1

Research Article

Prognostic Factors and Treatment Outcome of Nasopharyngeal Carcinoma with Bone Metastases

Chiraz Nasr1,2, Nour Zidi1,2, Chaker Zaidi1,2, Rim Abidi, 1,2 Asma Belaid1,2, Lotfi Kochbati1,2, Farouk Benna1,2

1
Departement of Radiotherapy, Salah Azaiz Institute, Boulevard du 9 avril 1938, Bab Saadoun, Tunis, Tunisia

2
Faculty of Medicine of Tunis, Tunis El Manar University, Tunis, Tunisia

Corresponding author: Chiraz Nasr, Departement of Radiotherapy, Salah Azaiz Institute, Boulevard du 9 avril 1938, Bab Saadoun, Tunis,

Tunisia. Email: chiraz_ammar@yahoo.fr

Citation: Nasr C, Zidi N, Zaidi C, Abidi R, Belaid A, Kochbati L, Benna F. Prognostic Factors and Treatment

Outcome of Nasopharyngeal Carcinoma with Bone Metastases [J]. J Nasopharyng Carcinoma, 2017, 4(1): e35.

doi:10.15383/jnpc.35.

Competing interests: The authors have declared that no competing interests exist.
Conflict of interest: None.

Copyright: 2017 By the Editorial Department of Journal of Nasopharyngeal Carcinoma. This is an open-

access article distributed under the terms of the Creative Commons Attribution License, which permits

unrestricted use, distribution, and reproduction in any medium, provided the original author and source are

credited.

Abstract: This study was aimed to investigate prognostic factors of nasopharyngeal carcinoma (NPC) patients

with bone metastases. A total of 72 NPC patients with bone metastases were treated in Salah Azaiz Cancer

Institute between 2000 and 2012. Of the 72 patients, 33 patients had synchronous bone metastasis and 39 had

metachronous bone metastasis. The survival rate was calculated by Kaplan-Meier method and compared by

log-rank test. The 2- and 5- year survival rates of the 72 patients were 45.4 % and 21.7 %, respectively. The

median survival was 23 months (range 2144 months). Univariate analysis showed that the patients with

synchronous bone metastasis had significantly poorer overall survival (OS) than that of the patients with

metachronous bone metastasis (14 vs. 28 months, P=0.004). The use of biphosphonate therapy was a prognostic

factor of NPC with bone metastasis. Patients with only single bone metastases had better survival. Our study

revealed that the time of metastases and the use of biphosphonates were prognostic factors associated with better

OS. Curative treatment should be considered for patients with single bone metastasis.

Keywords: Prognostic factor; Nasopharyngeal carcinoma; Bone metastasis; Overall survival; Biphosphonate

Introduction Nasopharyngeal carcinoma (NPC) is a common epithelial

malignancy in Tunisia, with an intermediate incidence[1,2]. The

JNPC http://www journalofnasopharyngealcarcinoma org/ e-ISSN 2312-0398 Published:2017-03 -30 DOI:10 15383/jnpc.35
2

standardized incidence rate between 1999 and 2003 was estimated node examination and endoscopic examination of the nasopharynx

at 3.4 cases per 100 000 according to the North Tunisian registry[3]. associated with biopsy. The regional evaluation included computed

Radiotherapy with concomitant chemotherapy has increased tomography (CT) scans or/and magnetic resonance imaging (MRI)

survival[4]. But this cancer remains highly malignant with of the head and neck. Distant metastases were diagnosed by

extensive infiltration, early lymphatic spread, and predilection for imaging studies: chest radiographs, abdominal ultrasonography,

distant metastases[5,6]. thoracic and abdominal CT scans, and bone scintigraphy. In the

The most frequent metastasis location is the bone (70%80%)[6,7]. case of doubt, bone scan and/or MRI was completed.

