1

Review
Clinical application value and progress of PET/CT in nasopharyngeal carcinoma
Fengwei Zeng, Muhua Cheng
Department of Nuclear Medicine, The Third Hospital Affiliated Sun Yat-sen University, Guangdong, Guangzhou 510630, China
Corresponding author: Cheng Muhua, Professor, M.D.; E-mail: marka@21cn.com

Citation: Zeng FW, Cheng MH. Clinical application value and progress of PET/CT in nasopharyngeal carcinoma. J
Nasopharyng Carcinoma, 2014, 1(2): e2. doi:10.15383/jnpc.2.
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: Nasopharyngeal carcinoma (NPC) is one of common head and neck cancers which mainly threaten
people in Southeast Asia. PET/CT plays an important role in radiotherapy for NPC. This article reviews the
PET/CT in the diagnosis, staging, guiding treatment, monitoring of therapy efficacy, focal residual and recurrence,
prognosis and progress of NPC.
Keywords: Nasopharyngeal carcinoma; Clinical application; PET/CT

Nasopharyngeal carcinoma (NPC) is one of the common head and

PET/CT) is superior to separate PET and conventional imaging

neck malignant tumors among southern China and Southeast

(CT, MRI, etc.) in the diagnosis, staging, guiding treatment,

Asian countries, which often occur in the pharyngeal recess. There

prognosis and so on[8-13]. In recent years, the 11C-choline PET/CT

is a close association between Epstein-Barr virus (EBV) and NPC

imaging in the diagnosis and staging of NPC patients have

pathogenesis[1]. The annual incidence per 100,000 persons ranged

obtained satisfactory results, especially in the T staging of

from 10 to 30[2-3]. At present, the main method of treatment for

NPC[14].

NPC is radiotherapy, which treatment effect is very satisfactory

This review is focused on the the value of PET/CT in the

for early NPC, local recurrence and distant metastasis. The 5-year

diagnosis, staging, therapeutic evaluation, guiding radiotherapy

overall survival rate is about 50%-70%[4-7]. Therefore, early

and prognosis of NPC, the diagnostic value of PET/CT in residual

diagnosis and staging of NPC patients is very important to

and recurrence of NPC and complications after NPC radiotherapy.

improve

the

survival

rate.

Positron

Emission

Tomography/Computed Tomography (PET/CT) images could

1 The value of PET/CT in the diagnosis of NPC

have a significant impact on diagnosing and staging malignant

The diagnostic performance of PET/CT is better than conventional

disease, monitoring of efficacy, prognostic and so on. A lot of

imaging examination such as PET, CT, MRI. Eighty-six cases of

researches indicated that fluor-18-fluorodeoxyglucose positron

NPC were analyzed retrospectively by Chen et al.[10], their result

emission tomography with computed tomography (18F-FDG

showed that

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18

F-FDG PET/CT, PET and CT accuracy in the

Published:2014-02 -27 DOI:10.15383/jnpc.2

2
18

diagnosis of NPC were 95.4%, 82.6%, 73.3%, respectively.

agent in the PET/CT and compared with

Furthermore, the differences between 18F-FDG PET/CT and either

patients with newly diagnosed and 5 patients recurrent NPC were

PET alone or CT alone were statistically significant (P<0.05). The

enrolled in the study. All of the patients with 11C-choline PET/CT

sensitivity, specificity, accuracy, positive predictive value and

were positive, but 13 cases were showed positive and 2 cases of

negative predictive value of PET/CT studies for diagnosis NPC

skull base and intracranial recurrence of NPC patients were

were 96%, 94.4%, 96% and 94.4%, respectively. Gordian et al.

showed negative. The sensitivity of 18F-FDG PET/CT in detecting

18

reported that

F-FDG PET/CT had sensitivity, specificity,

F-FDG PET/CT. Ten

NPC was 86.6%, compared with a 100% sensitivity for

11

C-

positive predictive value, negative predictive value and accuracy

choline PET/CT (t=2.143, P=0.483). The SUVmax of lesions

of 92%, 90%, 90%, 90%, and 91%, respectively, as compared

detected was higher using

with 92%, 65%, 76%, 86%, and 80% for PET, and 92%, 15%,

(SUVmax: 6.842.76 vs. 12.815.00, t=6.416, P<0.001), but the

60%, 60%, and 60% for conventional imaging (CT and MRI)[11].

