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1 Orl Oncology 47 (2011) Contents lists vilble t ScienceDirect Orl Oncology journl homepge: Comprison of PET/CT nd MRI for the detection of bone mrrow invsion in ptients with squmous cell crcinom of the orl cvity Ysser G. Abd El-Hfez,b, Chien-Cheng Chen c, Shu-Hng Ng c, Chien-Yu Lin d, Hung-Ming Wng e, Sheng-Chieh Chn, I-How Chen f, Shing-Fu Hun f, Chung-Jn Kng f, Li-Yu Lee g, Chih-Hung Lin h, Chun-T Lio f,, Tzu-Chen Yen, Nucler Medicine Deprtment, Moleculr Imging Center, Chng Gung Memoril Hospitl, Chng Gung University, Toyun, Tiwn, ROC b Rdiotherpy nd Nucler Medicine Deprtment, South Egypt Cncer Institute, Assiut University, Egypt c Deprtment of Dignostic Rdiology, Chng Gung Memoril Hospitl, Chng Gung University, Toyun, Tiwn, ROC d Deprtment of Rdition Oncology, Chng Gung Memoril Hospitl, Chng Gung University, Toyun, Tiwn, ROC e Deprtment of Medicl Oncology, Chng Gung Memoril Hospitl, Chng Gung University, Toyun, Tiwn, ROC f Deprtment of Otorhinolryngology, Hed nd Neck Surgery, Chng Gung Memoril Hospitl, Chng Gung University, Toyun, Tiwn, ROC g Deprtment of Pthology, Chng Gung Memoril Hospitl, Chng Gung University, Toyun, Tiwn, ROC h Deprtment of Plstic nd Reconstructive Surgery, Chng Gung Memoril Hospitl, Chng Gung University, Toyun, Tiwn, ROC rticle info summry Article history: Received 24 December 2010 Received in revised form 11 Februry 2011 Accepted 11 Februry 2011 Keywords: Bone invsion Orl cncer Mndible Mxill Squmous cell crcinom Positron emission tomogrphy (PET)/ computed tomogrphy (CT) Fluorodeoxyglucose Mgnetic resonnce imging Our im ws to retrospectively ssess the dignostic performnce from combined positron emission tomogrphy/computed tomogrphy (PET/CT) nd mgnetic resonnce imging (MRI) for the detection of bone mrrow invsion of the mndible or mxill in ptients with orl cvity squmous cell crcinom (OCSCC). A totl of 114 ptients with OCSCC, rising from or butting the upper or lower lveolr ridge, underwent stging PET/CT nd MRI studies before surgery. The possibility of bone mrrow invsion on PET/CT nd MRI ws grded retrospectively on 5-point score. Histopthology ws tken s the reference stndrd. Sensitivity, specificity, predictive vlues nd likelihood rtios were clculted. Clinicl fctors ffecting the performnce, like tumor origin nd dentte sttus were lso explored. PET/CT ws found to be more specific thn MRI (83% vs. 61%, respectively, p = ) but less sensitive (78% vs. 97%, respectively, p = ). Dentte sttus nd tumor origin ffected the dignostic performnce of PET/CT. In ptients with positive MRI, sensitivity nd specificity of PET/CT were 78% nd 100% in dentte ptients with lveolr ridge tumors, 75% nd 80% in dentte ptient with buccl tumors, 90% nd 33% in edentulous ptients with lveolr ridge tumors nd 0% nd 63% for edentulous ptients with buccl tumors, respectively. PET/CT is more specific thn MRI nd cn be used to complement the role of MRI. A negtive MRI result cn confidently exclude the presence of bone mrrow invsion, while in ptients with positive MRI findings, negtive PET/CT my be useful to rule out bone mrrow invsion in dentte ptients. Ó 2011 Elsevier Ltd. All rights reserved. Introduction The preopertive detection of bone mrrow invsion involving both the mxill nd mndible in ptients with squmous cell crcinom of the orl cvity (OCSCC) is criticl to the plnning of surgery nd postopertive mngement. It is ccepted tht when Corresponding uthors. Address: Deprtment of Otorhinolryngology, Hed nd Neck Surgery, Hed nd Neck Oncology Group, Chng Gung Memoril Hospitl, Chng Gung University, 5 Fu-Hsin Street, Gweishn, Toyun 333, Tiwn, ROC. Tel.: x8466; fx: (C.-T. Lio). Deprtment of Nucler Medicine, Moleculr Imging Center, Chng Gung Memoril Hospitl, Chng Gung University, 5 Fu-Hsin Street, Gweishn, Toyun 333, Tiwn, ROC. Tel.: x2744; fx: (T.-C. Yen). E-mil ddresses: lioct@dm.cgmh.org.tw (C.-T. Lio), yen1110@dm.cgmh. org.tw (T.-C. Yen). the mndibulr bone mrrow is free of tumor, mndibulr continuity cn usully be preserved nd mrginl mndibulectomy my be oncologiclly sufficient for miniml corticl erosion. 1,2 However, once bone mrrow invsion hs occurred, much more extensive nd lengthy opertion involving segmentl mndibulectomy plus bone reconstruction is necessry to provide n dequte cler bony mrgin. 3,4 When tumor invdes the mxillry mrrow spces, greter resection mrgin nd extensive reconstruction my be required. Computed tomogrphy (CT) nd mgnetic resonnce imging (MRI) re the stndrd modlities used to evlute primry tumor sttus in ptients with OCSCC. In generl, MRI is preferred becuse of its superior soft-tissue contrst resolution, 5 but its dignostic ccurcy in the detection of bone mrrow invsion is still mtter of debte Indeed, few pst studies hve shown high sensitivity /$ - see front mtter Ó 2011 Elsevier Ltd. All rights reserved. doi: /j.orloncology

