FULL PAPER

British Journal of Cancer (2014) 110, 297–303 | doi: 10.1038/bjc.2013.715

Keywords: nasopharyngeal carcinoma; local recurrence; prognostic-score model; intensity-modulated radiotherapy (IMRT);
late complications

Prognostic model for survival of local

recurrent nasopharyngeal carcinoma
with intensity-modulated radiotherapy
Y-M Tian1,4, Y-H Tian2,3,4, L Zeng1,4, S Liu1, Y Guan1, T-X Lu1 and F Han*,1
1
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China,
Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 2Cancer
Research Institute, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China and 3Department
of Oncology, Armed Police Hospital of Guangdong Province, Guangzhou, Guangdong Province, People’s Republic of China

Background: Intensity-modulated radiotherapy (IMRT) is the main salvage treatment for advanced locally recurrent
nasopharyngeal carcinoma (NPC); however, survival outcomes vary. We aimed to construct a prognostic-score model to identify
patients who could benefit from salvage IMRT.

Methods: This retrospective study involved 251 patients with locally recurrent NPC. The following parameters were analysed
following IMRT: patient performance status, age, gender, late complications, T-stage of recurrence, synchronous nodal
recurrence, primary gross tumour volume (GTV-nx), disease-free interval, re-irradiation dose and chemotherapy. The model was
based on the hazard ratio coefficients of six significantly negative prognostic factors for survival.

Results: Significantly negative prognostic factors included Karnofsky Performance Status p70, age 450 years, late complications,
recurrent T3–4 stage, synchronous nodal recurrence and GTV-nx 430 cm3. Three subgroups were defined according to model
scores: low risk (0–4), intermediate risk (5–8) and high risk (9–15). The 5-year overall survival rates were 64.3%, 32.2% and 7.7%,
respectively. The main cause of death was radiation-induced complications.

Conclusion: The prognostic-score model demonstrated that re-irradiation with IMRT is suitable for low-risk and intermediate-risk
patients but may be unsuitable for high-risk patients. Further research into the protection of critical adjacent organs to reduce late
complications in these patients is warranted.

Nasopharyngeal carcinoma (NPC) is common in southern China, a significant proportion of patients can achieve long-term survival
especially in the Guangdong province, where rates range from 20 following salvage therapy; therefore, aggressive treatment with
to 30 cases per 100 000 population (Yu and Yuan, 2002; Wei and curative intent is usually recommended (Lee et al, 1993; Yu et al,
Sham, 2005). Radiotherapy is the standard treatment for early 2005). Owing to the high risk of infiltration, most cases of
disease, and combined radiotherapy and chemotherapy is applied recurrent NPC are already extensive at diagnosis, and external
for advanced disease (Al-Sarraf et al, 1998; Wee et al, 2005). beam radiation therapy is often the only selection for salvage
Despite significant improvements in local control due to advances treatment. Conventional radiotherapy can be difficult, with a high
in radiotherapy and combined modality treatments, local recur- incidence of late complications due to the constraints of critical
rence remains a major cause of treatment failure in patients with structures in the vicinity of the target tumour, which would have
advanced NPC (Kam et al, 2004; Lee et al, 2005). However, already received a high dose of radiation during the first course

*Correspondence: Dr F Han; E-mail: [email protected]

4
These authors contributed equally to this work.
Received 2 August 2013; revised 12 October 2013; accepted 21 October 2013; published online 12 December 2013
& 2014 Cancer Research UK. All rights reserved 0007 – 0920/14

