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F-18 FDG PET-CT FUSION IN RADIOTHERAPY TREATMENT PLANNING FOR HEAD AND NECK CANCER Mary Koshy, MD,1 Arnold C. Paulino, MD,3 Rebecca Howell, MS,1 David Schuster, MD,2 Raghuveer Halkar, MD,2 Lawrence W. Davis, MD1 1 Department of Radiation Oncology, Division of Nuclear Medicine and Molecular Imaging, Emory Clinic and Emory University, Atlanta, Georgia 2 Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Emory Clinic and Emory University, Atlanta, Georgia 30322 3 Methodist Hospital/Baylor College of Medicine, Department of Radiation Oncology, 6565 Fannin St., MS-DB1-077, Houston, TX 77030. E-mail: [email protected] Accepted 30 November 2004 Published online 16 March 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20179 Abstract: Background. The fusion of fluoro-2-deoxy-Dglucose – positron emission tomography (FDG-PET) with CT scans has been shown to improve diagnostic accuracy and staging in non-small cell lung cancer. We report on the influence of PET-CT fusion on the management of patients with head and neck cancer. Methods. Thirty-six patients with intact primary head and neck cancers treated with radiation therapy (RT) received PETCT as part of treatment planning. Workup before PET-CT included a contrast-enhanced CT scan of the head and neck and chest X-ray; patients with nasopharyngeal and paranasal sinus primary tumors also underwent MRI. Results. Changes in TNM score and American Joint Committee on Cancer stage occurred in 13 patients (36%) and five patients (14%), respectively, based on PET-CT. RT volume and dose were altered in five patients (14%) and four patients (11%), Correspondence to: A. C. Paulino Dr. Mary Koshy is a recipient of a 2004 Young Oncologist Travel Grant Award from the American Radium Society. Abstract presented in part at the 86th Annual Meeting of the American Radium Society, May 1 – 5, 2004 at Napa Valley, California. B 2005 Wiley Periodicals, Inc. 494 respectively. Five patients initially were seen with carcinoma of unknown primary, and PET-CT confirmed oropharyngeal primary tumors in two. PET-CT data also detected a synchronous lung cancer in one patient. Conclusion. PET-CT fusion may have a significant impact on staging and determination of RT treatment volume and dose. A 2005 Wiley Periodicals, Inc. Head Neck 27: 494 – 502, 2005 Keywords: PET-CT; head and neck cancer; functional imaging; radiotherapy treatment planning; staging Fluoro-2-deoxy-D-glucose – positron emission tomography (FDG-PET) has recently played an important role in the staging process for head and neck cancer. FDG-PET identifies primary lesions, nodal disease, distant metastasis, and secondary tumors in patients with head and neck cancer. In 15 studies of head and neck cancer published since 2000, the reported sensitivity of nodal detection with PET was 87%, and specificity was 95%, in contrast to CT/MRI, which was found to have a sensitivity of 77% and a specificity of 87%.1 – 6 In small series of patients with head and neck PET-CT Fusion in Radiotherapy Treatment Planning for Head and Neck Cancer HEAD & NECK June 2005 cancer, PET has also played a significant role in the detection of suspected recurrence and residual disease, with a sensitivity and specificity of up to 100%, in contrast to the 75% sensitivity and 80% specificity of CT/MRI.7 – 10 Recently, combined PET-CT scanning has been introduced with the advantage of providing anatomic information of the CT scan in conjunction with the functional information of the PET scan. Historically, PET information for T classification has not been as superior as for nodal staging, primarily because of a lack of anatomic information. PET-CT provides critical structural information about the tumor and its relationship to adjacent soft tissue and surrounding bone, muscle, and cartilage and allows functional imaging to become a component of radiation treatment planning. This fused image provides both the anatomic delineation of the tumor and biologic information, which can aid in identifying target volumes.10 The use of PET-CT fusion in non-small cell lung cancer (NSCLC) has been found to have a significant impact on staging, changes in patient management, and radiation therapy (RT) treatment volumes.11 – 16 In addition, the use of PET-CT fusion has been shown to result in more accurate staging of both the primary