European Journal of Radiology

European Journal of Radiology 82 (2013) 366 373 Contents lists available at SciVerse ScienceDirect European Journal of Radiology journa l h o me pa ge: www.elsevier.com/locate/ejrad Review Accuracy of whole-body FDG-PET and FDG-PET/CT in M staging of nasopharyngeal carcinoma: A systematic review and meta-analysis Ming-Che Chang a,b,1,4, Jin-Hua Chen c,2,4, Ji-An Liang d,e,1, Kuang-Tao Yang a,1, Kai-Yuan Cheng b,3, Chia-Hung Kao d,f, a Department of Nuclear Medicine and PET Center, Changhua Christian Hospital, No. 135, Nanxiao Street, Changhua 500, Taiwan b Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, No. 666, Buzih Road, Beitun District, Taichung City 40601, Taiwan c Biostatistics Center and Graduate Institute of Biostatistics, China Medical University, No. 91, Hsueh-Shih Road, Taichung 404, Taiwan d School of Medicine, China Medical University, Taichung, Taiwan e Department of Radiation Oncology, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan f Department of Nuclear Medicine and PET Center, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan a r t i c l e i n f o Article history: Received 20 April 2012 Received in revised form 8 June 2012 Accepted 9 June 2012 Keywords: Nasopharyngeal carcinoma PET PET/CT Staging Meta-analysis a b s t r a c t Background: A meta-analysis was conducted to evaluate the accuracy of whole-body positron emission tomography (PET) or PET/CT in M staging of nasopharyngeal carcinoma (NPC). Methods: Through a search of relevant English language studies from October 1996 to September 2011, pooled estimated sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and summary receiver operating characteristic (SROC) curves of whole-body PET or PET/CT in M staging of NPC were calculated. Results: Three PET and 5 PET/CT studies were identified. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FDG-PET or PET/CT were 0.83 (95% confidence interval [CI], 0.77 0.88), 0.97 (95% CI, 0.95 0.98), 23.38 (95% CI, 16.22 33.69), and 0.19 (95% CI, 0.13 0.25), respectively. The area under curve was 0.9764 and Q* index estimate was 0.9307 for FDG-PET or PET/CT. Conclusion: Current evidence confirms the good diagnostic performance of the whole-body FDG-PET or PET/CT in M staging of NPC. 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Nasopharyngeal carcinoma (NPC) is a high frequent epithelial malignancy of head and neck in southern China, Hong Kong, Singapore and Taiwan and occurs 10 30 persons per 100,000 per year [1]. NPC has a higher incidence of distant metastasis compared with other head and neck cancers [2]. Distant metastasis is the most important prognostic factor [3,4]. As many as 11 36% of patients with NPC present overt distant metastasis at initial diagnosis and the skeleton is the most frequent site [5 12]. Treatment failure may eventually develop in patients with occult dissemination at Corresponding author at: Department of Nuclear Medicine and PET Center, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan. Tel.: +886 4 22052121x7412; fax: +886 4 22336174. E-mail addresses: 135834@cch.org.tw (M.-C. Chang), chenjh12@gmail.com (J.-H. Chen), hope.jal@msa.hinet.net (J.-A. Liang), 135834@cch.org.tw (K.-T. Yang), kycheng@ctust.edu.tw (K.-Y. Cheng), d10040@mail.cmuh.org.tw (C.-H. Kao). 1 Tel.: +886 4 22052121x7412; fax: +886 4 22336174. 2 Tel.: +886 4 22053366x6118; fax: +886 4 22078539. 3 Tel.: +886 22391647 3985; fax: +886 4 22390263. 4 M.C. Chang and J.H. Chen contributed equally to this work. the time of primary radiotherapy [13]. Early detection of distant metastasis is essential for precise staging, optimal managements, and accurate comparison between different therapeutic protocols in patients with advanced disease. Conventional workup with chest radiography, abdominal ultrasonography, and skeletal scintigraphy was recommended routinely performed in M staging of NPC for high-risk (N3) disease and, on the institutional basis, for intermediate risk (N1 and N2) disease [14]. This combination had a sensitivity of only 32.8% [15]. Positron-emission tomography (PET) using 18F-fluoro-2- deoxy-d-glucose (18F-FDG) is a widely used technique in the M assessment of NPC in recent years because of its unique capability of providing functional data on tumor metabolism. The integration of PET and CT further provides more anatomic details and intrinsically align functional and morphological data sets. Although many studies on the value of whole-body FDG-PET or PET/CT have been done [16 19], patient population, imaging techniques, study design, and results vary widely between studies, making it difficult to accurately assess the diagnostic value of FDG-PET or PET/CT. We performed a meta-analysis to evaluate whole-body FDG-PET or PET/CT for M staging of nasopharyngeal carcinoma. 0720-048X/$ see front matter 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejrad.2012.06.031