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BRITISH JOURNAL OF CANCER Prognostic model for recurrent NPC with IMRT

of radiotherapy. As such, the 5-year overall survival (OS) rate is poor, condition. For example, patients with severe complications, poor
with a range of only 8–36% (Teo et al, 1998; Lee et al, 2000; Zheng status and/or diabetes were prescribed a relatively low dose of
et al, 2005). The introduction of intensity-modulated radiotherapy 60 Gy to the GTV, and more attention was given to sparing the
(IMRT) can provide a more favourable balance between target adjacent organs.
coverage and the sparing of adjacent organs (Hsiung et al, 2002). The prescribed doses were 60–70 Gy to the GTV and 50–54 Gy
Preliminary reports have demonstrated that better disease control to the CTV in 27–35 fractions. All patients received full-course
and patient survival can be achieved with a relatively low incidence IMRT with 6 MV X-rays generated using a Clinac-600C linear
of late complications by using IMRT in patients with locally accelerator (Varian Medical Systems, Palo Alto, CA, USA).
recurrent NPC (Lu et al, 2004; Chua et al, 2005; Roeder et al, 2011;
Han et al, 2012; Hua et al, 2012; Qiu et al, 2012). Chemotherapy. Cisplatin-based induction or concurrent
Along with other solid tumours, locally recurrent NPC is a chemotherapy was administered in 126 patients with rT3–4 and/
highly heterogeneous disease (Lee et al, 2000; Hua et al, 2012), and or bulky gross tumours. The groups included 46 patients with
patient survival following IMRT varies, ranging from several concurrent chemoradiotherapy, 67 patients with induction
months to long-term survival. Therefore, developing a model to chemotherapy followed by radiotherapy and 13 patients with
predict the survival outcomes in patients with locally advanced induction and concurrent chemotherapy.
NPC could facilitate the identification of those patients who would Patient assessment and follow-up. After treatment completion,
most benefit from IMRT. Such a model could also contribute to the patients were evaluated at least once every 3 months during the
design of clinical trials for locally recurrent NPC. The aim of this first 3 years and then every 6 months thereafter until death.
study was to design a prognostic-score model for this purpose Magnetic resonance imaging or CT of the head and neck, chest
through the retrospective investigation of prognostic factors and X-ray radiography and abdominal ultrasonography were
outcomes in patients with locally recurrent NPC following IMRT. performed annually. Severe radiation toxicities secondary to
treatment were assessed and scored according to the radiation
morbidity scoring criteria of the Radiation Therapy Oncology
MATERIALS AND METHODS Group (RTOG).
Statistical analysis. Overall survival, local-regional failure-free
Patient selection and pretreatment evaluation. A total of 251 survival (LRFFS) and distant failure-free survival (DFFS) were
patients with locally recurrent NPC were diagnosed and received calculated using the Kaplan–Meier method. Differences between
re-irradiation using IMRT at the Sun Yat-Sen University Cancer survival curves were compared using the log-rank test. Univariate
Centre between January 2001 and May 2009. Local recurrence was and multivariate analyses were performed using the Cox propor-
confirmed by biopsy for most of the patients. Those patients with tional hazards model. The time periods were calculated from the
recurrence in inaccessible sites, such as the skull base and date when recurrence was diagnosed to the date of each event or
intracranial cavity, were diagnosed radiologically according to the last follow-up. Disease-free interval was defined as the time
local disease progression. between the completion of the primary radiotherapy to