For NPC with distant metastasis, the chemotherapy has been Treatment

demonstrated as an important palliative treatment[6]. However, RT Patients with Synchronous Bone Metastasis

to the primary tumor improved local control effects[7,8]. Our study The first line chemotherapy was made with Cisplatin in

was designed to investigate prognostic factors of NPC patients combination with doxorubicin or fluorouracil, or docetaxel or

with bone metastases and different treatment outcomes. paclitaxel and fluorouracil or capecitabine only. This

chemotherapy was followed by locoregional radiotherapy was

Patients and Methods
used in 51.5% of cases (referred to synchronous subgroups of
Patients
patients, n=17) with curative doses (7074 Gy) and in 30.3%
The medical records of 72 patients with NPC from January 2000
(referred to synchronous subgroups of patients, n=10) with
and December 2012 were retrospectively evaluated at the
contracted doses. Radiotherapy of bones metastases and
Department of Radiotherapy in the Salah Azaiz Cancer Institute.
bisphosphonates was also used.
All patients were diagnosed as bone metastasis with or without a
Patients with Metachronous Bone Metastasis
visceral metastatic site. The M1 stage distant metastases were
Curative treatment was administrated. The primary chemotherapy
subdivided into synchronous or metachronous bone metastases.
was nearly three cycles exclusively based with Cisplatin (100
The synchronous bone metastases were defined at the time of
mg/m2, day1) in combination with doxorubicine (90 mg/m2, day1)
initial staging. The metachronous bone metastases were defined as
or fluorouracil or paclitaxel-fluorouracil or docetaxel-fluorouracil.
metastasis that developed after primary RT. Thirty-three patients
This chemotherapy was followed by locoregional radiotherapy
had synchronous bone metastases and thirty-nine patients had
concomitant to chemotherapy or locoregional radiotherapy only.
metachronous metastases. All patients satisfied the criteria for
One patient had concurrent chemoradiation.
stage IV of the American Joint Committee on Cancer (AJCC, 2012)
The locoregional radiotherapy consisted of conventional two
TNM stages. The median duration of follow up for the population
dimensions RT with a photon beam of cobalt 60 gamma or linear
was 24.5 months.
accelerator. A mean total dose of 72 Gy was administrated.
Study Protocol
The treatment of bone metastases consisted of salvage
Our data were obtained from the clinical records and imagings. All
chemotherapy based on the majority on capicitabine.
courses of RT and chemotherapy were reviewed in details.
Cyclophosphamide or Cisplatin in combination with fluorouracil
All patients had pretreatment evaluation including a complete
or doxorubin or gemcitabin, were also used. Radiotherapy of
history, physical examination, especially the head and neck lymph
bones metastases and bisphosphonates was also used.

JNPC http://www journalofnasopharyngealcarcinoma org/ e-ISSN 2312-0398 Published:2017-03 -30 DOI:10 15383/jnpc.35
3

Statistical Analysis followed by pelvis (n=35, 48.6%), rib (n=23, 31.9%), limb (n=23,

Statistical analyses were performed using SPSS software 20 (SPSS 31.9%) and sternum (n=11, 15.27%). The most common site of

Inc., Chicago, IL, USA). Metastatic survival was calculated from visceral metastases was liver (n=17, 23.6%) followed by lung (n=8,

the diagnosis of NPC at the time of death. Overall survival was 11.1%) (Table 2).

calculated by Kaplan Meier methods. Survival differences for Table 2. Characteristics of bone metastases
Variable Number of Percentage(% referred to all
prognostic factors were compared with the log-rank test. The
patients (n) population)
Metastatic onset
P-value under 0.05 was considered as statistically significant.
Synchronous 33 45.83
Metachronous 39 54.16
Metastatic site
Results
Bone + visceral 25 34.70
Bone only 47 65.27
Characteristics of the Population
Number of bone metastatic sites
1 10 13.90
Information of 72 NPC patients with bone metastatic over
2 11 15.30
3 4 5.55
20002012 were collected. The age of patients at the first meeting
>3 22 30.55
Bone metastatic site
ranged from 17 to 75 years (mean 45.56 years). The gender ratio
Spine 54 75.00
Pelvis 35 48.61
was 4.53 (male vs. female). All patients had histologically
Rib 23 31.94
Limb 23 31.94
confirmed undifferentiated carcinoma (WHO Type ). T4 was
Sternum 11 15.27
Visceral site
recorded in 43.5% of cases (n=31). N3 nodal status rates were
Liver 17 23.61
Lung 8 11.11
recorded in 56.6% of cases (n=41). Overall, 33 patients (45.8%)
Others 5 6.94

