Clinical Usefulness of Fused PET/CT Compared with PET Alone or CT Alone in Nasopharyngeal Carcinoma Patients

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1 Clinical Usefulness of Fused PET/CT Compared with PET Alone or CT Alone in Nasopharyngeal Carcinoma Patients YEN-KUNG CHEN 1, CHEN-TAU SU 2, HUEISCH-JY DING 3, KWAN-HWA CHI 4, JI-AN LIANG 5, YEH-YOU SHEN 1, LIANG-KUNG CHEN 2, CHIA-LU YEH 1, ALFRED C. LIAO 1 and CHIA-HUNG KAO 6 Departments of 1 Nuclear Medicine and PET Center, 2 Medical Imaging and 4 Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 3 Department of Radiological Technology, I-Shou University, Kaohsiung, Taiwan; Departments of 5 Radiation Therapy and Oncology and 6 Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan, R.O.C. Abstract. The diagnostic accuracy of fused positron emission tomography/computed tomography (PET/CT) was compared with CT alone and PET alone in the staging and re-staging of nasopharyngeal carcinoma (NPC) patients. Patients and Methods: Eighty-six fluorine-18 2-fluoro-2- deoxy-d-glucose (FDG) PET/CT studies were retrospectively performed in 70 patients with NPC, 20 patients for primary tumor staging and 50 patients for re-staging after treatment. Each lesion was analyzed visually and assigned a score on a 5-point scale. Each study was interpreted in 3 ways: PET images were evaluated in the absence of CT data, CT images in the absence of PET data and fused PET/CT images. The results of these images were correlated with histological findings, as well as long-term radiological and clinical followup (the shortest follow-up period after imaging was 6 months). PET, CT and PET/CT accuracy were compared by a McNemar test. Results: Fused PET/CT correctly characterized the tumor-node-metastasis system stage in 82 out of 86 studies (95.4%; 95% CI: 90.9% to 99.9%). PET alone and CT alone were found to be accurate in 71 out of 86 studies (82.6%; 95% CI: 74.5% to 90.6%) and 63 out of 86 studies (73.3%; 95% CI: 63.9% to 82.6%), respectively. Furthermore, the differences between PET/CT and either PET alone or CT alone were statistically significant (p<0.05). Overall, the study-based analysis of PET/CT for staging NPC demonstrated 48 true-positive, 2 false-negative, 34 true-negative and 2 false-positive studies. The sensitivity, Correspondence to: Chia-Hung Kao, MD, Department of Nuclear Medicine and PET Center, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan, R.O.C. Tel: , Ext. 3475, Fax: , d10040@ Key Words: Positron emission tomography, computed tomography, PET/CT, 18 F-fluorodeoxyglucose, nasopharyngeal carcinoma. specificity, accuracy, positive predictive value and negative predictive value of FDG-PET/CT studies for staging NPC were 96%, 94.4%, 95.4%, 96% and 94.4%, respectively. Conclusion: PET/CT is more accurate than PET alone or CT alone for the depiction of NPC. Fused PET/CT is a valuable imaging tool in patients for staging diagnosis of NPC. Nasopharyngeal carcinoma (NPC) is an epithelial malignancy occurring worldwide, with particularly high frequencies in southern China, Hong Kong, Singapore and Taiwan (1, 2). Imaging is vital for staging and treatment. The initiation of a stage-adapted therapy is known to improve patient survival for a variety of malignant tumors (3, 4). Computed tomography (CT) and magnetic resonance imaging mainly provide anatomical information on the extent of the primary site and regional metastases. The lack of functional information frequently limits their value for assessment of disease aggressiveness (5, 6). Furthermore, differentiation of scar or recurrent lesions after radiotherapy may be difficult without additional functional data. Fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) provides functional data on tumor metabolism and has been demonstrated to be of complementary value to morphological imaging studies (7, 8). However, limited anatomic information in FDG-PET images frequently renders the localization of a lesion and its potential infiltration into adjacent organs difficult. Sometimes, it is difficult to differentiate between normal and abnormal FDG uptake without detailed anatomical information. Thus, functional datasets should be read in conjunction with morphological images for maximal diagnostic benefit. Image fusion and side-by-side image evaluation of morphological and functional datasets have been proposed. Dual-modality PET/CT tomographs provide the technical basis for intrinsically aligned functional and /2006 $

