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Vol. 4, No. 2, 2004 The Journal of Applied Research 222 scan results, CT and MRI results, treat- ments performed, tumor recurrence, and clinical outcome. This data was ana- lyzed to determine the utility of FDG- PET in the identification of primary tumors and/or recurrent disease. Results: FDG-PET identified 100% of all primary tumors examined with initial diagnostic intent (n=8). In addition, 1 case of lymphoid hyperplasia was cor- rectly identified as nonmalignant. Of 22 PET scans performed for tumor surveil- lance, 16 scans identified recurrent dis- ease and 5 scans were correctly interpreted as negative. One scan showed an area of increased metabo- lism at the base of tongue suspicious for malignancy that later proved to be an inflammatory process (1 false positive). Conclusion: FDG-PET was an effective imaging modality in the evaluation of Fluorodeoxyglucose Positron Emission Tomography in the Evaluation of Tumors of the Nasopharynx, Paranasal Sinuses, and Nasal Cavity Brendan C. Stack, Jr, MD, FACS * Val J. Lowe, MD Robert V. Lane, MD * Division of Otolaryngology-HNS, Penn State University Milton S. Hershey Medical Center, Hershey, Pennsylvania. Department of Nuclear Medicine and PET facility, Mayo Clinic Foundation, Rochester, Minnesota. Department of Otolaryngology-HNS, University of Missouri Health Sciences Center, Columbia, Missouri. This study was presented at the 5th International Conference on Head and Neck Cancer in San Francisco, California, July 29-August 2, 2000. KEY WORDS: Positron emission tomography, paranasal sinuses, nasopharynx, and skull base ABSTRACT Introduction: The purpose of this study was to review the clinical utility of 2- [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the diagnostic evaluation of a series of patients with tumors of the nasophar- ynx, paranasal sinuses, and nasal cavity. Methods: The study group included 16 patients from a single institution who underwent a total of 31 FDG-PET scans for the evaluation of various histologic types of masses of the nasopharynx, nasal cavity, and paranasal sinuses for diagnosis and or surveillance. A review of the patients’ medical records was per- formed in order to obtain all data including tumor type and location, PET

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Vol. 4, No. 2, 2004 • The Journal of Applied Research222

scan results, CT and MRI results, treat-ments performed, tumor recurrence,and clinical outcome. This data was ana-lyzed to determine the utility of FDG-PET in the identification of primarytumors and/or recurrent disease.

Results: FDG-PET identified 100% ofall primary tumors examined with initialdiagnostic intent (n=8). In addition, 1case of lymphoid hyperplasia was cor-rectly identified as nonmalignant. Of 22PET scans performed for tumor surveil-lance, 16 scans identified recurrent dis-ease and 5 scans were correctlyinterpreted as negative. One scanshowed an area of increased metabo-lism at the base of tongue suspicious formalignancy that later proved to be aninflammatory process (1 false positive).

Conclusion: FDG-PET was an effectiveimaging modality in the evaluation of

Fluorodeoxyglucose PositronEmission Tomography in theEvaluation of Tumors of theNasopharynx, Paranasal Sinuses,and Nasal CavityBrendan C. Stack, Jr, MD, FACS*

Val J. Lowe, MD†

Robert V. Lane, MD‡

*Division of Otolaryngology-HNS, Penn State University Milton S. Hershey Medical Center,Hershey, Pennsylvania.†Department of Nuclear Medicine and PET facility, Mayo Clinic Foundation, Rochester,Minnesota.‡Department of Otolaryngology-HNS, University of Missouri Health Sciences Center, Columbia,Missouri.

This study was presented at the 5th International Conference on Head and Neck Cancer in SanFrancisco, California, July 29-August 2, 2000.

KEY WORDS: Positron emissiontomography, paranasal sinuses,nasopharynx, and skull base

ABSTRACTIntroduction: The purpose of this studywas to review the clinical utility of 2-[18F]-fluoro-2-deoxy-D-glucose positronemission tomography (FDG-PET) in thediagnostic evaluation of a series ofpatients with tumors of the nasophar-ynx, paranasal sinuses, and nasal cavity.

