Clinical Study Prognostic Value of Classifying Parapharyngeal

Hindawi Publishing Corporation
BioMed Research International
Article ID 749515
Clinical Study
Prognostic Value of Classifying Parapharyngeal
Extension in Nasopharyngeal Carcinoma Based on
Magnetic Resonance Imaging
Guo-Yi Zhang,1 Ying Huang,2 Xue-Feng Hu,1 Xiang-Ping Chen,1 Tao Xu,1 Li-Zhi Liu,3
Wei-Hong Wei,1 Guo-Sen Huang,1 Miao-Miao Zhou,1 Ze-Li Huang,1 and Yue-Jian Wang1
1
Cancer Center, Cancer Research Institute, Foshan Hospital, Sun Yat-sen University, Foshan, Guangdong 528000, China
Department of Radiation Oncology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of
Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China
3
Imaging Diagnosis and Interventional Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center
of Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China
2
Correspondence should be addressed to Yue-Jian Wang; [email protected]
Received 4 June 2014; Accepted 29 July 2014
Academic Editor: An Liu
Copyright © Guo-Yi Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Purpose. To subclassify parapharyngeal extension in nasopharyngeal carcinoma (NPC) and investigate its prognostic value and
staging categories based on magnetic resonance imaging (MRI). Methods and Materials. Data from 1504 consecutive NPC patients
treated with definitive-intent radiotherapy were analyzed retrospectively. Sites of parapharyngeal extension were defined by MRI.
Overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by the
Kaplan-Meier method and compared with the log-rank test. Hazard consistency and hazard discrimination were determined by
multivariate analysis with Cox proportional hazards models. Results. 1104 patients (73.4%) had parapharyngeal extension; 1.7–
63.8% had involvement of various anatomic sites. The hazard ratio for death was significantly higher with extensive parapharyngeal
extension (lateral pterygoid muscle of masticator space and beyond or parotid space) than with mild extension (medial pterygoid
muscle of masticator space, or carotid, prestyloid, and prevertebral or retropharyngeal space). OS, LRFS, and DMFS with extensive
parapharyngeal extension were similar to those in T4 disease; OS, LRFS, and DMFS with mild parapharyngeal extension were
significantly higher than in those T3 disease (all P ≤ 0.015). Conclusions. Parapharyngeal extension in NPC should be subclassified
as mild or extensive, which should be regarded as stages T2 and T4 diseases, respectively.
1. Introduction
Nasopharyngeal carcinoma (NPC) has a strong invasive
tendency and often develops parapharyngeal extension, with
a prevalence of 72–83% at diagnosis [1–10]. Parapharyngeal
extension in NPC indicates tumor invasion beyond the
pharyngobasilar fascia and into the parapharyngeal, masticator, prevertebral, or parotid space, which are separated
by the cervical fascias; the parapharyngeal space can be
subdivided into the prestyloid, carotid, and retropharyngeal
spaces (Figure 1).
The prognostic significance of parapharyngeal extension in NPC has not been resolved [1–12] and the recommendations in published staging systems pertaining to
parapharyngeal extension are ambiguous [13–16]. Chua et al.
[1] reported that lateral tumor invasion beyond the line
joining the free edge of the medial pterygoid plate to the
styloid process was an independent prognostic factor. Other
studies have shown that paraoropharyngeal extension or
posterolateral tumor invasion beyond a line drawn from
the styloid process to the midpoint of the posterior edge
of the great occipital foramen also has some value as an
indicator of poorer prognosis [3–5]. However, using the
American Joint Committee on Cancer (AJCC) definition
of parapharyngeal extension beyond the pharyngobasilar
fascia or subclassifying the degree of parapharyngeal extension according to the presence or absence of carotid space
2
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Table 1: Characteristics of 1504 patients with nasopharyngeal
carcinoma.