2 Y.G. Abd El-Hfez et l. / Orl Oncology 47 (2011) nd specificity, 10,11 wheres others demonstrted high sensitivity but low specificity. 6 9 The preopertive detection of bone mrrow invsion my be theoreticlly enhnced with the use of combined positron emission Tble 1 Generl chrcteristics of the study prticipnts. Prmeter n % Sex Mle 2 (1.8) Femle 112 (98.2) Age, yers Medin (rnge) 50 (29 77) Antomicl subsites Tongue 6 (5.3) Floor of the mouth 6 (5.3) Buccl 47 (41.2) Alveolr ridge 39 (34.2) Hrd plte 2 (1.8) Retromolr trigone 14 (12.3) Dentte sttus Dentte 64 (56.1) Edentulous 50 (43.9) Metl-relted rtifcts No 53 (46.5) Yes 61 (53.5) Clinicl T-sttus T1 3 (2.6) T2 34 (29.8) T3 15 (13.2) T4 62 (54.4) Pthologicl T-sttus T1 3 (2.6) T2 38 (33.3) T3 14 (12.3) T4 59 (51.8) Pthologicl bone mrrow invsion No 77 (67.5) Yes 37 (32.5) Site of mrrow invsion Mndible 34 (29.8) Mxill 2 (1.8) Both 1 (0.9) Bone mngement MM b 16 (14) SM c 36 (31.6) MM + MX d 36 (31.6) SM + MX 26 (22.8) The numbers in prentheses indicte the rnge of the dt. Unless otherwise indicted, vlues re given s numbers of ptients (percentges in prentheses). b Mrginl mndibulectomy. c Segmentl mndibulectomy. d Mxillectomy. tomogrphy (PET)/CT imging tht detects metbolic nomlies vi differences in tissue glucose uptke. However, reltively few studies hve ddressed this question The purpose of our study ws therefore to ssess nd compre the dignostic ccurcy of PET/CT nd MRI in detecting bone mrrow invsion involving both the mxill nd mndible in ptients with OCSCC nd lso to explore possible clinicl fctors, which might ffect the performnce of these modlities. Mterils nd methods Ptients This retrospective study ws pproved by the Institutionl Review Bord t our hospitl, nd ll ptients provided written informed consent. The study popultion consisted of 114 ptients with newly dignosed OCSCC who were referred to our hospitl between June 2006 nd December Inclusion criteri were dignosis of SCC, originting from the lveolr ridge (upper or lower) or other orl cvity subsites but involving the lveolr ridge, preopertive PET/CT nd MRI stging studies nd surgicl mngement. All ptients underwent mrginl or segmentl mndibulectomy, either with or without inferior mxillectomy. Segmentl mndibulectomy ws performed in the presence of: () bone mrrow invsion detected by conventionl modlities (CT/MRI nd orthopntogrm); (b) n edentulous trophic mndible; nd (c) tumors close to the mndible precluding mrginl resection. Tumor mrgins were sent for frozen section. If frozen section mrgins were positive, dditionl tissue ws excised nd sent for frozen section in order to ensure tht mrgins were tumor-free. The surgicl defects were repired with primry closure or reconstructed by free or locl flps. Ptients were clssified s edentulous if they lost one or more tooth t the site of the tumor, either the upper or lower lveolr ridge, s seen in the immedite post-surgicl specimens. Histopthology The surgicl specimens were fixed in 10% formlin solution nd declcified for period of one dy. Specimens were inked nd soft tissue ws removed to grossly evlute the bone. In the presence of gross bone invsion, representtive 5 mm section of the bone tumor interfce ws prepred. In the bsence of gross invsion, 2 sections (5 mm ech) were tken from the site with the deepest tumor invsion. All sections were H&E stined in 5 lm thickness nd reviewed by single pthologist who ws wre of the clinicl stging. Tble 2 Dignostic performnces of PET/CT nd MRI for the detection of bone mrrow invsion in ptients with squmous cell crcinom of the orl cvity. Imging modlity FN TP b TN c FP d Totl Sensitivity Specificity PPV f NPV g Accurcy LR+ h LR i PET/CT (71 86) 83 (76 90) 69 (61 78) 89 (83 95) 82 (74 89) 4.6 ( ) 0.3 ( ) MRI j 97 (94 100) 61 (52 70) 55 (46 65) 98 (95 101) 73 (65 81) 2.5 ( 0.4 to 5.4) 0.0 ( 0.3 to 0.4) b c d e f g h i j Flse negtive. True positive. True negtive. Flse positive. Confidence intervl. Positive predictive vlue. Negtive predictive vlue. Positive likelihood rtio. Negtive likelihood rtio. Two cses hd severe metl rtifcts nd could not be interpreted on MRI.