Methods: The study group included 16patients from a single institution whounderwent a total of 31 FDG-PET scansfor the evaluation of various histologictypes of masses of the nasopharynx,nasal cavity, and paranasal sinuses fordiagnosis and or surveillance. A reviewof the patients’ medical records was per-formed in order to obtain all dataincluding tumor type and location, PET

primary and recurrent tumors of thenasopharynx, paranasal sinuses, andnasal cavities in our series. As a func-tional scanning modality, FDG-PET isparticularly useful in tumor surveillancewhere normal anatomy has been dis-rupted by prior surgery or radiation.Our series reaffirms the results of simi-lar series with respect to the use of PETin these particular sub sites of the headand neck.

INTRODUCTIONPositron emission tomography (PET) isa nuclear medicine scan, which allowsfor a physiologic examination of tissueglucose metabolism. PET images arecomputer generated from tomographicdetection of radiation emitted from asource trapped within hyper metabolictissues. These tissues exist physiological-ly (brain, cardiac muscle, etc.) but alsoexist with the rapid cell proliferation ofmalignancy.

18-fluoro-2-deoxy glucose (FDG),the positron source, is intravenouslyadministered and taken intracellular as apotential energy source by tumor cells inhigher concentrations than most non-malignant tissue and then is arrested inthe second step of glucose metabolismbecause of the 2-deoxy modification tothe glucose molecule. There it remainsintracellular as a positron source untilradioactive decay is completed. Positronsreact with electrons, which result in theproduction of 2 photons at 180 degreesfrom each other. Coincident detection ofphoton pairs leaving the body by anarray of crystals within the gantry allowfor computer localization of the emissionsource (malignant tumor) and conse-quently image creation.

PET theoretically offers advantagesin head and neck oncology (most ofwhich is squamous cell carcinoma,HNSCC) for diagnosis of small primarytumors and early recurrences wherechanges in anatomy might escape detec-tion by clinical exam, endoscopy, or con-

ventional imaging (computerized tomog-raphy, [CT] or magnetic resonance imag-ing [MRI]). PET has been reported asgreater than 90% sensitive and specificfor HNSCC across heterogeneous subsites and stages, both in diagnostic andsurveillance settings.1,2 Clinical examplesof these situations in HNSCC includethe unknown primary, occult cervicalnodal metastasis which occur at a rateup to 30%, and surveillance of recurrentdisease in the previously treated patient.Besides surveillance because of risk,PET is an especially helpful tool fordiagnosis of the at risk patient withsymptoms (dysphagia, otalgia, or headand neck pain) where physical andimaging findings are non-specific.Finally, when treatment is employed thatdoes not extirpate the disease(chemotherapy with radiation), PETallows for post treatment assessment oftumor response.

The nose, paranasal sinuses,nasopharynx, and skull base are areaswith limited accessibility by physicalexam. Office endoscopy has aided intheir examination but its interpretationcan be confounded by mucus, inflamma-tion, and cicatrix. Conventional imagingof these areas is limited for the samereasons. PET imaging may be a helpfuladjunct for diagnosis and/or surveillanceof these areas of the head and neck,especially when other clinical data isambiguous.

MATERIALS AND METHODSThe study group included 16 consecutivepatients who underwent a total of 31FDG-PET scans for the evaluation ofvarious histologic types of masses of thenasopharynx, nasal cavity, and paranasalsinuses. All patients reviewed were diag-nosed and/or treated at the St. LouisUniversity Health Sciences Center, St.Louis, Missouri from 1995 to 1998(Tables 1 and 2). Demographic descrip-tion of the study population includes 6males, 10 females mean age of 58.4

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years. A retrospective review of thepatients’ medical records was performedin order to obtain all data includingtumor type and location, PET scanresults, CT and MRI results, treatmentsperformed, disease status, and clinicaloutcome. These data were analyzed todetermine the utility of FDG-PET in theidentification of primary tumors and/orrecurrent disease. Of the 16 patientsstudied, follow-up ranged from 18months to 4 years (Table 1) and between1 to 4 scans were evaluated per patient.

