1

Research Article
Feasibility and efficiency of concurrent chemo-radiotherapy for nasopharyngeal carcinoma patients
Imene Essaidi, Chiraz Nasr, Lotfi Kochbati, Mongi Maalej
Radio-Oncology Department Salah Azaiz Cancer Institute, boulevard du 9-Avril, 1006 Tunis, Tunisia

Citation: Essaidi I, Nasr C, Kochbati L, Maalej M. Feasibility and efficiency of concurrent chemo-radiotherapy for
nasopharyngeal carcinoma patients. J Nasopharyng Carcinoma, 2015, 1(21): e21. doi:10.15383/jnpc.21.
Competing interests: The authors have declared that no competing interests exist.
Conflict of interest: None.
Copyright: 2014 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:
Purpose: To evaluate the feasibility and efficiency of concurrent chemo-radiotherapy (CCRT) in nasopharyngeal
carcinoma (NPC) patients. Patients and Methods: We reviewed data of 33 non-metastatic NPC patients who had
been treated with CCRT between January 2004 and December 2006.The Median age of patients was 41 year-old
and the male/female ratio was 3.According to the 2002 TNM staging system, T3-T4 locally advanced tumors and
N2-N3 nodal status rates were 67% and 46%, respectively. All patients had undifferentiated carcinoma and received
conventional fractionated 2D conventional radiotherapy (RT)with a total dose of 70-74 Gyand concurrent weekly
intravenous cisplatin (40 mg/m2). Results: The acute toxicities were all manageable. Grade 3-4 mucositis and skin
reaction were seen in 6 patients (18%). RT interruption for a week occurred in 1 patient because of a Grade 3
dysphagia. All patients finished their planned RT. Four patients (12%) refused to complete the concurrent
chemotherapy (CT) and 5 other patients (15%) did not receive the planned cycles of CT because of renal and/or
hematologic toxicities. After a median follow-up of 58 months, 6 patients (18%) developed loco-regional relapse
associated with distant metastasis in 4 cases (12%), and 6 patients (18%) developed distant metastases alone. Fiveyear overall survival and disease-free survival rates were 70 and 63%, respectively. A univariate analysis for
prognostic factors was also performed. Overall survive was affected by Stage T4, Stage N3, age >40 years, and
cycles of CT 5.Patients who received more than 5 cycles of cisplatin had also significantly better disease free
survival and metastasis free survival. Conclusion: The results of our study have shown that CCRT for loco
regionally advanced NPC is both feasible and effective, with acceptable toxic effects. On univariate analysis, the
age >40 years, Stage T4, Stage N3, and cycles of CT 5 had a significantly poor outcome.
Keywords: chemo-radiotherapy; nasopharyngeal carcinoma; feasibility; efficiency; toxicities

pathology, clinical presentation and response to treatment [1, 2].

BACKGROUND
Nasopharyngeal

carcinoma (NPC) is

distinct

other

This neoplasm has a notable ethnic and geographic distribution

malignancies in the head and neck with respect to its epidemiology,

with a high prevalence in Southeast Asian and North African

JNPC http://www.journalofnasopharyngealcarcinoma.org/

from

e-ISSN 2312-0398

Published:2015-03-23 DOI:10.15383/jnpc.21

populations. It is relatively frequent in Tunisia with incidence rates

Median

of 3.4/ 100.000 population in males and 1.6/ 100.000 population in

Sex

females [3]. NPC ishighlyradiosensitive.Although early-stage NPC

41 years

Range (11-66 years)

Male

25

76

is highly radiocurable, the cure rate with RT alone for

Female

24

locoregionally advanced NPC is low [4-6]. Because NPC is a

Pathology

chemosensitive tumor, CT added to RT in various manners should

WHO type III

33

100

be a method to improve survival rates [7-17]. Since the early

T stage (TNM 2002)

1990s, more than 15 randomized clinical trials and 4 meta-

T0

analyses have been published on the use of induction, concurrent

T1

and adjuvant CT in the treatment of locoregionally advanced NPC

T2

24

[6-22].The predominant finding of these studies is a survival

T3

15

46

advantage associated with the use ofCCRTwith or without

T4

21

adjuvant CT (ACT)over RT alone.Since then, CCRT with or

N stage (TNM 2002)

without ACT has become the standard treatment modality for

N0

18

patients with advanced NPC, although the rate of acute toxicities

N1

12

36

was significant especially when ACT was prescribed.