2 morphological data sets, and has been shown to be superior to whole-body MRI for staging of malignancy (9). Preliminary studies have reported promising results when malignant diseases in the head and neck were assessed with combined PET/CT (10-12). NPC is one of the few head and neck malignancies prone to neck nodes or distant metastases, regardless of the primary tumor size. Therefore, the primary treatment of NPC is radiotherapy and chemotherapy, which require detailed anatomical and functional images. The aim of this study was to compare the sensitivity, specificity and accuracy of dual-modality PET/CT in staging NPC patients relative to CT alone and PET alone. Patients and Methods Patients. Eighty-six FDG-PET examinations of 70 NPC patients in our PET center, from March 2002 to October 2004, were retrospectively studied. Twenty patients (median age 46.3±15.6; 14 men and 6 women) underwent PET/CT scan for primary tumor staging and another 50 patients (median age 50.7±12.8; 38 men and 12 women) for restaging after treatment. The reasons for the PET/CT studies included staging of recently diagnosed NPC (n=18), detection of an unknown primary tumor (n=2), evaluation of residual disease after radiotherapy (n=33) and detection of clinically suspected distant metastatic disease (n=17). All patients gave informed consent to participate in the study according to the guidelines established by the local ethics committee and the Helsinki Declaration. FDG-PET imaging protocol. All patients were imaged with the PET/CT system (Discovery LS, GE Medical Systems, Waukesha, WI, USA). The patients were required to fast for at least 8 hours before the PET/CT scan; furthermore, patients had to be well hydrated and have avoided strenuous work and exercise for 24 h prior to the scan. Patients were scanned in as many sequential images as necessary to include the entire head, thorax, abdomen and pelvis. On the PET/CT scanner, the PET attenuation correction factors were calculated from the CT images. The CT was performed using a 4 detector-row spiral CT (Light-Speed) scanner. Acquisitions occurred at 5-7 bed positions and had the following parameters: 140 kv, 40 ma, 0.8 s per CT rotation, a pitch of 6, a table speed of 22.5 mm/s, coverage of ,011.5 mm and an acquisition time of s. The CT was performed before the emission acquisition. The CT data were resized from a 512x512 matrix to a 128x128 matrix to match the PET data so that the images could be fused and CT transmission maps generated. The transaxial resolution (full width at half maximum) of the PET/CT was 4.8 mm. After i.v. injection of 370 MBq (10 mci) of FDG, emission images were acquired for 5 min per bed position. The uptake period between the FDG injection and the beginning of the emission scan was 60±10 min (range, 50 to 70). The image datasets were obtained by iterative reconstruction (ordered-subset expectation maximization method). The images were displayed in 3 orthogonal projections and as whole-body maximum-pixelintensity reprojection images for visual interpretation. A workstation (Xeleris, Elegems, Haifa, Israel) was used for image display and analysis. Figure 1. Flowchart of newly diagnosed NPC patients enrolled in this study. Abbreviations: CT, computed tomography; PET, position emission tomography;, negative finding; +, positive finding. Image interpretation. All study findings were retrospectively interpreted jointly by and in consensus with one experienced physician trained in diagnostic radiology and one nuclear medicine physician. They were aware of the patient s clinical