tumor and nodal disease compared with PET alone, CT alone, and visual correlation of PET and CT.17,18 More accurate methods of staging may lead not only to more precise RT volumes and doses but also to overall clinical patient management. Here, we report on the clinical impact of PET-CT fusion on the management of patients with intact head and neck cancer. Specifically, we looked at how PET-CT altered the TNM and American Joint Committee on Cancer (AJCC) stage, as well as RT volume and dose. MATERIALS AND METHODS The subjects of this single-institution retrospective study included 36 consecutive patients seen at our department with intact squamous cell carcinoma of the head and neck region. The primary site location was oropharynx in 17 patients, nasopharynx in five patients, larynx in four patients, paranasal sinuses in three patients, oral cavity in two patients, hypopharynx in two patients, and unknown primary in three patients. Table 1 illustrates the sites and subsites within the head and neck. There were eight women and 28 men, with a mean age of 56 years Patients. Table 1. Primary site location in 36 patients undergoing PET-CT fusion. Primary site Frequency Oropharynx Tonsil Base of tongue Valleculla Soft palate Nasopharynx Larynx Supraglottis Glottis Paranasal sinuses Maxillary sinus Hypopharynx Posterior pharyngeal wall Oral cavity Floor of mouth Oral tongue Unknown primary Total 17 (9) (4) (2) (2) 5 4 (2) (2) 3 (3) 2 (2) 2 (1) (1) 3 36 Abbreviation: PET, positron emission tomography. (range, 32 – 80 years). All patients except one were initially seen with a new diagnosis of malignancy of the head and neck and underwent routine workup with clinical examination, contrast-enhanced CT of the head and neck, and chest X-ray. Patients with unknown primary cancers metastatic to cervical nodes had endoscopic biopsies and tonsillectomy. Patients with nasopharyngeal and paranasal sinus primary tumors also underwent MRI of the head and neck. One patient had a history of carcinoma of unknown primary tumor treated with right neck dissection 3 years previously and was seen with recurrent disease and a primary tumor in the vallecula. For the 36 patients, most were initially seen with advanced locoregional disease. The PET-CT scan was acquired for AJCC TNM staging and for radiation treatment planning before treatment onset.19 At the time of FDG-PET imaging, no patients had clinical or radiologic evidence of distant metastases or synchronous tumors by CT scan and MRI of the head and neck and chest X-ray. At our institution, all patients with head and neck cancer requiring RT receive intensity modulated radiation therapy (IMRT). All of the patients were treated with IMRT technique, except for one patient with metastatic disease to the esophagus, who received palliative threedimensional conformal RT. Three patients underwent neck dissections before chemoradiation. Platinum-based chemotherapy was given concurrently with RT in 31 patients (86%). PET-CT Fusion in Radiotherapy Treatment Planning for Head and Neck Cancer HEAD & NECK June 2005 495 Table 2. Tumor (T) classification before and after PET-CT. Pre – PET-CT classification T0 T1 T2 T3 T4 Total No. patients by post – PET-CT classification No. patients T0 T1 T2 T3 T4 Upstage ratio Downstage ratio 5 7 7 5 12 36 3 — — — — 3 2 7 — — — 9 — — 6 — — 6 — — — 4 — 4 — — 1 1 12 14 2/5 0/7 1/6 1/6 0/12 4/36 0/5 0/7 0/6 0/6 0/12 0/36 Abbreviation: PET, positron emission tomography. 444 MBq) of 18F FDG was injected, and 45 to 60 minutes was allowed for uptake before patient imaging. Patients were instructed to minimize any talking, chewing, swallowing, or movement of the head, because these activites can influence muscular uptake in the masticator muscles, tip of the tongue, face, neck, and larynx.20,21 Non – contrast-enhanced CT imaging for attenuation correction anatomic correlation was performed first from the vertex of the skull to below the kidneys. An RT head holder was used for immobilization. First, the CT scan was completed using 180-mA tube current, 140-kV tube voltage, 0.5-second tube rotation, helical pitch of 1:1, and reconstructed slice thickness of 4.25 mm. The CT portion was acquired in less than 30 seconds. Neither IV nor oral contrast was used. Immediately after the CT scan, a PET emission scan was acquired starting at the skull vertex with an acquisition time of 5 minutes