RT
M
RT
T
LP
T
MP
M
LP
CS
CS
MP
Figure 1: Axial section through the nasopharynx showing the
relationship between various anatomic sites of parapharyngeal
extension surrounding the nasopharynx, which are divided by the
three layers of the cervical fascia: deep (dark blue line), middle
(bright green line), and superficial (orange line). Parapharyngeal
extension includes involvement of the masticator space (MS, blue),
prestyloid space (PSS, purple), carotid space (CS, green), retropharyngeal space (RPS, pink), prevertebral space (PVS, yellow), and
parotid space (PS, brown). Compared with the anatomic masticator
space, the staging masticator space (the region within the red line)
excludes the medial and lateral pterygoid muscles but includes the
retromaxillary fat pad. MP: medial pterygoid muscle; LP: lateral
pterygoid muscle; M: masseter muscle; T: temporalis muscle; RT:
retromaxillary fat pad.
involvement, parapharyngeal extension had no prognostic
significance in NPC [7–10]. The definitions of parapharyngeal
extension used in these studies vary widely, and most patients
were staged on the basis of computed tomography (CT)
scans. Conversely, two studies based on magnetic resonance
imaging (MRI) suggested that involvement of any part of the
anatomic masticator space should be regarded as T4 disease
[11, 12].
In light of these discrepancies, this study aimed to identify
appropriate subclassifications (lateral, posterior, posterolateral, and inferior spread) for parapharyngeal extension in
NPC and to reassess the prognostic value and staging categories for parapharyngeal extension based on MRI in patients
with NPC treated with definitive-intent radiotherapy.
2. Materials and Methods
2.1. Patients. This retrospective study was approved by the
institutional review board and all examinations were performed after written informed consent had been obtained
from the patients or their next of kin. From December 2002
to October 2006, 1504 ethnic Chinese patients (1145 males,
mean age 46 years, range 13–76 years; 358 females, mean age
43 years, range 18–75 years) with newly diagnosed, untreated,
and nondisseminated NPC who were subsequently treated
with definitive-intent radiotherapy were enrolled in the
study. Patients whose treatment deviated from institutional
guidelines due to advanced age or organ dysfunction were
excluded. All patients underwent pretreatment evaluation
Characteristic
WHO pathologic classification
Type 1
Type 2
Type 3
T classification
T1
T2
T3
T4
N classification
N0
N1
N2
N3
AJCC 2010 stage
I
II
III
IVa-b
Number of patients∗
17 (1.1)
168 (11.2)
1319 (87.7)
278 (18.5)
220 (14.6)
587 (39.0)
419 (27.9)
344 (22.9)
901 (59.9)
207 (13.8)
53 (3.4)
101 (6.7)
311 (20.7)
638 (42.4)
454 (30.2)
AJCC: American Joint Committee on Cancer; WHO: World Health Organization.
∗
Numbers in parentheses are percentages.
including MRI of the neck and nasopharynx, chest radiography, abdominal sonography, and a whole-body bone scan.
Medical records and imaging studies were reviewed and all
patients were restaged according to the 2010 AJCC TNM
staging system for NPC [15]. Table 1 shows the patients’
pathologic classification, T classification, N classification, and
overall stage.
2.2. Imaging Protocol. All patients underwent MRI using
a 1.5 T system (Signa CV/I; GE Healthcare, Milwaukee,
WI) employing a spin echo technique. The region from the
suprasellar cistern to the inferior margin of the sternal end of
the clavicle was examined with a head and neck combined
coil. T1-weighted images in the axial, coronal, and sagittal
planes (repetition time 500–600 ms, echo time 10–20 ms)
and T2-weighted images in the axial plane (repetition time
4000–6000 ms, echo time 95–110 ms) were obtained before
injection of the contrast material. After intravenous injection
of Gd-DTPA at a dose of 0.1 mmol/kg body weight, T1weighted axial and sagittal sequences and T1-weighted fatsuppressed coronal sequences were performed sequentially,
with parameters similar to those used before Gd-DTPA
injection. The section thicknesses and interslice gaps were
5 mm and 1 mm for the axial plane and 6 mm and 1 mm for
the coronal and sagittal planes.