N2

11

34

The aim of this retrospective study is to evaluate the feasibility and

N3

12

efficiencyof CCRT in locoregionally advanced NPC patients.

Treatment plan: All patients were treated with a radical intent

PATIENTS AND METHODS

Patient characteristics:A total of 33 patients with a histologically
confirmed diagnosis of non-metastatic NPC were treated with
CCRT at Salah Azaiz Institute between January 2004 and
December 2006.The patient age at presentation ranged from 11 to
66 years (median, 41). Of the 33 patients, 25 were males and 8
were females(male/female ratio=3).The initial staging evaluation
included a complete history and physical examination, endoscopy
and biopsy, complete blood count determination, liver and renal
function tests, chest X-ray, abdominal ultrasonography, CT-scan
of the nasopharynx and neck region, and bone scintigraphy.
Patients underwent clinically staging according to the 2002 TNM
staging system.T3-T4 locally advanced tumors and N2-N3 nodal
status rates were 67 and 46%, respectively. All 33 patients had the
undifferentiated (WHO Type III) variant of NPC (Table 1).

using a combination of CT and RT. They received conventional

2D RT using a telecobalt unitwith bilateral parallel opposing fields
to the primary tumor and upper neck, and a single anterior field to
the lower neck with a central shield. After 42-44Gy, the primary
tumor was boostedusing bilaterally opposed reduced portals and
the posterior cervical lymphatic chains were treated with
appropriate electrons (6-9 MeV). The total dose planned was70-74
Gy to the primary tumourand the involved lymph nodesin daily
fractions of 2 Gy, 5 d/wk. Patients received IV cisplatin at 40
mg/m2 weekly during the entire duration of a 7 weeks course of
external RT. The complete blood picture and biochemistry were
checked weekly before CT was administered. The number of
cycles of cisplatin that could be given depending on the patients
tolerance.
Patient evaluation and follow-up: Acute RT-related toxicities were

Table 1. Patient characteristics

Characteristics

No. of patients

Age

documented according to the Radiation Therapy Oncology Group

Percentage (%)

guidelines [23] and CT-related toxicities by the WHO criteria [24].

At each follow-up visit, a complete physical examination
(including endoscopy if required) was performed. A post-therapy

JNPC http://www.journalofnasopharyngealcarcinoma.org/

e-ISSN 2312-0398

Published:2015-03-23 DOI:10.15383/jnpc.21

CT scan or MRI of head and neck was obtained for all patients at 3
months after treatment.
Statistical methods: Study endpoints include acute toxicities,

Table 2. Acute toxicities

Acute toxicities

(MRFS). All survivals were calculated from the date of

histologically confirmed diagnosis to the date of the observed
endpoints or to the date of the last follow-up. Survival endpoints
were analyzed using the Kaplan-Meier method. Univariateanalyse
was performed for evaluation of the prognostic factors. The Logrank test was used to compare the curves and p-values < 0.05 were
considered to be statistically significant.
RESULTS

Grade 3 (%)

(%)

overall survival (OS), disease-free survival (DFS), loco-regional

relapse-free survival (LRRFS) and metastasis relapse-free survival

Grade 1-2

Grade 4
(%)

Mucositis

26 (79%)

5 (15%)

1 (3%)

Skin reaction

25 (76%)

4 (12%)

2 (6%)

Dysphagia

16 (48%)

1 (3%)

Vomiting

21 (64%)

4 (12%)

Leukopenia

13 (39%)

2 (6%)

Anemia

6 (18%)

1 (3%)

Thrombocytopenia

1 (3%)

Renal impairment

4 (12%)

Table 3. Compliancetotreatment

Toxicity and Compliance: The acute toxicities were all reversible

Cycles of cisplatin
and acceptable. The major side effects were mucositis (97%), skin

No. of patients

Percentage (%)