M.-C. Chang et al. / European Journal of Radiology 82 (2013) 366 373 367 2. Materials and methods 2.1. Search strategy and study selection A comprehensive computer search for relevant articles was conducted in Pubmed, MEDLINE, and the Cochrane Library from October 1996 to September 2011. The search strategy was based on the combination of the following keywords (1) positron-emission tomography or positron-emission tomography and computed tomography; (2) nasopharyngeal carcinoma; (3) staging or distant metastasis; (4) sensitivity, specificity, false-negative, or falsepositive. The full text review and final analysis was limited to articles published in English language. Conference abstracts and letters to the journal editors were excluded because they contained limited data. Reference lists were manually screened for additional relevant articles. Two reviewers (K.C.H. and C.M.C.) independently judged study eligibility. Disagreements were resolved by consensus. The inclusion criteria were: (1) whole-body FDG-PET or PET/CT was used to detect distant metastasis of nasopharyngeal cancer; (2) histopathology analysis and/or clinical and imaging follow-up were used as the reference standard; (3) only studies which a 2 2 table could be constructed for true-positive, true-negative, falsepositive, and false-negative values were included; (4) the studies were based on per patient statistics; (5) when data or subsets of data were presented in more than 1 article, the article with the most details or the most recent article was chosen; (6) the studies including at least 10 patients were selected for inclusion in the study, since very small studies may be vulnerable to selection bias; (7) studies have been published as a peer reviewed article in the English language; and (8) no article about patients with M0 carcinoma by conventional imaging techniques were included. 2.2. Data extraction and quality assessment applied. We also calculated SROC curves and the Q* index. (Q* index is the best statistical methods to reflect the diagnostic value. It is defined by the point where sensitivity and specificity are equal, which is the point closest to the ideal top-left corner of the SROC space) [25]. A Z-test was performed to determine whether the Q* index of PET-CT was significantly different with that of PET. All analysis was performed using MetaDiSc, version 1.4. 3. Results 3.1. Study selection and characteristics analysis The initial search identified a total of 77 potential studies (Fig. 1). Review of the titles and abstracts excluded 65 studies. These included seven reviews, 12 case reports, 15 studies not associated with NPC, 24 studies not detecting distant metastasis in patients with NPC, three studies not published in English, and one study which did not utilize FDG tracer. The criteria excluded a further four of the remaining 12 studies: three about patients with carcinoma staged as M0 by conventional imaging techniques and one for having insufficient information to construct a 2 2 table. Finally, eight studies [15,19,26 31] met the inclusion criteria and were selected (Table 1). 3.2. Study characteristics Table 1 summarizes the eight studies enrolled in this review, including 5 PET/CT studies (including two studies presenting both PET alone and PET/CT information, total of 472 patients) and 3 PET studies (597 patients). A total of 172 of 1069 eligible patients (16.1%) had distant metastasis. The median prevalence of distant metastasis was 14.6% (range 4.8 26.7%). Six studies were prospective and two were retrospective study design. In two FDG-PET/CT Two reviewers (K.C.H. and C.M.C.) independently extracted the relevant data from each article and recorded them on a standardized form. Disagreements were resolved by consensus. Reviewers were not blinded with regard to information about the journal name, the authors, the author s affiliation, or year of publication, since this has been shown to be unnecessary [20]. In addition, for each study the following information was noted: (1) year of publication and origin; (2) sample size; (3) age distribution of study population; (4) reference standard tests; and (5) imaging details and imaging system (PET or PET/CT). We assess the methodological quality of the studies using the quality assessment for studies of diagnostic accuracy (QUADAS) tool [21]. It is the first systematically developed evidence-based quality assessment tool to be used in systematic review of diagnostic accuracy studies. In addition, for each study, the following design criteria were also assessed: cross-sectional design (vs case-control design); and prospective data collection. 2.3. Statistical analysis The analysis was based on summary receiver operating characteristic (SROC) curves [22,23]. The sensitivity and specificity for each study were used to construct SROC curves [23,24]. The pooled sensitivity and specificity were weighted average estimators. The sample size was the weight for each study. The degree of heterogeneity among different studies was reported using the Cochran chi-square statistic. When there was no heterogeneity observed (p > 0.05), a fixed-effect model was used to calculate diagnostic odds ratio, positive likelihood ration, and negative likelihood ratio for whole-body FDG-PET or PET/CT. In case heterogeneity was observed (p < 0.05), a random-effect model was Fig. 1. Flow chart of selection process of eligible studies.

