Tc-Methylene Diphosphonate Planar Skull Bone Scan in Detecting Basal Skull Lesions in Nasopharyngeal Carcinoma

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1 99m Tc-Methylene Diphosphonate Planar Skull one Scan in Detecting asal Skull Lesions in Nasopharyngeal Carcinoma Ming-Che Wu 1, Nan-Tsing Chiu 2, i-fang Lee 2 1 Department of Nuclear Medicine, MacKay Memorial Hospital, Taipei, Taiwan 2 Department of Nuclear Medicine, Cheng-Kung University Hospital, Tainan, Taiwan Received 10/2/2000; revised 11/17/2000; accepted 12/2/2000. For correspondence or reprints contact: Ming-Che Wu, M.D., Department of Nuclear Medicine, MacKay Memorial Hospital, 92, Section 2, Chung-San North Road, Taipei 10449, Taiwan. Tel: (886) ext. 3369, Fax: (886) ext. 2925, leon@ms2.mmh.org.tw ackground: The authors evaluated the performance of 99m Tc-MDP planar skull bone scan in detecting basal skull lesions in patients with nasopharyngeal carcinoma, proposed a strategy for effective use of planar and SPECT skull bone scan in the imaging of NPC patients, and evaluated the influence of increased mastoid bone uptake on the interpretation of planar skull bone scans. Methods: One hundred and seventeen patients with nasopharyngeal carcinoma underwent whole body, bilateral planar skull, and skull SPECT bone scans. The findings for the skull base and mastoid bone on planar and SPECT images as interpreted by three nuclear medicine physicians from different hospitals were compared to reach a consensus. The SPECT consensus was then used as the final result for performance evaluation of the planar images. Results: The planar skull bone scan had a sensitivity of 78%, a specificity of 77%, an accuracy of 78%, a positive predictive value of 94%, and a negative predictive value of 45%. The consensus results and performance between the patients with and without mastoid lesions showed no significant statistical differences. Conclusion: We recommend NPC patients with negative or equivocal findings on planar skull bone scan undergo skull SPECT for further evaluation while those with positive findings may save the SPECT unless otherwise indicated. Increased uptake in mastoid bone does not adversely affect the reading of planar skull bone scan. Key words: bone scan, nasopharyngeal carcinoma, SPECT, skull base nn Nucl Med Sci 2001;14:1-6 Single-photon emission computed tomography (SPECT) bone scan has been reported to better detect and define lesions in deep skull bones [1-5] than X-ray computed tomography, magnetic resonance imaging, and planar scintigraphy and has been suggested to be included in the routine work-up of patients with nasopharyngeal carcinoma (NPC) [5], which tends to invade the skull base. Nevertheless, in a busy clinic with limited facilities and resources it is not always possible to carry out SPECT for every patient suspected to have deep-seated basal skull lesions and that may explain why planar skull lateral images have long been relied upon for assessment of possible direct basal skull invasion by NPC [6]. While most nuclear medicine practitioners may be satisfied with planar images and confident of their image reading, the true value of this practice remains unknown. The aim of this study was to evaluate the performances of planar skull bone scans using SPECT results as the gold standard and proposed a strategy for effective use of planar and SPECT skull bone scan in the imaging of NPC patients. The influence of increased mastoid bone uptake on the scan reading was also evaluated.