5 cycles

19

58

> 5 cycles

14

42

reaction (94%), nausea and vomiting (76%), dysphagia (51%), and

leukopenia (45%). Most of these side effects were Grade 1-2.
Severemucositis and skin reaction (Grade 3-4) were seen in 6
Events and survival: After a median follow-up of 58 months
patients (18%). RT interruption for a week occurred in 1 case
(range, 3-94 months), 6 patients (18%) developed loco-regional
because of a Grade 3 dysphagia. Renal function impairment was
relapse associated with distant metastasis in 4 cases (12%), and 6
found in 4 cases (12%). All the 33 patients included in this study
patients (18%) developed distant metastases alone. Five-year
finished their planned RT. The median number of cycle of
overall survival (OS), disease-free survival (DFS), loco-regional
cisplatin administrated was 5 cycles (range, 2-7 cycles). Four-teen
relapse-free survival (LRRFS) and metastasis relapse-free survival
patients (42%) received more than 5 cycles of cisplatin.
(MRFS) rates were 70, 63, 80, and 68%, respectively (Fig. 1).
Fourpatients (12%) refused to complete the concurrent CT, while 5
other patients (15%) did not receive the planned cycles of CT
because of renal and/or hematologic toxicities (Tables 2 and 3).

Figure 1. Overall survival (OS), Disease-Free Survival (DFS), Loco-regional Relapse-free Survival (LRRFS) and Metastasis Relapse-Free Survival (MRFS).

Prognostic factors: On univariate analysis, the age >40 years,

significant pejorative impact on OS(Table 4 and Fig.2). On the

Stage T4, Stage N3, and cycles of CT 5 had a statistically

other hand, Stage T4 had a statistically significant influence on

JNPC http://www.journalofnasopharyngealcarcinoma.org/

e-ISSN 2312-0398

Published:2015-03-23 DOI:10.15383/jnpc.21

LRRFS, Stage N3had a statistically significant influence on MRFS

significantly better DFSand MRFS than those who received less

and patients who received more than 5 cycles of cisplatin had

than

or

equal

to

cycles

of

CT.

Table 4. Prognostic factors for clinical outcome.

OS
Prognosticfactors

5-y (%)

Age

DFS
p

5-y (%)

0.018

LRRFS
p

5-y (%)

0.003

MRFS
P

5-y (%)

0.046

0.002

40 years

88

88

94

94

> 40 years

50

44

65

37

T stage

0.085

0.026

0.619

0.005

T0T1T2a

80

80

100

80

T2bT3

81

70

90

70

T4

28

29

34

57

N stage

0.028

0.491

0.03

0.018

N0N1

82

74

88

79

N2

67

58

73

67

N3

25

25

67

25

Cycles of cysplatin
> 5 cycles

87

5 cycles

53

0.033

87
39

0.007

87

0.31

72

87

0.002

49

Figure 2. Overall survival (OS) stratified by prognostic factors: Age, T stage, N stage, and cycles of CT.

JNPC http://www.journalofnasopharyngealcarcinoma.org/

e-ISSN 2312-0398

Published:2015-03-23 DOI:10.15383/jnpc.21

DISCUSSION

improve overall survival (OS), especially in the T3 to T4

NPC is highly radiosensitive andchemosensitive, and an excellent

subgroup(For the CCRT arm, the 5-year OS and PFS rates were

disease control can be achieved using combined modality

70.3 and 60.2%, respectively). In terms of toxicity and compliance

chemoradiation even in patients with locally advanced disease [25].

to CT, the systemic and local toxicities were generally acceptable,

The American Intergroup 0099 study, using both concurrent

60% of patients completed at least 5 cycles of concurrent cisplatin,

cisplatin and RT followed by ACT with cisplatin and fluorouracil

and only 44% completed the planned 6 cycles of concurrent

(FU) was the first randomized trial to show a survival benefit with

cisplatin during RT [10]. Kim and al have retrospectively reviewed

CCRT.Its outcome established the treatment standard in the United

their experience of both weekly and 3-weekly regimens. They

States as standard of care for locally advanced NPC [7].Afterward,

have found weekly scheduling practical and feasible for CCRT in

even in Asian countries where NPC is prevalent, the treatment

NPC, resulting in decreased interruptions in radiation treatment

efficacy of CCRT with or without ACT was confirmed in many

and minimal acute toxic events without compromising local

clinical studies. Since then, we conclude that CCRT with or

control [27]. There is a trend for centers in the endemic regions

without ACT is also applicable to patients in endemic areas and

opting for the weekly regimen due to the more favorable toxicity

should be standard of practice in locally advanced disease [8-10].

