Use of 18F-FDG PET/CT in the Diagnosis, Staging, Response Assessment and Prognosis
of Nasopharyngeal Carcinoma: an Updated Review
Xiaomin Ou1, Zhongyi Yang2, Chaosu Hu1
1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, China
2Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, China
1,2Department of Oncology, Shanghai medical college, Fudan University, China
Corresponding author: Chaosu Hu; Email: email@example.com
Abstract: Nasopharyngeal carcinoma (NPC) is endemic in southern China and part of Southeast Asia. The main treatment for nasopharyngeal carcinoma is radiotherapy. The accurate diagnosis of the tumor extension and the delineation of target volume mostly depend on imaging. The imaging with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT), which provides both anatomic and biological information of tumor, plays an important role in the management of NPC. With the help of 18F-FDG PET/CT, a better diagnosis of cervical nodal involvement and distant metastasis has a great impact on radiotherapy planning and treatment strategy. 18F-FDG PET/CT image provides additional biological information, to help in differentiating the post-radiation inflammation and local residual/recurrent disease. For locally advanced disease, 18F-FDG PET/CT is a better and more sensitive approach for the assessment and surveillance of therapeutic response of NPC , as well as detecting of early relapses and metastasis, , compared with conventional workup. Various PET/CT parameters have been correlated with response and survival. Higher 18F-FDG uptake has been proven to predict poorer response and worse outcome. The combination of EBV DNA copies and PET/CT scan seems to be a useful and effective strategy in the follow-up of NPC.
Keywords: Nasopharyngeal Carcinoma; 18F-FDG; PET/CT; Diagnosis; Staging; Response Assessment; Prognosis
Nasopharyngeal carcinoma (NPC) is endemic in southern China and part of Southeast Asia . In southern China, the prevalence is > 20/100,000 person-years . Owing to the specific anatomic location and highly responsive to radiation, the main treatment for NPC is radiotherapy. It is difficult to obtain the information of tumor extension by pathology. The accurate diagnosis of the tumor extension and the delineation of target volume mostly depend on imaging. Magnetic resonance imaging (MRI) has a good capacity to depict the detailed anatomic information and has been widely used in the management of NPC. However, MRI only provides anatomic and volumetric information, and does not reveal the biological status of tumor cells. The advent of positron emission tomography (PET/CT), especially 18F-fluorodeoxyglucose PET/CT has facilitated the anatomic and biological assessment of the tumors. Various studies demostrated that 18F-FDG PET/CT imaging had been actively integrated with the management of NPC. The purpose of this article is to review the role of 18F-FDG PET/CT in staging, response assessment, diagnosis of residual diseases, predicting outcome and post-treatment surveillance of NPC.
The staging of NPC has a major influence on treatment strategy. In early cases, radiotherapy is enough to control the disease. In locally advanced disease (III-IVb), concurrent chemoradiotherapy is the main treatment modality, whereas the value of neoadjuvant chemotherapy and adjuvant chemotherapy is still in debate. In cases with distant metastasis, chemotherapy is the main treatment and radiotherapy will give according the response to chemotherapy. Accurate staging and diagnosis of tumor extension is very important for treatment strategy and target volume delineation.
MRI is commonly used in assessment of local involvement of NPC, which can clearly show the involvement of soft tissue, bone as well as the intracranial lesion [3, 4]. On the contrary, 18F-FDG PET/CT appears to be inferior to MRI for assessment of local invasion, such as the involvement of parapharyngeal space, skull base, and intracranial lesions [5, 6]. Owing to the high glucose metabolism of brain tissue, it is hard for 18F-FDG PET/CT to clearly distinguish the intracranial extension. Using the MRI as a reference, Lim  et al reported that 18F-FDG PET/CT could only detect 42.7% of intracranial invasion. King reported  that 18F-FDG PET/CT undermapped the extent of local invasion in approximately half of patients. Ng  demonstrated that 18F-FDG PET/CT downstages 22.5% of patients with regards to T staging. On the other hand, 18F-FDG PET/CT could not identify some early tumor involvement of nasopharyngeal mucosa, due to a low tumor burden.