history, which was provided by the referring physician, but were unaware of the results of other imaging studies if they had been performed. Initially, only the attenuation-corrected PET images in transaxial, coronal and sagittal planes, and maximum intensity projections were reviewed. The images were analyzed visually and lesions with abnormal FDG uptake were recorded. An abnormal FDG uptake was defined (a) as radiotracer accumulation that was thought to be outside of the normal anatomic structures, such as normal laryngeal muscle activity, (b) as uptake that was higher than background activity in the neck or in the location of the normal anatomic structures and (c) as asymmetric and/or of higher intensity than is normally seen. To determine the readers certainty of their decision for each lesion, a 5-point scale was used: 1, definitively not; 2, unlikely; 3, undecided; 4, likely; or 5, definite. An 18 F-FDG PET result of 4 or 5 was considered positive, while a grade of 1, 2, or 3 was considered negative. The radiologist used the same 5-point scale as was applied to the CT images of PET/CT. Afterward, PET/CT images were made available, and the initial findings (i.e. grading of lesions and anatomic location) were amended if necessary. Data analysis. The PET, CT and PET/CT image results were correlated with the histological, endoscopic, surgical and long-term imaging study findings (contrast material-enhanced CT, MR imaging and ultrasonography) as well as with the clinical follow-up periods (the shortest follow-up period after imaging was 6 months). Lesions that had been detected by PET but which were not biopsied were considered to be true-positive findings if the disease became obvious on a follow-up image study, such as MRI or contrast material-enhanced CT. Abnormal foci seen on PET/CT that were not verified during follow-up were considered falsepositive findings. When no abnormality was seen on PET/CT and when there was no further intervention, the result was considered to be a true-negative, if, by other imaging modalities or by clinical follow-up, no disease was identified within 6 months of the PET/CT examination. A study-based analysis of PET/CT was performed. If more than one lesion was present in the same PET/CT study, at least one lesion with a true-positive PET/CT finding was considered a truepositive study of PET/CT. If any one of the lesions with a negative histological finding, long-term radiological and clinical follow-up result was detected by PET/CT, the PET/CT finding was classified 1472

3 Chen et al: Fused PET/CT in Nasopharyngeal Carcinoma Patients Table I. Accuracy of different imaging procedures for assessing T-N-M stage in newly diagnosed NPC patients. Site TP TN FP FN Sensitivity(%) Specificity(%) PPV(%) NPV(%) Accuracy(%) PET Primary ( ) ( ) Regional node Distant ( ) 66.7( ) ( ) Overall ( ) ( ) CT Primary ( ) ( ) Regional node ( ) ( ) 90.0( ) Distant ( ) 66.7( ) ( ) Overall ( ) ( ) PET/CT Primary ( ) ( ) Regional node Distant ( ) 66.7( ) ( ) Overall ( ) ( ) CT: computed tomography, FN: false-negative, FP: false-positive, NPV: negative predictive value, PET: positron emission tomography, PPV: positive predictive value, TN: true-negative, TP: true-positive. as a false-positive PET/CT study. If any one of the lesions was not detected by PET/CT, the PET/CT finding was classified as a falsenegative study of PET/CT. Any difference of opinion was resolved by consensus. Differences in the assessment of the tumor-node-metastasis system stage between the different imaging procedures (CT alone, PET alone and fused PET/CT) were tested for significance (p value <0.05) by McNemar s test. Sensitivities, specificities, negative predictive values, positive predictive values and accuracies with exact 95% confidence intervals (CIs) to detect malignant primary tumor (T stage), lymph nodes (N stage) and distant metastases (M stage) were calculated. Results Among the 20 newly diagnosed NPC patients, 4 patients were staged as T1, 6 T2, 6 T3 and 4 T4 (Figure 1). Bilateral neck