profile and comparable efficacy. For these reasons, we adopted in

The overall magnitude of benefit of CCRT has been previously

our study a concurrent weekly cisplatin (40 mg/m2) protocol, all

reported in the Meta-analysis of Chemotherapy in Nasopharyngeal

patients had relatively good compliance, and 58% of patients

Carcinoma (MAC-NPC) study [19]. This analysis demonstrated

completed at least 5 cycles of concurrent cisplatin. No fatal

that CT led to asignificant benefit in overall survival (OS) and

toxicity related to planed treatment was observed. Although a high

progression-free survival (PFS). The effect was most significant

incidence of grade 1 or 2 mucositis, vomiting, and leukopenia, our

for the concurrent group. Combined modality treatment using

CCRT protocol was more tolerable, with less severe grade 3 to 4

concurrent cisplatin-based CT is thus far the only strategy

toxicities than many previous trials.

supported by several large randomized studies to improve survival.

Interestingly, 2 retrospective reports revealed that the dose of

Since the publication of this meta-analysis, many clinical trials

cisplatin during the CCRT had a significant prognostic impact.

[13-17, and 22] and meta-analyses [20, 21] have clearly

They found that the number of cycles of concurrent cisplatin-based

demonstrated that CT administered concurrently with RT as the

CT was significantly associated with OS in the stage III subgroup,

most efficacious. The roles of neoadjuvantCT (NACT), and ACT

but not in stage IV [28, 29]. A possible explanation for this may be

in OS, and their impact on locoregional control and distant

the fact CCRT for these patients with such high-risk disease may

metastases still remain controversial.

not be enough to improve their outcome significantly. This will

At present, concurrent CT during the course of RT should be

thus warrant further exploration of NACT or ACT as an additional

considered the standard of care. Weekly (30-40 mg/m2) as well as

treatment modality of this subset of patients. In our study, patients

3-weekly (100 mg/m2) cisplatin-based regimens are accepted as

who received more than 5 cycles of cisplatin during CRT had

standard practice. Toxic effects are considerable with the 3-weekly

betterprognosis than those who did not. This is consistent with the

schedule as revealed by the Intergroup study[7] in which only 63%

findings of the previous study [28, 29]. Limited by the fact that

of patients having received all three 3-weekly-courses of

these were retrospective analyses, the causal relationship between

concurrent 100mg/m2 cisplatin. In the phase III randomized trial

cycles of cisplatin and improvement in OS is not clearly defined.

from Hong Kong, low-dose cisplatin (40 mg/m2) given in a

However, until further confirmatory studies are available, these

weekly cycle during the entire course of RT has been shown to

results should at least enable us to advise our patients that

JNPC http://www.journalofnasopharyngealcarcinoma.org/

e-ISSN 2312-0398

Published:2015-03-23 DOI:10.15383/jnpc.21

compliance to CT during CCRT may influence prognosis.

advanced NPC.They found that NACT followed by CCRT was

Despite patients included in our retrospective study did not receive

well tolerated but could not significantly improve prognosis in

ACTfollowing CCRT, a 5-year OS rate of 70% a 5-year DFS rate

terms of overall survival, loco-regional failure-free survival or

of 63% were obtained. These results are in line with published data

distant metastasis failure-free survival [36]. Perhaps, this might be

[7-10] and highlight the need of further phase III trials to assess

related with the fact that NACTdelayed the time of RT.

the role of ACT following CCRT.Recently, Chen and al have

While results of numerous randomized clinical trials have

published the findings of their randomized phase III trial of CCRT

confirmed efficacy of CCRT over RT alone for loco-regionally

and ACT versus CCRT alone involving over 500 patients with

advanced NPC, the question arises as to whether the CCRT has an

non-metastatic stage III-IV NPC. At a median follow-up for 38

impact on the outcome of early stage disease. Chen and colleagues

months, there was no significant difference in the estimated 2-year

published their randomized phase III prospective study of stage II

failure free survival rate in the CCRT and ACT versus the CCRT

NPC patients. Patients were randomized to either conventional RT

alone arms. In terms of toxicity, 42% of the 205 patients on the

alone (n = 114) or CCRT (n = 116) with concurrent weekly

ACT arm experienced grade 3-4 toxicities during ACT, with 17%

cisplatin at 30 mg/m2. At a median follow-up at 60 months, the

of

addition of CT statistically improved the 5-year OS rate (94.5 vs

patients

having

toxicities[30].A

experienced

recent

significant

meta-analysis

hematological

hasshown

similar

85.8%, p= 0.007), PFS (88 vs 79%, p=0.017, and MRFS (95 vs

findings[31].One possible way to select better patients suitable for

84%, p=0.007). Surprisingly, there was no statistically significant

an adjuvant approach may be assessment of plasma EBV DNA

difference in the 5-year LRRFS rate (93 vs 91.1%, p= 0.29) [37].