Retropharyngeal lymph node metastasis
The involvement of retropharyngeal lymph nodes are frequently seen in NPC, presented in 72% of patients with NPC and 94% of all patients with nodal disease . The diagnosis of involvement of retropharyngeal nodes on imaging has been based on the axial diameter of nodes, the presence of necrosis and enhancement. Mancuso et al.  found that the maximum diameter of retropharyngeal nodes in normal people identified by CT was 5 to 8 mm in young adults and 3 to 5 mm in adults. A recent MRI study by Lam et al.  in Chinese population found that normal retropharyngeal nodes were smaller than 4 mm in the maximum diameter of the shortest axis. Based on these studies, Lam and King et al [8, 10] suggested that over 4-5mm size in the shortest axis of nodes was used as the diagnostic criteria for an abnormal retropharyngeal node. A study by Tang et al.  has compared the diagnostic value of PET/CT and MRI in retropharyngeal nodes in NPC. The detection rates of retropharyngeal lymph node metastasis by MRI was significantly higher than that by PET/CT (44.8% vs. 24.1%, p<0.001). The maximum standard uptake value (SUVmax) of PET/CT was positively correlated with the minimal axial diameter of retropharyngeal lymph node. There were only 5.8% of nodes with a SUVmax greater than 2.5 for retropharyngeal lymph nodes with axial diameter < 10mm. In retropharyngeal nodes ≥10 mm in diameter, the percentage rose to 88.2%  [please offer references here]. Therefore, PET/CT is inferior to MRI in demonstrating tumor involvement in retropharyngeal nodes, especially in nodes with shortest diameter smaller than 10 mm. Moreover, PET/CT failed to identify retropharyngeal nodes when they were close to or merged with primary tumors [5, 6]. It yielded false-positive results in cases of direct bulky parapharyngeal invasion as well .
Cervical lymph node metastasis
The metastasis of cervical lymph nodes is frequent in NPC. It has been reported that 60%-88.1% of patients have regional nodal involvement at presentation [11-14]. The diagnosis of cervical nodal metastasis has an influence on the planning of radiotherapy as well as the modification of treatment strategy. The diagnosis of cervical nodal involvement by MRI is often based on nodal size, the presence of necrosis and enhancement. Several studies have compared the accuracy of PET/CT and MRI to diagnose cervical nodal metastasis in head and neck cancers [15-19]. PET/CT is generally more sensitive than MRI to detect nodal metastasis, with a sensitivity of 74.7%-96.5%, whereas the sensitivity of MRI is 52.6%-93%.However, there is no significant advantage of PET/CT in specificity, with a specificity of 87%-98% (the specificity of MRI 79%-95%). To our best knowledge, there are four studies comparing the diagnostic efficacy of PET/CT and MRI in NPC [5, 6, 20, 21]. In three out of four studies [6, 21, 22], PET/CT yielded a higher accuracy in diagnosing cervical nodal involvement. With PET/CT images, metastasis in morphologically benign lymph nodes may be correctly identified and the false metastatic lesions in enlarged lymph nodes may be excluded. In general, 18F-FDG PET/CT is a highly sensitive and accurate tool to detect cervical nodal metastasis, which influences the N stage and the planning of radiotherapy. However, 18F-FDG PET/CT still yields a low percentage of false-positive and false-negative. Most of the false-positive cases were proved to be inflammatory hyperplasia  and most of false negative cases were micro-metastases in cervical nodes less than 1 cm in diameter [23, 24].
In regards to diagnosis of distant metastasis, several studies have concordantly shown that PET/CT is more accurate than conventional workup such as chest radiography, chest CT, abdominal ultrasound and bone scan [25-27]. Yen reported  that PET/CT could detect additionally 12.9% of distant metastasis, among patients diagnosed as M0 by conventional workup. The patient-based sensitivity and specificity of 18F-FDG PET for distant metastases were 100% and 86.9%, respectively. Chang et al.  demonstrated that the sensitivity and specificity of 18F-FDG PET for distant metastases were 100% and 90.1%. In another study by Liu  et al., 18F-FDG PET was found to be more effective than conventional workup. On region-based analyses, 18F-FDG PET was more sensitive than skeletal scintigraphy [27, 31] and chest radiography  for detecting bone metastases and pulmonary metastases, respectively. In addition, 18F-FDG PET/CT was more sensitive to detect distant nodal metastasis . The frequencies of mediastinal and abdominal nodal metastasis were 4.5% and 3.4%, identified by 18F-FDG PET/CT [15. All these cases were associated with supraclavicular fossa node involvement, and might represent the further caudal lymphatic spread of NPC beyond the supraclavicular nodes. These metastases were often missed by conventional workup, thus PET/CT has completely changed the treatment strategy from radiotherapy to chemotherapy.
In a word, 18F-FDG PET/CT played a significant role in determining cervical nodal metastasis and distant metastasis. Considering patients with a N3 disease have a significantly greater risk of distant metastasis , we recommend 18F-FDG PET/CT for staging, especially in N3 stage for NPC patients.