368 M.-C. Chang et al. / European Journal of Radiology 82 (2013) 366 373 Table 1 Clinical Characteristics for selected studies. Author Year Origin N Mean/ median age Study design Population Male (%) T3 T4 (%) N2 N3 (%) DM (%) Execution for reference standard Chang et al. 2005 Taiwan 95 47 Prospective Newly (N = 85) and recurrent (N = 10) Liu et al. 2006 Taiwan 202 49.6 Prospective Newly Chen et al. 2006 Taiwan 70 46.3/50.7 Retrospective Newly (N = 20) and recurrent (N = 50) Liu et al. 2007 Taiwan 300 50 Prospective Newly 69.5 47.4% 62.1% 14.7 Pathologic evaluation and other examination, and follow-up for at least 6 mo 82.8 46.5% 61.4% 15 Pathologic evaluation and other examination, and follow-up for at least 6 mo 74.3 NA NA 26.7 Pathologic evaluation and other examination, and follow-up for at least 6 mo 70 49.0% 66.7% 20.3 Histologic analysis or close clinical and imaging follow up for 12 mo Comoretto et al. 2008 Italy 63 52 Retrospective Treated NPC 69.8 NA NA 4.8 Pathologic evaluation, and follow-up for at least 6 mo Chua et al. 2009 Singapore 78 50 Prospective Newly Ng et al. 2009 Taiwan 150 48.17 Prospective Newly Ng et al. 2009 Taiwan 111 48.9 Prospective Newly 76.9 44.9% 55.1% 7.7 Histologic analysis or close clinical and imaging follow up for 6 mo 74 44.7% 46.7% 12 Histologic analysis or close clinical and imaging follow up for 12 mo 75.7 57.7% 54.1% 14.4 Histologic analysis or close clinical and imaging follow up for 12 mo An ECAT EXACT HR+ PET camera; 370 MBq FDG; 40-min uptake period; Accelerated maximal likelihood An ECAT EXACT HR+ PET camera; 370 MBq FDG; 40-min uptake period; Accelerated maximal likelihood A Discovery LS PET/CT camera; 370 MBq FDG; 60-min uptake period; Ordered-subset expectation maximization An ECAT EXACT HR+ PET camera; 370 MBq FDG; 40-min uptake period; Accelerated maximal likelihood A Discovery LS PET/CT camera; 350 400 MBq FDG; 60-min uptake period; Ordered-subset expectation maximization A dedicated PET/CT scanner A Discovery ST 16 PET/CT camera; 370 MBq FDG; 50 70 min uptake period; Ordered-subset expectation maximization A Discovery ST 16 PET/CT camera; 370 MBq FDG; 50 70 min uptake period; Ordered-subset expectation maximization Abbreviations: DM, distant metastasis; PET, positron emission tomography; PET/CT, positron emission tomography/computed tomography; FDG: fluorodeoxyglucose; MBq, megabecquerel.