3 290 Y.G. Abd El-Hfez et l. / Orl Oncology 47 (2011) PET/CT imging Ptients were sked to fst for t lest 6 h before the strt of the PET study. Serum glucose level ws determined t the time of intrvenous injection of 370 MBq (10 mci) of 18 F-FDG nd ll the ptients hd glucose concentrtions <200 mg/dl. PET/CT imges were cquired using combined PET/CT scnner (Discovery ST 16, GE Helthcre). To minimize FDG physiologicl uptke, speech or swllowing ws forbidden unless strictly necessry from the intrvenous injection of FDG to the completion of the study. No muscle relxnts were used. Before PET cquisition, helicl CT imges were obtined for ntomicl locliztion/ttenution correction (AL/AC) from the hed to the proximl thigh Tble 3 Differences in sensitivity, specificity nd ccurcy between PET/CT nd MRI for the detection of bone mrrow invsion in ptients with squmous cell crcinom of the orl cvity. Modlity PET/CT p FN TP b TN c FP d MRI FN e TP b f TN c g FP d b c d e f g Flse negtive. True positive. True negtive. Flse positive. Difference in sensitivity by McNemr s test. Difference in specificity by McNemr s test. Difference in re under the curve (AUC) by ROC curve nlysis. ccording to stndrdized protocol. The following settings were used: trnsverse 10-mm collimtion, 16-slice mode, 120 kvp, uto mas (rnge ), 0.5 s tube rottion, 17.5 mm/s tble speed nd pitch No intrvenous contrst mterils were dministered for the CT scn. CT dt ws resized from mtrix to mtrix to mtch the PET dt to llow for imge fusion nd genertion of CT trnsmission mps. Emission dt were cquired from the hed to the proximl thigh t 50 min fter intrvenous injection of the trcer. Dt were cquired in two-dimensionl mode (3 min per tble position). The study ws performed with the rms positioned long the side of the body nd hed holder ws used. We did not perform dedicted regionl study for the hed nd neck region in ll prticipnts following the whole-body cquisition. After CT-bsed AC, PET imges were reconstructed with n ordered subset expecttion mximiztion itertive reconstruction lgorithm (4 itertions nd 15 subsets). Slice thickness ws 3.75 mm. All dt were then trnsferred to the processing worksttion (Xeleris Worksttion, GE Helthcre). CT scns were displyed with bone lgorithm nd fused PET/CT imges were evluted in the xil, sgittl, nd coronl plnes in the defult window level. No threshold ws pplied. Stndrdized uptke vlue (SUV) ws defined s the highest ctivity concentrtion per injected dose per body weight (in kilogrms) fter correction for rdioctive decy. Bone mrrow invsion ws considered to be present if there ws focl FDG uptke within the mrrow spces contiguous with the primry tumor. MRI imging All ptients were exmined using either 1.5-T MRI (Inter, Philips Medicl Systems) or 3.0-T (Mgnetom Trio, Siemens Tble 4 Assocition of different clinicl chrcteristics with sensitivity, specificity nd positive likelihood rtios of PET/CT in 65 ptients with squmous cell crcinom of the orl cvity nd positive MRI for mrrow invsion. Chrcteristic n FN TP b TN c FP d Sensitivity p Specificity p LR+ f Antomicl subsite g Buccl (21 65) * 62 (40 83) ( 3.5 to 5.7) Alveolr ridge (77 99) 63 (46 79) 2.3 ( 2.8 to 7.5) Differentition Well/moderte (68 89) (54 79) ( 1.6 to 6.3) Poor (34 99) 80 (52 108) 3.3 ( 9.1 to 15.8) Metl-relted rtifcts No (63 94) (63 94) ( 3.3 to 10.6) Yes (64 91) 60 (44 76) 1.9 ( 2.5 to 6.4) Dentl sttus Dentte (61 93) (74 99) * 5.8 ( 2.9 to 14.4) Edentulous (65 92) 50 (34 66) 1.6 ( 2.4 to 5.6) Primry tumor size (cm) 64.8 (ROC) (75 96) (52 81) ( 2.2 to 7.4) > (47 86) 75 (57 93) 2.7 ( 3.9 to 9.3) SUV of the primry tumor (73 98) (60 90) ( 3.1 to 9.9) > (58 87) 62 (45 78) 1.9 ( 2.6 to 6.4) Ptient groups g Dentte lveolr ridge (52 108) * # i Dentte buccl (48 102) * 67 (37 96) ( 6.9 to 11.4) Edentulous lveolr ridge (78 102) < * 40 (21 59) ( 3.3 to 6.3) Edentulous buccl h (26 88) 0.0 ( ) b c d e f g h i Flse negtive. True positive. True negtive. Flse positive. Confidence intervl. Positive likelihood rtio. Only the two mjor subsites (buccl nd lveolr ridge) were nlyzed for this prmeter. Reference group. Flse-positive rte equls zero, consequently positive likelihood rtio (LR+) is infinity. * Sttisticlly significnt difference.