2.3. Image Assessment. Two experienced radiologists (Y.Z.L.
and L.Z.L., with 10 and 12 years’ experience in MRI of
NPC, resp., at the time of the study) separately evaluated
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the images. Any disagreements were resolved by consensus.
MRI findings of parapharyngeal extension were assessed at
the following sites: medial pterygoid muscle, lateral pterygoid
muscle, staging masticator space (tumor involvement beyond
the anterior surface of the lateral pterygoid muscle), prestyloid space, retropharyngeal space, anterior carotid space,
posterior carotid space (the demarcation of the anterior
and posterior carotid space was the posterior edge of the
internal jugular vein), prevertebral space, parotid space,
and paraoropharyngeal space (Figure 1). Paraoropharyngeal
extension was defined as parapharyngeal involvement of
tumor below the C1/C2 interspace [3].
2.4. Treatment. All patients were treated with definitiveintent radiotherapy. Most of the patients (805, 53.5%) were
treated with conventional techniques based on CT simulation, but 621 (41.3%) patients received intensity-modulated
radiation therapy (IMRT) and 78 (5.2%) underwent threedimensional conformal radiotherapy (3DCRT). Details of the
radiotherapy techniques used at our cancer center have been
reported previously [17–19].
During the study period, based on the AJCC 2002
staging system, our institutional guidelines recommended
radiotherapy alone for stage I disease, concomitant chemoradiotherapy (CCRT) for stage II disease, and induction or
adjuvant chemotherapy together with CCRT for stage III
to IVB disease. Overall, 101 study patients were treated
with radiotherapy only and 317 received CCRT; induction
chemotherapy and CCRT were delivered to 423 patients and
adjuvant chemotherapy and CCRT were delivered to 663
patients.
2.5. Followup and Statistical Analysis. Complete follow-up
data were available for 97.4%, 96.5%, and 73.6% of the 1504
patients at 3 years, 5 years, and 8 years, respectively. The
duration of followup was calculated from the first day of
treatment to either the day of death or the day of the last
examination. Patients were followedup at least once every 3
months during the first 2 years and every 6 months thereafter
until death. The median follow-up period was 110 months
(range 2–128 months).
SPSS version 16.0 (IBM, Armonk, NY) was used for
all statistical analyses and the timing of all events was
measured from the start of treatment. The time to the first
defining event was assessed for the following end points:
overall survival (OS), local relapse-free survival (LRFS),
and distant metastasis-free survival (DMFS). Actuarial rates
were calculated by the Kaplan-Meier method and compared
using the log-rank test [20]. Multivariate analyses using Cox
proportional hazards models were employed to test hazard
consistency and hazard discrimination by backward elimination of insignificant explanatory variables [21]. Two-tailed 
values of <0.05 were considered statistically significant.
3. Results
3.1. Pattern of Failure. One hundred and seventy patients
(11.3%) developed local recurrence, 220 (14.6%) developed
distant metastases, and 446 (29.7%) died. For the entire
3
patient population, 5-year OS, LRFS, and DMFS ± standard
deviation were 80.9% ± 1.0%, 89.7% ± 0.8%, and 86.3% ±
0.9%, respectively, and 8-year OS, LRFS, and DMFS were
70.3% ± 1.2%, 87.6% ± 0.9%, and 84.4% ± 1.0%, respectively.
3.2. Prevalence of Parapharyngeal Extension by Anatomic
Site. Of the 1504 patients, 1104 (73.4%) were diagnosed with
parapharyngeal extension. Among these 1104 patients, the
retropharyngeal and prestyloid spaces were the most commonly involved sites, followed by the prevertebral space,
anterior carotid space, medial pterygoid muscle, lateral
pterygoid muscle, posterior carotid space, paraoropharyngeal space, parotid space, and staging masticator space,
with incidences of 63.8% (960/1504), 62.5% (940/1504),
39.0% (587/1504), 29.4% (442/1504), 20.7% (311/1504), 8.8%
(132/1504), 7.4% (111/1504), 3.3% (50/1504), 2.6% (39/1504),
and 1.7% (26/1504), respectively. The most common sites of
tumor involvement were thus adjacent to the nasopharynx
and the least common were more distant to the nasopharynx.