lymph node metastases were detected in 16 out of the 20 NPC patients, unilateral neck lymph node metastases were detected in 3 out of the 20 NPC patients and 1 of the 20 NPC patients had no lymph node metastasis. Distant metastases to the spine were detected in 2 out of the 20 NPC patients (Table I). No biopsy of bilateral neck lymph nodes was performed after weighing the risk and benefits, except for 2 patients with enlarged neck lymph nodes due to an unknown primary tumor (before PET scan and primary tumor biopsy). The T stage was accurately determined in 18 out of 20 untreated NPC patients (90%; 95% CI: 76.9% to 100%) with fused PET/CT. Both PET alone and CT alone correctly assessed the T stage in 15 out of 20 untreated NPC patients (75%; 95% CI: 56% to 94%). Among the 20 primary NPC patients, 15 were both PETpositive and CT-positive, 3 were PET-positive but CTnegative (Figure 2), 3 were PET-negative but CT-positive (Figure 3), and 2 were both PET-negative and CT-negative. The N stage could be differentiated more easily with PET than with the CT scan. PET/CT was found to be accurate in 100% (20/20) patients, where PET alone and CT alone accurately determined regional lymph node involvement in 20 out of 20 patients (100%) and 18 out of 20 patients (90%, 95% CI: 76.9% to 100%), respectively. PET, CT and PET/CT accurately differentiated M0 and M1 disease in 19 out of 20 untreated NPC patients (95%, 95% CI: 85.5% to 100%). A comparison of CT, PET and PET/CT did not reveal a statistically significant difference (p>0.05). For re-staging, 66 imaging studies were performed in 50 patients (Table II); among whom, 12 patients underwent the examination twice, 2 three times and 36 only once. Residual and recurrent primary tumors were found on PET images after radiotherapy and chemotherapy in 8 out of the 66 imaging studies, except one was not found in the CT image. Regional lymph node metastases were found on PET images in 11 out of 66 studies and were confirmed by either biopsy or neck lymph node dissection, expect for 2 retropharyngeal lymph nodes confirmed by follow-up imaging studies. There were involved 2 retropharyngeal lymph nodes, 3 level II neck lymph nodes, 2 level IV neck lymph nodes, 4 supraclavicular lymph nodes and 2 submandibular lymph nodes. Three falsepositives were found in the PET images in high jugular, low jugular and submental lymph nodes due to lymphoid hyperplasia. PET images revealed distant metastases to bones (n=10), lungs (n=7), livers (n=4) and para-aortic lymph nodes (n=2). Residual and recurrent T stage were accurately determined in 66 out of 66 studies (100%) with 1473

4 Figure 2. A 71-year-old woman with recently diagnosed NPC underwent PET/CT scan for staging. The PET/CT was performed by a GE discovery LS PET/CT hybrid imaging scanner. The arrows point to an increased FDG uptake in the left nasopharyx in the transaxial (B) image and increased signal in the same region in MRI (D). CT images of the nasopharynx look normal (A). In addition, a combination of the anatomical (A) and physiological (B) PET/CT images show left nasopharynx lesion with hypermetabolism (C). fused PET/CT imaging studies. PET correctly assessed the residual and recurrent T stage in 64 out of 66 studies (97%, 95% CI: 92.8% to 100%) and CT was accurate in 62 out of 66 studies (93.9%; CI: 88.2% to 99.7%). Regarding the N stage of NPC patients with post-treatment, PET/CT was found to be accurate in 50 out of 50 patients. PET alone and CT alone accurately determined regional lymph node involvement in 63 out of 66 studies (95.5%, 95% CI: 90.4% to 100%) and in 58 out of 66 studies (87.9%, 95% CI: 80% to 95.8%), respectively. PET/CT correctly differentiated M0 and M1 disease in 64 out of 66 post-treatment NPC patients (97%, 95% CI: 92.8% to 100%). Both PET alone and CT alone correctly determined M stage in 60 of out 66 studies (90.9%, 95% CI: 84% to 97.8%). Furthermore, the differences between PET/CT and CT alone were statistically significant (p<0.05). The fused PET/CT images provided significantly more accurate interpretations of overall tumor-node-metastasis system stage than either PET alone or CT alone (Table III). The fused PET/CT correctly characterized the tumor-nodemetastasis system stage in 82 out of 86 studies (95.4%; 95% CI: 90.9% to 99.9%). Side by side PET and CT were found to be accurate in 71 out of 86 studies (82.6%; CI: 74.5% to 90.6%) and 63 out of 86 studies (73.3%; CI: 63.9% to 1474