4 Y.G. Abd El-Hfez et l. / Orl Oncology 47 (2011) Helthcre, Erlngen, Germny) MRI scnner. The MRI exmintions were performed using hed-nd-neck synergic coil to cover the entire neck from the skull bse to the thorcic inlet. T2- nd T1- weighted fst/turbo spin echo sequences were pplied in the xil plne. Post gdolinium contrst enhnced T1-weighted fst/turbo spin echo sequences with ft sturtion were pplied in the xil, coronl, nd sgittl plnes t 4-mm slice thickness. All dt were rchived in DICOM formt nd trnsferred to stnd-lone worksttion for processing. All of the imging nlysis ws performed on picture rchiving nd communiction system (PACS) worksttion (Centricity 1.0; GE Helthcre, Milwukee, WI, USA). Tumor invsion into the bone mrrow ws dignosed by replcement of the mrrow ft of the involved mndible or mxill by contiguous tumors with bnorml T1 hypointensity, T2 hyperintensity, nd definite contrst enhncement. Bone erosion ws considered to be present if there ws ny irregulr bone thinning while bone destruction ws dignosed in the presence of complete corticl bone loss. MR imge distortions or rtifcts close to the mxill or mndible were crefully recorded. Imge interprettion PET/CT imges were reviewed by one nucler physicin (6 yers experience in generl nucler medicine, 2 yers in PET/CT) nd one hed-nd-neck rdiologist (20 yers experience), nd consensus ws reched vi joint reevlution of the imges. All MRI dt were red by n independent hed-nd-neck rdiologist (7 yers experience), who ws blinded to PET/CT findings. The reders were wre of tumor origin nd side. The imges were evluted qulittively for the presence of bone mrrow invsion on 5-point score, in which score of 0 indicted tht bone mrrow invsion ws definitely bsent; score of 1, bone mrrow invsion ws probbly bsent; score of 2, mbiguous cses chrcterized by corticl bone erosion in the bsence of overt bone destruction; score of 3, bone mrrow invsion ws probbly present; nd score of 4, bone mrrow invsion ws definitely present. A score of 2 or less ws considered negtive. SUV ws not considered in the imge interprettion. Sttisticl nlysis Receiver operting chrcteristic (ROC) curve nlysis ws performed to ssess discrimintive power of PET/CT nd MRI for bone mrrow invsion. Histopthology ws tken s the reference stndrd; sensitivity, specificity, predictive vlues nd likelihood rtios were clculted for expressing test performnce. Ctegoricl dt nd pired redings were nlyzed using the Chi-squred (v 2 ) test nd the McNemr s test, respectively. We determined the optiml cutoff vlues for tumor size nd mximum SUV by ROC nlysis bsed on the presence of bone mrrow invsion. SUVmx ws compred in two sub-groups using Student s t-test for independent smples. All sttisticl nlyses were two-sided nd the significnce level ws fixed t Tble 5 Flse-negtive nd flse-positive results of PET/CT for the detection of bone mrrow invsion in ptients with squmous cell crcinom of the orl cvity. No. Antomicl subsite Dentl sttus Metlrelted rtifcts Differentition ct pt b Tumor size (cm) SUV c primry tumor Bone mngement Mrrow invsion 1 AR d Dentte + MD f T4 T SM i + 2 FN l 4 TP n 2 Buccl Edentulous + MD f T4 T SM i +MX j + 2 FN l 4 TP n 3 AR d Edentulous + MD f T4 T SM i + 0 FN l 4 TP n 4 Buccl Edentulous + WD g T4 T SM i +MX j + 2 FN l 4 TP n 5 Buccl Edentulous + PD h T4 T SM i +MX j + 2 FN l 4 TP n 6 Buccl