3.3. Subclassification of Masticator, Carotid, and Paraoropharyngeal Space Extension. The prognostic value of the grade
of lateral tumor spread was analyzed to determine an optimal
subclassification for masticator space invasion. There was no
significant difference in hazard ratio (HR) for OS, LRFS,
or DMFS between patients with lateral pterygoid muscle
invasion and those with staging masticator space invasion
( = 0.727,  = 0.765, and  = 0.842, resp.), whereas patients
with medial pterygoid muscle invasion had significantly
lower HRs for death and distant metastasis than those with
lateral pterygoid muscle invasion ( = 0.006 and  = 0.011,
resp.) (Table 2). When masticator space invasion was graded
as involvement of the medial pterygoid muscle versus
involvement of the lateral pterygoid muscle and beyond,
significant differences in HRs for death and distant metastasis
were observed between the two groups ( = 0.005 and  =
0.006, resp.; Table 2).
To investigate the prognostic significance of posterolateral or inferior tumor spread, we compared differences in
HR between anterior and posterior carotid space involvement
and between paranasopharyngeal and paraoropharyngeal
extension. The HRs for OS, LRFS, and DMFS in patients
with anterior carotid space invasion were similar to those of
patients with posterior carotid space invasion ( = 0.618,
 = 0.621, and  = 0.085, resp.), as were these values for
patients with paraoropharyngeal extension compared with
patients with paranasopharyngeal extension ( = 0.482,  =
0.072, and  = 0.312, resp.) (Table 2). These results suggest
that subclassifications of carotid space or paraoropharyngeal
extension are unnecessary.
3.4. Classification of Parapharyngeal Extension. Based on
the above findings, HRs for death according to anatomic
site (prestyloid space, carotid space, retropharyngeal space,
prevertebral space, medial pterygoid muscle, lateral pterygoid muscle and beyond, and parotid space) were further
analyzed to subclassify parapharyngeal extension. There were
significant differences in the HR for death between patients
4
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Table 2: Incidence of tumor parapharyngeal extension by anatomic site.
Death
Anatomic site
HR∗ (95% CI)
Masticator space
None
0.551 (0.400–0.760)
Medial pterygoid muscle
0.623 (0.445–0.873)
Lateral pterygoid muscle
1
Staging masticator space
0.906 (0.522–1.573)
Masticator space
None
0.885 (0.651–1.202)
Medial pterygoid muscle
1
Lateral pterygoid muscle and beyond 1.572 (1.143–2.163)
Carotid space
None
0.735 (0.586–0.921)
Anterior carotid space
1
Posterior carotid space
1.085 (0.787–1.497)
Parapharyngeal extension
None
0.678 (0.494–0.931)
Paranasopharyngeal
1
Paraoropharyngeal
1.169 (0.756–1.809)
∗
Local failure
HR∗ (95% CI)


<0.001
0.006
0.727
0.433
0.005
0.008
0.618
0.016
0.482
0.457 (0.267–0.782)
0.940 (0.566–1.561)
1
1.147 (0.467–2.819)
0.004
0.812
0.486 (0.302–0.780)
1
1.091 (0.678–1.754)
0.003
0.693 (0.482–0.996)
1
1.035 (0.802–1.507)
0.048
0.659 (0.395–1.099)
1
1.734 (0.952–3.158)
0.110
0.765
0.720
0.621
0.072
Distant metastasis
HR∗ (95% CI)

0.394 (0.256–0.606)
0.584 (0.386–0.884)
1
1.067 (0.563–2.023)
<0.001
0.011
0.675 (0.439–1.037)
1
1.734 (1.172–2.567)
0.073
0.689 (0.502–0.947)
1
1.425 (0.952–2.132)
0.832 (0.523–1.325)
1
1.257 (0.857–2.213)
0.842
0.006
0.022
0.085
0.439
0.312
HR adjusted for age, gender, chemotherapy, T category, and N category according to the seventh edition AJCC system.
and extensive invasion (involvement of lateral pterygoid
muscle and beyond of masticator space or parotid space).