M.-C. Chang et al. / European Journal of Radiology 82 (2013) 366 373 369 Table 2 Quality assessment. Author Year Quality items Quality Score 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Chang et al. [30] 2005 + + + + + + + + + 64% (9/14) Liu et al. [26] 2006 + + + + + + + + + 64% (9/14) Chen et al. [29] 2006 + + + + + + + + + + 71% (10/14) Liu et al. [14] 2007 + + + + + + + + + 64% (9/14) Comoretto et al. [27] 2008 + + + + + + + + 57% (8/14) Chua et al. [28] 2009 + + + + + + + + + 64% (9/14) Ng et al. [25] 2009 + + + + + + + + + + 71% (10/14) Ng et al. [18] 2009 + + + + + + + + + 64% (9/14) Methodological quality was assessed using quality assessment of diagnostic accuracy studies criteria [20]. Quality item 1: Was the spectrum of patients representative of the patients who will receive the test in practice? Quality item 2: Were selection criteria clearly described? Quality item 3: Is the reference standard likely to correctly classify the target condition? Quality item 4: Is the time period between reference standard and index test short enough to be sure that the target condition did not change between the two tests? Quality item 5: Did the whole sample, or a random selection of the sample, receive verification using a reference standard of diagnosis? Quality item 6: Did patients receive the same reference standard regardless of the index test result? Quality item 7: Was the reference standard independent of the index test (i.e., the index test did not form part of the reference standard?) Quality item 8: Was the execution of the index test described in sufficient detail to permit replication of the test? Quality item 9: Was the execution of the reference standard described in sufficient detail to permit replication? Quality item 10: Were the index test results interpreted without knowledge of the results of the reference standard? Quality item 11: Were the reference standard results interpreted without knowledge of the results of the index test? Quality item 12: Were the same clinical data available when test results were interpreted as would be available when the test is used in practice? Quality item 13: Were uninterpretable/intermediate test results reported? Quality item 14: Were withdrawals from the study explained? studies presenting both PET alone or PET/CT information [29,30], only the data of PET/CT were analyzed. The median prevalence of patients was 47.0% (range 44.7 57.7%) for T3 T4 tumor and 58.3% (range 46.7 66.7%) for N2 N3 disease. In one study [27] only the information about the detection of bone metastasis was able to be analyzed. In the 8 retrieved articles, 4 articles contained data of per-region analyses [15,19,26,31]. In the others, 1 article [27] analyzed distant metastasis specifically in the bone region, one study [29] with the data of per-region analysis but insufficient to construct a 2 2 table and the other 2 studies had no per-region analysis. 3.3. Quality assessment Table 2 showed generally moderate quality scores of the included studies with a median score of 64% (range, 57 71%). The study by Chen et al. and Ng et al. obtained the highest quality score. All studies had proper spectrum of patients (item 1), well-described selection criteria (item 2) and replicable reference standards for all the patients to classify the status of distant metastasis (items 3, 4, 5 and 9). All studies had a suboptimal design in regard to the examination with the same reference standard, for that biopsy was examined to confirm the diagnosis of suspicious lesions detected by FDG-PET or PET/CT scans while follow-up was attempted for those a biopsy was not feasible or had a negative scan (item 6). In two studies the diagnosis of distant bone metastasis was not independent of the FDG-PET (item 7) because distant bone metastasis was considered in cases of presence of multiple asymmetric foci of increased radionuclide uptake over the skeleton on PET without reasonable explanations other than bone metastases, and unequivocal imaging studies with a concordant clinical course. All studies described FDG-PET or PET/CT technique in detail (item 8). Only one study interpreted their findings with knowledge of clinical data (item 12), four studies applied masking for interpretation of FDG-PET or PET/CT findings, while three studies were unclear concerning whether the clinical data was known or not. None of the enrolled studies mentioned uninterpretable or intermediate FDG- PET or PET/CT findings (item 13). Three studies explained reasons for patients withdrawal (item 14). 3.4. Meta-analysis Table 3 shows the result of diagnostic accuracy of whole-body FDG-PET or PET/CT in the selected studies. Fig. 2 shows the forest plot of sensitivity and specificity, and Fig. 3 reveals the positive and negative likelihood ratios of FDG-PET or PET/CT for M staging of nasopharyngeal carcinoma. The chi-square values of sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 19.35 (p < 0.05), 12.12 (p = 0.097 > 0.05), 10.76 (p = 0.149 > 0.05), and 8.16 (p = 0.319 > 0.05), respectively, indicating heterogeneity for sensitivity but homogeneity for specificity, positive likelihood ratio and negative likelihood ratio between studies. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence interval (CI) of Table 3 Results of FDG-PET or PET/CT in M staging of nasopharyngeal carcinoma. Author PET camera PET technique TP FP TN FN Chang et al. [30] PET 370 MBq F-18 FDG; 40-min uptake 14 8 73 0 Liu et al. [26] PET 370 MBq F-18 FDG; 40-min uptake 21 2 170 9 Chen et al. [29] PET/CT 370 MBq F-18 FDG; 60 min uptake 23 3 60 0 Liu et al. [14] PET 370 MBq F-18 FDG; 40-min uptake 50 7 232 11 Comoretto et al. [27] PET/CT 350 400 MBq F-18 FDG; 40-min uptake 3 1 59 0 Chua et al. [28] PET/CT 370 MBq F18-FDG; 60-min uptake 5 2 70 1 Ng et al. [25] PET/CT 370 MBq F-18 FDG; 50 70 min uptake 13 3 129 5 Ng et al. [18] PET/CT 370 MBq F-18 FDG; 50 70 min uptake 13 3 92 3 Abbreviations: PET, positron emission tomography; PET/CT, positron emission tomography/computed tomography; TP, true-positive; FP, false-positive; TN, true-negative; FN, false negative.