T/B ratio was much higher for

The reports of whole body 18F-FDG PET/CT scans, performed 43

(18.627.95 vs. 1.380.59, t=8.801, P<0.001). Because

NPC patients were analyzed retrospectively (Wang et al.), their

choline uptake in normal brain was lower than

results demonstrated that the overall accuracy, specificity,

(0.380.09 vs. 10.011.90, t=19.68, P<0.001). Compared with18F-

sensitivity, positive predictive value, negative predictive value of

FDG PET/CT,

18

intracranial invasion in 6 of 12 patients, skull base invasion in 4 of

F-FDG PET/CT were 95.3%, 100.0%, 85.7%, 93.8%, and

11

18

F-FDG than using

11

C-choline than for

14 patients, and orbital invasion in 3 of 3 patients.

MRI)

2.2 The N staging of NPC

65.5%,

79.4%,

64.7%,

81.8%,

and

57.9%,

respectively[13].

C-choline

18

18

F-FDG
11

C-

F-FDG

C-choline PET/CT improved the delineation of

100.0%, respectively, and those of conventional imaging (CT and

were

11

Neck lymph node metastases was the common clinical symptoms

in patients with NPC. Lee et al.[20] did a retrospective analysis of

2 The value of PET/CT in the staging of NPC

4768 patients, 75.8% of patients were discovered neck lymph

2.1 The T staging of NPC

node metastases at initial diagnosis. Chen et al.[10] had compared

18

of 18F-FDG PET/CT, PET and CT on detecting neck lymph node

F-FDG PET/CT is benefited in the T staging of NPC. Chen et

al.[10] compared

18

F-FDG PET/CT, PET and CT in the detect of

metastases of the NPC patients, PET/CT was found to be accurate

primary site of NPC, the T stage was accurately determined in 18

in 100% (20/20), where PET alone and CT alone accurately

cases out of 20 cases with 18F-FDG PET/CT. Both PET alone and

determined lymph node involvement in 20 out of 20 patients

CT alone correctly assessed the T stage 15 cases out of 20 cases.

(100%) and 18 out of 20 patients. Hu et al.[8] conducted a study

Lin et al.[15] in the diagnosis of 68 cases of NPC patients indicated

which was to compare the diagnostic value of

that coincidence rate of

18

18

F-FDG PET/CT

F-FDG PET/CT with MR was 95.5%

with that of MRI in detecting nodal metastasis of NPC. Among the

(65 cases) on lesion. Three cases were clearly displayed by

105 patients, nodal metastasis patterns shown on PET/CT and

PET/CT, but not by MRI. However, many studies showed

18

F-

MRI were diverse in 35 patients. Thirty cervical nodes were

FDG PET/CT in the diagnosis NPC with local invasion such as

positive on PET/CT, but negative on MRI. Twenty-five of them

skull base, intracranial area, orbital apex, parapharyngeal space

were later confirmed positive by follow-up. Thirty-seven cervical

was not so well compared with MRI. Because the high

nodes were negative on PET/CT, but positive on MRI. Twenty-

physiological metabolism of brain and eye muscle affected skull

one of them were confirmed negative by follow-up. Lin et al.[15]

base, intracranial area, orbital apex show. In addition, soft tissue

analyzed 68 cases of NPC patients with lymph node metastases

resolution and parapharyngeal space invasion of MRI was better

and found that 39 out of 138 positive lymph nodes whose

than that of PET/CT. Wu et al.[14] used

diameters were <1 cm and identified by 18F-FDG PET/CT, which

11

C-choline as a imaging

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Published:2014-02 -27 DOI:10.15383/jnpc.2