levels. An early post-CCRT detection of high EBV DNA levels

The intensity-modulated radiotherapy (IMRT) is widely employed

may be an indication to administer ACT. Chan and al are

as an alternative to conventional RT in NPC patients with stage I-

conducting a clinical trial with the use of post-RT EBV DNA to

II disease, but its role in association with CT is still unknown.

select high-risk patients to be randomized to receive ACT versus

Thamet al evaluated the treatment outcome of 107 patients with

observation. This study is ongoing and results expected in the

stage IIB NPC after IMRTwith or without CT. They found that

coming 2 years [32].

IMRT without concurrent CT provides good treatment outcome

Lin and al pointed out that CCRT was inadequate for high-risk

with acceptable toxicityand without significant difference in

patients (nodal size >6 cm, supraclavicular node metastases, 1992

patients treated with CT [38].As there are no published prospective

AJCC stage T4N2, and multiple neck node metastases with 1

data on the impact of CCRT in stage II NPC patients treated with

node >4 cm) with similar 5-year OS compared to RT alone (55.8%

IMRT, a defining conclusion of CCRT in the IMRT-era for early

vs. 46.3%, p= 0.176) [33]. One strategy to further improve the

stage NPC patients cannot be drawn. The practice of CCRT in

efficacy of CT for high-risk NPC patients is to use more

stage II disease is acceptable as long as a balance is taken with the

aggressive treatment with NACT in addition to CCRT. Induction

associated short and long-term toxicities of concurrent CT.In

CT is generally better tolerated than ACT and might provide early

anothertrial, 868 non-metastatic NPC patients treated by IMRT

eradication of distant micro-metastases. In addition, NAC could

were analyzed retrospectively. With a median follow-up of 50

shrink the primary tumor to give wider margins for irradiation. A

months, the 5-year estimated disease specific survival (DSS), local

several phase II clinical studies, using intensive NACT followed

recurrence-free survival (LRFS), regional recurrence-free survival

by CCRT, have shown encouraging toxicity profiles and disease

(RRFS) and distant metastasis-free survival (DMFS) were 84.7%,

control [34, 35].Liang and al have published the first meta-

91.8%, 96.4% and 84.6%, respectively. The toxicity profile was

analysisto evaluate the efficacy and toxicity of the NACT followed

very low. Concurrent chemotherapy failed to improve survival

by CCRT versus CCRT with or without AC for loco-regionally

rates for patients with advanced locoregional disease and increased

JNPC http://www.journalofnasopharyngealcarcinoma.org/

e-ISSN 2312-0398

Published:2015-03-23 DOI:10.15383/jnpc.21

the severity of acute toxicities [39].

alone for advanced nasopharyngeal carcinoma: positive effect on

overall and progression-free survival. J ClinOncol. 2003;2:631-7.

CONCLUSION

9. Kwong DL, Sham JS, Au GK, Chua DT, Kwong PW, Cheng

Our study confirms that weekly cisplatin concurrent with RT for

AC, Wu PM, Law MW, Kwok CC, Yau CC, Wan KY, Chan RT,

locally advanced nasopharyngeal cancers was found tolerable with

Choy

a high efficiency and provides further evidence on the prognostic

nasopharyngeal carcinoma: a factorial study. J ClinOncol.

significance of CT dosing during the concurrent phase with RT.

2004;22:2643-53.