370 M.-C. Chang et al. / European Journal of Radiology 82 (2013) 366 373 Fig. 2. Forest plot of sensitivity and specificity of whole-body positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) for M staging of nasopharyngeal carcinoma. FDG-PET or PET/CT were 0.83 (0.77 0.88), 0.97 (0.95 0.98), 23.38 (16.22 33.69), and 0.19 (0.13 0.25), respectively. The SROC plot presents a global summary of test performance and shows the tradeoff between sensitivity and specificity. Each data point in the SROC plot represents a separate study. Fig. 4 shows SROC curves and the Q* index of FDG-PET or PET/CT in M staging of nasopharyngeal carcinoma. The area under curve was 0.9764 and Q* index estimate was 0.9307 for FDG-PET or PET/CT, suggesting an outstanding performance (Fig. 4). For each specific region, 3 articles analyzed metastasis in lung [19,26,31], one in chest [15], 2 in mediastinum [19,31], 4 in liver [15,19,26,31], 5 in bone [15,19,26,27,31], and 2 in distant lymph node [26,31]. The data were too few to be pooled analyzed in lung, chest, mediastinum and distant lymph node. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence interval (CI) of FDG-PET or PET/CT to detect regional metastasis were 0.78 (0.68 0.85), 0.98 (0.97 0.99), 40.32 (23.94 67.91), and 0.24 (0.17 0.35) for the bones, and 0.53 (0.35 0.70), 1.00 (0.99 0.98), 135.9 (35.51 520.12), and 0.47 (0.34 0.66) for the liver, respectively. 4. Discussion TNM stage is the major prognostic factor of patient survival in most cancer, including nasopharyngeal carcinoma [32 34]. Accurate staging is necessary, as the treatment is directly dependent on stage [35]. Our meta-analysis suggested that 172 (15.9%) of 1085 studies in 1069 eligible patients in the selected studies had distant metastases. With the application of FDG-PET or PET/CT in primary staging and post-therapy management of nasopharyngeal carcinoma, distant metastases could be detected earlier. This would have a considerable impact on patient staging and stratification, thereby permitting the development of more reliable treatment protocols. FDG-PET was found to be more globally effective than conventional work-up. In the study of Liu et al. [15] evaluating 300 NPC patients with FDG-PET and conventional work-up including chest radiography, abdominal ultrasonography and skeletal scintigraphy, FDG-PET scan was found to be more effective (area under the ROC curve, AUC = 0.941) than conventional work-up (AUC = 0.657). Ng et al. [19] also presented that PET/CT were more sensitive and accurate than conventional work-up (81.3% vs. 25.0% in sensitivity and 94.6% vs. 88.3% in accuracy). Similar results were also demonstrated in the study of Chua et al. [29] comparing FDG-PET/CT and conventional work-up (83.3% vs. 33.3% in sensitivity and 96.2% vs. 85.9% in accuracy). Because the most frequent distant-site is the skeleton [7], conventional skeletal scintigraphy using technetium-99m-labeled diphosphonates has been one of the most important diagnostic technique in M staging of nasopharyngeal carcinoma.[36] Whole-body PET was found to be more sensitive than skeletal scintigraphy in two studies head-to-head comparing FDG-PET with bone scinitigraphy using standard imaging technique [15,27], and another one comparing FDG-PET and FDG-PET/CT with CT combined the skeletal scintigraphy.[29] In the Liu s study [15] studying 300 patients, the region-based analysis showed that FDG-PET had an accuracy of 95.0%, significantly more effective than 87.7% for the skeletal scintigraphy. In another study by Liu et al. [27] specified in comparison between FDG-PET and skeletal scintigraphy in 202 patients, FDG-PET also showed significantly more sensitive and accurate than skeletal scintigraphy (70.0% vs. 36.7% in sensitivity and 94.6% vs. 88.6% in accuracy, respective). In the study of Chua et al. [29] evaluating FDG-PET, FDG-PET/CT and CT combined the skeletal scintigraphy in 78

M.-C. Chang et al. / European Journal of Radiology 82 (2013) 366 373 371 Fig. 3. Likelihood ratios of whole-body positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) for M staging of nasopharyngeal carcinoma. consecutive patients, FDG-PET FDG-PET/CT had higher sensitivity and accuracy than the CT-skeletal scintigraphy staging. In the present meta-analysis, the pooled sensitivity with 95% CI (0.83 [0.77 0.88]) and pooled specificity (0.97 [0.95 0.98]) indicated that whole-body FDG-PET or PET/CT had a very high accuracy. Likelihood ratios permit characterizing clinical diagnostic tests to establish diagnoses for the individual patient [37]. Both Fig. 4. The summary receiver operating characteristic (SROC) curves and the Q* index of whole-body positron emission tomography (PET) or PET/CT for M staging of nasopharyngeal carcinoma.

