THE COMPARISON OF THREE DIFFERENT MALIGNACY EVALUATION CRITERIA OF CERVICAL LYMPH NODES IN ORAL CAVITY CANCER USING F-18 FDG PET-CT

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1 Acta Medica Mediterranea, 2015, 31: 183 THE COMPARISON OF THREE DIFFERENT MALIGNACY EVALUATION CRITERIA OF CERVICAL LYMPH NODES IN ORAL CAVITY CANCER USING F-18 FDG PET-CT ERDEM SÜRÜCÜ 1, YUSUF DEMIR 1, BERNA DEĞIRMENCI POLACK 2 1 Yüzüncü Yil University, School of Medicine, Department of Nuclear Medicine, Van - 2 Dokuz Eylül University, School of Medicine, Department of Nuclear Medicine, Izmir, Turkey ABSTRACT Aims: Our aim was to evaluate the diagnostic role of Fluorine-18 fluorodeoxyglucose Positron emission tomography-computed tomography (F-18 FDG PET-CT) using three different criteria published in the literature and to compare the diagnostic value of these three parameters in patients with oral cavity cancers (OCC). Materials and methods: 16 patients (4 female; 12 male, years) were included in this study. Malignancy in the lymph nodes was evaluated according to these 3 criteria: 1: Visual assessment 2: The ratio of maximum standard uptake value (SUVmax) in tumor/ adjacent muscle tissue (T/M), 3: SUVmax adjusting to the size of lymph nodes. The histopathological evaluation of the surgery was recorded according to the neck levels. The sensitivity, specificity, negative predictive values (NPV) and positive predictive values (PPV) of F-18 FDG PET-CT for each malignancy criteria and receiver operating characteristic (ROC) curves were obtained for SUVmax and T/M. Results: Histopathological evaluations revealed 5 patients had metastatic lymph nodes (N+) whereas 11 patients had benign lymph nodes (N-). 14 of 43 lymph nodes that were visualized in CT of F 18 FDG PET-CT were evaluated as malignant whereas 29 of 43 lymph nodes were evaluated as benign. The average of SUVmax and T/M ratios of visually malignant lymph nodes were 7.67±4.95 and 7.10±3.18, respectively. The average of SUVmax and T/M ratios of visually benign lymph nodes were 1.69±0.43 and 1.49±0.48, respectively. The highest sensitivity, specificity, NPV and PPV were obtained in the criteria of T/M ratios with the threshold value of SUVmax (regardless from the size) as 3.4 and T/M ratio as 3.2 which is obtained from our population using ROC curve, 93% sensitivity, 96% specificity were calculated. Conclusion: This study indicates that F 18 FDG PET-CT is a reliable method for the correct evaluation of primary tumor and N staging in OCC. This study showed that T/M ratios in the lymph nodes could be used to evaluate malignancy with a highest diagnostic accuracy. Key words: F-18 FDG PET-CT, oral cavity cancers, lymph node, malignancy. Received June 18, 2014; Accepted October 02, 2014 Introduction According to the cases and deaths, the number of new cases of oral cavity and pharynx cancer was 11.0 per 100,000 men and women per year. Deaths from this cancer were 2.5 per 100,000 men and women per year. 5 years surviving rate is 62.7% in the data between Oral cavity and pharynx cancer, 31% are diagnosed at the local stage, 47% of patients have regional disease (local lymph node metastasis), 18% has distant metastasis. The 5-year survival for oral cavity and pharynx cancer is 82.7%, 60.5%, and 37.3% in localized, regional and distant disease, respectively. The estimated new cases and deaths were approximately and 8000, respectively. They are mostly epidermoid carcinomas (90 95%). They are more common in men and mostly diagnosed between the sixth and seventh decade of life (1). Significant proportion of patients (57%) have lymph node metastasis (N+) at the diagnosis and this reduces survival by 50% (2). Therefore, lymphatic metastasis is the most important prognostic factor. Early diagnosis provide high cure rate in patients with OCC. Therefore, the initial diagnosis and lymph node staging is very important for treatment and prognosis.