DD.Concurrent

and

adjuvant

chemotherapy

for

10. Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH,
REFERENCES

Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan

1. Boussen H, Bouaouina N, Gamoudi A, Mokni N, Benna F,

DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam

Boussen I, Ladgham A. EMC oto-rhino-laryngologie : Cancers du

MK, Leung TW, Johnson PJ, Choi PH, Zee BC.Overall survival

nasopharynx. Elsevier Masson, 2007.

after

2. Altun M, Fandi A, Dupuis O, et al: Undifferentiated

radiotherapy alone in locoregionally advanced nasopharyngeal

nasopharyngeal

carcinoma. J Natl Cancer Inst. 2005;97:536-9.

cancer

(UCNT):

Current

diagnostic

and

concurrent

cisplatin-radiotherapy

compared

with

therapeutic aspects. Int J RadiatOncolBiol Phys. 1995; 32:859-77.

11. Lee AW, Lau WH, Tung SY, Chua DT, Chappell R, Xu L, Siu

3. Registre des cancers Nord-Tunisie. Donnes 1999-2003.

L, Sze WM, Leung TW, Sham JS, Ngan RK, Law SC, Yau TK,

Evolution 1994-2003. Projections lhorizon 2024.

Au JS, O'Sullivan B, Pang ES, O SK, Au GK, Lau JT; Hong Kong

4. Yeh SA, Tang Y, Lui CC, Huang YJ, Huang EY. Treatment

Nasopharyngeal Cancer Study Group. Preliminary results of a

outcomes

with

randomized study on therapeutic gain by concurrent chemotherapy

nasopharyngeal carcinoma treated with radiotherapy alone. Int J

for regionally-advanced nasopharyngeal carcinoma: NPC-9901

RadiatOncolBiol Phys. 2005;62:672-9.

Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J

5. Lee AW, Poon YF, Foo W, Law SC, Cheung FK, Chan DK,

ClinOncol. 2005;23:6966-75.

Tung SY, Thaw M, Ho JH. Retrospectiveanalysis of 5037 patients

12. Chua DT, Ma J, Sham JS, Mai HQ, Choy DT, Hong MH, Lu

with nasopharyngealcarcinoma treated during 1976-1985:Overall

TX, Min HQ. Long-term survival after cisplatin-based induction

survival and patterns of failure. Int JRadiatOncolBiol Phys. 1992;

chemotherapy and radiotherapy for nasopharyngeal carcinoma: a

23:261-270, 6.

pooled data analysis of two phase III trials.J ClinOncol.

6. Teo P, Yu P, Lee WY, Leung SF, Kwan WH, Yu KH, Choi P,

2005;23:1118-24.

Johnson

primary

13. Wee J, Tan EH, Tai BC, Wong HB, Leong SS, Tan T, Chua

radiotherapy in 903 non-disseminated nasopharyngealcarcinoma

ET, Yang E, Lee KM, Fong KW, Tan HS, Lee KS, Loong S, Sethi

evaluated by computed tomography.Int J RadiatOncolBiol Phys.

V, Chua EJ, Machin D. Randomized trial of radiotherapy versus

1996;36:291-304.

concurrent

7. Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T,

chemotherapy in patients with American Joint Committee on

Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley

Cancer/International Union against cancer stage III and IV

JF.Chemoradiotherapy versus radiotherapy in patients with

nasopharyngeal cancer of the endemic variety. J ClinOncol.

advanced nasopharyngeal cancer: phase III randomized Intergroup

2005;23:6730-8.

study 0099. J ClinOncol. 1998;16:1310-7.

14. Lee AW, Tung SY, Chua DT, Ngan RK, Chappell R, Tung R,

8. Lin JC, Jan JS, Hsu CY, Liang WM, Jiang RS, Wang WY.Phase

Siu L, Ng WT, Sze WK, Au GK, Law SC, O'Sullivan B, Yau TK,

III study of concurrent chemoradiotherapy versus radiotherapy

Leung TW, Au JS, Sze WM, Choi CW, Fung KK, Lau JT, Lau

and

PJ.

late

complications

Significant

of

prognostic

849

patients

factorsafter

JNPC http://www.journalofnasopharyngealcarcinoma.org/

e-ISSN 2312-0398

chemoradiotherapy

followed

by

adjuvant

Published:2015-03-23 DOI:10.15383/jnpc.21

WH. J Natl Cancer Inst. 2010;102:1188-98.

carcinoma: a meta-analysis. ZhonghuaEr Bi Yan HouTou Jing

15. Lee AW, Tung SY, Chan AT, Chappell R, Fu YT, Lu TX, Tan

WaiKeZaZhi. 2008;43:218-23.