Diagnosis of local recurrence and residual lesions
Persistent or recurrent disease at primary site
Radiation, after radiotherapy of NPC, causes inflammatory reaction, distorting of the anatomic structures and the growth of scar tissue  [please offer references here]. These changes make the diagnosis of persistent or recurrent disease more difficult. MRI was commonly used in determining local recurrence and persistent lesions. However, false positive were noted due to the inflammatory reaction and anatomic distortion. Thus, scholars tried to integrate 18F-FDG PET/CT with the diagnosis of recurrence and residual disease. To our best knowledge, four studies [29-32] used both 18F-FDG PET and MRI in determining recurrence of NPC. Two studies [33, 34] showed no false negative and few false positive, resulting in a sensitivity of 100% and specificity of 92.9%- 93.4% of PET/CT. However, in another study , the sensitivity and specificity of 18F-FDG PET for the detection of recurrent NPC at the primary site were 91.6% and 76.0%, respectively, with 1 false negative and 6 false positive. In the report of Comoretto , there was a trend toward greater accuracy of MRI over PET/CT in detecting residual and/or recurrent NPC at the primary site (92.1% for MRI vs. 85.7% for PET/CT, p=0.16). In these studies [31, 32], the false positive cases of PET/CT were attributed to subacute/ chronic inflammation, while false negative cases of PET/CT were due to superficial involvement of mucosa or intracranial invasion. Comoretto suggested that the advantage of MRI over PET/CT was probably attributed to the following reasons: MRI provided additional information in assessing skull base involvement and intracranial invasion while FDG PET/CT was not considered a trustworthy method for the study of the intracranial disease due to the physiologically high FDG uptake by brain; MR imaging examination was subjected to a dynamic contrast-enhanced study that could facilitate differentiation between fibrosis and residual disease . Moreover, it is worthwhile to note that radiation induced necrosis could be present with significant uptake of FDG [35, 38], which could be misdiagnosed by both MRI and PET/CT . In consideration of advantages and pitfalls of both techniques, we recommend using both MRI and 18F-FDG PET/CT in determining local recurrence and residual disease. Close clinical follow-up and biopsy are warranted to confirm the diagnosis.
Persistent or recurrent disease at cervical lymph nodes
In terms of the diagnosis of recurrent or persistent cervical nodes, 18F-FDG PET/CT appears to add significant information to MRI findings. Ng  reported the sensitivity and specificity for detecting recurrent and residual nodal diseases by PET/CT was 90.0% and 88.9%. Comoretto  reported that the sensitivity and specificity for PET/CT in depicting residual and recurrent nodal diseases were 95.2% and 97.6%, while the sensitivity and specificity for MRI were 90.5% and 90.5%. No significant difference was observed between MRI and PET/CT (p=0.08). Both the studies demonstrated that 18F-FDG PET/CT were a highly sensitive and accurate tool to detect nodal diseases. However, some problems should be taken into consideration. 18F-FDG PET may not be sensitive enough to detect micro-metastases in nodes [23, 24]. At this time, neither anatomic nor metabolic imaging provides sufficient resolution power for the detection of microscopic lesion . On the other hand, the false positive cases of 18F-FDG PET/CT were mostly due to inflammatory hyperplasia of lymph nodes .
Therapeutic response assessment
Although intensity modulated radiation therapy (IMRT) has brought significant improvement in overall survival of NPC, a certain part of patients develop local recurrence. Once recurrence, the outcomes is poor and the quality of life is bad. Therefore, it is urgent to develop a way to predict treatment response before its onset, to allow a more aggressive treatment strategy.
Conventional imaging such as CT and MRI are used in current clinical practice for response assessment. However, there are some pitfalls of these techniques. CT and MRI are used to measure the anatomic volume changes of the tumor, which would delay after chemotherapy and radiotherapy. In addition, they cannot differentiate residual tumor from inflammation and fibrosis from surround normal tissue [41-43]. Functional imaging such as 18F-FDG PET/CT has been introduced in treatment response assessment since it could provide additional biologic information. 18F-FDG PET/CT has been used to evaluate treatment response in various malignancies, including esophageal cancer, lung cancer, colorectal cancer, et al [44-47]. To our knowledge, there are very few studies focusing on treatment response assessment of NPC. In a study of T4 NPC reported by Yen et al , the baseline and post-treatment (3 months post-chemoradiation) SUVmax correlated with local response. There is a trend of difference of baseline SUVmax between responders (patients with local residual disease) and non-responders (patients without local residual disease). The decrease in SUVmax between baseline and 3 months post-chemoradiation were 62.9% for non-responders and 76.1% for responders. Non-responders had a significantly higher post-treatment SUVmax than the responders, with a cutoff value of SUVmax less than 4. Xie et al  demonstrated that patients who had a complete metabolic response (CMR) measured by FDG uptake at 1–5 months after radiotherapy had a higher overall survival (OS) than those who exhibited a partial metabolic response (PMR). Chan et al  performed a study to investigate the prognostic implication of post-chemoradiation PET/CT in locally advanced NPC patients. The results showed that PET finding of 3 months post-chemoradiation and total lesion glycolysis were independent prognostic factors of OS and disease-free survival (DFS). Post-therapy PET imaging at 3 months was more predictive of DFS than conventional workup and TNM stage. It is worthwhile to note that the difference between DFS of complete responders and non-complete responders evaluated by conventional workup did not reach a statistical significance in IVa-IVb NPC patients. Detailed analysis showed that conventional workup failed to detect 43% of therapeutic failures, including locoregional failure and distant metastasis of solitary organ sites. The follow-up of PET/CT in locally advanced NPC was more sensitive to detect early failure and hence changed the treatment strategy for them. Taken together, PET/CT appeared to be a more sensitive approach for surveillance of post-treatment NPC, especially for IVa-IVb patients.