were not assured of positive lymph nodes by MRI, accounting for

The corresponding accuracies were 96.2%, 93.6%, 89.7% and

28.0% (39/138). Ten patients underwent biopsy on their neck

85.9%. Tang et al.[25] discovered that 86 cases of the 583 eligible

lymph nodes. Fourteen out of 16 positive lymph nodes detected by

patients were found to have distant metastases. seventy-one

PET/CT were confirmed by pathological examination, while MRI

patients (82.6%) by 18F-FDG PET/CT were superior to 31 patients

was not certain about eight lymph nodes and found the other eight

(36.0%) by conventional imaging examination, and 34 cases cases

lymph nodes negative. Two cases detected by PET/CT changed its

detected by

N staging because of the lock lymph node metastasis. The results

Four cases accurately down-regulated its staging. Recently, some

of follow-up a total of 614 lymph nodes in 116 patients were

scholars applied the meta-analysis to evaluate the accuracy of 18F-

analyzed by Zhang et al.[21] showed that the sensitivity, specificity

FDG PEC/CT in distant metastases of NPS, the result showed 18F-

and accuracy of

18

F-FDG PET/CT in diagnosing node metastasis

were 93.2%, 98.2% and 95.4%, while those of MRI were 88.8%,

18

F-FDG PET/CT accurately up-regulated its staging.

FDG PET/CT had a better diagnostic efficiency than conventional

work-up on detecting distant metastases[26].

91.2% and 89.9%, respectively. Based on above studies, 18F-FDG

PET/CT was superior to MRI in diagnosing lymph node

3 The role of PET/CT in guiding treatment of NPC

metastasis. We should be alert to the false-positive and false-

3.1 Generation of gross tumor volume (GTV)

negative assessment based on 18F-FDG PET/CT scan findings that

Gross tumor volume and the determination scope of the tumor

may

inflammatory

invasion was the key to radiotherapy of the NPC patients. PET/CT

hyperplastic, large area lymph nodes of necrosis and node in

located biological target volume from metabolism, blood flow,

diameter less than spatial resolution limitation of PET[17, 22-23].

tissue

2.3 The M staging of NPC

angiogenesis, apoptosis and so on. In addition, PET/CT had

18

F-FDG PET/CT had a better diagnostic efficiency in M staging

obvious advantages over CT. It is difficult to generate GTV

of NPC. Lin et al.[15] discovered that 18F-FDG PET/CT showed the

according to the conventional imaging examination after

distant metastases to lung, bone, and liver occurred in eight

radiotherapy. Zheng et al.[9] identified that for the remaining 29

patients. The stage of 24 NPC patients was adjusted after PET/CT

patients, GTV based on PET/CT was smaller than GTV based on

scan, among which the stage of 12 patients was adjusted higher

CT in 24 (82.8%) cases and was greater in 5 (17.2%) cases. The

and that of 12 patients was adjusted lower, with a total adjustment

target volume had to be significantly modified in 9 of 29 patients,

rate of 35.3%, when he analyzed sixty-eight NPC patients. Ng et

as GTV based on 18FDG-PET images failed to be enclosed by the

al.

[17]

be

caused

by

retropharyngeal

nodes,

proliferation,

hypoxia,

tumor

specific

receptor,

found that PET/CT correctly modified M staging in eight

treated volume in the salvage treatment plan performed based on

patients (7.2%) and disclosed a second primary lung malignancy

GTV based on CT simulation images. But another research result

in one patient (0.9%) among the 111 NPC patients. Chua et al.[21]

of Zheng et al.[27] showed that 39 patients without distant

thought

18

F-FDG PET/CT was superior to PET alone, CT of the

metastasis proceeded to three-dimensional conformal radiotherapy

thorax and abdomen, skeletal scintigraphy and conventional

planning. Inadequate coverage of the GTVPET/CT and PTVPET/CT by

imaging examination comprising chest X-ray, abdomen ultrasound

the PTVCT occurred in 7 (18%) and 20 (51%) patients,

and bone scanning. The sensitivities and specificities of PET

respectively. This resulted in < 95% of the GTVPET/CT and

alone, CT of the thorax and abdomen, bone scanning and

PTVPET/CT receiving 95% of the prescribed dose in 4 (10%) and

conventional imaging examination were 83.3%, 83.3%, 66.7% and

13 (33%) patients, respectively. Xin et al.[28] considered simulate

33.3%, respectively. And the specificities of PET alone, CT of the

actual treatment in the detachable phantom, including clinical

thorax and abdomen, bone scanning and conventional imaging

treatment volume (CTV), tumor treatment volume (GTV), high

examination were 97.2%, 94.4%, 91.7% and 90.3%, respectively.