2 184 Erdem Sürücü, Yusuf Demir et Al Ultrasonography (USG), computed tomography (CT) and magnetic resonance (MR) generally is used for differentiation of malignant and benign lymph nodes (LNs). However, the false negative case rate in MR and CT is approximately 10-30% (3). F-18 FDG PET-CT was being started to be used for the evaluation of metabolic situation of LNs for last 1-2 decades. Additionally, distant metastasis can be evaluated with PET-CT more accurately. Even, it can help to detect primary tumor in the metastatic cancer of unknown primary origin (4). The sensitivity, specificity and accuracy of these modalities in detecting lymph node metastasis are summarized in Table 1 (5,6). Modality sensitivity specificity accuracy USG MR CT PET Table 1: Sensitivity, specificity and accuracy of PET, USG, MR, in detecting lymph node metastasis. There are different criteria in PET-CT for malignancy evaluation in the patients with head and neck cancers in the literature (visual and semiquantative evaluations) (7,8,9). Our aim was to evaluate the diagnostic role of F-18 FDG PET-CT using three different criteria published in the literature and to compare the diagnostic value of these three parameters in the patients with OCC. Matherials and methods Patients Sixteen patients (4 female; 12 male, age range, years) having a diagnosis of oral cavity SCC (squamos cell carsinoma) with biopsy of primary oral cavity lesions were included in this study between the years The patients that were treated neoadjuvant chemotherapy or radiotherapy (to the neck areas), patients with previous surgery history to the neck, patients with a secondary malignancy, diabetes and distant metastasis were excluded from the study. Our local institutional ethic committee in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments approved this study; informed consent was obtained from all the patients. FDG-PET-CT examinations and evaluation Whole-body FDG-PET/CT was performed with a combined PET/CT scanner (Philips GEMI- NI TF Netherlands) with 3D mod. After at least 6h of fasting, patients underwent PET-CT one hour after the intravenous injection of 8-12mCi ( MBq) F-18 FDG. An experienced radiologist on head and neck radiology evaluated the diagnostic CT or MR images. In the PET-CT, malignancy in the lymph nodes was evaluated according three criteria: 1. Visual assessment scoring according to the FDG uptake on a 5-point scale as follows: 0= No abnormal uptake, 1=benign, 2=probably benign, 3=probably malignant, 4=definitely malignant. Scores of 3 and 4 were considered to be positive results for tumor involvement (7). 2. The ratio of SUVmax in tumor/ adjacent muscle tissue (T/M), the cut-off value of 4.4 was accepted as a lymph node involvement (8) 3. SUVmax adjusting to the size of lymph nodes, Cut-off SUVmax 1.9 for <10 mm lymph nodes, Cut-off SUVmax 2.5 for mm lymph nodes, Cut-off SUVmax 3.0 and higher for 15 mm lymph nodes were accepted as a lymph node involvement (9). The final decision was made by histopathological evaluations. Statistical analysis SPSS (Statistical Package for the Social Sciences) for Windows 11.0 program (SPSS 11, Chicago, IL, USA) was used for statistical evaluation and descriptive analysis. Normal distribution of quantitative data was evaluated with histogram curves, Kolmogorov Smirnov and Shapiro Wilk tests. ROC (receiver operating characteristic) curves were obtained for SUVmax and T/M for the differentiation of malignant and benign LNs. Statistically significant level was accepted as at p<0.05. The sensitivity, specificity, negative (NPV) and positive predictive values (PPV) in F-18 FDG PET-CT were calculated for each criteria. Results Descriptive characteristics Mean FDG dosage given to 16 patients (12 Male, 4 Female) was 10.1±0.9. Eight of 16 patients had tongue cancer, four of 16 had buccal mucosal cancer, two of 16 had floor of mouth and two of 16 had lip cancer. Ipsilateral lymph node dissections

3 The comparision of three different malignacy evaluation criteria of cervical lymph nodes were performed in 14 of 16 patients, whereas bilateral lymph node dissections were performed in two of 16 patients. There were totally 32 malignant lymph nodes that were proven histopathologically. 5/32 (% 16) LNs were harvested from level 1, 17/32 (% 53) LNs from level 2, 9/32 (%28) LNs from level 3 and 1/32 (%0.03) LN from level 4. F-18 FDG PET-CT findings The primary tumors and cervical lymph nodes of 16 patients were evaluated with F-18 FDG PET- CT and diagnostic CT or MR. The average SUVmax of primary tumors was 8.76± lymph nodes that were observed in CT of PET-CT were evaluated regardless of the size. 14 of 43 LNs were malignant and 29 of 43 LNs were benign. Mean± SD of SUVmax and T/M ratios were shown in Table 2. SUVmax of primary tumor SUV max of visually malignant LNs SUV max of visually benign LNs SUV max of histopathologically malignant LNs SUV max of histopathologically benign LNs T/M ratios of visually malignant LN T/M ratios of visually benign LN Min Max Mean±SD ± ± ± ± ± ± ±0.48 The sensitivity, specificity, NPV, PPV and accuracy of F-18 FDG PET-CT for each criteria and CT/MR in patient basis for the LN evaluation were demonstrated in Table 4. sensitivity specificity NPV PPV accuracy Visually assesment T/M ratio SUVmax adjusting to the size of LN CT/MR Table 4: The sensitivity, specificity, NPV, PPV and accuracy of F-18 FDG PET-CT for each criteria and CT/MR in patient basis. In the ROC analysis, with the threshold value of SUVmax as 3.4 regardless from the size for malignancy evaluation which is obtained from our population, 93% sensitivity, 96% specificity (Area under the curve (AUC) =0.990, p<0.00) and with the threshold value of T/M ratio as 3.2 %93 sensitivity, %96 specificity (AUC=0.968, p<0.00) were calculated (Table 5) (figure 1). SUVmax (regardless from the size) Cut off Sensitivity specificity T/m ratio Table 5: Sensitivity and specificity values of the cut-off values for SUVmax and T/M ratio obtained from ROC curve in the evaluation of benign and malignant LN. T/M ratios of histopathologically malignant LN ±3.44 T/M ratios of histopathologically benign LN ±0.71 Table 2: Mean± SD of SUVmax and T/M ratios in primary tumor and LNs. SUVmax of malignant and benign LNs according to the neck levels were given in Table 3. Malign LN Benign LN SUVmax T/M ratios SUVmax T/M ratios 1.level 8.70± ± ± ± level 9.72± ± ± ± level 7.53± ± ± ± level ± ±0.32 Table 3: Mean ± SD SUVmax of malignant and benign lymph nodes according to the neck levels. Fig. 1: ROC curves for SUVmax and T/M ratio. Discussion LN involvement by the tumor is the most important factor for prognosis in the patients with OCC. Metastatic LN involvement reduces survival up to 50% in the patients. Inadequate staging and treatment may cause high recurrence rate (10).