had synchronous metastasis, and 39 (54.2%) had metachronous

Treatment Outcome
metastases (25 had bone metastasis associated with visceral
Patients with Synchronous Bone Metastasis
metastasis, 47 had only bone metastases, and 22 had more than 3
Within synchronous bone metastasis group (n=33), 27 patients
metastatic sites, Table 1).
(81.8%, referred to synchronous subgroups of patients) had
Table 1. Study population characteristics
Item Number of Percentage (% referred to all neoadjuvant chemotherapy. This chemotherapy was followed by
patients (n) population)
All cases 72 locoregional radiotherapy in 81.8% of cases (referred to
Age (years) Mean 45.65 Range (1775)
Gender synchronous subgroups of patients, n=27). Different modalities
Male 59 81.94
Female 13 18.05
were used. Seventeen patients received conventional 2D with of a
Histology (WHO)
Type
mean dose of 72 Gy to the primary tumor and the cervical areas
Type / 72 100
T stage (TNM2009) initially involved. Fifty-four Gy was given to the remaining
T4 31 43.5
T3 11 15.27 cervical areas bilaterally. Ten patients had contracted dose: 9
T2 22 30.55
T1 5 6.94 patients received 30 Gy in 10 sessions and 1 patient received 36
Tx 3 4.16
N stage (TNM2009)
Gy in 12 sessions.
N3 41 56.94
N2 15 20.83 The local radiotherapy of bone metastases was administered in 15
N1 8 11.11
N0 7 9.72 patients (45.4%, referred to synchronous subgroup). There were
Nx 1 1.38
different protocols of contracted dose (dose / fraction ranging from

The most common site of bone metastasis was spine (n=54, 75%), 4 Gy to 8.5 Gy).

JNPC http://www journalofnasopharyngealcarcinoma org/ e-ISSN 2312-0398 Published:2017-03 -30 DOI:10 15383/jnpc.35
4

Biphosphonates was also used in 36.3% cases in this group (76.9%, referred to metachronous subgroup) received local

(referred to synchronous subgroup, n=12). radiotherapy. Different regimens of palliative radiotherapy were

Patients with Metachronous Bone Metastasis used to treat the bone metastases (dose/fraction ranging from 3 Gy

Initial Treatment: Within metachronous bone metastasis group to 8.5 Gy).

(n=39), 34 patients had initially locally advanced tumor (87.1% Bipohosphonate treatment was offered as an adjuvant therapy to

referred to metachronous subgroup). As initial treatment of NPC, 53.8% of patients (referred to metachronous subgroup, n=21).

37 patients (94.8% referred to metachronous subgroup) had Survival

neoadjuvant chemotherapy. Different protocols of chemotherapy The median overall survival (OS) rate was 23 months (range

were used 64.1% of patients (referred to metachronous subgroup, 2144 months). The 2- and 5-year OS rates of the 72 patients were

n=25) received adriamycin with Cisplatin. This chemotherapy was 45.4% and 21.7%, respectively. There was a significant difference

followed by concurrent chemoradiation in 4 cases (10.2%, referred in term of OS between the group of patients who had synchronous

to metachronous subgroup) and by locoregional radiotherapy bone metastases and the patients with metachronous bone

without chemotherapy in 27 cases (69.2%, referred to synchronous metastases (P=0.04), the 2-year OS rate was 37.4% and 47.7%,

subgroup). Six patients had metastatic progression with respectively, and the 5-year OS rate was 12.5% and 27.9%,

neoadjuvant chemotherapy (15.3% referred to metachronous respectively (Fig.1A, Table 3).

subgroup patients and those had not received locoregional In terms of metastatic sites, univariate analysis showed that the

radiotherapy. spine involvement of bone metastases had a poorer OS (17 months)

We recorded two patients that had not a neoadjuvant chemotherapy, than those with peripheral (19 months) or mixed involvement (26

one patient had concurrent chemoradiation without neoadjuvant months), but this difference was not significant (P=0.228) (Fig.1E,

chemotherapy and the other had only locoregional radiotherapy. Table 3). The median OS rate was 24 months and 19 months in the

Thirty three patients had loco-regional radiotherapy of the tumor patients with and without spine involvement (P=0.49),

and nodes. They received a dose ranged from 70 to 74 Gy to the respectively (Fig.1F, Table 3).

primary tumor and the cervical areas initially involved, and 50 to The number of bone metastases (single vs. multiple) was not