372 M.-C. Chang et al. / European Journal of Radiology 82 (2013) 366 373 positive likelihood ratio and negative likelihood ratio were calculated and served as our measurements of diagnostic accuracy. Likelihood ratios of >10 increase the estimate of probability high enough to rule in disease, and <0.1 decrease the estimate low enough to consider the disease ruled out (indicating high accuracy). Our measurement found a positive likelihood ratio value of 23.38 for FDG-PET or PET/CT. The value was high enough to suggest that positive FDG-PET or PET/CT findings may provide a reasonable shift in confirming distant metastasis in patients with nasopharyngeal carcinoma. On the other hand, negative likelihood ratio for FDG-PET or PET/CT was found to be 0.19. The value suggests that a negative examination result of FDG-PET or PET/CT has only weak power to exclude distant metastasis and could not be used alone as a justification. For instance, Ng et al. [19] found that PET had higher sensitivities that CT in the bone, mediastinum and liver, but it displayed a lower sensitivity that CT in the lung (50% vs. 83.3%). Small lung lesion may be seen on the CT but not evident on the PET. There are several potential limitations in our meta-analysis. First, the exclusion of conference abstracts, letters to the editors and non-english-language studies may have led to publication bias. Although publication bias can be tested by using funnel posts, the limited number of included studies could have decreased the power of detection publication bias in the present meta-analysis. Second, the presence of clinical heterogeneity (heterogeneity originated by the inclusion of patients at different stages of disease and other clinical characteristics, different imaging methodologies, and the manners of reference test) influence the generalizability of the results of FDG-PET or PET/CT. Third, meta-analysis often fails to account for verification or work-up difference between studies. Finally, the current study was unable to identify if FDG-PET/CT is better than FDG-PET alone. Upon review the literature, two studies [29,30] compared fused FDG-PET/CT with FDG-PET alone in their patient groups, and both them reveal no statistically significant difference for assessing M stage. Therefore, we believed that no evidence revealing that FDG-PET/CT is better than FDG-PET in assessment of M staging. In addition, the technique for metaregression could explore the heterogeneity between sensitivity and specificity. The potential characteristics in model may (or not) influence diagnostic accuracy. In our study, PET and PET/CT was as predictor variable in meta-regression model (rdor = 0.97; 95% CI: 0.21 4.46; p-value = 0.9656). The results show that the accuracy estimations were the same between PET and PET/CT. So we combined PET and PET/CT in our meta-analysis study. In conclusion, current evidence confirms the good diagnostic performance of the whole-body FDG-PET or PET/CT in M staging of nasopharyngeal carcinoma. Conflicts of interest No potential conflicts of interest were disclosed. Acknowledgements We would like to thank the grant support of the study projects (DMR-101-061 and DMR-101-062) of our hospital; Taiwan Department of Health Clinical Trial and Research Center and for Excellence (DOH102-TD-B-111-004), Taiwan Department of Health Cancer Research Center for Excellence (DOH102-TD-C-111-005); and International Research-Intensive Centers of Excellence in Taiwan (I-RiCE) (NSC101-2911-I-002-303). References [1] Huang DP. Epidemiology of nasopharyngeal carcinoma. Ear, Nose, and Throat Journal 1990;69:222 5. [2] Sham JS, Cheung YK, Chan FL, Choy D. Nasopharyngeal carcinoma: pattern of skeletal metastases. British Journal of Radiology 1990;63:202 5. [3] Baujat B, Audry H, Bourhis J, et al. 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