per bed position with a one-slice overlap at the borders of the 14.6-cm field of view. Data were reconstructed using OSEM iterative reconstruction with two iterations and 28 subsets. Postprocessing with a post filter at 5.45-mm full width at half maximum (FWHM), and a loop filter at 3.91-mm FWHM on a 128 128 matrix was then carried out. Images All patients initially received a planning CT simulation scan (with 100 mL intravenous [ IV ] contrast injected at rate of 2 mL/second) on the General Electric (GE) light speed scanner (General Electric, Milwaukee, WI) in the radiation therapy department. The planning volume was scanned with 2.5-mm increments. Patients were simulated in the supine position and immobilized with a head mask and scanned in the RT position. These CT imaging studies were subsequently fused to the hybrid PET-CT images. PET-CT scans were performed either on the same day or within 1 week of the CT simulation scan. Before the PET-CT, all patients were required to fast for 4 hours but were encouraged to drink water. All imaging and data acquisition was performed on an integrated PET-CT system (Discovery LS, GE Medical Systems, Milwaukee, WI), and patients were scanned in the same position (immobilized with a head mask) as they were in their radiation simulation CT scan. The PET/CT integrates an eight-slice helical CT scanner (Light Speed Plus; General Electric) and a PET scanner (Advance NXi; General Electric). CT and PET images are hardware coregistered in a single session. Typically, 10 to 12 mCi (370 – CT Simulation and PET-CT Scan Procedure. Table 3. Nodal (N) classification before and after PET-CT. No. patients by post – PET-CT classification Pre – PET-CT classification N0 N1 N2a N2b N2c N3 Total No. patients N0 N1 N2A N2B N2C N3 Upstage ratio Downstage ratio 5 8 2 14 5 2 36 3 1 2 1 — — 7 1 7 — — — — 8 — — — — — — 0 1 — — 12 — — 13 — — — 1 5 — 6 — — — — — 2 2 2/5 0/8 0/2 1/14 0/5 0/2 3/36 0/5 1/8 2/2 1/14 0/5 0/2 4/36 Abbreviation: PET, positron emission tomography. 496 PET-CT Fusion in Radiotherapy Treatment Planning for Head and Neck Cancer HEAD & NECK June 2005 Table 4. American Joint Committee on Cancer stage before and after PET-CT. No. patients by post – PET-CT stage Pre – PET-CT stage No. patients I II III IVA IVB IVC 1 2 10 21 2 0 36 1 — — — — — 1 — 1 1 — — — 2 — — 8 — — — 8 — — 1 20 — — 21 — — — — 1 — 1 — 1 — 1 1 — 3 I II III IVA IVB IVC Total Upstage ratio Downstage ratio 0/1 1/2 1/10 1/21 1/2 0/0 4/36 0/1 0/2 1/10 0/21 0/2 0/0 1/36 Abbreviation: PET, positron emission tomography. were viewed on a Xelerus (GE Medical Systems) workstation. PET and CT data sets were then sent by means of a DICOM (Digital Imaging and Communication in Medicine) protocol to the CT simulation workstation for image coregistration. The radiation planning CT was then fused to the CT of the hybrid PET-CT, and these data were used for dose calculation and sent to the ECLIPSE treatment planning system (Varian, Palo Alto, CA). Three or more reference anatomic landmarks were matched and fused, with a maximum acceptable error of 5 mm. Table 5. Summary of changes in management with PET-CT. Patient no. and disease site Pre – PET-CT TNM (AJCC stage) Post – PET-CT TNM (AJCC stage) 1 Maxillary sinus T3N0M0 (III) T4aN0M0 (IVA) 2 Unknown primary (base of tongue) T0N2bM0 (IVA) T1N2bM0 (IVA) 3 Unknown primary (valleculla) T0N1M0 (III) T1N1M0 (III) 4 Tonsil T2N2bM0 (IVA) T2N2cM0 (IVA) 5 Larynx T2N0M0 (II) T2N2cM1 (IVC) 6 Tonsil T2N1M0 (III) T2N0M0 (II) 7 Soft palate T4bN2cM0 (IVB) T4bN2cM1 (IVC) 8 Hypopharynx T4aN2cM0 (IVA) T4aN2cM1 (IVC) 9 Hypopharynx T1N0M0 (I) T1N0M0 (I) Hypopharynx and T4N2M0 NSCLC (IIIB) Management changes Increase in PTV to encompass tumor identified on PET Decrease in initial PTV as primary site was found (nasopharynx not included); primary tumor in oropharynx received higher RT dose Decrease in initial PTV as primary site was found (nasopharynx not included); primary tumor in oropharynx received higher RT dose Increase in PTV to include PET identified tumor extension to deep muscles of tongue and contralateral (right) neck disease; increase in RT dose to right neck Diffuse metastatic disease and bilateral neck metastasis seen only on PET; RT intent changed from curative to palliative; RT volume decreased to include only esophageal mass causing dysphagia; and RT dose decreased to palliative 30 Gy. No change