Despite the application of IMRT and chemotherapy, there are occasions of local failure and distant metastasis. The identification of prognostic factors would be helpful in risk stratification and tailoring the treatment strategy for the high-risk patients, such as higher radiation dose or more aggressive chemotherapy. 18F-FDG PET/CT has been investigated in prognosis of various malignancies, and the uptake of 18F-FDG has been correlated with aggressive behavior and poor prognosis [51-54].
Recently, several studies have reported the prognostic value of 18F-FDG PET/CT of OS and DFS in NPC. In a study by Lee et al , 18F-FDG-PET uptake, as determined by calculating SUVmax, is a valuable tool to evaluate prognosis in NPC patients receiving concurrent chemoradiotherapy. The study also suggested that SUVmax of the node higher than that of the primary site and SUVmax of 8 or higher were associated with poorer prognosis. Xie et al  demonstrated that locally advanced NPC patients with an pretreatment SUVmax below 8.0 had a significantly better OS and DFS than patients with an SUVmax above 8.0. The patients who showed with PMR had a significantly lower 5-year OS and DFS than patients with CMR at 1-5 months after radiation. Similarly, Chan et al  reported that both SUVmax of primary tumor and metastatic nodes were independent predictors of DFS of NPC patients as well. Significantly better DFS was found in patients with primary tumor SUVmax<7.5 and nodal SUVmax <6.5, respectively.
Interestingly, other studies suggested that pretreatment SUVmax are more related to distant metastasis. As Chan reported , SUVmax on 18F-FDG represented an important independent prognostic factor for distant recurrence, more predictive than traditional TNM stage. A SUVmax > 12.0 indicated significantly poorer distant control. Then a further investigation  with a larger sample size (196 NPC patients with III-IV disease) demonstrated that a high SUVmax of neck lymph nodes independently predicted distant failure-free survival (DMFS) and a higher total lesion glycolysis independently predicted OS and DFS. In a study enrolling 371 NPC patients treated with IMRT , patients with a lower SUVmax of primary tumor and metastatic lymph nodes had a significantly better 5-year DMFS but show no significance in local or regional control. The SUVmax of the primary tumor and neck lymph nodes were independent prognostic factor of DMFS in NPC patients treated with IMRT.
Such discrepancies can be related to different inclusion criteria, to different number of patients recruited and to the change of failure patterns due to IMRT. With the advent of IMRT and the application of chemotherapy, the locoregional control of NPC has been greatly improved. The main failure pattern is distant metastasis. Detailed studies of TNM stages have shown that T stage failed to predict local recurrence rate when IMRT was delivered [61, 62], whereas notable differences were observed among the distant metastasis rate of N0-N3 disease . According to the report by Sun  et al, the DMFS of N0, N1, N2 and N3 were 96.8% 85%, 73.5% and 62.1% (p<0.001), respectively. Thus, the higher metabolic activity of tumor, especially the higher SUVmax of the metastatic lymph nodes might reflect a more aggressive metastatic potential, which correlated with distant metastasis.
In addition, PET/CT parameters other than SUVmax have been received more and more attentions in the prognosis of solid cancers [64-69]. SUVmax is a semiquantitative index and can be influenced by the volume of interest which is visually delineated on side-by-side analysis with CT or MRI under most circumstances. Metabolic tumor volume (MTV), defined as the volume of tumor tissues with increased FDG uptake, usually measured from PET/CT images by automatic contouring methods, is theoretically a better predictor of outcome than SUVmax . Total lesion glycolysis represents metabolic activity throughout the entire tumor above a minimum threshold , might reflect the metabolic burden better than SUVmax. In a study  to evaluate the predictive value of MTV of pharyngeal carcinomas, most of the cases (76.8%) were nasopharyngeal carcinoma. MTV was shown to be the only significant predictor of short-term response and DFS, with a cutoff value of MTV≤ 40ml by multivariate analysis. SUVmax failed to reach a statistical significance to predict response and DFS. In the study by Chan , a high SUVmax of neck lymph nodes independently predicted DMFS and a higher total lesion glycolysis independently predicted OS and DFS. A better predictive value of MTV and total lesion glycolysis of OS and DFS has been proved in other head and neck cancers [60-62], lung cancer , breast cancer , et al.