5 Chen et al: Fused PET/CT in Nasopharyngeal Carcinoma Patients Figure 3. A 49-year-old man with recently diagnosed NPC underwent PET/CT scan for staging. The FDG-PET/CT study was performed by a GE discovery LS PET/CT hybrid imaging scanner. The arrow points to mucosa thickening in the right Rosenmulla fossa in the transaxial (A) image. However, in the FDG-PET image, faint FDG uptake in the right nasopharynx (B) was detected. Table II. Accuracy of different imaging procedures for assessing T-N-M restage in post-treatment NPC patients. Site TP TN FP FN Sensitivity(%) Specificity(%) PPV(%) NPV(%) Accuracy(%) PET Primary ( ) 80.0( ) ( ) Regional node ( ) 78.6( ) ( ) Distant ( ) 77.8( ) ( ) Overall ( ) 75.0( ) ( ) *CT Primary ( ) 94.8( ) 70.0( ) 98.2( ) 93.9( ) Regional node ( ) 89.3( ) 57.1( ) 96.2( ) 87.9( ) Distant ( ) 95.7( ) 88.9( ) 91.7( ) 90.9( ) Overall ( ) 75.7( ) 71.0( ) 80.0( ) 75.8( ) PET/CT Primary Regional node Distant ( ) 91.3( ) ( ) Overall ( ) 93.8( ) ( ) CT: computed tomography, FN: false-negative, FP: false-positive, NPV: negative predictive value, PET: positron emission tomography, PPV: positive predictive value, TN: true-negative, TP: true-positive. *Significant difference (p<0.05) compared with PET/CT. Table III. Overall TNM system assessment of NPC in 86 studies by the different imaging procedures. TP TN FP FN Sensitivity(%) Specificity(%) PPV(%) NPV(%) Accuracy(%) *PET *CT PET/CT ( ) 72.2( ) 81.8( ) 83.9( ) 82.6( ) ( ) 75.7( ) 79.6( ) 66.7( ) 73.3( ) ( ) 94.4( ) 96.0( ) 94.4( ) 95.4( ) CT: computed tomography, FN: false-negative, FP: false-positive, NPV: negative predictive value, PET: positron emission tomography, PPV: positive predictive value, TN: true-negative, TP: true-positive. *Significant difference (p<0.05) compared with PET/CT. 1475

6 82.6%), respectively. Furthermore, the differences between PET/CT and either PET alone or CT alone were statistically significant (p<0.05). Overall, the study-based analysis of FDG-PET/CT for staging NPC demonstrated 48 true-positive, 2 false-negative, 34 true-negative and 2 false-positive results. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of FDG-PET/CT studies for staging NPC were 96%, 94.4%, 95.4%, 96% and 94.4%, respectively. False-positive FDG-PET/CT results in 2 patients were due to a nodular goiter and a solitary pulmonary nodule (granuloma) with intense FDG uptake. False-negative FDG-PET/CT results in 2 patients were due to the primary tumor showing no definite FDG uptake on the PET image and without definite mucosa change in the nasopharynx on the CT image. Discussion NPC is a radiosensitive head and neck malignancy prone to distant metastases. Induction chemotherapy followed by concurrent chemotherapy has been the preferred therapeutic regimen to treat patients with advanced disease (13). Accurate initial assessment of the primary site of NPC and nodal involvement as well as an evaluation of metastasis are crucial in the staging, treatment planning and prognosis judgement in patients with NPC (14-16). The major indications for FDG-PET are (a) staging of regional lymph node (17); (b) predicting response to chemotherapy or radiotherapy; (c) detecting local recurrence or distant metastasis (6); and (d) detection of unknown primaries in patients with upper neck lymph node metastasis. Primary malignancies of the nasopharynx are often understaged during clinical examination. Five percent of patients with head and neck squamous cell carcinoma who present with metastatic cervical nodes had no identifiable primary site on clinical examination. FDG- PET has been shown to reveal unknown primary