metabolic gross treatment volume (FGTV). Its size 107 cm, 44

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Published:2014-02 -27 DOI:10.15383/jnpc.2

cm, 22 cm, respectively. The CTV put 0.3 cm into PTV. The

2.5 (range 0-6.9) one month after radiotherapy (P<0.001). The

radiation dose of PTV, GTV and FGTV were set to 1.8 Gy, 2.0Gy,

medium SUVmax of regional lymph node lesion was 9.3 (range 2.5-

and 1.8 Gy, respectively, which would achieve good efficacy.

31.5) before treatment, and reduced to 3.1 (range 0-15.8) after

Therefore,

18

F-FDG PET/CT image-guided dynamic intensity-

radiotherapy with a dose of 50 Gy, then, decreased to 2.4 (range 0-

modulated radiation therapy (IMRT) is feasible.

7.2) after radiotherapy. The medium SUVmax of regional lymph

3.2

node lesions was 1.5 (range 0-5.4) one month after radiotherapy

Guiding radiotherapy treatment modality and rescue

(P<0.01). The efficacy of 41 NPC patients who underwent

therapy

F-

F-

FDG PET/CT scan were reported by Xie et al.[30]. The mean

FDG PET/CT examination. Law et al.[12] found that forty-eight

SUVmax was 7.3 (range 3.2-20.7) before treatment, and the

patients underwent a staging PET/CT, in which 4 cases (8%) of

SUVmax<2.5 of 26 patients with metabolic complete remission

NPC changed the primary treatment modality, 12 cases (25%)

after treatment, the remaining 15 patients SUVmax2.5. Another

changed treatment modality or dose and 32 cases (66%) was no

study of Xie et al. reported that the median SUVmax was 8.55

change in treatment modality. Zheng et al.[9] discovered that all 33

(range 2.8-24.6) in 62 NPC patients before treatment. Fifty-eight

patients were referred for salvage treatment in the pre-FDG-PET

of the 62 patients treatment responses were evaluated by 18F-FDG

decision, after knowledge of the FDG-PET results, the decision to

PET/CT scan. The post-treatment PET/CT scan did not show any

offer salvage treatment was withdrawn in 4 of 33 patients (12.1%),

abnormal

as no abnormal uptake of FDG was found at nasopharynx.

response, MCR) in 35 patients, and the remaining 23 patients with

Spontaneous remission was observed in repeat biopsies and no

SUVmax2.5[31]. Law et al.[12] found that PET/CT had higher

local recurrence was found in these 4 cases. Thirty-three patients

negative predictive value than conventional imaging examination

Some radiotherapy modality for NPC may be changed after

with NPC had 45

18

18

18

F-FDG PET/CT examinations were analyzed

retrospectively[11]. In this study, Gordin et al. found that imaging

FDG

uptake

(SUVmax<2.5,

metabolic

complete

(CT or MRI) that were 93 %, 91%, respectively in 21 NPC

patients, and had fewer equivocal results than MRI.

with PET/CT eliminated the need for previously planned

diagnostic procedures in 11 patients, induced a change in the

planned therapeutic approach in 5 patients, and guided biopsy to a

recurrence of NPC

specical metabolically active area inside an edematous region in

Radiotherapy of NPC would cause regional tissue radioactive

3 patients.