in RT dose or volume; based on the finding of N0 status with PET, a decision to not give chemotherapy and treat with RT alone Curative to palliative intent; no change in initial RT dose or PTV; change in patient’s chemotherapy regimen Curative to palliative intent; no change in initial RT dose or PTV; change in patient’s chemotherapy regimen This patient had a 2.5 cm RLL cavitating lesion seen on PET-CT; lung biopsy revealed adenocarcinoma, and the patient was taken to surgery; Pathology revealed a T4N2M0 stage IIIB NSCLC Abbreviaitons: PET, positron emission tomography; PTV, planning target volume; RT, radiation therapy; NSCLC; non-small cell lung cancer; RLL, right lower lobe. PET-CT Fusion in Radiotherapy Treatment Planning for Head and Neck Cancer HEAD & NECK June 2005 497 The PET-CT scan was interpreted with all available clinical information. In general, scans were interpreted by either a board-certified nuclear radiologist (DS) or nuclear medicine physician (RH). A focus was considered positive if activity was significantly above expected background and could not be explained by a normal structure. The post-PET TNM stage was determined by the PET-CT fusion findings. The postPET TNM stage was compared with the TNM stage based on clinical examination and diagnostic CT scan, MRI, and chest X-ray. Findings suspicious for the presence of distant metastasis or second primary cancers were confirmed either histologically or by the combination of additional imaging tests and clinical follow-up. The gross tumor volume (GTV) using the PET-CT and CT were contoured; based on the GTV, corresponding clinical target volume (CTV), and planning target volume (PTV) for both PET-CT and CT were derived and compared with each other. For contours involving the PET-CT, the 50% intensity level relative to tumor maximum was used to delineate the borders of the GTV. RESULTS The impact of PET-CT on TNM score, AJCC stage, and overall patient management was analyzed. Overall, PET-CT altered the TNM score in 13 patients (36.1%) and the AJCC stage in five patients (13.9%). The changes in tumor status and nodal status frequently did not have an impact on overall stage but did have a significant impact on radiation volume covered and dose given. In some patients found to have distant metastasis, and hence a change in the metastasis score, the use of chemotherapy also changed. Overall, PET-CT changed the management of nine patients (25%). Among the 36 patients who were initially seen with head and neck cancer and underwent PET-CT for staging and RT planning, four patients had their tumor score increase, whereas none had their tumor score decrease (Table 2). For nodal disease, three patients had their nodal score increase, whereas four patients had their score decrease after PETCT (Table 3). The AJCC stage was altered by PET-CT in five (14%) of 36 patients; in four patients, the AJCC stage increased, whereas in one it decreased (Table 4). Three patients were found to have distant metastasis, and their disease was upstaged to stage IVC (Table 5). One patient had a supraglottic laryngeal cancer with extension to the esophagus in addition to bilateral neck adenopathy, axillary, and mediastinal adenopathy (Table 5, patient 5). Another patient had a soft palate carcinoma with bilateral neck adenopathy and multiple right lung nodules (Table 5, patient 7). In both patients 5 and 7, pathologic confirmation of metastatic disease was not done because of clinical presentation of widespread dissemination of disease. Another patient had a hypopharyngeal cancer with bilateral neck metastasis and a left lower lobe lung mass. Biopsy of this lung lesion showed similar histologic features to the primary cancer and was consistent with a metastasis (Table 5, patient 8). Nine patients (25%) had a change in management because of the PET-CT. Table 5 lists the management changes because of PET-CT. Impact of PET-CT on Management. Five patients had a change in RT volume, and four had a change in RT dose (patients 2 – 5). Changes in RT volume were secondary to more extensive disease requiring a larger volume to irradiate (patients 1 and 4), discovery of the primary site in two patients with Radiotherapy. Impact of PET-CT on Staging. 