Dentte MD f T4 T SM i +MX j + 2 FN l 4 TP n 7 AR d Edentulous MD f T4 T SM i + 0 FN l 4 TP n 8 RMT e Dentte MD f T4 T SM i + 0 FN l 4 TP n 9 RMT e Edentulous WD g T4 T SM i +MX j 4 FP m 4 FP m 10 Buccl Edentulous + MD f T4 T MM k +MX j 4 FP m 4 FP m 11 AR d Edentulous + MD f T4 T SM i 4 FP m 4 FP m 12 Buccl Edentulous + MD f T4 T SM i 3 FP m 4 FP m 13 Buccl Edentulous MD f T4 T SM i +MX j 3 FP m 4 FP m 14 Buccl Dentte + MD f T4 T MM k +MX j 4 FP m 4 FP m 15 Buccl Dentte + WD g T4 T MM k +MX j 3 FP m 4 FP m 16 AR d Edentulous WD g T4 T SM i +MX j 3 FP m 4 FP m 17 AR d Edentulous + PD h T4 T MM k +MX j 4 FP m 4 FP m 18 Buccl Dentte + WD g T2 T MM k +MX j 4 FP m 2 TN o 19 AR d Edentulous + WD g T2 T MM k 3 FP m 2 TN o 20 AR d Edentulous + PD h T3 T SM i +MX j 4 FP m 2 TN o 21 Buccl Edentulous MD f T2 T MM k +MX j 3 FP m 1 TN o b c d e f g h i j k l m n o Clinicl tumor sttus. Pthologicl tumor sttus. Stndrdized uptke vlue. Alveolr ridge. Retromolr trigone. Modertely differentited. Well differentited. Poorly differentited. Segmentl mndibulectomy. Mxillectomy. Mrginl mndibulectomy. Flse negtive. Flse positive. True positive. True negtive. PET/CT score PET/CT result MRI score MRI result

5 292 Y.G. Abd El-Hfez et l. / Orl Oncology 47 (2011) Results Generl chrcteristics One hundred fourteen ptients with squmous cell crcinom of the orl cvity were enrolled (Tble 1). The medin time intervl between dignostic studies (PET/CT nd MRI) nd surgery ws 2 dys (rnge: 1 21 dys for PET/CT; 1 56 dys for MRI). The two studies (PET/CT nd MRI) were done within 4 weeks of ech other, except for one ptient, who underwent MRI 54 dys before PET/CT. Histopthologicl exmintion reveled the presence of mrrow invsion in 37 ptients (32.5%). More thn 85% of the ptients hd the hbits of cigrette smoking nd betel quid chewing. The predominnt tumor origins were buccl mucos (41.2%) nd lveolr ridge (34.2%). Sixty-one ptients hd metl-relted rtifcts; in two of them, the MRI ws severely distorted nd uninterpretble. These two ptients were excluded from ny subsequent comprtive nlyses. The presence of metl rtifcts did not ffect the performnce of PET/CT. However, we encountered single flse negtive result due to misregistrtion between PET nd CT. The FDG ctivity seemed to be displced by few millimeters from the site of CT-detected corticl erosion (scored 2 by consensus). Dignostic performnce MRI showed the highest sensitivity nd negtive predictive vlues (97% nd 98%, respectively) with only one flse negtive result (Tble 2). However, low specificity nd positive predictive vlues were encountered (61% nd 55%, respectively). Twenty-nine flsepositive results were seen. Sensitivity nd specificity of PET/CT were 78% nd 83% respectively with 8 flse negtive nd 13 flsepositive results. Combined PET/CT ws significntly more specific (83% vs. 61%, p = ) nd less sensitive thn MRI (78% vs. 97%, p = ). The overll ccurcy ws comprble (Tble 3). Clinicl fctors ffecting PET/CT performnce Tumor origin nd dentte sttus were found to ffect the dignostic performnce of PET/CT. Bone mrrow invsion ws significntly higher in edentulous ptients thn in dentte ptients (23/ 50 vs. 14/64, p = 0.009). In dentte ptients, PET/CT hd higher Figure 1 Imging findings of 56-yer-old mn with dignosis of squmous cell crcinom of the left buccl mucos, (A) coronl fused PET/CT imge of the tumor mss without FDG uptke within the mrrow cvity of the mndible. The corresponding non-contrst-enhnced CT imge (B) demonstrted the presence of corticl bone erosion only. Post gdolinium contrst enhncement coronl T2 (C) nd T1 (D) MR weighted imges showed left buccl-gum cncer, with hyperintensity nd enhncement in the bone mrrow of left mndible, suggesting bone mrrow invsion. Pthologicl results were positive for mrrow invsion.