4 186 Erdem Sürücü, Yusuf Demir et Al Wooglar et al. showed 28% micrometastasis in patients with clinical N0 disease, so the initial diagnosis and staging are very important in patient s management. It was reported that intranodal tumor burden in LN metastasis is more restrictive criteria than nodal size (5, 7, 11). Intranodal tumor burden may result in high metabolism in the tumor. There are different criteria in PET-CT for malignancy evaluation in patients with head and neck cancers in the literature (visual and semiquantitative evaluations). In our study we compared the sensitivity, specificity, NPV, PPV, and accuracy of three criteria published in literature for LN evaluation in F-18 FDG PET-CT. In a study with visual assessment, Shu-Hang et al. demonstrated that the sensitivity, specificity, NPV, PPV, and accuracy were 75, 93, 94, 72, 90% for PET; 53, 95, 89, 69, 86% for just CT/MR and 78, 95, 95, 77 and 91% for CT/MRI+F-18 FDG PET, respectively (7). In our study, the sensitivity, specificity, NPV, PPV, and accuracy of visual assessment were 100%, 72, 100, 63, 81, respectively. Shu-Hang et al used the same visual evaluation criteria as we used in our study but the number of patients of Shu-Hang study was higher than our study and also PET-CT device in their study is different from device in our study that resulted different values. Kubota et al. found the sensitivity, specificity, NPV, PPV, and accuracy of T/M ratio in F-18 FDG PET 88, 78, 91, 70, 81% and 75, 30, 67, 39, 47% in CT/MR, respectively (8). In our study, the sensitivity, specificity, NPV, PPV, and accuracy of T/M ratio in F-18 FDG PET-CT were found as 100%. T/M ratio reached the highest value in between three different evaluation methods. Although the method of adjusting SUVmax to the size of lymph nodes has been reported 79% sensitivity and specificity 99% (9), we found the lowest sensitivity and specificity (54% and 36%) in our patient group. However, if the number of LNs smaller than 10 mm is higher in our study than their study, our sensitivity and specificity values might be lowered secondary to remaining under the resolution limit of LNs. As a solution, it can be useful to make partial volume correction with phantom studies. The sensitivity and NPV of three criteria were higher than CT/MR. The specificity of visual assessment was similar with CT/MR. However, The specificity, PPV and accuracy of T/M ratio were higher than CT/MR. It has been reported that the specificity of F-18 FDG PET in LN evaluation was higher than CT/MR( 12-17). Only two studies reported relatively low specificity values than the others (18, 19). However, these two studies had small number of patients (38 and 12 patients) compared to other studies with higher specificity. The specificity of our study was also low which is most probably related to the small number of patients; this was the major limitation of our study. In our study, we analyzed 43 number of LNs in 16 of patients. When we reviewed the literature, the studies investigating the diagnostic value of evaluation methods in F-18 FDG PET-CT to find the optimal method for metastatic involvement of LNs, one or two different methods were described and compared in each study. To our knowledge our study was the first comparing three published different LN evaluation method in F-18 FDG PET-CT in oral cavity cancer. The threshold values of SUVmax (regardless from the size) and T/M ratio 3,4 and 3.2 respectively in order to differentiate malignancy in LNs in our study. At these threshold levels, 93% sensitivity and 96% specificity were obtained by using ROC curve. (Area under the curve (AUC) =0.990, p<0.00). Given to the high sensitivity and specificity we obtained, the threshold values can also be used for differentiation of LN malignancy Conclusions According to literature, if the cut-off T/M ratio was set as 4.4, sensitivity and specificity were 75% and 82%, respectively. In our study, we found 100% sensitivity and specificity at this threshold value. In our study, according to ROC analysis, if the cut-off T/M ratio was set as 3.2, sensitivity and specificity were 93% and 96%, respectively. Although the sensitivity of visual assessment in our study was higher than that the published in the literature, T/M ratios of the LN can be used to evaluate malignancy with a highest sensitivity and specificity values. The method adjusting SUVmax to the size seems to have high sensitivity and NPV but lowest specificity, PPV and accuracy. Further studies with the high number of patients are needed.