Location of NPC relapse
Numerous studies have shown the circulating EBV DNA levels correlated with treatment outcome. Pretreatment EBV DNA copies are a good prognostic factor for NPC. In most patients, the EBV DNA copies drops to baseline after radiotherapy. The rise of EBV DNA copies during follow-up usually precedes the relapse of disease. Since both EBV DNA copies and 18F-FDG PET/CT have the predictive potential, there have been some efforts in combing these two parameters.
Mäkitie et al  performed the first study combing EBV DNA copies and 18F-FDG PET/CT in response evaluation and prognosis prediction. The results showed that reduction in EBV DNA copies and normal PET scans after treatment were consistent among patients who had residual abnormality on MRI. Persistent elevated EBV DNA copies and abnormal PET scans after treatment suggest residual disease. Ma et al  tried to explore the relationship between EBV DNA copies and metabolic activity in NPC. The study revealed significant correlation between pretreatment SUVmax of primary tumor and pretreatment EBV DNA copies, but further regression analysis did not confirm a significant association between them. Wang et al  investigated the combination of plasma EBV DNA copies and 18F-FDG PET scan in the detection of recurrent nasopharyngeal carcinoma. In this study, all the patients were monitored by an EBV DNA assay every 3-6 months. 18F-FDG PET scan was performed once the abnormal EBV DNA copies or clinically suggestive signs of recurrence were noted. The plasma EBV DNA assay correctly predicted all NPC recurrences, and PET had high capacity to localize potential lesion sites. The sensitivity and specificity of PET/CT to detect relapse lesion were 81.8% and 77.1%, respectively. The screening of EBV DNA and location of recurrence by PET/CT appeared to be a useful and effective way of follow-up in NPC patients.
Taken together, 18F-FDG PET/CT has played an instrumental role in the management of NPC. 18F-FDG PET/CT may sensitively determine cervical nodal metastasis and distant metastasis. With the help of 18F-FDG PET/CT, a better diagnosis of cervical nodal involvement and distant metastasis has a great impact on treatment strategy and radiotherapy planning. 18F-FDG PET/CT provides additional biological information, which helps to differentiate the post-radiation inflammation and local residual/recurrent disease. For locally advanced disease, 18F-FDG PET/CT appears to be a better and more sensitive approach for therapeutic response assessment and surveillance, and detecting of early relapses and metastasis of NPC, compared with conventional workup. However, 18F-FDG PET/CT is inferior to the MRI in the T staging and identifying the metastasis of retropharyngeal nodes, 18F-FDG PET/CT still yields a low percentage of false-positive and false-negative due to be inflammatory hyperplasia and micro-metastases in cervical nodes.
Various PET/CT parameters, including SUVmax, MTV and total lesion glycolysis have been correlated with response and survival. There is some evidence suggesting MTV and total lesion glycolysis are better indexes to reflect tumor burden and predict OS and DFS. The combination of EBV DNA copies and PET/CT scan seems to be a useful and effective strategy in the follow-up of NPC.
1. Huang DP. Epidemiology and aetiology. In: Hasselt CAV, Gibb AG, editors. Nasopharyngeal carcinoma. Hong Kong: The Chinese University Press; 1991. p. 23-44.
2. Parkin DM, Whelan SL, Ferlay J, et al., editors. Cancer incidence in five continents. Vol 7. Lyon, France: International Agency for Research on Cancer; 1997. p. 334-7. (IARC scientific publications no. 143).
3. Emami B, Sethi A, Petruzzelli GJ. Influence of MRI on target volume delineation and IMRT planning in nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2003;57:481-8.
4. Chang JT, Lin CY, Chen TM, et al. Nasopharyngeal carcinoma with cranial nerve palsy: the importance of MRI for radiotherapy. Int J Radiat Oncol Biol Phys 2005;63:1354-60.
5. King AD, Ma BB, Yau YY, et al. The impact of 18F-FDG PET/CT on assessment of nasopharyngeal carcinoma at diagnosis. Br J Radiol 2008;81:291-8.
6. Ng SH, Chan SC, Yen TC, et al. Staging of untreated nasopharyngeal carcinoma with PET/CT: comparison with conventional imaging work-up. Eur J Nucl Med Mol Imaging 2009;36:12-22.
