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MR for lymph node staging in head and neck cancer
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FDG PET/MR for lymph node staging in head and neck cancer Ivan Platzek a,∗ , Bettina Beuthien-Baumann b , Matthias Schneider c , Volker Gudziol d , Hagen H. Kitzler e , Jens Maus f , Georg Schramm f , Manuel Popp b , Michael Laniado a , Jörg Kotzerke b , Jörg van den Hoff f a
Dresden University Hospital, Department of Radiology, Fetscherstr. 74, 01307 Dresden, Germany Dresden University Hospital, Department of Nuclear Medicine, Fetscherstr. 74, 01307 Dresden, Germany Dresden University Hospital, Department of Oral and Maxillofacial Surgery, Fetscherstr. 74, 01307 Dresden, Germany d Dresden University Hospital, Department of Otolaryngology, Fetscherstr. 74, 01307 Dresden, Germany e Dresden University Hospital, Department of Neuroradiology, Fetscherstr. 74, 01307 Dresden, Germany f Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstr. 400, 01328 Dresden, Germany b c
a r t i c l e
i n f o
Article history: Received 24 February 2014 Received in revised form 16 March 2014 Accepted 19 March 2014 Keywords: PET/MR Head and neck cancer Lymph node metastasis Staging
a b s t r a c t Objective: To assess the diagnostic value of PET/MR (positron emission tomography/magnetic resonance imaging) with FDG (18F-fluorodeoxyglucose) for lymph node staging in head and neck cancer. Materials and methods: This prospective study was approved by the local ethics committee; all patients signed informed consent. Thirty-eight patients with squamous cell carcinoma of the head and neck region underwent a PET scan on a conventional scanner and a subsequent PET/MR on a whole-body hybrid system after a single intravenous injection of FDG. The accuracy of PET, MR and PET/MR for lymph node metastases were compared using receiver operating characteristic (ROC) analysis. Histology served as the reference standard. Results: Metastatic disease was confirmed in 16 (42.1%) of 38 patients and 38 (9.7%) of 391 dissected lymph node levels. There were no significant differences between PET/MR, MR and PET and MR (p > 0.05) regarding accuracy for cervical metastatic disease. Based on lymph node levels, sensitivity and specificity for metastatic involvement were 65.8% and 97.2% for MR, 86.8% and 97.0% for PET and 89.5% and 95.2% for PET/MR. Conclusions: In head and neck cancer, FDG PET/MR does not significantly improve accuracy for cervical lymph node metastases in comparison to MR or PET. © 2014 Published by Elsevier Ireland Ltd.
1. Introduction Malignant head and neck tumors are predominantly squamous cell carcinoma [1]. Head and neck cancer is among the malignancies with the highest worldwide incidence [2,3]. Both the choice of therapy and prognosis in head and neck cancer are influenced
∗ Corresponding author. Tel.: +49 351 458 18223/+49 174 164 3356; fax: +49 351 458 5758. E-mail addresses: [email protected] (I. Platzek), [email protected] (B. Beuthien-Baumann), [email protected] (M. Schneider), [email protected] (V. Gudziol), [email protected] (H.H. Kitzler), [email protected] (J. Maus), [email protected] (G. Schramm), [email protected] (M. Popp), [email protected] (M. Laniado), [email protected] (J. Kotzerke), j.van den [email protected] (J. van den Hoff).