The pretreatment evaluation involved a complete medical the diagnosis of recurrence in patients who had achieved a complete
history, and physical examinations included the patient’s perfor- response. The following factors were included in the analyses:
mance status and any severe complications (i.e., trismus, radiation patients’ characteristics (performance status, age, gender and late
encephalopathy, cranial nerve palsy and mucosa necrosis). complications); disease characteristics (T-stage of recurrence,
A complete blood count, renal and liver function tests and synchronous nodal recurrence, GTV-nx and DFI); and treatment
nasopharyngoscopy were required. Magnetic resonance imaging methods (chemotherapy, re-irradiation dose). A P-value o0.05
(MRI) or computed tomography (CT) of the nasopharynx and was considered significant.
neck was performed for the staging evaluations. Chest X-rays, The regression coefficient (b) for each independent prognostic
abdominal sonography and bone scans were performed to detect factor was derived from the Cox regression equation (HR ¼ eb),
distant metastases. Positron emission tomography-CT (PET-CT) where HR is the hazard ratio. This value was then converted into
was performed at the physician’s discretion. All patients with an integer to provide a score index for the prognostic-score model.
recurrent NPC were re-staged according to the classification
system of the American Joint Committee on Cancer (AJCC; 2002).
Intensity-modulated radiotherapy. Target volumes were deli- RESULTS
neated according to our institution’s treatment protocol, in
agreement with the International Commission on Radiation Units Clinicopathological characteristics. The clinicopathological char-
and Measurements (ICRU) reports 50 and 62. The gross tumour acteristics of the patients are given in Table 1. The median age was
volumes (GTVs) at the primary site (GTV-nx) and neck (GTV-nd) 45 years (range, 21–75 years). Approximately 39 out of 251 (15.5%)
included the total disease volumes visualised using CT or MRI. The patients presented with late complications after the first course of
clinical target volumes (CTVs) were designed to encompass radiotherapy, including 16 patients with trismus, 10 with radiation
microscopic disease by including the GTV plus a 1- to 1.5-cm encephalopathy, 9 with cranial nerve palsy and 4 with mucosa
margin; smaller margins (o3 mm) were applied near critical necrosis (xerostomia and hearing loss were not included).
intracranial structures or the spinal cord. The CTV also included Treatment planning and dosimetry. The median minimum,
the entire nasopharynx and lymph node-positive regions. mean and maximum doses for the GTV-nx were 57.5 Gy (range,
No elective re-irradiation of the uninvolved regional lymph nodes 33.3–70.5 Gy), 70.7 Gy (range, 61.1–79.7 Gy) and 76.7 Gy (range,
was performed (Figure 1). Additional 2- to 3-mm margins were 65.5–85.8 Gy), respectively. The median percentage of the GTV
added to the CTV and GTV to create the planning target volume receiving 95% of the prescribed dose (V95) was 98.1% (range,
(PTV) for setup variability and internal motion. The organs at risk 56.1–100%); the median dose encompassing 95% of the GTV-nx
(OARs) included the brainstem, spinal cord, optic nerves, optic (D95) was 68.1 Gy (range, 64.5–71.4 Gy).
chiasm, pituitary gland, lens, temporal lobes, parotid glands,
temporomandibular joints and mandible. The dose constraints to Patient survival outcomes. The median follow-up period was 40.0
the OARs were limited by the threshold doses, the disease-free months (range, 3.0–147.0 months). A total of 15 patients were lost
interval (DFI) after primary radiotherapy and the patient’s general to follow-up between 6.0 and 61.0 months. Local-regional failure