498 FIGURE 1. PET component of PET-CT scan shows the primary tumor in the larynx (a), contralateral neck disease (b), and upper mediastinal node (c). This patient was treated to the primary site only with palliative radiotherapy using a lower dose. PET-CT Fusion in Radiotherapy Treatment Planning for Head and Neck Cancer HEAD & NECK June 2005 FIGURE 2. PET-CT image of a patient with squamous cell carcinoma of the posterior pharyngeal wall. CT image is shown on the left, and PET image is shown on right. Arrows point to the primary tumor. cervical metastasis from an unknown primary tumor, eliminating the need to treat the nasopharyngeal area (patients 2 and 3), and discovery of widespread distant metastasis, which required only the symptomatic area to be irradiated (patient 5). Three patients had an increase, whereas one had a decrease in RT dose because of PETCT. Both patients who had their primary sites discovered after PET-CT received a higher dose to the oropharyngeal primary tumor (patients 2 and 3). One patient was discovered to have contralateral neck disease requiring a higher dose to the right side of the neck (patient 4). Another was treated only to 3000 cGy as palliative treatment to a symptomatic laryngeal tumor with esophageal extension and distant metastasis (patient 5, Figure 1). In the four patients in whom PET-CT downstaged nodal status, both radiation volumes and dose were not changed on the basis of PETCT findings. Borderline adenopathy, as identified on CT alone, was still treated on the assumption that node-positive disease was present and was included as part of the high-dose target volume. Three patients had a change in chemotherapy management. A decision not to give chemotherapy was made in a patient whose disease was downstaged after PET-CT from T2N1M0 cancer of the tonsil to T2N0M0. This patient had a 1.5-cm lymph node that was positive on CT but negative on PET-CT; he received radiation alone, with the RT dose and volume remaining unchanged (patient 6). In two patients, a change in chemotherapy regimens was made because of discovery of distant metastasis. One patient with a soft palate primary tumor Chemotherapy. FIGURE 3. Images of the same patient as in Figure 2, showing lung metastasis in left upper lobe of lung. CT image is shown on the left, and PET image is shown on the right. Arrows point to site of distant metastasis. Biopsy of this lesion was consistent with a head and neck primary tumor. This patient was treated with a different chemotherapy regimen because of this finding. PET-CT Fusion in Radiotherapy Treatment Planning for Head and Neck Cancer HEAD & NECK June 2005 499 was treated with cisplatin during RT and because of distant spread was given post-RT chemotherapy consisting of paclitaxel and gemcitabine (patient 7). Another patient with a hypopharyngeal primary tumor had his chemotherapy changed from cisplatin to carboplatin and docetaxel because of pulmonary metastasis (patient 8, Figures 2 and 3). One patient underwent a right lower lobe lobectomy and mediastinal node sampling after chemoradiation for a posterior pharyngeal wall cancer, because the PET-CT revealed a 2-cm cavitating mass with a standardized uptake value of 8.5. Pathologic examination of the specimen from lobectomy revealed an adenocarcinoma with mediastinal node spread. His disease was then staged as a T4N2M0 or stage IIIB NSCLC, and he is currently awaiting adjuvant treatment (patient 9). Surgery. DISCUSSION This single-institution study confirms previous results showing that PET is able to identify the primary lesion and regional lymph node involvement in patients with head and neck cancer.1 – 7 The increased sensitivity and specificity of PET in the nodal staging of head and neck cancer has been well documented, and the anatomic information added by combined PET-CT can lead to even greater accuracy in the staging process. A number of studies have evinced a clear role for PET-CT fusion in the management and RT planning of NSCLC.11 – 16 Less data are available regarding the role of PET-CT fusion in patients with head and neck cancer. In two recent studies of patients with head and neck cancer, PET-CT fusion was found to have an impact on RT target delineation.22,23 In a study of 21 patients with nasopharyngeal or oropharyngeal primary tumors, Nishioka et al22 found that PET-CT detected 39 positive nodes in contrast to only 28 nodes detected by clinical examination and CT/MRI. In four patients, the nodal status was increased, which impacted on target