54 Gy was given to the remaining cervical areas bilaterally, 2 Gy significant to predict OS (P=0, 647) (Fig.1B, Table 3).

per session, 5 sessions per week. The median OS of patients who had number of bone metastases

Salvage Treatment: For the salvage treatment, 18 patients (46.1%, superior to 3 sites was 24 months compared to 20 months for those

referred to metachronous subgroup) had chemotherapy. There who had bone metastases inferior to 3 sites, but this difference was

were different protocols of chemotherapy; 10 patients (25.6% not significant (P=0.31) (Fig.1D, Table 3).

referred to metachronous subgroups of patients) received Patients with bones metastases only, not associated with visceral

capecitabine, 7 patients (17.9% referred to metachronous subgroup) metastases had a better 2-year OS rate of 48.7% compared with

received combined chemotherapy with Cisplatin and 1 patient those who associated visceral metastases (10.5%). The difference

received cyclophosphamide (2.5% referred to metachronous was not significant (P=0.277) (Fig.1C, Table 3).

subgroup). The group of patients with T12 tumors had a median OS rates (28

Concerning palliative radiotherapy of bone metastasis, 30 patients months) better than those had T34 tumors (19 months), but this

JNPC http://www journalofnasopharyngealcarcinoma org/ e-ISSN 2312-0398 Published:2017-03 -30 DOI:10 15383/jnpc.35
5

difference is not significant (P=0.361) (Fig.1G, Table 3).

The median OS rates of the group N01 was 12 months compared

to 26 months for N23, and the difference was significant

(P=0.007) (Fig.1H, Table 3).

The use of bisphosphonates was significant in predicting OS

(P=0.001). The median OS was 33 months in the group of patients

treated with biphosphonates compared to 15 months for those not

(Fig.1I, Table 3).

C

The comparison between different types of first chemotherapy of

the patient with metachrone metastases was not statistically

significant (P=0.88). Among patients with metachronous

metastasis 30 patients with bone metastases had radiotherapy and

9 had not. The 2-year OS rate was 55% and 68%, respectively.

The difference between the two subgroups on the OS rate was not

significant (P=0.27).

JNPC http://www journalofnasopharyngealcarcinoma org/ e-ISSN 2312-0398 Published:2017-03 -30 DOI:10 15383/jnpc.35
6

F I
U

A: by time of metastases; B: by number of bone metastatic sites; C: by

association to visceral metastasis; D: by number of bone metastatic sites;
E: by metastatic site; F: by spinal involvement or not; G: by T stage; H:
by N stage; I: by biphosphonate treatment.
Fig. 1: Kaplan Meier plot showing overall survival divided by time

order of bone metastases.

Table 3. Analysis of overall survival by clinical factors (all population)

Variables Median 2-years(%) 5-years(%) P value
OS
(months)
Metastatic onset
Synchronous 14 37.4 12.5 0.004*
Metachronous 28 47.7 27.9
G Metastatic site
Spine involvement 17 19.5 14.6 0.228
Peripheral 19 35 -
involvement
Mixed involvement 26 54.5 29,5
Spine involvement
Yes 24 47.1 22.9 0.490
No 19 35 -
Number of bone metastases (only bone metastases)
Single 12 30 20 0.647
Multiple 24 54.5 14.2
Number of metastatic bone(only bone metastasis)
>3 24 57.6 18.8 0.31
<=3 20 13.1 -
Association to visceral metastases
Yes 19 10.5 - 0.277
No 23 48.7 15.6
T stage
T12 28 54.8 23.5 0.361
H T34 19 19 -
N stage
N01 12 16 - 0.007*
N23 26 58.5 24.7
Biphosphonates
Yes 33 64 43.4 0.001*
No 15 30.3 7.4
*P<0.05

Among the patients with synchronous metastasis, the locoregional

radiotherapy for the primary tumor with curative dose was

JNPC http://www journalofnasopharyngealcarcinoma org/ e-ISSN 2312-0398 Published:2017-03 -30 DOI:10 15383/jnpc.35
7

delivered to 17 patients, and the total 2-year OS rate was 31%. Ten NPC patients with distant metastasis at initial diagnosis, those with

patients had locoregional radiotherapy with palliative doses, and a single metastasis had an excellent survival with 3-year OS rate of

the 2-year rate was 12%. The comparison was not significant. 65.8% compared to only 25.9% for those with multiple metastases