T, Chua DT, O'sullivan B, Xu SL, Pang ES, Sze WM, Leung TW,

22. Chen Y, Liu MZ, Liang SB, et al. Preliminary results of a

Kwan WH, Chan PT, Liu XF, Tan EH, Sham JS, Siu L, Lau

prospective

WH.Preliminary results of a randomized study (NPC-9902 Trial)

chemoradiotherapy plus adjuvant chemotherapy with radiotherapy

on

and/or

alone in patients with locoregionally advanced nasopharyngeal

accelerated fractionation for locally advanced nasopharyngeal

carcinoma in endemic regions of China. Int J RadiatOncolBiol

carcinoma. Int J RadiatOncolBiol Phys. 2006;66:142-51.

Phys.2008;71:1356-64.

16. Lee AW, Tung SY, Chan AT, Chappell R, Fu YT, Lu TX, Tan

23. Cox JD, Stetz J, Pajak TF: Toxicity criteriaof the Radiation

T, Chua DT, O'Sullivan B, Tung R, Ng WT, Leung TW, Leung SF,

Therapy Oncology Group(RTOG) and the European Organization

Yau S, Zhao C, Tan EH, Au GK, Siu L, Fung KK, Lau WH.A

for

randomized trial on addition of concurrent-adjuvant chemotherapy

JRadiatOncolBiol Phys. 1995;31:1341-6.

and/or

24. Miller AB, Hoogstraten B, Staquet M, et al:Reporting results

therapeutic

gain

accelerated

by

concurrent

fractionation

chemotherapy

for

locally-advanced

randomized

Researchand

trial

Treatment

of

comparing

Cancer

concurrent

(EORTC).

Int

nasopharyngeal carcinoma.RadiotherOncol. 2011;98:15-22.

of cancer treatment. Cancer. 1981;47:207-214.

17. Zhang L, Zhao C, Peng PJ, Lu LX, Huang PY, Han F, Wu

25. Perri F, Bosso D, Buonerba C, Lorenzo GD, Scarpati

SX.Phase III study comparing standard radiotherapy with or

GD.Locally

without weekly oxaliplatin in treatment of locoregionally

andemerging treatment strategies. World J Clin Oncol.2011;2:377-

advanced nasopharyngeal carcinoma: preliminary results. J

383.

ClinOncol. 2005;23:8461-8.

26. Chan AT, Gregoire V, Lefebvre JL, et al. Nasopharyngeal

18. Huncharek M, Kupelnick B.Combined chemoradiation versus

cancer: EHNS-ESMOESTRO Clinical Practice Guidelines for

radiation therapy alone in locally advanced nasopharyngeal

diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl. 7)

carcinoma: results of a meta-analysis of 1,528 patients from six

[vii83-85].

randomized trials. Am J ClinOncol. 2002;25:219-23.

27. Kim TH, Ko YH, Lee MA, et al. Treatment outcome of

19. Baujat B, Audry H, Bourhis J, Chan AT, Onat H, Chua DT,

cisplatin-based concurrent chemoradiotherapy in the patients with

Kwong DL, Al-Sarraf M, Chi KH, Hareyama M, Leung SF,

locally advanced nasopharyngeal cancer. Cancer Res Treat.

Thephamongkhol K, Pignon JP; MAC-NPC Collaborative

2008;40:62-70.

Group.Chemotherapy

nasopharyngeal

28. Lee AW, Tung SY, Ngan RK, et al. Factors contributing to the

carcinoma: an individual patient data meta-analysis of eight

efficacy of concurrent-adjuvant chemotherapy for locoregionally

randomized trials and 1753 patients.Int J RadiatOncolBiol Phys.

advanced nasopharyngeal carcinoma: combined analyses of NPC-

2006;64:47-56.

9901 and NPC-9902 Trials. Eur J Cancer. 2011;47:65666.

20. Zhang L, Zhao C, Ghimire B, Hong MH, Liu Q, Zhang Y, Guo

29. Loong HH, Ma BB, Leung SF, et al. Prognostic significance of

Y, Huang YJ, Guan ZZ. The role of concurrent chemoradiotherapy

the total dose of cisplatin administered during concurrent

in the treatment of locoregionally advanced nasopharyngeal

chemoradiotherapy in patients with locoregionally advanced

carcinoma among endemic population: a meta-analysis of the

nasopharyngeal carcinoma. RadiotherOncol. 2012;104:300-4.

phase III randomized trials. BMC Cancer. 2010;10:558.