6 Y.G. Abd El-Hfez et l. / Orl Oncology 47 (2011) Figure 2 Imging findings of 41-yer-old mn with dignosis of squmous cell crcinom of the right buccl mucos, (A) trnsxil fused PET/CT imge of the tumor mss tht shows intense FDG uptke (SUVmx = 22.3) nd it violtes the bone boundry of the mxill. The corresponding coronl non-contrst-enhnced CT imge (B) demonstrted the presence of corticl discontinuity, nd lso evidence of some periodontl disese. The lesion scored 4 on PET/CT by consensus. Post gdolinium contrst enhncement xil T2 (C) nd T1 (D) MR weighted imges showed right upper gum cncer without bnorml signl intensity t right mxill, suggestive of no bone mrrow invsion. Pthologicl result ws negtive for mrrow invsion. specificity (94% vs. 63%, p = ) nd positive likelihood rtio ([LR+], 13.1 vs. 2.1). A totl of 13 flse-positive results were encountered, 10 of them were seen in edentulous ptients. Interestingly, ll the flse-positive results were in ptients who hd the hbit of betel quid chewing. Alveolr ridge nd buccl mucos represented the two mjor tumor origins in our study (n = 39 nd 47, respectively). Tumors originting in the lveolr ridge were significntly ssocited with more bone mrrow invsion (25/39 vs. 7/47, p < ). Considering only these two subsites, PET/CT offered significnt dvntges in terms of sensitivity (88% vs. 43%, p < ) nd positive predictive vlue (81% vs. 30%, p < ) in lveolr ridge tumors compred with buccl tumors. There ws trend towrd higher sensitivity, specificity, nd LR+ when the size of the tumors ws less thn 4.8 cm or the SUV vlues less thn mg/ml. MRI ws positive in 65 ptients; 29 of them were flsely positive. Given this high flse positive rte, we tried to identify subgroup of ptients with MRI-positive findings in whom PET/CT my be useful (Tble 4). Among these 65 ptients, MRI gve flse-positive results in 53.6% of dentte ptients (15/28). PET/CT successfully excluded the presence of bone mrrow invsion in 13 of these 15 cses. In lveolr ridge tumors (n = 33), PET/CT lso excluded disese in 5 out of 8 flsely positive MRI results. Flse-negtive nd flse-positive results of PET/CT for the detection of bone mrrow invsion in this study re shown in Tble 5. Discussion Assessment of fcil bones invsion by OSCC is importnt for hed nd neck surgicl oncologists before tretment plnning. In the pst, we lrgely relied on the findings from physicl exmintion plus conventionl imges, such s pnorex X-ry, CT nd/or MRI with unstisfying results, especilly when ptients hd certin degree of dentl problems. Studies from other groups hve shown tht both PET/CT nd SPECT/CT my be cliniclly useful, with vrying degrees of sensitivity ( %, 92%, %, %) nd specificity (85 100%, 86%, %, %) for PET/CT, SPECT/CT, CT, nd MRI, respectively In this study, we found sensitivity nd specificity of 78% nd 83% for PET/CT, nd 97% nd 61% for MRI, respectively. Our dt suggest tht PET/CT my complement the role of MRI for dignosing bone mrrow invsion in ptients with orl cvity cncer. A negtive MRI