by tumor location, tumor invasion of adjacent structures and the presence of metastases [4,5]. Magnetic resonance imaging [6] is widely used in head and neck imaging due to its excellent soft tissue contrast, which can improve tumor detection and delineation in comparison to CT. However, the sensitivity of MR for metastatic lymph node disease is rather low, as it relies on morphological criteria for lymph node evaluation [7]. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been shown to have better sensitivity for cervical lymph node metastases in comparison to both computed tomography (CT) and MR [8,9]. Because of its relatively low spatial resolution [10,11] and low soft tissue contrast, PET is not suited as a standalone imaging modality in head and neck cancer. Hybrid PET/MR systems combine the unique metabolic imaging capabilities of PET with the superb soft tissue contrast of MR. Combined PET/MR thus appears to be a promising modality for head and neck imaging. The aim of this study was to prospectively assess the diagnostic value of PET/MR (positron
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emission tomography/magnetic resonance imaging) with FDG (18F-fluorodeoxyglucose) for lymph node staging in patients with head and neck cancer. 2. Materials and methods 2.1. Patients The prospective study was approved by the institutional ethics committee and all patients signed a written informed consent form. Between January 2011 and February 2012, 61 patients with squamous cell carcinoma of the upper aerodigestive tract were prospectively enrolled and underwent FDG PET/MR. Inclusion criteria were as follows: histologically proven squamous cell carcinoma of the upper aerodigestive tract, no treatment prior to PET/MR, and lymph node histology available after surgery. Twenty-three patients had to be excluded as they did not receive surgical treatment and thus no histological correlation for lymph node findings was available. Consequently, 38 patients (30 men and 8 women) who received surgical treatment were included in the study. The mean age of these patients was 63 yr (age range, 43–82 yr). Tumor locations included the floor of the mouth (n = 10), tongue (n = 9), mandible (n = 7), maxilla (n = 3), larynx (n = 2), piriform sinus (n = 2), lower lip (n = 1), hypopharynx (n = 1), soft palate (n = 1), buccal plane (n = 1) and the palatoglossal arch (n = 1). All patients included in the study had surgery after the PET/MR exam described below. Histology was available for all patients and served as standard of reference. In total, 67 (88.1%) of 76 neck sides were dissected (391 lymph nodes levels, 1289 lymph nodes). Neck dissection specimens were marked by the surgeon to identify lymph node levels in analogy to the classification introduced by the American Academy Committee for Head and Neck surgery and Oncology [12] and thus to allow correlation between histology results and imaging findings. Cervical lymph nodes were assigned to the following groups: Level Ia: submental lymph node group; Level Ib: submandibular lymph node group; Level IIa: upper jugular group, anterior, lateral or medial to the internal jugular vein; Level IIb: upper jugular group, posterior to the internal jugular vein; Level III: middle jugular group; Level IV: lower jugular group; Level V: posterior triangle group; Level VI: anterior compartment group. The surgeons were not blinded to PET/MR findings. 2.2. PET All patients underwent standalone PET and combined PET/MR on the same day after a single FDG injection. The patients were instructed to restrain from food intake for at least 6 h before FDG injection, while fluid intake (water or non-sugar added tea) was encouraged. PET imaging was performed with a dedicated PET scanner (ECAT EXACT HR+, Siemens, Erlangen, Germany, axial field of view of 15.5 cm, reconstructed isotropic spatial resolution ≈6.5 mm). 4.5 MBq FDG/kg body weight were applied intravenously before the examination (263–411 MBq FDG/patient, 345 MBq on average). Blood glucose level at the time of the injection varied between 4.2 and 9.2 mmol/l (average 5.7 mmol/l). Time between the tracer application and the start of the PET scan varied between 53 and 110 min (average 64 min). Emission and transmission scanning (68Ge/68Ga rod sources) covered the body from the proximal femora to the base of the skull. 2.3. PET/MR After the first PET scan the patient was transferred to the adjacent PET/MR scanner (Ingenuity TF PET/MR, Philips Medical Systems, Best, The Netherlands). The PET component of the system features time-of-flight technology, an axial field of view of 18 cm,