damaging, mucosal thickening, soft tissue swelling, fibrosis or

The value of PET/CT in diagnosis of residual and

scar tissue formation and so on, meanwhile, metastases maybe

4 The value of PET/CT in NPC therapeutic evaluation

occur in other tissues. Correct evaluation of regional and systemic

Assessment of early treatment effect helped to adjust therapy

disease progression was of great significance to prolong survival

method and reduce the complications. Lesions of metabolic

and improve life quality. The radiotherapy techniques in

reduced before and after radiotherapy, namely the reduction of

continuous improvement, but the local residual NPC and

18

recurrence

F-FDG uptake were consistent with the pathological changes of

tumor tissue. A study of Lin et al.[29] was to evaluate the treatment

response of

18

F-FDG PET/CT. The medium SUVmax of primary

rate

were

still

as

high

as

10%-30%

after

radiotherapy[7,9,30], which mainly because NPC tumor cells were

resistant to radiation therapy in the GTV region[32]. Chen et al. [10]
18

tumor lesion was 11.1 (range 3.4-26.9) in 61 NPC patients before

indicated that the cases of T stage detected by

treatment, then, reduced to 3.5 (range 0-8.1) after radiotherapy

PET, CT were 66, 64 and 62, respectively in sixty-six patients

with a dose of 50 Gy, and decreased to 3.1 (range 0-8.2) after

with residual and recurrence NPC. The cases were 6, 63 and 58 in

radiotherapy. The medium SUVmax of primary tumor lesion was

N stage and 64, 60 and 60 in M stage, respectively. There are three

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F-FDG PET/CT,

Published:2014-02 -27 DOI:10.15383/jnpc.2

cases of false-positive lymph nodes, which mainly occurred in

indicators in the evaluation of the prognosis of NPC[30,39-40]. NPC

jugular vein and submental lymph node hyperplasia. Thirty-eight

patients having tumors with an MTV< 30 cm3 had significantly

NPC patients with radiotherapy were reported by Yu et al. [33]. 18F-

better 5-year overall survival (OS) (84.6% vs. 46.7%, P=0.006)

FDG PET/CT scan was a better tool than CT alone for the

and disease-free survival (DFS) (73.1% vs. 40.0%, P=0.014) than

detection of recurrence or residue, a litter better than PET alone.

patients with an MTV30 cm3 were reported by Xie et al.[30]. And

The sensitivity and specificity of

18

F-FDG PET/CT, CT and PET

the patients with MI <130 had significantly higher 5-year OS

were 100%, 77.8%, 100%, and 89.5%, 84.2%, 80.0%,

(88.0% vs. 43.8%, P=0.002) and DFS (76.0% vs. 37.5%,

respectively. There are also false-negatives and false-positives

P=0.005) than other patients. A study of 196 patients with primary

occurred. The false-negative was mainly muscle uptake, while

stage III-IV NPC showed that MI values greater than 330

false-positive was mainly lymph nodes and lung lesions

independently predicted OS (P=0.0014) and DFS (P=0.0005) as

inflammatory intake. However, some scholars believed that the

independent predictors of local failure-free survival[39]. Tang et

accuracy of MRI over PET/CT in detecting residual or recurrent

al.[25] analysed that pretreatment N staging and EBV DNA level

NPC at the primary site (accuracy rate 92.1% vs. 85.7%)[34].

were significant risk factors for distant metastases.

18

F-FDG

PET/CT was not superior to conventional imaging examination for

6 The evaluation of PET/CT in prognosis of NPC

detecting distant metastases in very low-risk patients (N 0-1 and

SUV was used to reflect glycometabolism of carcinoma, which is

EBV DNA<4 000 copies/mL, P=0.062), but was superior for the

the most common indicator of PET/CT and the most important

low-risk patients (N 0-1 and EBV DNA4 000 copies/mL, N 2-3

indicator of prognosis evaluation of NPC. Some studies indicated

and EBV DNA<4 000 copies/mL, P=0.039) and intermediate-risk

the higher the T staging of NPC, the higher SUVmax[35-36]. The

patients (N 2-3 and EBV DNA4 000 copies/mL, P<0.001). Fifty-

worst prognosis was found in patients with the greater SUVmax.

six NPC transferred patients were reported by Chen et al. [40]. The

The prognosis would become worse, when SUVmax of lymph

research found that EBV DNA titre>5000 copies/mL (P=0.001),

nodes metastasis (SUVmax-N) was higher than SUVmax of primary

and MTV>110 mL (P=0.013) were independent risk factors for

lesions(SUVmax-T)[31]. Chan et al. believed that patients with

progression-free survival (PFS) and OS.

SUVmax-T<7.5 and SUVmax-N<6.5 (P=0.042 and

7 The diagnostic value of PET/CT in complications after NPC

P=0.019,

respectively) would have significantly better 2 year DFS[37]. The

study of Hung et al.

[38]

radiotherapy

showed that 371 NPC patients with

Radiotherapy was the main therapeutic method for NPC.