delineation. Parotid sparing became possible in 71% of patients whose upper neck areas near the parotid glands were tumor free by PET-CT, and, except for one patient, no recurrences were seen at 18 months when the PET-CT – defined volumes were used as the GTV.22 Daisne et al23 reviewed 10 patients with locally advanced oropharyngeal cancers who had MRI and PET coregistration with CT simu- 500 lation images. They found that the average GTV was 37% larger when MRI and PET were coregistered with CT compared with CT alone. In this study, we found that the role of PETCT in staging has important ramifications for clinical management, particularly with respect to radiation dose given, radiation target volumes covered, and the decision to give chemotherapy. PET-CT fusion altered the TNM score in 38% and AJCC stage in 14% of patients. The primary tumor was identified in 33 (92%) of the patients in this study, and the three patients in whom tumor was not identified had a diagnosis of carcinoma of unknown primary tumor. In regional lymph node involvement, PET-CT increased the nodal score of three patients and decreased the nodal score in four patients. Physiologic uptake in normal organs in the head and neck such as the cricoarytenoid muscles, salivary glands, tongue, and tonsils can make interpretation of PET data difficult, despite the fact that such uptake is symmetric and can usually be distinguished from cancer.20,21,24,25 With the recent advent of combined PET-CT, interpretation of PET becomes less difficult and anatomic delineation becomes more precise. Certainly, there are limitations in this study. First, the quality of image fusion between CT and PET-CT images was evaluated subjectively by use of three anatomic reference points in the head and neck for the registration process. An error of 5 mm between the fused images was the upper limit for what was considered an acceptable registration, and a discrepancy of 2 to 3 mm was the standard for most of the fused images. This may have a slight impact on determination of GTV on the basis of PET-CT. Second, we did not have histologic confirmation of borderline lymph nodes, because most of our patients with locally advanced disease underwent chemoradiation. In some patients, lymph nodes that did not meet size criteria for disease on CT exhibited increased FDG uptake on fused images, and in others, lymph nodes that appeared enlarged on CT failed to have any FDG uptake on PET-CT. When PET-CT findings were not in accord with CT findings for nodal detection, this had a direct impact on prophylactic radiation doses to the neck and what was considered as GTV. Patients who had a positive neck node on PET-CT but not on CT alone had change in RT volume and dose to take into account the PET-CT ‘‘gross disease’’ instead of the CT ‘‘subclinical disease.’’ The reverse, however, was not true. We PET-CT Fusion in Radiotherapy Treatment Planning for Head and Neck Cancer HEAD & NECK June 2005 did not change our RT volumes and doses when there was CT-positive lymphadenopathy that was negative on PET-CT. Furthermore, for two of the three patients with metastatic disease detected by PET-CT, pathologic confirmation was not obtained, and there is a possibility that they had a synchronous cancer rather than distant metastasis. However, this seems unlikely, because the two patients with unbiopsied distant tumors had widespread disease. Third, we acknowledge that the consistency of target delineation with PET by visual determination and not by standardized uptake value can be subjective, and this is why we rely on our nuclear medicine colleagues to tell us the areas of abnormality. Other potential problems with PETCT fusion that must always be considered include patient movement during the combined PET-CT and patient position being different between the CT simulation and the PET-CT. Fourth, we found that three patients had a change in chemotherapy management, with two having a change from cisplatin to another type of regimen. Although cisplatin and RT are used in our institution for curative therapy for many locally advanced head and neck cancers, this may not be the standard chemotherapy in other centers. It may be that the chemotherapy regimens used for metastatic disease (paclitaxel/ gemcitabine and carboplatin/docetaxel) in our institution are used in others as first-line chemotherapy for curative