7 294 Y.G. Abd El-Hfez et l. / Orl Oncology 47 (2011) scn could confidently exclude the presence of mrrow invsion in ptients with OCSCC. However, positive results obtined with this modlity cnnot lwys be considered true positive nd PET/CT scn my help to mke the dignosis. We encountered single flse negtive MRI result. Our findings concerning the high negtive predictive vlue of MRI were well in line with the results of previous studies In our experience, there re two possible resons to explin the higher flse-positive results. First, Tiwn is n endemic re for betel quid chewing, nd orl cncers in ssocition with trismus with subsequent poor orl hygiene re commonly seen in clinicl prctice. 16,17 Betel quid chewing ws observed in 87% of ptients in this study. There were 28 flse-positive results out of 99 ptients chewing betel quid compred to 1/15 ptients not hving this hbit (positive predictive vlue = 51% vs. 88%, p = 0.02). Second, ll the studied tumors were involving the lveolr ridge, which could elicit locl inflmmtory response. It hs been reported tht MRI my yield flsely positive results in inflmmtory odontogenic disese. 18 We encountered 8 flse-negtive PET/CT findings (Tble 5); in 4 of them, the non-optimized CT intended for AC/AL ws unble to detect sites of miniml bone brekthrough. We ssume tht more optimized CT protocol for the hed nd neck region my dd to the dignostic yield of PET/CT. The other 4 flse-negtive PET/CT results were either due to low trcer uptke in the bone mrrow (ptients # 1 nd # 6), misregistrtion of the CT nd PET imges (Ptient # 5) or retrction of the edentulous lveolr ridge (Ptient # 2), which misled the locliztion of FDG uptke (Fig. 1). PET/CT showed significntly higher flse positive rte in edentulous compred to dentte ptients (37% vs. 6%, p = ). The reson for tht my be explined by: () Repeted episodes of periodontitis re common in edentulous ptients which my show vidity to FDG (Fig. 2). 19 (b) The men SUV of the primry tumor ws significntly higher in edentulous compred to dentte ptients (15.2 vs. 12.6, p = 0.036). High FDG uptke my produce spillover effect, leding to overestimtion of the exct tumor extension (Fig. 3). 20 In this study, the sensitivity nd positive predictive vlue of PET/CT were significntly lower for buccl compred to lveolr ridge tumors; however, the negtive predictive vlue, LR+ nd overll ccurcy remined comprble. Of note, mong ll the flse-positive results encountered by PET/CT, the men SUV within buccl tumors ws higher, though not significntly, thn tht seen in lveolr ridge tumors (17.8 vs. 12.3, p = 0.1). Our study is not without importnt limittions. A hed nd neck PET/CT study ws not performed in ll prticipnts following the whole-body cquisition. No contrst medi were used routinely for the CT portion of PET/CT. Moreover, the CT portion of PET/CT ws not optimized for dignostic purpose. In ddition, the inevitble prtil volume effect in PET/CT should be considered. Finlly, this study is retrospective single-reder nlysis, which reflects single center experience. Strengths of our report include the lrge smple size, the use of histopthologicl exmintion s the gold stndrd for comprison, nd the homogeneity of dignosis nd tretment plns. Figure 3 Imging findings of 43-yer-old mn with dignosis of squmous cell crcinom of the right buccl mucos, (A) coronl fused PET/CT imge of the tumor mss tht shows intense FDG uptke (SUVmx = 22) nd it violtes the bone boundry of the mndible. The corresponding coronl non-contrst-enhnced CT imge (B) demonstrted the presence of corticl erosion in the edentulous lveolr socket nd possible brekthrough. Post gdolinium contrst enhncement coronl T2 (C) nd T1 (D) MR weighted imges showed right buccl-gum cncer with mild bone erosion on the edentte lveolr socket. No bnorml signl intensity t right mndible, indicting bone cortex invsion without bone mrrow involvement. Pthologicl result ws positive for both periostel nd corticl invsion but negtive for mrrow invsion.