298 www.bjcancer.com | DOI:10.1038/bjc.2013.715

Prognostic model for recurrent NPC with IMRT BRITISH JOURNAL OF CANCER

100
CTV1 GTV
90

Ratio of total structure volume (%)

80

70

CTV1 60

GTV 50

40 TL (R) TL (L) BS
30

20

10

0
0 1,000 2,000 3,000 4,000 5,000 6,000
Dose (cGy)

Figure 1. Representative MR images and treatment plan of one patients. Axial T1-weighted (A), contrast-enhanced T1-weighted (B), and coronal
contrast-enhanced fat-saturated T1-weighted MR images (C) show a left-sided recurrent NPC with lateral extension to parapharygneal space and
superior extension into the left intracranial cavity. (D–F) Delineation of target volume and dose-volume histogram (DVH) included temporal lobe
(TL) and brainstem (BS).

was confirmed in 48 out of 251 (19.1%) patients, including 43 out Significant xerostomia, hearing loss and trismus were common,
of 48 (89.6%) with local failure and 5 out of 48 (10.4%) with and 102 out of 251 (40.6%) patients developed at least one of
regional failure. Distant metastases occurred in 37 out of 251 these conditions. Those patients with rT3–4 tumours or GTV-nx
(14.7%) patients, including five patients with local failure. The 430 cm3 exhibited significantly higher incidences of mucosa
3-year and 5-year LRFFS rates were 80.6% and 75.1%, respectively. necrosis than patients with rT1–2 stage tumours (36.8 vs 26.1%;
The 3-year and 5-year DFFS rates were 86.1 and 80.6%, P ¼ 0.04) or with GTV-nx p30 cm3 (38.7 vs 23.0%; Po0.01).
respectively.
A total of 159 out of 251 (63.3%) patients died during this study. Univariate analyses. The statistically significant negative prog-
Of these, 77 out of 159 (48.4%) deaths were due to radiation- nostic factors for OS were Karnofsky Performance Status (KPS)
induced injuries, including 41 out of 77 (53.2%) from mucosa p70, age 450 years, severe late complications, rT3–4 tumours,
necrosis or massive haemorrhage, 14 out of 77 (18.2%) from GTV-nx 430 cm3 and mean re-irradiation dose 468.0 Gy.
radiation encephalopathy and 22 out of 77 (28.6%) from other Synchronous nodal recurrence was marginally significant in
radiation-related injuries. In addition, 37 out of 159 (23.3%) predicting poor OS. These results, including P-values, are
patients died due to local-regional failures and 32 out of 159 summarised in Table 2. The statistically significant negative
(20.1%) due to distant failures. Other causes responsible for 15 out prognostic factors for LRFFS were KPS p70 (HR: 3.64;
of 159 (9.4%) deaths included 3 out of 15 (20.0%) cases of cardiac Po0.01), rT3–4 tumours (HR: 3.68; Po0.01) and DFI o24
disease, 2 out of 15 (13.3%) cases of leukaemia, 2 out of 15 (13.3%) months (HR: 2.14; P ¼ 0.01). The only significant negative
cases of intracranial infection, 1 out of 15 (6.7%) case of digestive prognostic factor for DFFS was recurrence of rT3–4 tumours
diseases and 5 out of 15 (33.3%) unknown causes. The 3-year and (HR: 1.53; P ¼ 0.03).
5-year OS rates were 53.2% and 41.1%, respectively.
Multivariate analyses. The significant independent negative
Late complications. Treatment was not interrupted due to severe prognostic factors for OS were KPS p70, age 450 years, severe
acute toxicity in any of the patients. However, most patients late complications, rT3–4 tumours, synchronous nodal recurrence
developed mild to moderate acute toxicities, including mucositis, and GTV-nx 430 cm3. These results, including P-values, are
xerostomia and otitis media. Approximately 20 out of 251 (8.0%) summarised in Table 3. The survival curves of patients according
patients experienced grade-3 acute mucositis, 18 of who underwent to the different prognostic factors are shown in Figures 2 and 3.
concurrent chemoradiotherapy. After the completion of IMRT, 84 Significant independent negative prognostic factors for LRFFS were
out of 251 (33.4%) patients developed mucosa necrosis, 61 out of KPS p70 (HR: 3.06; P ¼ 0.04) and rT3–4 tumours (HR: 5.46;
251 (24.3%) developed temporal lobe necrosis and 19 out of 251 P ¼ 0.02). However, no significant independent factor was
(7.6%) developed cranial neuropathy during the follow-up period. associated with DFFS by multivariate analysis.

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BRITISH JOURNAL OF CANCER Prognostic model for recurrent NPC with IMRT

Table 1. Clinical characteristics Table 2. Univariate analysis of variables correlated with overall survival

Characteristic N (%) 5-year OS

Characteristic (%) HR (95% CI) P-value
Karnosky performance score
KPS, 470/p70 42.3/14.4 2.65 (1.50–4.67) o0.01a
470 238 (94.8) Gender, male/female 41.5/39.8 1.13 (0.79–1.63) 0.48
p70 13 (5.2) Age (year), p50/450 43.3/37.5 1.48 (1.08–2.03) 0.02a
Significant complications, 46.1/15.4 2.36 (1.60–3.47) o0.01a
Gender no/yes
DFI (month), 424/p24 42.7/39.5 1.05 (0.77–1.43) 0.73
Male 195 (77.7)
Female 56 (22.3) rT
Age (year) rT1 81.8 Baseline
rT2 64.5 2.50 (0.67–6.64) 0.22
Median 45
rT3–4 32.4 3.00 (1.89–4.7) o0.01a
Range 21–75
Synchronous nodal recurrence, 43.0/31.7 1.43 (0.98–2.11) 0.06
Pathology no/yes
Volume of GTV-nx (cm3), 59.9/26.9 1.52 (1.30–1.97) o0.01a
WHO I 5 (2.0) p30/430
WHO II–III 196 (78.0) Chemotherapy, yes/no 35.4/47.0 1.31 (0.96–1.79) 0.09
Imaging findings only 50 (20.0) Re-irradiation dose (Gy), 48.9/36.9 1.50 (1.05–2.14) 0.02a
p68/468
Presence of significant complications
Abbreviations: CI ¼ confidence interval; DFI ¼ disease-free interval; HR ¼ hazard ration;
No 212 (84.5)
KPS ¼ Karnosky performance score.
Yes 39 (15.5) a
Statistically significant.