7. Lim TC, Chua ML, Chia GS, et al. Comparison of MRI, CT and 18F-FDG-PET/CT for the detection of intracranial disease extension in nasopharyngeal carcinoma. Head Neck Oncol 2012;4:49.
8. King AD, Ahuja AT, Leung SF, et al. Neck node metastases from nasopharyngeal carcinoma: MR imaging of patterns of disease. Head Neck 2000;22:275-81.
9. Mancuso AA, Harnsberger HR, Muraki AS. Workbook for MRI and CT of the head and neck. 2nd ed. Baltimore: Williams & Wilkins; 1991. p 211.
10. Lam WWM, Chan YL, Leung SF, Metreweli C. Retropharyngeal lymphadenopathy in nasopharyngeal carcinoma. Head Neck 1997;19:176–181.
11. Tang LL, Ma J, Chen Y, et al. The values of MRI, CT and PET-CT in detecting retropharyngeal lymph node metastasis of nasopharyngeal carcinoma. Ai Zheng 2007;26:737-41.
12. King AD, Ahuja AT, Leung SF, et al. Neck node metastases from nasopharyngeal carcinoma: MRI of patterns of disease. Head Neck 2000; 22:275–81.
13. Chong VF, Fan YF, Khoo JB. Retropharyngeal lymphadenopathy in nasopharyngeal carcinoma. Eur J Radiol 1995; 21: 100–5.
14. Sham JST, Choy D, Wei WI. Nasopharyngeal carcinoma: orderly neck node spread. Int J Radiat Oncol Biol Phys 1990; 19:929–933.
15. Ng SH, Chang JT, Chan SC, et al. Nodal metastases of nasopharygneal carcinoma: patterns of disease on MRI and FDG PET. Eur J Nucl Med Mol Imaging 2004;31:1073-80.
16. Adams S, Baum RP, Stuckensen T, Bitter K, Hör G. Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer. Eur J Nucl Med 1998;25:1255–60.
17. Braams JW, Pruim J, Freling NJ, et al. Detection of lymph node metastases of squamous-cell cancer of the head and neck with FDG-PET and MRI. J Nucl Med 1995;36:211–6.
18. Dammann F, Horger M, Mueller-Berg M, et al. Rational diagnosis of squamous cell carcinoma of the head and neck region: comparative evaluation of CT, MRI and 18F FDG PET. AJR Am J Roentgenol 2005;184:1326–31.
19. Ng SH, Yen TC, Liao CT, et al. 18F-FDG PET and CT/MRI in oral cavity squamous cell carcinoma: a prospective study of 124 patients with histologic correlation. J Nucl Med 2005;46:1136–43.
20. Kim MR, Roh JL, Kim JS, et al.Utility of 18F-fluorodeoxyglucose positron emission tomography in the preoperative staging of squamous cell carcinoma of the oropharynx. Eur J Surg Oncol 2007;3 :633–8.
21. Zhang GY, Hu WH, Liu LZ, et al. Comparision between PET/CT and MRI in diagnosing lypmph node metastasis and N staging of nasopharygneal carcinoma. Zhonghua Zhongliu Zazhi 2006;28:381-4.
22. Hu WH, Zhang GY, Liu LZ, et al. Comparison between PET-CT and MRI in detecting nodal metastasis of nasopharyngeal carcinoma. Ai Zheng 2005;24:855-60.
23. Yen RF, Hong RL, Tzen KY, Pan MH, Chen TH. Whole-body 18F-FDG PET in recurrent or metastatic nasopharyngeal carcinoma. J Nucl Med 2005;46:770-4.
24. Brink I, Klenzner T, Krause T, et al. Lymph node staging in extracranial head and neck cancer with FDG PET: appropriate uptake period and size-dependence of the results. Nuklearmedizin 2002;41:108–3.
25. Yen TC, Chang JT, Ng SH, et al. The value of 18F-FDG PET in the detection of stage m0 carcinoma of the nasopharynx. J Nucl Med 2005;46:405-10.
26. Chang JT, Chan SC, Yen TC, et al. Nasopharyngeal carcinoma staging by (18)f-fluorodeoxyglucose positron emission tomography. Int J Radiat Oncol Biol Phys 2005;62:501-7.
27. Liu FY, Lin CY, Chang JT, et al. 18F-FDG PET can replace conventional work-up in primary M staging if neonkeratinizing nasopharyngeal carcinoma. J Nucl Med 2007;48:1614-9.
28. Liu FY, Chang JT, Wang HM, et al. [18F]fluorodeoxyglucose positron emission tomography is more sensitive than skeletal scintigraphy for detecting bone metastasis in endemic nasopharyngeal carcinoma at initial staging. J Clin Oncol 2006;24:599-604.