Among this same group, the analysis of the 2-year OS rate of (P=0.001). Khanfir et al.[12] identified a worse survival in patients

patients who had radiotherapy of bone metastases was 19%. On with multiple metastatic sites (P=0.001) and multiple bone

the other hand, the 2-year OS rate of those who had not irradiated metastasis (P=0.001). Similarly, Teo et al.[11] found that patients

for the bone metastasis was 37.5%. This difference was not with multiple types of metastases had a poorer survival compared

significant (P=0.087). with a single type of metastasis (P=0.001).

In the current study, the association between bone metastasis with

Discussion
visceral metastasis worsened the OS, but the difference was not
This current study investigated the survival of NPC patients with
statistically significant (P=0.27). Zeng et al.[8] identified that the
bone metastatic, and identified the prognostic factors of this
presence of visceral metastasis, especially liver metastases was
population. The median OS rate was 23 months in this population,
associated with poor OS by univariate analysis. Ong et al. [13], who
and was similar compared to previous reports. In a large cohort
defined a prognostic index score for metastatic nasopharyngeal
study of 312 patients reported by Shen et al.[9] the median OS was
carcinoma, founded that liver and lung metastasis was associated
23.4 months. Cao et al.[10] reported a median OS estimated for
with a worse OS.
33.3 months for 116 NPC patients with bone metastases at the first
Metastasis to spine is an unfavorable predictor for OS in NPC
failure after primary treatment.
patients with bone metastasis. Shen et al.[13] identified that
The time of developing distant bone metastases influenced the OS.
metastasis to the spine was significantly associated with
This study demonstrated that synchronous bone metastasis was
unfavorable OS (20.4 vs. 37.9 months; P=0.001). Multivariate
associated with a poorer prognosis and survival compared to those
analysis showed that spine involvement (present vs. absent) was an
with metachronous bone metastasis (14 months vs. 28 months,
independent prognostic factor for OS. In our study we didnt find
[11]
P=0.04). Teo et al. reported that patients who presented with
any significant difference between groups with and without spine
distant metastasis at diagnosis had a significantly worser survival
involvement.
than those who developed distant metastasis after radiotherapy.
Cao et al.[10] reported that patients with early T classification
Multiple bone metastases (vs. single) and the number of metastatic
(T1T2) and early N classification (N0N1) were associated with
sites (more than three vs. three or fewer) worsened the survival,
a longer OS. In our series, we failed to identify the relationship
[9]
but the differences are not significant. Shen et al. has
between OS and T, N classification. The use of radiotherapy to the
demonstrated that patients with more than three bones metastatic
primary tumor in NPC patients with synchronous metastases was a
sites had a significantly poorer OS than the patients with three or
controversial debate. Many reports have demonstrated the benefits
fewer metastatic sites (16.2 vs. 32.4 months; P=0.001). The
of radiotherapy for OS improvement[8,14,15]. Zeng et al.[8] founded
patients with multiple metastatic sites had a significantly poorer
that the application of radiotherapy (median dose: 70 Gy) after
OS than the patients with single metastatic site (20.8 vs. 39 months;
chemotherapy was a positive factor associated with survival. The
[8]
P=0.004). In a retrospective analysis of Zeng et al. , among 234
3-year OS of patients was 48.2% and 12.4% for patients receiving

JNPC http://www journalofnasopharyngealcarcinoma org/ e-ISSN 2312-0398 Published:2017-03 -30 DOI:10 15383/jnpc.35
8

radiotherapy after chemotherapy and those receiving bisphosphonates should be used in all patients with bone

chemotherapy alone, respectively (P<0.001). Similar to this report, metastases in solid tumors. The initiation of treatment was

Tian et al.[14] analyzed the OS of 85 NPC patients, who had recommended when the bone metastases was diagnosed and the

synchronous liver metastasis, with and without the application of patients can be given any anticancer therapy[22].