7
6
5
4
3
2
95% CI lower bounds
1
T1
PSS
RPS
CS
PVS
MMS LMS
PS
Figure 2: HR for death according to anatomic site of parapharyngeal
extension (HR adjusted for age, gender, chemotherapy, and N
category according to the seventh edition AJCC system). PSS:
prestyloid space; RPS: retropharyngeal space; CS: carotid space;
PVS: prevertebral space; MMS: medial pterygoid muscle of masticator space; LMS: lateral pterygoid muscle of masticator space and
beyond; PS: parotid space.
with T1 disease (AJCC 2010 staging system) (HR = 1) and
those with invasion of other sites. The HRs associated
with prestyloid space, carotid space, retropharyngeal space,
prevertebral space, and medial pterygoid muscle invasion
were similar to each other, whereas those associated with
the lateral pterygoid muscle and beyond and parotid space
invasion were significantly higher than the others (Figure 2).
Therefore, we propose that the parapharyngeal extension
should be divided into two grades: mild invasion (involvement of medial pterygoid muscle of masticator space or
prestyloid, carotid, prevertebral, or retropharyngeal spaces)
3.5. Staging Categories for Parapharyngeal Extension. To
assess the prognostic value and staging categories for different degrees of parapharyngeal extension in NPC, we
divided T2–T4 patients (AJCC 2010 staging system) into four
groups: group 1, mild parapharyngeal invasion; group 2, T3
without extensive parapharyngeal invasion; group 3, all T4
(excluding patients staged as T4 because of masticator space
invasion); and group 4, extensive parapharyngeal extension.
No significant difference was observed among these groups
with respect to gender, age, N classification, or radiation
technique (Table 3). The survival curves for OS, LRFS, and
DMFS in these groups are shown in Figure 3. The OS, LRFS,
and DMFS of patients with mild parapharyngeal extension
were significantly higher than those of T3 patients without
extensive parapharyngeal extension ( = 0.015,  = 0.008,
and  < 0.001, resp.). By contrast, the OS, LRFS, and DMFS
of patients with extensive parapharyngeal extension were
close to those of patients with T4 disease ( = 0.052,  =
0.193, and  = 0.115, resp.). Hence, mild and extensive
parapharyngeal extension should be classified as stage T2 and
T4 disease, respectively.
4. Discussion
Parapharyngeal extension of NPC can occur via four pathways: lateral spread to the masticator space or prestyloid
space; posterolateral spread to the carotid space or parotid
space; posterior spread to the prevertebral space or retropharyngeal space; and inferior spread to the paraoropharyngeal
space. In previous studies, investigators have focused on
the prognostic significance of parapharyngeal extension in
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5
1.0
1.0
0.9
0.9
Local relapse-free survival
Overall survival
0.8
G1
G2
0.7
0.6
0.5
G3
0.4
G4
0.3
0.2
P
0.1
0.0
G1
0.015
G2
G2
G3
<0.001
<0.001
Factor
G4
0
12
24
36
G3
G1
G2
0.8
G3
0.7
0.6
G4
0.5
0.4
0.3
0.2
<0.001
<0.001
48 60 72 84
Months after treatment
96
P
0.1
0.052
0.0
108 120
G1
0.008
G2
G2
G3
<0.001
<0.001
G4
<0.001
<0.001
Factor
0
12
24
36
G3
0.193
48 60 72 84 96
Months after treatment
(a)
108 120
(b)
1.0
G1
Distant metastasis-free survival
0.9
G2
0.8
0.7
G3
0.6
G4
0.5
0.4
G2
G3
<0.001
<0.001
G4
<0.001
<0.001
G2
0.2
P
0.1
0.0
G1
<0.001
Factor
0.3
0
12
24
36
48 60 72 84
Months after treatment
G3
0.115
96
108 120
(c)
Figure 3: OS (a), LRFS (b), and DMFS (c) curves for patients with NPC stratified according to grade of parapharyngeal extension and T
category. G1: mild parapharyngeal extension; G2: T3 without extensive parapharyngeal extension; G3: all T4 (excluding patients staged as T4
because of masticator space invasion); G4: extensive parapharyngeal extension.