9 cm overlap between bed positions and a reconstructed isotropic spatial resolution of ≈5.5 mm. The PET/MR exam consisted of a low-resolution nondiagnostic “attenuation MR scan” (atMR) of the head, neck, and thorax, followed by a PET scan and a diagnostic MR scan of the head and neck region. atMR is a nondiagnostic T1-weighted gradient echo scan used for PET attenuation correction. As recommended by the manufacturer, it covers head, neck, and thorax. Although the patient is positioned in a 16-channel phased array neurovascular coil from the start of the PET/MR exam, atMR scans are acquired with the integrated quadrature body coil. The acquisition time for the atMR was 2:20 min. The effects of the phased array coil on the PET attenuation are taken into account via a corresponding vendor provided template which is included into the final attenuation image. Average time between the tracer injection and start of the second PET scan was 177 min (143–225 min). Three bed positions were used to cover the complete head and neck region. Emission time was 6 min for each bed position and PET data were acquired in 3D mode. Attenuation correction in the Philips Ingenuity TF PET/MR is based on segmentation of the atMR scan mentioned above in three tissue classes (air, lung tissue, soft tissue) [13]. Subsequently, corresponding linear attenuation coefficients (0 cm−1 for air, 0.022 cm−1 for lung tissue, 0.096 cm−1 for soft tissue) are assigned to the tissue classes. The position of the patient on the scanner table remains unchanged during the whole exam in order to achieve the best possible image overlay of both imaging modalities. Diagnostic MR images were acquired with a 16-channel phased array neurovascular coil. A transverse short tau inversion recovery (STIR) turbo spin echo (TSE) sequence was acquired with 4354 ms/30 ms(repetition time/echo time), 30 slices, 4 mm slice thickness, a field of view of 250 × 180 mm and a 512 × 370 matrix. The acquisition time was 4:21 min. A coronal STIR TSE sequence was performed with 4354 ms/60 ms, 30 slices, 3 mm slice thickness, a field of view of 250 × 199 mm and a matrix of 512 × 407. The acquisition time was 4:47 min. A transverse T1-weighted TSE sequence was performed with 450 ms/9.2 ms, 24 slices, 4 mm slice thickness, a field of view of 250 × 159 mm and a matrix of 512 × 325. Acquisition time was 3:50 min. 0.2 ml/kg body weight Gd-DTPA (Magnevist® , Bayer Schering Pharma, Berlin, Germany) were administered intravenously, followed by 20 ml saline flush. A transverse T1-weighted TSE sequence with spectral presaturation with inversion recovery [14] was performed after contrast injection with 656 ms/9.2 ms, 25 slices, 4 mm slice thickness, a field of view of 250 × 159 mm and a matrix of 512 × 325. Acquisition time was 5:31 min. A coronal T1-weighted high-resolution isotropic volume examination (THRIVE) gradient echo sequence with fat saturation was performed after contrast injection with 7.5 ms/3.6 ms, 2 mm slice thickness, 150 slices, a field of view of 250 × 199 mm and a matrix of 256 × 203. Acquisition time was 3:17 min. Total imaging time for the PET/MR exam was 38 min, including 18 min PET scan time. Fused PET/MR images were created using vendor provided fusion software (Philips Fusion Viewer). 2.4. Image interpretation MR images were evaluated by two board certified radiologists (with seven and eight years experience in head and neck MR, respectively) without access to the PET data. MR image evaluation was performed on a Philips Extended MR Workspace (EWS) console. Lymph nodes with a minimal transverse diameter of 10 mm or more were considered metastatic [15,16]. Lymph node necrosis and contour irregularities were also considered a sign of metastatic
Please cite this article in press as: Platzek I, et al. FDG PET/MR for lymph node staging in head and neck cancer. Eur J Radiol (2014), http://dx.doi.org/10.1016/j.ejrad.2014.03.023
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Fig. 1. A small, histologically proven squamous cell carcinoma adjacent to the mandible. The tumor is easily recognized on the hybrid PET/MR image (C, arrow). The lesion was not visible using MR alone: (A) short tau inversion recovery (STIR) image; (B) corresponding contrast enhanced T1 turbo spin echo (TSE) image with fat saturation.
disease. In case of differing results the final decision was met together in consensus. PET scans were evaluated by two nuclear medicine physicians (with 20 years and 6 years of experience in PET, respectively) without access to other imaging modalities, including MR images. In case of differing results the final decision was met together in consensus. The ROVER® software package (ABX advanced biochemical compounds, Radeberg, Germany) [17] was used for PET evaluation. Lesions which appeared to have increased tracer uptake in comparison to the salivary glands or muscles were considered suggestive for malignancy [18]. PET/MR images were evaluated by a board-certified radiologist (with seven years experience with head and neck MR) and a boardcertified nuclear-medicine physician (with 20 years of experience in PET) in consensus. The readers were blinded for earlier results from PET and MR readings. The time interval between evaluation sessions for PET/MR and evaluation sessions for PET and MR was at least four weeks in order to eliminate bias from earlier consensus readings. Lymph node levels were rated according to a five-point scale: 0 = benign, 1 = probably benign, 2 = equivocal, 3 = probably malignant, 4 = malignant. Neck sides received a score identical to the highest rating of any lymph node level located on this side.
