 to 66 Gy in many recent protocols.
However, a recent analysis showed that patients
treated with IMRT often receive a brachial plexus
dose > 60 Gy, with 70% and 30% of patients receiving doses of > 66 and > 70 Gy, respectively.22 It
should also be noted that the brachial plexus is best
imaged, and delineated, with gadolinium-enhanced
T1-weighted coronal and sagittal MRI sequences,
and usually cannot be visualized on CT.22
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Conclusion
If head and neck cancer patients are treated with
IMRT or other highly conformal radiotherapy techniques, it is important that all relevant organs at risk
are delineated and rigorous dose-restrictions are applied. It is to be expected that the prospective collection of dosimetric data along with the corresponding functional outcomes will allow the development
of more precise dose-response curves.
References
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B E L G I A N
Correspondence address
Authors: P. Dirix, S. Nuyts
Department of Radiation Oncology, Leuvens Kankerinstituut (LKI), University Hospital Leuven, Campus
Gasthuisberg, Leuven, Belgium.
Please send all correspondence to:
Dr. P. Dirix
Department of Radiation Oncology
Leuvens Kankerinstituut (LKI)
University Hospital Leuven, campus Gasthuisberg
Herestraat 49
B – 3000 Leuven
Belgium
Tel: 0032 (0)16 34 76 00
Fax: 0032 (0)16 34 76 23
Email: [email protected]
Financial support: Piet Dirix is a research assistant
(aspirant) of the Research Foundation Flanders (FWO).
Sandra Nuyts is supported by a grant from the Klinisch
Onderzoeksfonds (KOF) of the University Hospitals
Leuven.
Conflicts of interest: the authors have nothing to disclose and indicate no potential conflicts of interest.
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