29. Tsai MH, Shiau YC, Kao CH, Shen YY, Lin CC, Lee CC. Detection of recurrent nasopharyngeal carcinomas with positron emission tomography using 18-fluoro-2-deoxyglucose in patients with indeterminate magnetic resonance imaging findings after radiotherapy. J Cancer Res Clin Oncol 2002;128:279-82.
30. Yen RF, Hung RL, Pan MH, et al. 18-fluoro-2-deoxyglucose positron emission tomography in detecting residual/recurrent nasopharyngeal carcinomas and comparison with magnetic resonance imaging. Cancer 2003;98:283-7.
31. Ng SH, Joseph CT, Chan SC, et al. Clinical usefulness of 18F-FDG PET in nasopharyngeal carcinoma patients with questionable MRI findings for recurrence. J Nucl Med 2004;45:1669-76.
32. Comoretto M, Balestreri L, Borsatti E, et al. Detection and restaging of residual and/or recurrent nasopharyngeal carcinoma after chemotherapy and radiation therapy: comparison of MR imaging and FDG PET/CT. Radiology 2008;249:203-11.
33. Zhong JL, Liang BL, Ding ZX, et al. Significance of dynamic enhanced MRI in differential diagnosis of radiofibrosis and recurrent nasopharyngeal carcinoma at the basilar clivus. Ai Zheng 2006;25:105–9.
34. Hung GU, Tsai SC, Lin WY. Extraordinarily high F-18 FDG uptake caused by radiation necrosis in a patient with nasopharyngeal carcinoma. Clin Nucl Med 2005;30:558-9.
35. Liu SH, Chang JT, Ng SH, Chan SC, Yen TC. False positive fluorine-18 fluorodeoxy-D-glucose positron emission tomography finding caused by osteoradionecrosis in a nasopharyngeal carcinoma patient. Br J Radiol 2004;77:257-60.
36. Mancuso AA, Drane WE, Mukherji S. The promise FDG in diagnosis and surveillance of head and neck cancer. Cancer 1994;74:1193–5.
37. Chong VFH, Fan YF. Detection of recurrent nasopharyngeal carcinoma: MR imaging versus CT. Radiology 1997;202:463–70.
38. Olmi P, Fallai C, Colagradne S, Giannardi G. Staging and follow up of nasopharyngeal carcinoma: Magnetic resonance imaging versus computerized tomography. Int J Radiat Oncol Biol Phys 1995;32:795– 800.
39. Ng SH, Chang TC, Ko SF, Wan YL, Tang LM, Chen WC. MRI in recurrent nasopharyngeal carcinoma. Neuroradiology 1999;41:855–62.
40. Kostakoglu L, Goldsmith SJ. 18F-FDG PET evaluation of the response to therapy for lymphoma and for breast, lung, and colorectal carcinoma. J Nucl Med 2003;44:224 –39.
41. Grigsby PW, Siegel BA, Dehdashti F, Rader J, Zoberi I. Posttherapy [18F] fluorodeoxyglucose positron emission tomography in carcinoma of the cervix: Response and outcome. J Clin Oncol 2004;22:2167–71.
42. Swisher SG, Erasmus J, Maish M, et al. 2-fluoro-2-deoxy-Dglucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma. Cancer 2004;101:1776 –85.
43. Vansteenkiste J, Fischer BM, Dooms C, Mortensen J. Positron-emission tomography in prognostic and therapeutic assessment of lung cancer: Systemic review. Lancet Oncol 2004;5:531–40.
44. Yen TC, Lin CY, Wang HM, et al. 18F-FDG-PET for evaluation of the response to concurrent chemoradiation therapy with intensity-modulated radiation technique for Stage T4 nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2006;65:1307-14.
45. Xie P, Yue JB, Fu Z, Feng R, Yu JM. Prognostic value of 18F-FDG PET/CT before and after radiotherapy for locally advanced nasopharyngeal carcinoma. Ann Oncol 2010;21:1078-82.
46. Chan SC, Kuo WH, Wang HM, et al. Prognostic implications of post-therapy (18)F-FDG PET in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy. Ann Nucl Med 2013;27:710-9.
47. Greven KM, Williams 3rd DW, McGuirt Sr WF, et al. Serial positron emission tomography scans following radiation therapy of patients with head and neck cancer. Head Neck 2001;23:942–6.
48. Allal AS, Slosman DO, Kebdani T, et al. Prediction of outcome in head-and-neck cancer patients using the standardized uptake value of 2-[18F]fluoro- 2-deoxy-D-glucose. Int J Radiat Oncol Biol Phys 2004;59:1295–300.