RESULTSPET had 100% sensitivity (n=8) of all pri-mary tumors investigated prior to treat-ment in our small series. Our experiencedemonstrated PET specificity by correctlyimaging one nasopharynx mass as normaluptake (SUV-standard uptake values)that turned out to be benign lymphoidhyperplasia on permanent pathology.

Twenty two scans were performedfor post treatment tumor surveillance.Sixteen scans demonstrated recurrenttumor and 5 scans showed no evidenceof recurrence. One false positive scanwas noted at the tongue base, which wasbiopsy negative and never developed

into a clinical tumor on further surveil-lance examinations (specificity 97%)(Table 2). Several cases below demon-strate various scenarios when PET maybe useful for diagnosis or surveillance ofsinonasal, nasopharyngeal, and skullbase malignancies.

Case 1A patient with a history of extensivesinus exenteration for ethmoid sinuscancer underwent routine imaging of theskull base with CT and MRI and wasjudged to have recurrent maxillary sinusneoplastic disease and postoperativechanges elsewhere in the operative field.PET indicated a recurrence in the eth-moid sinus, not in the maxillary (Figure1). The patient successfully underwent asecond resection of recurrence, whichwas localized to the ethmoid sinuseswithout maxillary sinus extension.

Case 2A patient with nasopharynx cancer wastreated with chemotherapy and radia-tion and had a complete clinicalresponse. The patient complained of earpain 2 months following completion oftreatment, which was evaluated, by CTand PET (Figure 2). The CT scan wasread as negative, as was the PET.Persistence of symptoms promptedrepeat CT and PET imaging 10 monthsfollowing the completion of treatment.Again the CT was reported as negative.

Table 1. Patient CharacteristicsSite No. Path StageMaxillary 3 SCC (2) III (2)

Lymph IVNasopharynx 9 WHO I (5) III (4)

WHO II (2) IV (4)WHO III (2) N/A

Ethmoid 1 SCC IVFrontal 1 Small III

Cell CaNasal Cavity 2 SCC II

Melanoma N/A*SCC indicates squamous cell carcinoma; WHO, World Health Organization; NA, not available; and Lymph,lymphoma. Roman numerals are AJCC Staging SCC of the head and neck.

Table 2. Outcomes of Patients Studied byPET at Last Follow-UpNo evidence of disease 6Alive with recurrence 8Dead of disease 2

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The PET was read as positive in thenasopharynx and these results were con-firmed by a biopsy shortly thereafter.

Case 3A patient with nasopharynx tumorunder went a surveillance exam by CTand PET, 15 months following treat-ment. The CT was read as negative, thePET as positive but no biopsy confirmedthe recurrence. Three months later, anMRI showed evidence of recurrence.Repeat PET at this time showed localprogression of disease and then biopsyconfirmed recurrence (Figure 3).

DISCUSSIONThe diagnosis of HNSCC is imperfectand is limited by current technology.Initial assessment is often initiated bycomplaints of pain, throat obstruction,

or the development of a neck mass.Once a biopsy confirms the diagnosis ofHNSCC, a staging work up ensues whichcan include imaging and endoscopy.Imaging most often utilizes CT but mayalso involve MRI. This imaging usuallyencompasses the primary site and theneck but may also assess the brain, skullbase, and lungs. Endoscopy may be per-formed in the office or may require anoperative procedure depending on pri-mary location, patient cooperation, andadequacy of airway. Imaging, biopsies,and endoscopy produce the data neces-sary to stage the patient’s cancer for thepurposes of prognostication and clinicaldecision-making.

Primary and Secondary TumorsPET has some value in detecting pri-mary tumors but may not be a preferredmethod for initial screening, diagnosis,and staging. By the time there is enoughclinical or symptomatic evidence for sus-picion of head and neck cancer, primarytumors are often advanced enough to bedetected by palpation or physical exami-nation with the exception of some skullbase tumors. In these obvious cases, rou-tine PET would be an unnecessaryexpense. Di Martino et al comparedPET to CT and color-coded sonographyfor detecting primary head and necklesions and found PET to be the mostreliable method, although panendoscopyhad a similar sensitivity and specificity.3

PET is less expensive than panen-doscopy and requires no risk associated

Figure 1 Ethmoidsinus recurrencedetected by PETsurveillance.