tumors in approximately 30-50% of patients with metastatic disease to the lymph nodes in the neck who had no detectable primary tumor during clinical examination (18). However, the tumor size may be exaggerated due to the scatter phenomenon of radiation in FDG-PET images. Also, intense FDG uptake may obscure the uptake by adjacent enlarged lymph nodes, thereby resulting in false-negative results. In this study, of the 20 NPC enrolled, primary NPC without FDG uptake was found in 5 patients, no definite mucosa change of the nasopharynx was found on CT images in 5 patients, an intense FDG uptake without mucosa change in the nasopharynx was observed in 3 patients, mucosa thickening without FDG uptake in the nasopharynx was found in 3 patients and no FDG uptake or mucosa change was found in the nasopharynx in 2 patients. Therefore, a fused PET/CT is likely to result in more accurate tumor staging than PET or CT alone (19). FDG-PET is superior to CT and MRI for detecting cervical lymph nodal metastases (16, 20). However, FDG- PET has poor anatomical resolution and cannot accurately assess lymph node size. Although PET is better suited for assessing metastasis in lymph nodes that appear morphologically normal according to size criteria, CT is more accurate for assessing the level and size of nodes, the number of nodes in conglomerate nodal masses and the presence of extracapsular spread (17, 20). Therefore, fused PET/CT is likely to result in more accurate nodal staging than PET alone or CT alone. In generally, false-positive results may occur with FDG- PET because of infections, physiologically increased uptake in structures such as the tonsils, salivary glands and muscles, uptake in reactive non-neoplastic lymph nodes and, recent surgery, noninfectious inflammation and granulation at the surgical site (21). The major advantage of CT is to help correctly differentiate the physiological uptake that would otherwise be mistaken for tumor on PET alone. Fused images with PET/CT allow for direct correlation between FDG metabolic uptake and anatomic structures, thus reducing false-positive results. Standardized uptake values (SUVs) may be useful in distinguishing between malignant and benign FDG uptake, although there is overlap between them. It is important to evaluate the patient s clinical history and physical findings to distinguish between benign and malignant FDG uptake (16, 20). False-negative results with PET/CT may occur under the following conditions: (a) the patient was scanned too early after completion of chemotherapy or radiation therapy; (b) malignancy was present in structures with a physiologically elevated metabolism; (c) tumor size was below the resolution of the current PET/CT scanner; or (d) the tumor was low in cell density or low metabolic rate of FDG. A delayed view with prolonged emission time may be helpful in detecting tumors (22). CT has the ability to depict abnormal anatomy and abnormal contrast enhancement due to pathological changes. However, CT is limited in the depiction of pathological changes in normal-sized structures, such as lymph nodes or of lesions that do not have good contrast with the surrounding tissue, resulting in a reduced sensitivity. In this study, we did not use contrast medium on the examinees because the use of intravenous contrast material may complicate the analysis by introducing additional attenuation-correction artifacts (17, 20). Our data showed that PET/CT is a valuable imaging tool in patients for initial staging and re-staging of NPC. The falsenegative and false-positive rates may be decreased by fused PET/CT. PET/CT is strongly recommended as a standard 1476