DFI (month)

424 133 (53.0)

p24 118 (47.0)
Table 3. Multivariate analysis of variables correlated with overall survival
rT stage (2002AJCC)

T1 22 (8.8) Characteristic HR (95% CI) P-value

T2 31 (12.4)
KPS, 470/p70 2.43 (1.18–5.26) 0.01
T3 90 (35.9)
Age, p50/450 1.66 (1.22–2.54) o0.01
T4 108 (43.0)
Significant complications, no/yes 2.51 (1.65–4.05) o0.01
Presence of synchronous nodal recurrence
rT
No 212 (84.5)
rT1 Baseline
Yes 39 (15.5)
rT2 2.10 (0.65–5.24) 0.21
Volume of GTV-nx (cm3) rT3–4 2.54 (1.31–5.51) o0.01
Synchronous nodal recurrence, no/yes 1.64 (1.09–2.31) 0.02
p30 100 (39.8) GTV-nx (cm3), p30/430 1.57 (1.16–1.98) o0.01
430 151 (60.2)
Abbreviations: CI ¼ confidence interval; GTV ¼ gross tumour volume; HR ¼ hazard ratio;
Prior radiation dose (Gy) KPS ¼ Karnosky performance score.

Median 70
Range 64–82

Chemotherapy stratification groups, based on the prognostic scoring system:

(I) the low-risk group (total score, 0–4) included 79 out of 251
Yes 126 (50.2) (31.5%) patients; (II) the intermediate-risk group (total score, 5–8)
No 125 (49.8) included 146 out of 251 (58.2%) patients; and (III) the high-risk
group (total score, 9–15) included 26 out of 251 (10.6%) patients.
Abbreviations: DFI ¼ disease-free interval; GTV ¼ gross tumour volume; KPS ¼ Karnosky
performance score.
The median survival periods of the patients in these groups were
DFI, interval time from the end of first course of radiotherapy to recurrence at diagnosis. 62.0, 25.5 and 8.5 months, respectively (Po0.001; Figure 4). The
5-year OS rates were 64.3%, 32.2% and 7.7%, respectively. The survival
curves were distinctly separated between these groups (Figure 3D).

Scoring of patients according to the prognostic-score model.

The prognostic-score model was based on the regression
coefficients of the six significantly independent negative prognostic DISCUSSION
variables, as described above. A score of 2 or 3 was assigned for
each factor, according to the HR (n) value (Table 4). If a factor was In the management of locally recurrent NPC, aggressive treatment,
not independently significant, a score of 0 was recorded. The including surgery or re-irradiation, instead of chemotherapy alone
maximum possible score for each patient was 15. The prognostic is usually recommended to improve the chance of long-term
score for each of the 251 patients was calculated from the sum of survival (Lee et al, 1993; Yu et al, 2005). Chemotherapy is
the individual scores. Patients were then assigned to three risk considered a palliative treatment for advanced recurrence, which is

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Prognostic model for recurrent NPC with IMRT BRITISH JOURNAL OF CANCER

1.0 1.0 1.0

0.8 0.8 0.8

Overall survival
Overall survival

Overall survival
0.6 0.6 0.6
Age-50 (P = 0.02) Without complications
0.4 KPS >70 (P < 0.01) 0.4 (P <0.01)
0.4
Age > 50
0.2 0.2 0.2 With complications
KPS-70

0.0 0.0 0.0

0 30 60 90 120 150 0 30 60 90 120 150 0 30 60 90 120 150
Time (months) Time (months) Time (months)

Figure 2. Kaplan–Meier survival curves for OS according to KPS (A), age (B) and significant complications (C).