Figure 2 Recurrent nasopharyngeal cancerdetected by PET surveillance.

Figure 3 Recurrent nasopharyngeal cancerdetected by PET and not CT (top). Recurrentnasopharyngeal cancer detected by PET andMRI (bottom).

with general anesthesia. Stokkel et alstudied the use of PET in detecting sec-ond primary neoplasms and found PETto significantly increase the rate ofdetection of second primaries than byconventional imaging.3 The significanceis that a synchronous second primarymay be small and escape detection and ametachronous second primary occurs ina treated field where physical exam,endoscopy, and conventional imagingmay yield ambiguous.

RecurrencePET has proven to be particularly valu-able in the detection of recurrent dis-ease when anatomic or fascial planesand fibrotic tissues have been distortedby, or resulted from previous treatment.The sensitivity of PET in detectingrecurrent disease has been reported tobe between 92% to 100% and the speci-ficity has been reported between 61% to96%. Several studies have examined theuse of PET surveillance after radiother-apy5-7 and that it is superior to CT8 orMRI9 in this context.

Detection of Occult Primary TumorsOccult primary disease presents a particu-lar problem in treatment decisions forhead and neck cancer. At least one studysuggested that PET was not effective inthis context. Greven et al studied 13patients with occult primary disease andfound that PET provided an accuratelocalization in 1 case and provided falsepositives in 6 cases.10 Several other stud-ies, many using larger samples, have foundPET to be effective in localizing primarytumors of unknown origin.11-14 Overall,the current weight of evidence favors arole for PET in the localization of tumorsof unknown origin. The nasopharynx isone of the classic locations of unknownprimaries of the head and neck.

Treatment Assessment Several studies have considered the use

of PET in assessing patients’ response totreatment, particularly after radiothera-py.15-17 Treatment assessment is per-formed shortly following therapy (6weeks to 6 months) and is to be distin-guished from surveillance exams (atgreater than 6 months). Greven et alfound that while PET was useful for ini-tial imaging of head and neck cancers,SUV’s were not useful for predictingoutcomes following primary radiationtherapy.18 Rege et al and others foundthat pretreatment PET was an inde-pendent predictor of which patientsachieve long-term local control with pri-mary radiation therapy.19 Lowe et alreported 100% sensitivity and specificityfor PET detection of recurrence in com-plete responding (CR) stage III/IVHNSCC patients with a greater sensitivi-ty than conventional imaging (P=0.013)or physical exam (P=0.002).20

Our series demonstrates PET to bea useful modality to image the paranasalsinus, nasopharynx, and skull base.Admittedly, the size of this series makesthe conclusion limited and somewhatanecdotal. These areas are difficult toassess under normal conditions. Posttreatment changes including flaps, grafts,implants, retained mucus, and cicatrixare confounding elements on directexamination and imaging. PET allowsfor a reliable means to discern treatmentartifact from recurrence and it candetect it earlier than conventional imag-ing. In order to determine the specificutility of PET for these subsites it willrequire a large, prospective, controlledstudy, which has yet to be done. For now,our series and the few others publishedfor this particular PET application willserve to indicate the usefulness of PETfor diagnosis and surveillance ofsinonasal and nasopharyngeal cancers.

CONCLUSIONWith respect to diagnosis, evaluation oftreatment, and surveillance for recur-

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rence, PET offers diagnostic advantagesto the unique and challenging area ofhead and neck anatomy, the paranasalsinuses, nasopharynx, and skull base.With an increased acceptance of PETfor management of HNSCC (includingcoverage by the US GovernmentMedicare program), PET should be rou-tinely considered for evaluation and sur-veillance of HNSCC especially of thesinuses, nasopharynx, and skull base notclearly examined by physical exam,endoscopy, and conventional imaging.

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