2 Wu MC et al Materials and Methods One hundred and seventeen patients with pathologically proved nasopharyngeal carcinoma referred to the Department of Nuclear Medicine at MacKay Memorial Hospital for bone scan from March 1996 to November 1997 were included in this study. The patients were aged from 15 to 70 years (mean: 47.0) and consisted of 91 males and 26 females. Forty-four patients were newly diagnosed cases and had received no treatment so far while the other seventythree had had radiotherapy ranging from 3 days to 10 years before the bone scan, of which eighteen had it within the past 12 months. etween 2 and 4 h after intravenous injection of 740 Mq (20 mci) of 99m Tc-methylene diphosphonate (MDP), each patient underwent whole body, skull bilateral, and skull SPECT bone scan using an Elscint SP-6 HR large field-of view gamma camera with a low-energy all-purpose collimator. Each planar skull image was acquired on a 256u256 matrix with total counts of 500,000. The SPECT data were acquired with 64u64 matrices for 30 s per frame at an angle step of 6 degrees in a circular orbit. Transaxial, coronal, and sagittal slices were reconstructed using a Hanning filter of cutoff frequency 2.3 and power factor 5 with attenuation correction. ll skull bilateral (117 pairs of left and right lateral) and SPECT images were interpreted independently by three nuclear medicine physicians from hospitals in different districts of this country. The physicians had no idea of which planar image correlating to which SPECT because all images were shuffled randomly and reviewed in no specific order. The reading of all lateral planar images was completed before the SPECT images to eliminate any influence of the interpreters residual memories from reading SPECT upon their positive-finding rate when interpreting planar images. The observers received no specific instructions in interpreting either planar images or SPECT. They simply used whatever experience or common sense acquired from former practice that ranged from 7 to 11 years. The results of each set of planar or SPECT images were recorded for each observer and then compared to reach a consensus. The SPECT consensus was then used as the final result, with which the results of planar images for each observer and their consensus were compared to evaluate their respective performance in sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. To evaluate the effect of increased mastoid bone uptake on the scan interpretation, the patients with increased uptake in mastoid areas as shown on skull SPECT were divided from those without and the performances of each observers and their consensus for both groups were analyzed again in the same way as described above. Results On SPECT, the observers failed to achieve unanimity in 12 patients, of which 11 were categorized as positive and one as negative by consensus. The overall results showed 95 patients with increased uptake in the skull base, either in the clivus or sphenoid bone, and 22 patients with negative findings. The prevalence is The results of planar images for observer,, C and the consensus as compared to the SPECT are listed in Table 1. The corresponding performance is shown in Table 2. Fisher exact test shows significant statistical difference in the frequency of true positive and false negative between observers and C (P = ) as well as between and C (P = ) but not between and. There is no significant statistical difference among the observers in other categories. The consensus had a sensitivity of 78%, a specificity of 77%, an accuracy of 78%, a positive predictive value of 94%, and a negative predictive value of 45%. Of the three observers, C had the highest sensitivity (90%), accuracy (86%), and negative predictive value (60%) but with the lowest specificity (68%) while had the lowest sensitivity (64%), accuracy (68%), and negative predictive value (35%) but the highest specificity (82%) similar to that of observer, who had a medial performance in other categories except the positive predictive value (95%), which was the highest among the three though apparently not significant. Figure 1 shows an example planar skull image that was reported positive by one observer but turned out to be negative on SPECT. Figure 2 shows a planar skull image that was reported negative by one observer but was positive on SPECT. Figure 3 shows a planar skull image with unanimous false negative results. The skull SPECT results showed 40 patients with increased uptake on the mastoid bone, either unilateral or nn Nucl Med Sci 2001;14:1-6 Vol. 14 No. 1 March

3 Skull bone scan in NPC Table 1. Reading results of planar images SPECT Positive Negative TP FN TN FP C Consensus ,,C: observers TP: true positive; FN: false negative; TN: true negative; FP: false positive Table 2. Performance of interpreters and consensus Figure 1. The planar skull image () was reported positive by one observer but was negative on SPECT () % Sens Spec ccu PPV NPV C Consensus ,,C: observers Sens: sensitivity; Spec: specificity; ccu: accuracy; PPV: positive predictive value; NPV: negative predictive value Table 3. Performance of interpreters and consensus on patient groups with and without increased mastoid uptake %M+/M- Sens Spec ccu PPV NPV 76/71 82/82 78/73 92/96 56/32 73/61 82/82 75/64 91/95 53/26 C 97/86 73/64 90/83 90/93 89/44 Consensus 83/76 82/73 83/75 92/94 64/33 M+: patient groups with increased mastoid uptake M-: patient groups without increased mastoid uptake,,c: observers Sens: sensitivity; Spec: specificity; ccu: accuracy; PPV: positive predictive value; NPV: negative predictive value Figure 2. planar skull image () reported negative by one observer was positive on SPECT () bilateral, while 77 patients without apparent abnormality. mong those with abnormality in the mastoid bone, 29 patients (29/40, 72.5%) also had abnormality in the skull base. In patients without mastoid bone lesions, 66 subjects (66/77, 85.7%) had skull base lesions. The consensus results of planar images for both groups showed no statistical differences (P = 0.083, Fisher exact test). The performance results of planar skull bone scan on each group are shown in Table 3. The consensus had a sensitivity of 83% versus 76% on patient groups with and without mastoid bone lesions, a specificity of 82% versus 73%, an accuracy of 83% versus Figure 3. planar skull image () reported negative by all observers was positive on SPECT () 75%, a positive predictive value of 92% versus 94%, and a negative predictive value of 64% versus 33%. The sensitivity, specificity, positive predictive rate, and negative predictive rate between the two groups also showed no significant statistical differences, though the negative predictive values of the two groups seemed quite different (with a low P value of 2001;14:

4 Wu MC et al Figure 4. patient with mastoid lesions that had no adverse effects on the results of the planar skull image (), which were true negative as shown on SPECT () 0.094, Fisher exact test), which we think may be caused by their different prevalence (72.5% versus 85.7%). Figure 4 shows a patient with mastoid lesions that had no adverse effects on the interpretation of the planar skull bone scan. Discussion Increased uptake of bone-seeking radiopharmaceuticals in the radiation therapy portal may be seen if bone imaging is carried out shortly after the radiation therapy [7,8]. Nevertheless, decreased uptake usually follows within 2-3 months and a return to normal osseous activity may not occur until 12 months or later [9]. s most osseous infiltration of malignancy results in increased osseous uptake, we only looked for increased uptake in the skull base as evidence of possible direct tumor invasion and regarded any suspected decreased uptake as normal or the consequence of radiotherapy. While increased skull base uptake may simply reflect radiotherapy in patients imaged less than 2 months after irradiation, the same findings in patients imaged longer after do not necessarily indicate malignancy involvement. Tumor invasion of basal skull is related to staging of nasopharyngeal carcinoma and is of prognostic importance [10]. Since bone biopsy is impractical, if not impossible, our main interest lies in whether there is increased uptake in the skull base suggesting the possibility of direct tumor invasion or recurrent tumor rather than the true causes of the increased uptake, which may be difficult to determine without long-term follow-up and may not be as important for the planning of future patient management. s shown in Table 1 and 2, observer C apparently adopted a more aggressive attitude toward reporting positive findings and had the highest true positive and lowest false negative findings with the highest sensitivity (90%), accuracy (86%), and negative predictive value (60%). On the contrary, observer had the highest false negative findings (34), the lowest sensitivity (64%), accuracy (68%), and negative predictive value (35%), reflecting a tendency to underreport positive findings. Observer seemed to have a reporting tendency between the two extremes but still more towards that of observer as reflected by the frequency of true positive and false negative findings and low negative predictive value (41%). The performance of consensus looked like an average of that of each observer in most categories except for the negative predictive value, which was an unimpressive 45%. The mostly better performance of observer C may be indicative of the virtues of aggressively reporting positive. Increased uptake in the mastoid bone, either reflecting serous otitis media [11,12] or radiotherapy, is not an infrequent finding in bone scans of NPC patients. On lateral skull images the uptake in the mastoid lesion may overlap that in the skull base if the lesion is large and intense enough or the image is a little bit oblique rather than true lateral and presumably causes false positive or false negative reading for the skull base. However, the analyses suggest that the presence of mastoid lesions does not affect the observers reading in a statistically significant way and even slightly, though not significant statistically, improve their performance in sensitivity, specificity, accuracy, and negative predictive value while the differences in positive predictive value are apparently insignificant and at most reflecting marginal higher false positive rate in some patients with mastoid lesions. Conclusion With a high prevalence of increased skull base uptake, planar skull bone scan shows high positive and low negative predictive values, we therefore recommend NPC patients with negative or equivocal findings on planar skull bone scan undergo skull SPECT for further evaluation while those with positive findings may save the SPECT unless otherwise indicated. lternatively, we would suggest adopting a low quali- nn Nucl Med Sci 2001;14:1-6 Vol. 14 No. 1 March

5 Skull bone scan in NPC tative threshold for reporting positive and reserving skull SPECT for those with equivocal findings on planar skull images. Moreover, the presence of mastoid lesions does not cause adverse effects on the interpretation of skull lateral bone scan and in its own right may not warrant further evaluation by skull SPECT. References 1. Israel O, Jerushalmi J, Frenkel, Kuten, Front D. Normal and abnormal single photon emission computed tomography of the skull: comparison with planar scintigraphy. J Nucl Med 1988;29: Yui N, Togawa T, Kinoshita F, Shimada F, kiyama Y. ssessment of skull base involvement of nasopharyngeal carcinoma by bone SPECT using three detectors system. Kaku Igaku 1992;29: Keogan MT, ntoun N, Wraight EP. Evaluation of the skull base by SPECT. comparison with planar scintigraphy and computed tomography. Clin Nucl Med 1994;19: Jansen P, Pillay M, de ruin HG, et al. 99m Tc-SPECT in the diagnosis of skull base metastasis. Neurology 1997;48: Lee CH, Wang PW, Chen HY, Lui CC, Su CY. ssessment of skull base involvement in nasopharyngeal carcinoma: comparisons of single-photon emission tomography with planar bone scintigraphy and X-ray computed tomography. Eur J Nucl Med 1995;22: Liu RS, Chen YK, Yeh SH, et al. Hypertrophic pulmonary osteoarthropathy in nasopharyngeal carcinoma: an early sign of pulmonary metastasis. Nucl Med Commun 1995;16: King M, Weber D, Casarett GW, urgener F, Corriveau O. study of irradiated bone. Part II. Changes in Tc-99m pyrophosphate bone imaging. J Nucl Med 1980;21: King M, Casarett GW, Weber D, urgener F, O Mara RE, Wilson G. study of irradiated bone. III. Scintigraphic and radiographic detection of radiationinduced osteosarcomas. J Nucl Med 1980;21: Hattner RS, Hartmeyer J, Wara WM. Characterization of radiation-induced photopenic abnormalities on bone scans. Radiology 1982;145: allenger JJ, Snow J, Jr. Otorhinolaryngology: head and neck surgery. 15th ed. altimore: Williams & Wilkins; 1996: Silver J, Mawad ME, Hilal SK, Sane P, Ganti SR. Computed tomography of the nasopharynx and related spaces. Part II: Pathology. Radiology 1983;147: Silver J, Sane P, Hilal SK. CT of the nasopharyngeal region. Normal and pathologic anatomy. Radiol Clin North m 1984;22: ;14:

6 Wu MC et al -99m-MDP m-MDP % 78% 77% 78% 94% 2001;14: (02) (02) leon@ms2.mmh.org.tw nn Nucl Med Sci 2001;14:1-6 Vol. 14 No. 1 March