NPC [1–12, 22–24]. However, the results of these studies are
somewhat unclear for several reasons. First, the definition
of parapharyngeal extension varies and always focuses on a
single pathway of spread. For example, the findings reported
by Chua et al. [1] and Sham and Choy [2] were based on lateral
parapharyngeal spread; by contrast, Ma et al. [3] and Heng
et al. [4] proposed that paraoropharyngeal extension should
be included in the NPC staging system on the basis of inferior
parapharyngeal spread. Second, the outcomes of most studies
were based on diagnoses made by CT. With recent advances
in the diagnosis of NPC due to the widespread availability
of MRI, the management strategy and prognostic factors
for this disease have been altered [25–27]. Given these
uncertainties, it is important to reassess the prognostic value
of parapharyngeal extension and to determine its appropriate
subclassification.
To the best of our knowledge, no studies have focused on
the subclassification of lateral, posterior, posterolateral, and
inferior parapharyngeal spread in NPC. Our study was based
on MRI findings and demonstrated that parapharyngeal
extension should be subclassified into two risk grades: mild
involvement (invasion of the medial pterygoid muscle of
the masticator space or the carotid, prestyloid, prevertebral, or retropharyngeal space) and extensive involvement
(invasion of the lateral pterygoid muscle of the masticator
space and beyond or the parotid space). The OS, LRFS,
and DMFS of patients with mild parapharyngeal extension
were significantly higher than those of T3 patients, and
patients with extensive parapharyngeal extension had OS,
LRFS, and DMFS similar to those of patients with stage T4
disease; therefore, it seems reasonable that mild and extensive
parapharyngeal extension should be classified as stages T2
6
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Table 3: Characteristics for 1504 patients with different grades of
parapharyngeal extension.
Characteristic
Gender
Male
Female
Age
<50 y
≥50 y
N classification
N0
N1
N2-3
Radiation technique
Conventional technique
IMRT
3DCRT
G1
Number of patients
G2
G3
G4

171
57
500
182
202
51
45
18
0.203
144
84
464
218
163
90
39
24
0.419
39
139
50
153
414
115
43
171
39
8
42
13
0.085
120
94
14
361
292
29
139
104
10
31
25
7
0.289
3DCRT: three-dimensional conformal radiotherapy; IMRT: intensitymodulated radiation therapy; G1: mild parapharyngeal extension; G2: T3
without extensive parapharyngeal extension; G3: all T4 (excluding patients
staged as T4 because of masticator space invasion); G4: extensive parapharyngeal extension.
and T4 diseases, respectively. This can offer considerable
improvement over existing methods for subclassifications of
parapharyngeal extension in patients with NPC and has the
potential to provide clinicians with reliable information for
prognostic prediction and personalizing therapy aimed at
NPC patients.
In the fifth and sixth edition AJCC staging system for
NPC, staging masticator space involvement was classified
as stage T4 disease and defined as lateral tumor extension
beyond the anterior surface of the lateral pterygoid muscle
[13, 14]. The current, seventh edition includes an adjustment
specifying tumor invasion into any part of the anatomic
masticator space as stage T4 [15]. Two recent MRI studies [11,
12] showed no significant difference in survival rate between
patients with involvement of the medial or lateral pterygoid
muscle and patients with involvement of the staging masticator space and suggested that subclassification of masticator
space involvement was unnecessary. However, we observed
significant differences in OS and DMFS between patients
with involvement of the medial pterygoid muscle and patients
with involvement of the lateral pterygoid muscle, which has
not been reported in previous studies. Therefore, we believe
that classification of masticator space spread as involvement
of the medial pterygoid muscle versus involvement of the
lateral pterygoid muscle and beyond reasonably reflects the
prognostic influence of the extent of masticator space spread
in NPC.