7 Chen et al: Fused PET/CT in Nasopharyngeal Carcinoma Patients clinical imaging modality in the staging of NPC and in the detection of recurrent disease after radiotherapy. It provides valuable information for localizing primary tumors in patients with neck nodal metastases from an unknown primary. References 1 Huang DP: Epidemiology of nasopharyngeal carcinoma. Ear Nose Throat J 69: , Vokes EE, Liebowitz DN and Weichselbaum RR: Nasopharyngeal carcinoma. Lancet 350: , Smythe WR: Treatment of stage I and II non-small-cell lung cancer. Cancer Control 8: , Forastiere A, Koch W, Trotti A and Sidransky D: Head and neck cancer. N Engl J Med 345: , Underhill TE, McGuirt WF and Williams DW III: Advances in imaging head and neck tumors. Curr Opin Otolaryngol Head Neck Surg 8: 91-97, Kao CH, ChangLai SP, Chieng PU, Yen RF and Yen TC: Detection of recurrent or persistent nasopharyngeal carcinomas after radiotherapy with 18-fluoro-2-deoxyglucose positron emission tomography and comparison with computed tomography. J Clin Oncol 16: , Gambhir SS, Czernin J, Schwimmer J, Silverman DH, Coleman RE and Phelps ME: A tabulated summary of the FDG PET literature. J Nucl Med 42: 1S-93S, Tsai MH, Huang WS, Tsai JJ, Chen YK, Changlai SP and Kao CH: Differentiating recurrent or residual nasopharyngeal carcinomas from post-radiotherapy changes with 18-fluoro-2- deoxyglucose positron emission tomography and thallium-201 single photon emission computed tomography in patients with indeterminate computed tomography findings. Anticancer Res 23: , Antoch G, Vogt FM, Freudenberg LS, Nazaradeh F, Goehde SC, Barkhausen J, Dahmen G, Bockisch A, Debatin JF and Ruehm SG: Whole-body dual-modality PET/CT and whole-body MRI for tumor staging in oncology. JAMA 290: , Syed R, Bomanji JB, Nagabhushan N, Hughes S, Kayani I, Groves A, Gacinovic S, Hydes N, Visvikis D, Copland C and Ell PJ: Impact of combined (18) F-FDG PET/CT in head and neck tumours. Br J Cancer 92: , Branstetter BF, Blodgett TM, Zimmer LA, Snyderman CH, Johnson JT, Raman S and Meltzer CC: Head and neck malignancy: is PET/CT more accurate than PET or CT alone? Radiology 235: , Schoder H, Yeung HW, Gonen M, Kraus D and Larson SM: Head and neck cancer: clinical usefulness and accuracy of PET/CT image fusion. Radiology 231: 65-72, Hong RL, Ting LL, Ko JY, Hsu MM, Sheen TS, Lou PJ, Wang CC, Chung NN and Lui LT: Induction chemotherapy with mitomycin, epirubicin, cisplatin, fluorouracil, and leucovorin followed by radiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol 19: , Yen TC, Chang JT, Ng SH, Chang YC, Chan SC, Lin KJ, Lin WJ, Fu YK and Lin CY: The value of 18 F-FDG PET in the detection of stage M0 carcinoma of the nasopharynx. J Nucl Med 46: , Yen RF, Hong RL, Tzen KY, Pan MH and Chen THH: Wholebody 18 F-FDG PET in recurrent or metastatic nasopharyngeal carcinoma. J Nucl Med 46: , Ng SH, Joseph CT, Chan SC, Ko SF, Wang HM, Liao CT, Chang YC, Lin WJ, Fu YK and Yen TC: Clinical usefulness of 18 F-FDG PET in nasopharyngeal carcinoma patients with questionable MRI findings for recurrence. J Nucl Med 45: , Kao CH, Hsieh JF, Tsai SC, Ho YJ, Yen RF, ChangLai SP and Chieng PU: Comparison of 18 F-2-fluoro-2-deoxyglucose positron emission tomography and computed tomography in detection of cervical lymph node metastases of nasopharyngeal carcinoma. Ann Otol Rhinol Laryngol 109: , Assar OS, Fischbein NJ, Caputo GR, Kaplan MJ, Price DC, Singer MI, Dillon WP and Hawkins RA: Metastatic head and neck cancer: role and usefulness of FDG PET in locating occult primary tumors. Radiology 210: , Pelosi E, Messa C, Sironi S, Picchio M, Landoni C, Bettinardi V,Gianolli L, Del Maschio A, Gilardi MC and Fazio F: Value of integrated PET/CT for lesion localisation in cancer patients: a comparative study. Eur J Nucl Med Mol Imaging 31: , Nishioka T, Shiga T, Shirato H, Tsukamoto E, Tsuchiya K, Kato T, Ohmori K, Yamazaki A, Aoyama H, Hashimoto S, Chang TC and Miyasaka K: Image fusion between 18 FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas. Int J Radiat Oncol Biol Phys 53: , Nakamoto Y, Tatsumi M, Hammoud D, Cohade C, Osman MM and Wahl RL: Normal FDG distribution patterns in the head and neck: PET/CT evaluation. Radiology 234: , Chen YK and Kao CH: Metastatic hepatic lesions are detected better by delayed imaging with prolonged emission time. Clin Nucl Med 30: , Received October 31, 2005 Revised January 9, 2006 Accepted January 23,