3. Results 3.1. Primary tumors The primary tumor was detected by PET/MR in 33 (86.8%) of 38 patients, by PET in 33 (86.8%) of 38 cases, and by MRI in 28 (74.7%) of 38 cases (Fig. 1). Tumors missed by MRI (10 of 38, 26.3%) included seven pT1 stage tumors (floor of the mouth: n = 3; mandible: n = 2; tongue: n = 1; palatoglossal arch: n = 1), two stage pT2 tumors (maxilla: n = 1, floor of the mouth: n = 1) and one pT3 tumor (located in the soft palate). All five tumors not diagnosed by PET and PET/MR were stage pT1 cases (floor of the mouth: n = 3; tongue: n = 1; mandible: n = 1). Among the five (13.1%) of 38 patients whose primary tumor was detected by PET/MR but not by MR, two had T1-, two had T2and one had T3-stage disease. 3.2. Cervical lymph node metastases Histopathology detected metastatic disease in 16 (42.1%) of 38 patients or 21 (31.3%) of 67 dissected neck sides. Eleven (28.9%) of 38 patients had unilateral and 5 (13.1%) of 38 patients had bilateral lymph node metastases. Thirty-eight (9.7%) of 391 lymph node levels contained metastatic lymph nodes. Seventy metastatic lymph nodes were identified using histopathology. The maximal diameter of metastases varied between 3 and 35 mm.
2.5. Statistical analysis Receiver operating characteristic (ROC) analysis was used to compare the accuracy of the three modalities. Sets of ROC curves were generated for the likelihood of malignancy in each lymph node level and for the likelihood of malignancy in each neck side. ROC analysis for the likelihood of malignancy in each neck side was included both because of possible clinical implications and to reduce possible clustering effects [19], which are more pronounced in lymph node level analysis because of the larger number of lymph node levels per patient. Sensitivity and specificity were also calculated, with equivocal cases considered positive. Cohen’s kappa was used to evaluate interrater agreement. MedCalc 12.0 (MedCalc Software, Ostend, Belgium) was used for ROC analysis and evaluation of interrater agreement. A pvalue < 0.05 was considered statistically significant.
Fig. 2. ROC curve generated for the detection of malignancy in a lymph node level. There was no significant difference between the AUCs (areas under the curve), representing the accuracy of the three imaging methods (PET/MR, PET and MR).
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Fig. 3. Cervical lymph node metastasis (arrow) in a patient with a squamous cell carcinoma of the right piriform sinus. (A) Nonenhanced T1-weighted turbo spin echo (TSE) image; (B) short tau inversion recovery (STIR) image; (C) fused PET/MR image. The metastasis was recognized on PET and PET/MR images because of the increased FDG uptake, but not on MR images, as the lymph node is not enlarged.
3.3. Level-based evaluation ROC curves based on the level-by-level accuracy of PET/MR, PET and MR are shown in Fig. 2. In the assessment of lymph node levels, the area under the ROC curve was 0.96 for PET/MR (95% CI: 0.94–0.98), 0.95 for PET (95% CI: 0.92–0.97) and 0.9 (95% CI: 0.86–0.92) for MR. There was no statistically significant difference for lymph node level assessment between PET/MR and MR (p = 0.07), PET and MR (p = 0.16), and PET/MR and PET (p = 0.29). On a level basis, sensitivity and specificity for metastatic involvement were 65.8% (25/38; 95% CI: 48.6–80.4%) and 97.2% (343/353; 95% CI: 94.9–98.6%) for MR, 86.8% (33/38; 95% CI: 72.0–95.6%) and 97.0% (343/353; 95% CI: 93.4–97.8%) for PET and 89.5% (34/38; 95% CI: 75.2–97.1%) and 95.2% (338/353; 95% CI: 93.1–97.6%) for PET/MR, respectively. An example for a lymph node metastasis recognized by PET/MR (and PET) but missed by MR is shown in Fig. 3. Scores assigned by the two nuclear medicine physicians who performed the evaluation were identical for 331 lymph node levels and different for 60 lymph node levels ( = 0.82). The radiologists who evaluated the MR images assigned identical scores for 340 (86.9% of 391 lymph node levels and different scores for 51 (13%) of 391 levels ( = 0.92). In the assessment of neck sides, the area under the ROC curve was 0.91 (95% CI: 0.82–0.97) for PET/MR, 0.9 (95% CI: 0.8–0.96) for PET and 0.82 (95% CI: 0.7–0.9) for MR. There were no significant differences between MR and PET/MR (p = 0.08), MR and PET (p = 0.18) and between PET and PET/MR (p = 0.25) regarding accuracy for metastatic lymph node involvement per neck side (Fig. 4). Sensitivity and specificity for neck side involvement in metastatic lymph node disease were 90.5% (19/21; 95% CI: 69.6–98.8%) and 84.8% (39/46; 95% CI: 80.2–94.5%) for PET/MR, 85.7% (18/21; 95% CI: 63.7–97.0%) and 84.8% (39/46: 95% CI: 71.1–93.7%) for PET and 66.7% (14/21; 95% CI: 48.0–85.4%) and 87.0% (40/46; 95% CI: 73.7–95.1%) for MR, respectively. Four neck sides classified as benign or rather benign (scores 0 or 1) by MR were rated as equivocal or rather malignant by PET/MR (scores 2 or 3). These included two neck sides contralateral to the primary tumor.