radiotherapy to the primary tumor. The 3-year OS of the patients About the treatment of painful bone metastasis with localized

receiving radiotherapy was up to 28.1%, significantly higher than radiotherapy, there was 2 modalities: single fraction protocol (1

those not receiving radiotherapy (5.7%). Yeh et al.[15], fraction of 8 Gy) and multifraction one (20 Gy in 4 fractions, 30

demonstrated that radiotherapy was proved to be an independent Gy in 10 fractions). Meta-analysis evaluating palliative

prognostic factor for OS of the NPC patients of stage . They radiotherapy showed that single fraction radiotherapy was

explained this by the fact that the radiotherapy produces equivalent to multifraction radiotherapy in relieving pain due to

significant regression of the primary tumors that can help to bone metastasis[23,24]. Complete response to pain was estimated to

reduce risks of death caused by progression of primary tumor. 30% with different modalities. In a systematic review, 16

Consequently, tumor necrosis will be reduced, also bleeding, nasal randomized trials comparing effects on painful bone metastasis

obstruction, and headaches. By the way the quality of life would between single fraction and multifraction schedule of localized

be greater. Radiotherapy is more promoted by the use of the radiotherapy were analyzed and no significant differences were

intensity-modulated radiotherapy (IMRT) that will improve the found for overall and complete responses for pain[25].

quality of treatment and reduce complications.

Conclusion
The role of chemotherapy has been demonstrated for NPC patients
Our study revealed that the time of metastasis and the use of
[6-16]
with distant metastases . Platiniumbased chemotherapy
bisphosphonates were prognostic factors associated with better
[16-18]
regimens achieved a high objective response rate . Cisplatin
OSs. Multiple bone metastases and visceral site were associated to
and infusional 5-fluorouracil was the most frequently used
poor prognosis.
[19,20]
treatment with 66%76% response rates .
Metastasis of NPC with bone only or not and the number of site
Our study founded a significant impact of biphosphonates
are predictive factors for prognosis. Curative treatment should be
treatment on survival of NPC patients with bone metastatic, which
considered for patients with single bone metastasis. More data
[21]
was in accordance with the report by Jin et al. . They
from clinical trials are needed.
retrospectively analyzed 307 NPC patients with bone metastases

References
and found that the patients treated by chemotherapy combined
[1] Frikha M, Toumi N, Ghorbel L, et al. Pediatric nasopharyngeal
with Zoledronic acid had a better progression (free survival) than
carcinoma: Anatomoclinic aspects, therapeutic results and
those treated with chemotherapy only (11.5 vs. 5.5 months, evolutive particularities[J]. Cancer Radiother, 2010, 14(3):
169175.
P<0.001) and OS (23.5 vs. 17.5 months, P<0.001).
[2] Ellouze R, Daoud J, Maalej M. Cancers du nasopharynx[M].
There was a review study recommending an international panel for
Dans: Maalej M. Cancrologie pratique. Tunis: Centre de
the use of bisphosphonates in solid tumors[22]. In fact Publication Universitaire, 1999: 161169.
[3] Ben Abdallah M, Zehani S, Hizem Ben Ayoub W, et al.
bisphosphonates was considered as a supportive therapy to reduce
Chapter V Nasopharyngeal Cancer[M]//North Tunisian
the cancer-related skeletal complications. It was recommended that