30.

21. Yang AK, Liu TR, Guo X, Qi GL, Chen FJ, Guo ZM, Zhang Q,

chemoradiotherapy plus adjuvant chemotherapy versus concurrent

Zeng ZY, Chen WC, Li QL.Concurrent chemoradiotherapy versus

chemoradiotherapy alone in patients with locoregionally advanced

radiotherapy alone for locoregionally advanced nasopharyngeal

nasopharyngeal carcinoma: a phase 3 multicentrerandomised

in

locally

advanced

JNPC http://www.journalofnasopharyngealcarcinoma.org/

e-ISSN 2312-0398

Chen

advanced

L,

Hu

nasopharyngeal

CS,

Chen

XZ,

carcinoma:

et

al.

Current

Concurrent

Published:2015-03-23 DOI:10.15383/jnpc.21

controlled trial. Lancet Oncol. 2012;13:163-71.

chemotherapy with cisplatin and 5-fluorouracil followed by

31. Liang ZG, Zhu XD, Zhou ZR, Qu S, Du YQ, Jiang

radiotherapy and concurrent cisplatin: a phase II study. Oncology.

YM.Comparison of concurrent chemoradiotherapy followed by

2008;74:158-166.

adjuvant chemotherapy versus concurrent chemoradiotherapy

36. Liang ZG, Zhu XD, Tan AH, Jiang YM, Qu S, Su F, Xu GZ.

alone in locoregionally advanced nasopharyngeal carcinoma: a

Induction

meta-analysis of 793 patients from 5 randomized controlled

chemoradiotherapy versus concurrent chemoradiotherapy with or

trials.Asian Pac J Cancer Prev. 2012;13:5747-52.

without adjuvant chemotherapy for locoregionally advanced

32. Chan A, Ngan RK, Hui EP, et al. A multicenter randomized

nasopharyngealcarcinoma: meta-analysis of 1,096 patients from 11

control

randomized controlled trials. Asian Pac J Cancer Prev.

trial

(RCT)

of

adjuvant

chemotherapy (CT)

in

chemotherapy

nasopharyngeal carcinoma (NPC) with residual plasma EBV DNA

2013;14:515-21.

(EBV

37.

DNA)

following

primary

radiotherapy

(RT)

or

Chen

QY,

Wen

Guo

L,

et

al.

nasopharyngeal carcinoma: phase III randomized trial. J Natl

estimate outcome of advanced nasopharyngeal carcinoma--is

Cancer Inst. 2011;103:1761-70.

concurrent chemoradiotherapy adequate? Int J RadiatOncolBiol

38.Tham IW, Lin S, Pan J, Han L, Lu JJ, Wee J.Intensity-

Phys. 2004;60:156-64.

modulated radiation therapy without concurrent chemotherapy for

34. Hui EP, Ma BB, Leung SF, et al. Randomized phase II trial of

stage IIb nasopharyngeal cancer.Am J ClinOncol. 2010;33(3):294-

concurrent

9.

without

in

Concurrent

33. Lin JC, Liang WM, Jan JS, Jiang RS, Lin AC.Another way to

or

alone

concurrent

chemoradiotherapy

with

radiotherapy

by

chemotherapy (CRT). J ClinOncol.2012;30.

cisplatin-radiotherapy

vs

YF,

followed

stage

II

neoadjuvantdocetaxel and cisplatin in advanced nasopharyngeal

39. Sun X, Su S, Chen C, Han F, Zhao C, Xiao W, Deng X, Huang

carcinoma. J ClinOncol. 2009;27:242-9.

S, Lin C, Lu T.Long-term outcomes of intensity-modulated

35. Ferrari D, Chiesa F, Codec C, Calabrese L, Jereczek-Fossa

radiotherapy for 868 patients with nasopharyngeal carcinoma: an

BA, Alterio D, Fiore J, Luciani A, Floriani I, Orecchia R, Foa P.

analysis of survival and treatment toxicities.RadiotherOncol.

Locoregionally advanced nasopharyngeal carcinoma: induction

2014;110(3):398-403.

JNPC http://www.journalofnasopharyngealcarcinoma.org/

e-ISSN 2312-0398

Published:2015-03-23 DOI:10.15383/jnpc.21