4. Discussion The results of the current study indicate that FDG PET/MR, MR alone, and PET alone have similar accuracy for lymph node staging
Fig. 4. ROC curve generated for the detection of malignancy in a neck side. In analogy to the ROC analysis of lymph node levels, the accuracy of PET/MR, PET and MR for metastatic lymph node disease per neck side does not differ significantly.
in head and neck cancer, regarding both individual lymph node levels and neck sides. While the sensitivity of PET/MR was higher than the sensitivity of MR, the difference was not pronounced enough to significantly affect accuracy. The study did not confirm our initial hypothesis that the use of FDG PET/MR would result in improved accuracy in comparison to MR. While PET/MR was able to identify metastatic disease in four neck sides classified as benign or rather benign by MR, including two contralateral neck sides, on the whole there was no statistically significant difference between the three methods. Our results imply that the additional cost and scan time of a PET/MR examination in comparison to MR are not justified in initial staging of head and neck cancer. To our knowledge, this is the first study which evaluated the role of FDG PET/MR for lymph node staging in head and neck cancer. Boss et al. [20] and Platzek et al. [21] have already demonstrated the feasibility of FDG PET/MR for evaluation of head and neck tumors. These initial reports did not include a comparison with lymph node histology. Our results show parrallels to a study by Nakamoto et al. [22], who found no significant advantage of software image fusion (FDG PET and MR) over MR for initial staging of head and neck cancer. However, this study did not include an evaluation based on lymph node-levels or neck sides. Image fusion is also not wholly comparable to hybrid PET/MR examinations, as the latter is performed without patient repositioning, thus reducing possible mismatch of PET and MR findings.
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The sensitivity and specificity of FDG PET and MR calculated in our study are similar to the results of previous studies which evaluated these imaging modalities [8,23–25]. However, while the current study did not find significant differences between FDG PET/MR and standalone MR, previous studies reported PET/CT to have superior accuracy for metastatic lymph node disease when compared to MR. For example, Ng et al. [9] found that FDG PET/CT has better sensitivity than CT and MR for metastatic lymph node involvement in carcinoma of the oral cavity. In contrast, Yoon et al. [25] found no significant differences between PET/CT, MR and CT regarding accuracy for metastatic lymph node disease in head and neck cancer, which is similar to our study. These differences may in part be caused by different patient selection criteria, as Ng et al. included only patients with no palpable metastatic neck disease, while this was not the case in our study. The inclusion of patients with palpable neck disease may minimize differences in outcome between imaging modalities, as it may be assumed that palpable lymph nodes are large enough to be detected by MR. Another possible contributing factor for the high accuracy of MR in our study may be the readers’s experience with head and neck MR. While Ng et al. state that the radiologists in their study had experience with head and neck MR, the level of experience is not specified. In contrast, Yoon et al. state that the radiologists responsible for the MR reading in their study had 5 and 12 years experience in head and neck MR, which is comparable to our study (7 and 8 years experience, respectively). In our study, the surgeons were not blinded to the results of PET/MR imaging, which is another possible source of bias. Technological differences between the current study and previous studies may also partially explain different results. The PET/MR system used in our study utilizes a 3 T magnet and time-of-flight PET technology. Both have the potential to improve the signal-tonoise-ratio, and thus image quality of MR and PET, respectively. The use of both technologies for head and neck imaging has not been evaluated yet. While time-of-flight PET improves PET image quality, it also may improve the visibility of inflammatory lymph nodes and lead to false positives. Our study has several limitations. The decision to include only patients with histologically proven primary tumors is a limitation of the study design, as it is not possible to provide meaningful data on accuracy for primary tumor detection. This limitation is a consequence