Carotid space invasion was an important factor in Min’s
staging system for NPC, with posterolateral tumor invasion
beyond a line drawn from the styloid process to the midpoint of the posterior edge of the great occipital foramen
classified as stage T3 disease [5]. Two previous studies have
reported that the prognostic importance of paraoropharyngeal extension differs from that of paranasopharyngeal
extension in NPC [3, 4]. Several researchers have stated
that the association of severe carotid space involvement or
paraoropharyngeal extension with poor outcomes may be
attributed to inadequate dose coverage. When sufficient dose
coverage was achieved, carotid space involvement had no
significant prognostic value in terms of disease outcome [7–
10]. In the present study, all 1504 patients were treated with
conventional techniques based on CT simulation, 3DCRT, or
IMRT, which ensure better tumor dose coverage. No significant difference in OS, LRFS, or DMFS was observed between
patients with anterior carotid space invasion and patients
with posterior carotid space invasion or between paraoropharyngeal extension and paranasopharyngeal extension. Therefore, we support the view that subclassification of carotid
space involvement or paraoropharyngeal extension in NPC
is unnecessary.
The retropharyngeal and prestyloid spaces are close to
the nasopharynx and are the most common sites of parapharyngeal extension in NPC. The prevertebral space, located
behind the retropharyngeal space, is also a high risk site
for tumor involvement. Prevertebral space involvement in
hypopharyngeal or laryngeal carcinoma is regarded as unresectable disease (T4b) and is usually associated with poor
survival [28]. However, excellent local control and long
term survival can be achieved in patients with prevertebral
space involvement in NPC if they are treated with curative
radiotherapy, especially IMRT. Our data indicate that the
OS, LRFS, and DMFS of patients with prevertebral space
involvement were approximately similar to those of patients
with retropharyngeal or prestyloid space involvement. Therefore, involvement of the prevertebral space, together with
the retropharyngeal and prestyloid spaces, may be classified
as mild parapharyngeal extension. However, the prognostic
importance of parotid space involvement in NPC has not
been emphasized in previous studies. Our data indicated that
parotid gland involvement was accompanied by lateral tumor
spread to the lateral pterygoid muscle, and the prognostic
importance of parotid gland involvement in NPC was similar
to that of lateral pterygoid muscle invasion.
It should be stressed that pathologic confirmation of
imaging findings is not possible in patients with NPC, who
are typically treated with radiotherapy rather than surgery,
thus determining the anatomic sites of parapharyngeal extension based on MRI alone could be inaccurate. Furthermore,
the generality of our results could be reduced by the fact
that some patients had incomplete follow-up data and that
patients came from an area in southern China with a high
incidence of NPC. Therefore, our proposals should be verified
in subsequent studies.
5. Conclusions
Based on our data, we propose that parapharyngeal extension
should be subclassified as mild or extensive and that mild
and extensive parapharyngeal extension should be classified
as stage T2 and stage T4 disease, respectively. Furthermore,
these grades can facilitate staging of NPC and enable a more
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tailored therapeutic approach with improved outcomes for
this disease.
Disclosure
The authors alone are responsible for the content and writing
of the paper.
Conflict of Interests
The authors declare that there is no conflict of interests
regarding the publication of this paper.
Authors’ Contribution
Guo-Yi Zhang and Ying Huang contributed equally to this
work.
Acknowledgments
This work was supported by Grants from the Natural Science Foundation of Guangdong Province (Grant
S2011040004296), the Science and Technology Planning Program of Guangdong Province (Grant 20120318050) and the
Science and Technology Key Project of Foshan City (Grant
201008051).
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