JNPC http://www journalofnasopharyngealcarcinoma org/ e-ISSN 2312-0398 Published:2017-03 -30 DOI:10 15383/jnpc.35
9
Registry of Cancer 1999-2003. Tunis: Salah Azaiz institute
and epidemiology research unit of Cancer in Tunisia: 2009.
[4] Wei WI, Sham JS. Nasopharyngeal carcinoma[J]. Lancet, 2005,
365(9476): 20412054.
[5] Lee AW, Ng WT, Chan YH, et al. The battle against
nasopharyngeal cancer[J]. Radiother Oncol, 2012, 104(3):
272278.
[6] Bensouda Y, Kaikani W, Ahbeddou N, et al. Treatment for
metastatic nasopharyngeal carcinoma[J]. Eur
Otorhinolaryngol Head Neck Dis, 2011, 128(2):7985.
[7] Nol G, Dessard-Diana B, Vignot S, et al. Treatment of
nasopharyngeal cancer: literature review[J]. Cancer Radiother,
2002, 6(2): 5984.
[8] Zeng L, Tian YM, Huang Y, et al. Retrospective analysis of
234 nasopharyngeal carcinoma patients with distant metastasis
at initial diagnosis: therapeutic approaches and prognostic
factors[J]. PLoS ONE, 2014, 9(9): e108070.
[9] Shen L, Dong J, Li S, et al. M1 stage subdivision and treatment
outcome of patients with bone-only metastasis
nasopharyngeal carcinoma[J]. Oncologist, 2015,
291298.
[10] Cao X, Han Y, He L, et al. Risk subset of the survival for
nasopharyngeal carcinoma patients with bone metastases: who
will benefit from combined treatment[J]. Oral Oncol, 2011,
47(8): 747752.
[11] Teo PM, Kwan WH, Lee WY, et al. Prognosticators
determining survival subsequent to distant metastasis from
nasopharyngeal carcinoma[J]. Cancer, 1996,
24232431.
[12] Khanfir A, Frikha M, Ghorbel A, et al. Prognostic factors in
metastatic nasopharyngeal carcinoma[J]. Cancer Radiother,
2007, 11(8): 461464.
[13] Ong YK, Heng DM, Chung B, et al. Design of a prognostic
index score for metastatic nasopharyngeal carcinoma[J]. Eur J
Cancer, 2003, 39(11): 15351541.
[14] Tian YM, Zeng L, Wang FH, et al. Prognostic factors in
nasopharyngeal carcinoma with synchronous liver metastasis:
a retrospective study for the management of treatment[J].
Radiat Oncol, 2013, 8: 272.
[15] Yeh SA, Tang Y, Lui CC, et al. Treatment outcomes of
JNPC http://www journalofnasopharyngealcarcinoma org/
patients with AJCC stage IVC nasopharyngeal carcinoma:
benefits of primary radiotherapy[J]. Jpn J Clin Oncol, 2006,
36(3): 132136.
[16] Fandi A, Bachouchi M, Azli N, et al. Long-term disease-free
survivors in metastatic undifferentiated carcinoma of
nasopharyngeal type[J]. J Clin Oncol, 2000, 18(6):
13241330.
[17] Au E, Ang PT. A phase II trial of 5-fluorouracil and
Ann cisplatinum in recurrent or metastatic nasopharyngeal
carcinoma[J]. Ann Oncol, 1994, 5(1): 8789.
[18] Foo KF, Tan EH, Leong SS, et al. Gemcitabine in metastatic
nasopharyngeal carcinoma of the undifferentiated type[J].
Ann Oncol, 2002, 13(1): 150156.
[19] Wang TL, Tan YO. Cisplatin and 5-fluorouracil continuous
infusion for metastatic nasopharyngeal carcinoma[J]. Ann
Acad Med Singap, 1991, 20(5): 601603.
[20] Chi KH, Chan WK, Cooper DL, et al. A phase II study of
outpatient chemotherapy with cisplatin, 5-fluorouracil, and
of leucovorin in nasopharyngeal carcinoma[J]. Cancer, 1994,
20(3): 73(2): 247252.
[21] Jin Y, An X, Cai YC, et al. Zoledronic acid combined with
chemotherapy bring survival benefits to patients with bone
metastases from nasopharyngeal carcinoma[J]. J Cancer Res
Clin Oncol, 2011, 137(10): 15451551.
[22] Aapro M, Abrahamsson PA, Body JJ, et al. Guidance on the
use of bisphosphonates in solid tumours: recommendations of
an international expert panel[J]. Ann Oncol, 2008, 19(3):
77(12): 420432.
[23] Wu JS, Wong R, Johnston M, et al.Cancer Care Ontario
Guidelines Initiative Supportive Care Group. Meta-analysis of
dose fractionation radiotherapy trials for the palliation of
painful bone metastasis[J]. Int J Radiat Oncol Biol Phys,
2003,55 (3):594605.
[24] Sze WM, Shelley MD, Held I, et al. Palliation of metastatic
bone pain: single fraction versus multifraction
radiotherapya systematic review of randomised trials[J].
Clin Oncol (R Coll Radiol), 2003, 15(6): 345352.
[25] Chow E, Harris K, Fan G, et al. Palliative radiotherapy trials
for bone metastases: a systematic review[J]. J Clin Oncol,
2007, 25(11): 14231436.
e-ISSN 2312-0398 Published:2017-03 -30 DOI:10 15383/jnpc.35