disease. Furthermore, one may argue that a patient with T2N1 tonsillar cancer could be treated with RT alone and not chemoradiation as done in our institution. Hence, the number of patients with change in management may have been overestimated and may only be six of 36 patients or 16.7%. Finally, one may speculate that a CT scan of the chest would have detected the synchronous lung primary tumor and two cases of metastatic disease to the lungs. We do not know whether this would be the case, because in our institution, it is not routine to order a CT scan of the chest unless there is an abnormality on chest X-ray. Data for lung cancer, however, demonstrate the superiority of PET-CT over CT scan alone in detecting lung disease.17 In our study, two of the five patients with carcinoma of an unknown primary tumor had primary disease confirmed by PET-CT findings. In a review of all reported series on PET and carcinoma of an unknown primary tumor, approximately 25% of primary tumors were detected by PET imaging.26 Patients with head and neck cancers are at a 4% per year risk of another second primary cancer of the upper aerodigestive tract developing, and second primary cancers are a leading cause of death in this population. PET has been shown to significantly increase the rate of detection of simultaneous second primary tumors, usually at an early stage, and distant metastasis.27 – 29 In addition to PET, data from PET-CT has been shown to have a significant impact on staging and treatment planning in patients with NSCLC. 11 – 18 The use of PET-CT data has changed radiation management from 26% to 100% of patients with NSCLC compared with CT-based treatment planning.10 In addition, the use of PET-CT in patients with NSCLC has resulted in more accurate staging, improved sparing of normal lung tissue in radiation planning, and a more consistent definition of what constitutes the GTV.14,17,30 This study found that PET-CT has a significant impact on the staging and clinical management of patients with head and neck cancer. In the future, the use of PET-CT in patients with head and neck cancer has the potential to result in more accurate staging and more precise target volume delineation and consequent radiotherapy volumes and doses. REFERENCES 1. Gambhir SS, Czernin J, Schwimmer J, et al. A tabulated summary of the FDG PET literature. J Nucl Med 2001; 42(5 Suppl):1S – 93S. 2. Di Martino E, Nowak B, Hassan HA, et al. Diagnosis and staging of head and neck cancer: a comparison of modern imaging modalities (positron emission tomography, computed tomography, color-coded duplex sonography) with panendoscopic and histopathologic findings. Arch Otolaryngol Head Neck Surg 2000;126:1457 – 1461. 3. Kau RJ, Alexiou C, Laubenbacher C, et al. Lymph node detection of head and neck squamous cell carcinomas by positron emission tomography with fluorodeoxyglucose F 18 in a routine clinical setting. Arch Otolaryngol Head Neck Surg 1999;125:1322 – 1328. 4. Adams S, Baum RP, Stuckensen T, et al. Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer. Eur J Nucl Med 1998;25:1255 – 1260. 5. Wong WL, Chevretton EB, McGurk M, et al. A prospective study of PET-FDG imaging for the assessment of head and neck squamous cell carcinoma. Clin Otolaryngol 1997;22: 209 – 214. 6. McGuirt WF, Williams DW III, Keyes JW Jr, et al. A comparative diagnostic study of head and neck nodal metastases using positron emission tomography. Laryngoscope 1995;105:373 – 375. 7. Schechter NR, Gillenwater AM, Byers RM, et al. Can positron emission tomography improve the quality of care for head-and-neck cancer patients? Int J Radiat Oncol Biol Phys 2001;51:4 – 9. PET-CT Fusion in Radiotherapy Treatment Planning for Head and Neck Cancer HEAD & NECK June 2005 501 8. Wong RJ, Lin DT, Schroder H, et al. Diagnostic and prognostic value of [(18) F] fluorodeoxyglucose positron emission tomography for recurrent head and neck squamous cell carcinoma. J Clin Oncol 2002;20:4199 – 4208. 9. Lowe VJ, Boyd JH, Dunphy FR, et al. Surveillance for recurrent head and neck cancer using positron emission tomography. J Clin Oncol 2000;18:651 – 658. 10. Paulino AC, Thorstad WL, Fox T. Role of fusion in radiotherapy treatment planning. Semin Nucl Med 2003;33: 238 – 243. 11. Kiffer JD, Berlangieri SU, Scott AM, et al. The contribution of 18F-fluoro-2-deoxy-glucose positron emission tomographic imaging to radiotherapy planning in lung cancer. Lung Cancer 1998;19:167 – 177. 