8 Y.G. Abd El-Hfez et l. / Orl Oncology 47 (2011) Conclusion PET/CT is more specific thn MRI nd cn be used to complement the role of MRI. A negtive MRI result cn confidently exclude the presence of bone mrrow invsion in ptients with squmous cell crcinoms of the orl cvity. In dentte ptients with positive MRI findings, negtive PET/CT my be useful to rule out bone mrrow invsion in dentte ptients. PET/CT hd significntly higher sensitivity nd positive predictive vlue in lveolr ridge tumors compred to buccl mucos tumors. Conflict of Interest None declred. Acknowledgements This work ws supported in prt by Grnt-in-Aid for FDG PET Reserch in Orl Cncer from Chng Gung Memoril Hospitl-Linkou (CMRPG370062). References 1. Brttelbort SW, Bhn SL, Ariyn SA. Rim mndibulectomy for cncer of the orl cvity. Am J Surg 1987;154(4): Ord RA, Srmdi M, Ppdimitrou J. A comprison of segmentl nd mrginl bony resection for orl squmous cell crcinom involving the mndible. J Orl Mxillofc Surg 1997;55(5): discussion Politi M, Cost F, Robiony M, Rinldo A, Ferlito A. Review of segmentl nd mrginl resection of the mndible in ptients with orl cncer. Act Otolryngol 2000;120(5): Wx MK, Bscom DA, Myers LL. Mrginl mndibulectomy vs segmentl mndibulectomy: indictions nd controversies. Arch Otolryngol Hed Neck Surg 2002;128(5): Ahmd A, Brnstetter BF. CT versus MR: still tough decision. Otolryngol Clin North Am 2008;41(1): Rjesh A, Khn A, Kendll C, Hyter J, Cherrymn G. Cn mgnetic resonnce imging replce single photon computed tomogrphy nd computed tomogrphy in detecting bony invsion in ptients with orl squmous cell crcinom? Br J Orl Mxillofc Surg 2008;46(1): Tsue TT, McCulloch TM, Girod DA, Couper DJ, Weymuller Jr EA, Glenn MG. Predictors of crcinomtous invsion of the mndible. Hed Neck 1994;16(2): Vn Cnn EM, Koole R, Oyen WJ, de Rooy JW, de Wilde PC, Slootweg PJ, et l. Assessment of mndibulr invsion of squmous cell crcinom by vrious modes of imging: constructing dignostic lgorithm. Int J Orl Mxillofc Surg 2008;37(6): vn den Brekel MW, Runne RW, Smeele LE, Tiwri RM, Snow GB, Cstelijns JA. Assessment of tumour invsion into the mndible: the vlue of different imging techniques. Eur Rdiol 1998;8(9): Bolzoni A, Cppiello J, Pizz C, Peretti G, Mroldi R, Frin D, et l. Dignostic ccurcy of mgnetic resonnce imging in the ssessment of mndibulr involvement in orl-orophryngel squmous cell crcinom: prospective study. Arch Otolryngol Hed Neck Surg 2004;130(7): Vidiri A, Guerrisi A, Pellini R, Mnciocco V, Covello R, Mttioni O, et l. Multidetector row computed tomogrphy (MDCT) nd mgnetic resonnce imging (MRI) in the evlution of the mndibulr invsion by squmous cell crcinoms (SCC) of the orl cvity. Correltion with pthologicl dt. J Exp Clin Cncer Res 2010;29: Bbin E, Desmonts C, Hmon M, Benteu H, Hitier M. PET/CT for ssessing mndibulr invsion by introrl squmous cell crcinoms. Clin Otolryngol 2008;33(1): Goerres GW, Schmid DT, Schuknecht B, Eyrich GK. Bone invsion in ptients with orl cvity cncer: comprison of conventionl CT with PET/CT nd SPECT/ CT. Rdiology 2005;237(1): Gu DH, Yoon DY, Prk CH, Chng SK, Lim KJ, Seo YL, et l. CT, MR, (18)F-FDG PET/CT, nd their combined use for the ssessment of mndibulr invsion by squmous cell crcinoms of the orl cvity. Act Rdiol 2010;51(10): Pentenero M, Cistro A, Brus M, Ferrris MM, Pezzuto C, Crnino R, et l. Accurcy of 18F-FDG-PET/CT for stging of orl squmous cell crcinom. Hed Neck 2008;30(11): Lio CT, Chng JT, Wng HM, Ng SH, Hsueh C, Lee LY, et l. Anlysis of risk fctors of predictive locl tumor control in orl cvity cncer. Ann Surg Oncol 2008;15(3): Lin CY, Wng HM, Kng CJ, Lee LY, Hung SF, Fn KH, et l. Primry tumor site s predictor of tretment outcome for definitive rdiotherpy of dvncedstge orl cvity cncers. Int J Rdit Oncol Biol Phys 2010;78(4): Imizumi A, Yoshino N, Ymd I, Ngumo K, Amgs T, Omur K, et l. A potentil pitfll of MR imging for ssessing mndibulr invsion of squmous cell crcinom in the orl cvity. Am J Neurordiol 2006;27(1): Shimmoto H, Ttsumi M, Kkimoto N, Hmd S, Shimosegw E, Murkmi S, et l. (18)F-FDG ccumultion in the orl cvity is ssocited with periodontl disese nd picl periodontitis: n initil demonstrtion on PET/CT. Ann Nucl Med 2008;22(7): Soret M, Bchrch SL, Buvt I. Prtil-volume effect in PET tumor imging. J Nucl Med 2007;48(6):

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