A 1.0
B 1.0

0.8
0.8

Overall survival
Overall survival

rT1–2 (P<0.01)
0.6 0.6
Without nodal recurrence
(P =0.06)
0.4 0.4
rT3–4
With nodal recurrence
0.2 0.2

0.0 0.0
0 30 60 90 120 150 0 30 60 90 120 150
Time (months) Time (months)

C 1.0 D 1.0

0.8 0.8
Overall survival

Overall survival

Volume of GTV-30cc (P<0.01) Low-risk group (P<0.01)

0.6 0.6

0.4 0.4
Volume of GTV>30cc Intermediate-risk group
0.2 0.2
High-risk group

0.0 0.0
0 30 60 90 120 150 0 30 60 90 120 150
Time (months) Time (months)

Figure 3. Kaplan–Meier survival curves for OS according to recurrent stage (A), presence of synchronous nodal recurrence (B), volume of GTV-nx
(C) and the different risk groups (D).

Table 4. Prognostic index score according to the HR (n value) not suitable for local aggressive therapies or patients with distant
metastases (Oksuz et al, 2004). Salvage surgical resection in
patients with early-stage recurrence has been shown to provide
Characteristic Score n (HR ¼ en)
3
satisfactory disease control and improved quality of life (Wei, 2000;
Volume of GTV-nx 430 cm 2 0.45
Hsu et al, 2001). Brachytherapy and stereotactic radiotherapy have
Synchronous nodal recurrence 2 0.49 also been used successfully in patients with NPC but are limited by
Age 450 years 2 0.51 the extension and volume of the disease (Law et al, 2002; Chua
KPS p70 3 0.89
et al, 2006). Hsiung et al (2002) demonstrated the superior dose
distribution and sparing of normal tissues with IMRT compared
With significant complications 3 0.92 with three-dimensional conformal radiotherapy as a boost or
Recurrent T3–4 3 0.93 salvage treatment for locally recurrent NPC. In a study by Lu et al
Maximum score 15 (2004), 100% loco-regional control (LRC) was achieved with IMRT
in 49 patients without any severe late complications after a median
Abbreviations: GTV ¼ gross tumour volume; HR ¼ hazard ratio; KPS ¼ Karnosky performance follow-up period of 9 months. Chua et al (2005) reported a 1-year
score.
According to the HR (n value), the maximum value of recurrent T3–4 is 1.5 times of the
LRC rate of 56% and an OS rate of 63% in 31 patients following
minimum value of volume of GTV-nx. To simplicity, we assume that the value of baseline is 2. IMRT. In this study, we found similar 5-year LRFFS and OS rates
of 75.1% and 41.1%, respectively, supporting these previous reports

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BRITISH JOURNAL OF CANCER Prognostic model for recurrent NPC with IMRT