SUVmax-T<9.3 and SUVmax-N<7.4 had a significantly better 5-

Meanwhile, temporal lobe, brain stem and cerebellum were

year distant metastasis-free survival (DMFS) (91.1% vs. 84.0%,

inevitably exposed to radiation field in the treatment, which would

and 83.7% vs.78.0%, respectively). The 5-year DMFSs of

lead to some patients occurred radiation encephalopathy (RE).

SUVmax-T9.3 and SUVmax-N7.4 group lower than other three

Wang et al.[41-42] found that

groups (84.3% vs. 94.6%-97.4%) in stage I-III NPC patients. The

anteromedial temporal lobes metabolic significantly decreased in

5-year DMFSs of SUVmax-T<9.3 and SUVmax-N<7.4 group

35 of the 53 NPC patients receiving radical radiotherapy (namely

higher than other three groups (91.6% vs. 68.5%-82.9%) in stage

70 lobes). However, CT displayed normal density in the 25

IVA-B patients.

temporal lobes lesions of the 35 delayed RE patients. And

In recent years, some scholars found tumour volume (TV) were

metabolism of unilateral temporal lobe obviously reduced in 18

positively correlated with T-stage in primary NPC[36]. Metabolic

cases (18 lobes). The incidence of brain stem metabolic reductions

tumor

(MI,

was 24.5% (13/53) in the investigated patients, including 4

MI=MTVSUVmean) from PET/CT were the semi-quantitative

patients with hypometabolic changes shown by PET and negative

volume

(MTV)

and

metabolic

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18

F-FDG PET/CT demonstrated

Published:2014-02 -27 DOI:10.15383/jnpc.2

finding shown by CT. According to the PET/CT imaging finding,

patterns. Head Neck, 2005. 27(7): p. 555-565.

the lesions could be classified as oedema type (56 temporal lobes),

6. Chee Ee Phua, V., et al., Treatment outcome for nasopharyngeal

liquefactive necrosis type (10 temporal lobes) and atrophic

carcinoma in University Malaya Medical Centre from 2004-2008.

calcification type (22 temporal lobe), and the former two types of

Asian Pac J Cancer Prev, 2013. 14(8): p. 4567-4570.

lesions may progress into the third type [42].

7. Sanguineti, G., et al., Carcinoma of the nasopharynx treated by

radiotherapy alone: determinants of local and regional control. Int

8 Conclusion

J Radiat Oncol Biol Phys, 1997. 37(5): p. 985-996.

In summary, PET/CT play an important role in radiotherapy for

8. Hu, W.H., et al., [Comparison between PET-CT and MRI in

NPC. Correct diagnosis and accurate staging are a prerequisite for

diagnosing nodal metastasis of nasopharyngeal carcinoma]. Ai

radiotherapy,

Zheng, 2005. 24(7): p. 855-860.

and

target

delineation

and

radiation

dose

determination are the key to radiation therapy. The efficacy of

9. Zheng, X.K., et al., Influence of [18F] fluorodeoxyglucose

radiotherapy, recurrence and residue of NPC, prognosis judgment

positron emission tomography on salvage treatment decision

have an important impact on the long-term quality of life and

making for locally persistent nasopharyngeal carcinoma. Int J

survival of patients. 11C-choline PET/CT in the diagnosis of skull

Radiat Oncol Biol Phys, 2006. 65(4): p. 1020-1025.

base and intracranial invasion of NPC patients are significantly

10. Chen, Y.K., et al., Clinical usefulness of fused PET/CT

better than

18

F-FDG PET/CT. However, there was no good

compared with PET alone or CT alone in nasopharyngeal

solution to identify lymph node metastases, inflammatory lymph

carcinoma patients. Anticancer Res, 2006. 26(2B): p. 1471-1477.

nodes, lung micrometastases and inflammatory lesions. The

11. Gordin, A., et al., Fluorine-18 fluorodeoxyglucose positron

application of new imaging agents for PET/CT is to be further

emission tomography/computed tomography imaging in patients

researched.

with carcinoma of the nasopharynx: diagnostic accuracy and

impact on clinical management. Int J Radiat Oncol Biol Phys,

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