12. Nestle U, Walter K, Schmidt S, et al. 18F-deoxyglucose positron emission tomography (FDG-PET) for the planning of radiotherapy in lung cancer: high impact in patients with atelectasis. Int J Radiat Oncol Biol Phys 1999; 44:593 – 597. 13. Erdi YE, Rosenzweig K, Erdi AK, et al. Radiotherapy treatment planning for patients with non-small cell lung cancer using positron emission tomography (PET). Radiother Oncol 2002;62:51 – 60. 14. Vanuytsel LJ, Vansteenkiste JF, Stroobants SG, et al. The impact of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) lymph node staging on the radiation treatment volumes in patients with non-small cell lung cancer. Radiother Oncol 2000;55:317 – 324. 15. Mah K, Caldwell CB, Ung YC, et al. The impact of (18) FDG-PET on target and critical organs in CT-based treatment planning of patients with poorly defined nonsmall-cell lung carcinoma: a prospective study. Int J Radiat Oncol Biol Phys 2002;52:339 – 350. 16. Kalff V, Hicks RJ, MacManus MP, et al. Clinical impact of (18) fluorodeoxyglucose positron emission tomography in patients with non-small-cell lung cancer: a prospective study. J Clin Oncol 2001;19:111 – 118. 17. Lardinois D, Weder W, Hany TF, et al. Staging of nonsmall-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 2003;348:2500 – 2507. 18. D’Amico TA, Wong TZ, Harpole DH, Brown SD, Coleman RE. Impact of computed tomography-positron emission tomography fusion in staging patients with thoracic malignancies. Ann Thorac Surg 2002;74:160 – 163. 19. Greene FL, Page DL, Fleming ID, et al, editors. American Joint Committee on Cancer staging handbook. 6th ed. New York: Springer; 2002. p 27 – 98. 20. Goerres GW, Von Schulthess GK, Hany TF. Positron emission tomography and PET CT of the head and neck: 502 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. FDG uptake in normal anatomy, in benign lesions, and in changes resulting from treatment. AJR Am J Roentgenol 2002;179:1337 – 1343. Goerres GW, Hany TF, Kamel E, et al. Head and neck imaging with PET and PET/CT: artifacts from dental metallic implants. Eur J Nucl Med Mol Imaging 2002;2: 367 – 370. Nishioka T, Shiga T, Shirato H, et al. Image fusion between 18FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas. Int J Radiat Oncol Biol Phys 2002;53:1051 – 1057. Daisne J, Duprez T, Weynant B, et al. Impact of image coregistration with computed tomography (CT), magnetic resonance (MR) and positron emission tomography with fluorodeoxyglucose (FDG-PET) on delineation of GTV’s in oropharyngeal, laryngeal and hypopharyngeal tumors. Int J Radiat Oncol Biol Phys 2002;54(S):15 – 16. Hustinx R, Smith RJ, Benard F, et al. Dual time point fluorine-18 fluorodeoxyglucose positron emission tomography: a potential method to differentiate malignancy from inflammation and normal tissue in the head and neck. Eur J Nucl Med 1999;26:1345 – 1348. Macapinlac H. Oncologic applications of PET in head, neck and thyroid. In: Wahl R, Buchanan J, editors. Principles and practice of positron emission tomography. Philadelphia: Lippincott Williams and Wilkins; 2002. p 157 – 165. Fogarty GB, Peters LJ, Stewart J, et al. The usefulness of fluorine 18-labelled deoxyglucose positron emission tomography in the investigation of patients with cervical lymphadenopathy from an unknown primary tumor. Head Neck 2003;25:138 – 145. Wax MK, Myers LL, Gabalski EC, et al. Positron emission tomography in the evaluation of synchronous lung lesions in patients with untreated head and neck cancer. Arch Otolaryngol Head Neck Surg 2002;128:703 – 707. Stokkel MP, Moons KG, ten Broek FW, et al. 18Ffluorodeoxyglucose dual-head positron emission tomography as a procedure for detecting simultaneous primary tumors in cases of head and neck cancer. Cancer 1999;86: 2370 – 2377. Goerres GW, Schmidt DT, Gratz KW, et al. Impact of whole body positron emission tomography on initial staging and therapy in patients with squamous cell carcinoma of the oral cavity. Oral Oncol 2003;36:547 – 551. Caldwell CB, Mah K, Ung YC, et al. Observer variation in contouring gross tumor volume in patients with poorly defined non-small-cell lung tumors on CT: the impact of 18FDG-hybrid PET fusion. Int J Radiat Oncol Biol Phys 2001;51:923 – 931. PET-CT Fusion in Radiotherapy Treatment Planning for Head and Neck Cancer HEAD & NECK June 2005