49. Oshida M, Uno K, Suzuki M, et al. Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose. Cancer 1998;82:2227–34.
50. Kitagawa Y, Sano K, Nishizawa S, et al. FDG-PET for prediction of tumour aggressiveness and response to intra-arterial chemotherapy and radiotherapy in head and neck cancer. Eur J Nucl Med Mol Imaging 2003;30:63–71.
51. Lee SW, Nam SY, Im KC, et al. Prediction of prognosis using standardized uptake value of 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography for nasopharyngeal carcinomas.Radiother Oncol 2008;87:211-6.
52. Xie P, Yue JB, Fu Z, Feng R, Yu JM. Prognostic value of 18F-FDG PET/CT before and after radiotherapy for locally advanced nasopharyngeal carcinoma. Ann Oncol 2010;21:1078-82.
53. Chan WK, Kwong DL, Yeung DW, Huang B, Khong PL. Prognostic impact of standardized uptake value of F-18 FDG PET/CT in nasopharyngeal carcinoma. Clin Nucl Med 2011;36:1007-11.
54. Chan SC, Chang JT, Wang HM, et al. Prediction for distant failure in patients with stage M0 nasopharyngeal carcinoma: the role of standardized uptake value. Oral Oncol 2009;45:52-8.
55. Chan SC, Chang JT, Lin CY, et al. Clinical utility of 18F-FDG PET parameters in patients with advanced nasopharyngeal carcinoma: predictive role for different survival endpoints and impact on prognostic stratification. Nucl Med Commun 2011;32:989-96.
56. Hung TM, Wang HM, Kang CJ, et al. Pretreatment (18)F-FDG PET standardized uptake value of primary tumor and neck lymph nodes as a predictor of distant metastasis for patients with nasopharyngeal carcinoma. Oral Oncol 2013;49:169-74.
57. Wong FC, Ng AW, Lee VH, et al. Whole-field simultaneous integrated-boost intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2010;76:138–45
58. Lin S, Pan J, Han L, et al.Nasopharyngeal carcinoma treated with reduced-volume intensity-modulated radiation therapy: report on the 3-year outcome of a prospective series. Int J Radiat Oncol Biol Phys 2009;75:1071-8.
59. Sun X, Su S, Chen C, et al. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: An analysis of survival and treatment toxicities. Radiother Oncol 2013 Nov 11. [Epub ahead of print]
60. Chung MK, Jeong HS, Park SG, et al. Metabolic tumor volume of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography predicts short-term outcome to radiotherapy with or without chemotherapy in pharyngeal cancer. Clin Cancer Res 2009;15:5861-8.
61. Kao CH, Lin SC, Hsieh TC, et al. Use of pretreatment metabolic tumour volumes to predict the outcome of pharyngeal cancer treated by definitive radiotherapy. Eur J Nucl Med Mol Imaging 2012;39:1297-305.
62. Ryu IS, Kim JS, Roh JL, et al. Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by 18F-FDG PET/CT in squamous cell carcinoma of the oral cavity. Eur J Nucl Med Mol Imaging 2013 Oct 1. [Epub ahead of print]
63. Chung HW, Lee KY, Kim HJ, Kim WS, So Y. FDG PET/CT metabolic tumor volume and total lesion glycolysis predict prognosis in patients with advanced lung adenocarcinoma. J Cancer Res Clin Oncol 2014;140:89-98.
64. Ulaner GA, Eaton A, Morris PG, et al. Prognostic value of quantitative fluorodeoxyglucose measurements in newly diagnosed metastatic breast cancer. Cancer Med 2013;2:725-33.
65. Romesser PB, Qureshi MM, Shah BA, et al. Superior prognostic utility of gross and metabolic tumor volume compared to standardized uptake value using PET/ CT in head and neck squamous cell carcinoma patients treated with intensity-modulated radiotherapy. Ann Nucl Med 2012;26:527–34.
66. Larson SM, Erdi Y, Akhurst T, et al. Tumor treatment response based on visual and quantitative changes in global tumor glycolysis using PET-FDG imaging. The visual response score and the change in total lesion glycolysis. Clin Positron Imaging 1999;2:159–71.
67. Mäkitie AA, Reis PP, Irish J, et al. Correlation of Epstein-Barr virus DNA in cell-free plasma, functional imaging and clinical course in locally advanced nasopharyngeal cancer: a pilot study. Head Neck 2004;26:815-22.
68. Ma BB, King A, Lo YM, et al. Relationship between pretreatment level of plasma Epstein-Barr virus DNA, tumor burden, and metabolic activity in advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2006;66:714-20.
69. Wang WY, Twu CW, Lin WY, et al. Plasma Epstein-Barr virus DNA screening followed by ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography in detecting posttreatment failures of nasopharyngeal carcinoma. Cancer 2011;117:4452-9.
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