5 The comparision of three different malignacy evaluation criteria of cervical lymph nodes References 1) Cancer statistics. oralcav.html 2) Lindberg R. Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer 1972; 29: ) Van den Brekel MW, Stel HV, Castelijns JA, et al. Cervical lymph node metastasis: assessment of radiologic criteria. 4) Surucu E, Ascioglu M.S, Sengoz T, Demir Y, Durak H. The value of F-18 FDG PET/CT for detecting primary foci in the metastatic cancer of unknown primary origin. Eastern Journal of Medicine (2014); 19: ) Stuckensen T, Kovacs AF, Adams S, Baum RP. Staging the neck in patients with oral cavity squamous cell carcinomas, a prospective comparison of PET, ultrasound, CT and MRI. J Cranio-Maxillofac Surg 2000; 28: ) Mahmood. F. Mafee, Galdino E. Valvassori, Minerva Becker, İmaging of the Head and Neck. İkinci baski ) Ng SH, Yen TC, Chang JT, Chan SC, Ko SF, Wang HM, Lee LY, Kang CJ, Wong AM, Liao CT. Prospective study of [18F] fluorodeoxyglucose positron emission tomography and computed tomography and magnetic resonance imaging in oral cavity squamous cell carcinoma with palpably negative neck. J Clin Oncol Sep 20; 24(27): ) Kubota K, Yokoyama J, Yamaguchi K, Ono S, Qureshy A, Itoh M, Fukuda H. FDG-PET delayed imaging for the detection of head and neck cancer recurrence after radio-chemotherapy: comparison with MRI/CT. Eur J Nucl Med Mol Imaging Apr; 31(4): ) Murakami R, Uozumi H, Hirai T, Nishimura R, Shiraishi S, Ota K, Murakami D, Tomiguchi S, Oya N, Katsuragawa S, Yamashita Y. Impact of FDG-PET/CT imaging on nodal staging for head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys Jun 1; 68(2): ) Woolgar JA, Vaughan ED, Scott J, et al., Pathological findings in clinically false-negative and false-positive neck dissections for oral carcinoma. Ann R Coll Surg Engl. 1994; 76: ) Crippa F, Leutner M, Belli F, et al. which kinds of lymph node metastases can FDG-PET detect? a clinical study in melanoma. J Nucl Med. 2004; 41: ) Wong WL, Chevretton EB, McGurk M, Hussain K, et al. A prospective study of PET-FDG imaging for the assessment of head and neck squamous cell carcinoma. Clin Otolaryngol 1997; 22: ) Laubenbacher C, Saumweber D, Wagner-Manslau C, Kau RJ, et al. Comparison of fluorine-18-fluorodeoxyglucose PET, MRI, and endoscopy for staging head and neck squamous cell carcinomas. J Nucl Med 1995; 36: ) Adams S, Baum RP, Stuchensen T, Bitter K, et al. Prospective comparison 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: ) Benchaou M, Lehman W, Slosman DO, et al. The role of FDG PET in the pre-operative assessment of N staging in head and neck cancer. Acta Otolaryngol 1996; 116: ) Bailet JW, Abemayor E, Jabour BA, et al. Positron emission tomography: a new, precise imaging modality for detection of primary head and neck tumors and assessment of cervical adenopathy. Laryngoscope. 1992; 102: ) Jabour BA, Choi Y, Hoh CK, et al. Extracranial head and neck: PET imaging with 2-[F-18] fluro-2-deoxy-dglucose and MR imaging correlation. Radiology. 1993; 186: ) Braams JW, Pruim J, Freling NJM, Nikkels PG, 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: ) Hlawitschka M, Neise E, Bredow J, Beuthien-Baumann B, Haroske G, Eckelt U, Franke WG. FDG-PET in the pretherapeutic evaluation of primary squamous cell carcinoma of the oral cavity and the involvement of cervical lymph nodes. Mol Imaging Biol Jan; 4(1): 91-8 Correspoding author ERDEM SÜRÜCÜ, MD Van Yüzüncü Yil University School of Medicine Department of Nuclear Medicine 65000, Van (Turkey)