Score nodal recurrence was related to poor survival, as these patients are
0 1 2 3 more prone to distant metastases, with a 5-year DFFS rate of
69.2%, compared with 82.1% in patients with local recurrence
VGTV-nx > 30 (cm3) alone. However, the difference was not significant.
No Yes The heterogeneity of locally recurrent NPC indicates that not all
Nodal recurrence patients will benefit from re-irradiation using IMRT, as they may
No Yes
experience poor disease control and severe late complications.
Age > 50 (y) Therefore, we constructed a prognostic-score model based on the
No Yes
six most significantly negative prognostic factors identified in
KPS-70
No Yes patients following IMRT, as described above. This model was used
Complications to stratify the patients into three subgroups according to low-,
No Yes intermediate- and high-risk scores. The aim was to discriminate
rT3–T4 between patients with good and poor prognoses and to select
No Yes candidates more suitable for re-irradiation using IMRT.
Total score 0 2 4 6 8 10 12
The patients in the low- and intermediate-risk groups achieved
Median survival (m) 85.6 71.2 61.0 32.5 23.3 10.4 5.5 good disease control and survival after IMRT, with median survival
periods of 62.0 months and 25.5 months, respectively, indicating
Figure 4. A prognostic model was built based on six patient and
that re-irradiation using IMRT can be a suitable option. However,
disease factors. The total score can be calculated in predicting the
the median survival of patients in the high-risk group was only 8.5
median survival according to the prognostic factors.
months. Some of the high-risk patients were unlikely to benefit
from high-dose re-irradiation due to poor disease control and
severe late complications. Therefore, further investigations to
that IMRT can be an effective salvage treatment in patients with establish effective treatment strategies, including chemotherapy
locally recurrent NPC. and targeted therapy, for these high-risk patients are warranted.
Poor performance status is known to be associated with old age, Although excellent disease control can be achieved with high-
and advanced disease and a high incidence of severe complications dose irradiation using IMRT, the benefits need to be balanced
often indicate that these patients are unable to tolerate high-dose against the risk of severe late complications, which remains the
IMRT and chemotherapy, resulting in poor survival and little or no main cause of death following treatment. Mucosa necrosis and
treatment benefit. A meta-analysis of head and neck cancers found massive haemorrhage are among the main challenges, and their
that the benefits of chemoradiotherapy decreased with increasing incidences are related to individual patient tolerance and radiation
age and that the proportion of deaths unrelated to the cancer dose (Marx, 1983; Hua et al, 2009). Furthermore, patients with
significantly increased with age (Pignon et al, 2009). Although age advanced or bulky disease experience significantly higher rates of
is accepted as a significant independent variable in the survival of mucosa necrosis. Other main causes of death include temporal lobe
patients with head and neck cancer (including primary NPC), the necrosis and poor medical conditions related to radiation exposure,
cutoff value reported in different studies has been inconsistent such as cranial nerve IX–XII palsy. To reduce the risk of late
(Chow et al, 2002; Corry et al, 2006). In agreement with an earlier complications, investigations to determine the optimal total dose
study (Oksuz et al, 2004), our results demonstrated that the patient and dose-fractions for disease control, while sparing adjacent
performance status and age have prognostic significance. The critical organs, are currently being conducted in our centre.
5-year OS rate in patients 450 years was only 37.5%, compared The purpose of this prognostic-score model was to enable those
with 43.3% in younger patients. patients who would most benefit from IMRT to be identified and
Complications before retreatment associated with the poor to facilitate improvements in the therapeutic ratio of re-irradiation
survival of patients with local recurrent NPC include trismus, in NPC. Our findings demonstrated that re-irradiation using IMRT
temporal lobe necrosis, cranial neuropathy (e.g., neuropathy of can be an appropriate choice for patients in the low- and
cranial nerves IX–XII) and mucosa necrosis. These conditions not intermediate-risk groups but may not be suitable for some high-
only affect quality of life but can lead to poor status or death, and risk patients, indicating that further research is required to reduce
they became more severe after re-irradiation. In this study, the the radiation dose to adjacent normal tissues.
5-year OS rate of patients with severe late complications was only
15.4% and the HR was 2.53. These findings indicate that a patient’s
characteristics, including performance status, age and severe late
complications, should be important considerations in planning CONFLICT OF INTEREST
salvage treatments using IMRT for local failure in NPC.
The prognostic factors that have been most consistently The authors declare no conflict of interest.
reported for local control and OS are disease characteristics, such
as the T-stage of recurrence and GTV-nx (Chua et al, 2005; Roeder
et al, 2011; Han et al, 2012; Hua et al, 2012; Qiu et al, 2012).
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Int J Radiat Oncol Biol Phys 61: 1107–1116. This work is published under the standard license to publish agree-
Lu TX, Mai WY, Teh BS, Zhao C, Han F, Huang Y, Deng XW, Lu LX, Huang SM, ment. After 12 months the work will become freely available and
Zeng ZF, Lin CG, Lu HH, Chiu JK, Carpenter LS, Grant WR, Woo SY, the license terms will switch to a Creative Commons Attribution-
Cui NJ, Butler EB (2004) Initial experience using intensity-modulated NonCommercial-Share Alike 3.0 Unported License.

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