of clinical routine, as patients presenting with suspicious findings of the oral cavity, the pharynx or larynx are usually biopsied before MR or CT is performed. The relatively long time between tracer injection and the start of PET/MR may also be a limiting factor. Usually, FDG PET scans start about 60 min after tracer injection, while in our study the time between the injection and the start of the PET component of the combined PET/MR exam was 177 min on average. Tumor FDG uptake increases with time, leading to higher SUVmax values at later time points [26]. This may improve the recognition of lymph node metastases. The longer interval after radiotracer application was a consequence of the preceding conventional PET scan, as described above. The combination of conventional PET and PET/MR in this study was dictated by ethical concerns, as at the beginning of the study, there was virtually no information about extracranial PET/MR available. In contrast, conventional FDG PET is a well established method in head and neck imaging. Thus by performing FDG PET/MR after the stand-alone PET, we were able to evaluate the new modality without additional radiotracer injection and thus avoid potential unnecessary radiation exposure. The study also does not include a comparison to PET/CT, which is more widely available than PET/MR. Comparison with FDG PET/CT is especially important, as some studies were able to show that the accuracy of FDG PET/CT is significantly better when compared to FDG PET [19,27]. As the current study found no significant difference in accuracy
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between PET/MR and PET, it is possible that PET/CT is superior to PET/MR too. While previous studies which compared the accuracy of CT and MR for cervical lymph node metastases do not support such a hypothesis [28], this issue deserves further investigation. 5. Conclusions The use of FDG PET/MR does not improve accuracy for initial lymph node staging in head and neck cancer in comparison to MR and FDG PET. Further studies are necessary to evaluate the possible role of PET/MR in suspected recurrence of head and neck cancer. Conflict of interest statement There was no conflict of interest. References [1] Curado MP, Hashibe M. Recent changes in the epidemiology of head and neck cancer. Curr Opin Oncol 2009;21(3):194–200. [2] Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA-Cancer J Clin 1999;49(1):33–64, 1. [3] Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010. [4] Johnson JT. A surgeon looks at cervical lymph nodes. Radiology 1990;175(3):607–10. [5] Denis F, Garaud P, Manceau A, et al. Prognostic value of the number of involved nodes after neck dissection in oropharyngeal and oral cavity carcinoma. Cancer Radiother 2001;5(1):12–22. [6] El-Husseiny G, Kandil A, Jamshed A, et al. Squamous cell carcinoma of the oral tongue: an analysis of prognostic factors. Br J Oral Maxillofac Surg 2000;38(3):193–9. [7] Ng SH, Yen TC, Liao CT, et al. 18F-FDG PET and CT/MRI in oral cavity squamous cell carcinoma: a prospective study of 124 patients with histologic correlation. J Nucl Med 2005;46(7):1136–43. [8] Hannah A, Scott AM, Tochon-Danguy H, et al. Evaluation of 18 Ffluorodeoxyglucose positron emission tomography and computed tomography with histopathologic correlation in the initial staging of head and neck cancer. Ann Surg 2002;236(2):208–17. [9] Ng SH, Yen TC, Chang JT, et al. 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 2006;24(27):4371–6. [10] Brambilla M, Secco C, Dominietto M, Matheoud R, Sacchetti G, Inglese E. Performance characteristics obtained for a new 3-dimensional lutetium oxyorthosilicate-based whole-body PET/CT scanner with the National Electrical Manufacturers Association NU 2-2001 standard. J Nucl Med 2005;46(12):2083–91. [11] De Ponti E, Morzenti S, Guerra L, et al. Performance measurements for the PET/CT Discovery-600 using NEMA NU 2-2007 standards. Med Phys 2011;38(2):968–74. [12] Robbins KT, Medina JE, Wolfe GT, Levine PA, Sessions RB, Pruet CW. Standardizing neck dissection terminology. Official report of the Academy’s Committee for Head and Neck Surgery and Oncology. Arch Otolaryngol Head Neck Surg 1991;117(6):601–5. [13] Schulz V, Torres-Espallardo I, Renisch S, et al. Automatic, three-segment, MRbased attenuation correction for whole-body PET/MR data. Eur J Nucl Med Mol Imaging 2011;38(1):138–52. [14] Spiro RH, Morgan GJ, Strong EW, Shah JP. Supraomohyoid neck dissection. Am J Surg 1996;172(6):650–3. [15] van den Brekel MW, Stel HV, Castelijns JA, et al. Cervical lymph node metastasis: assessment of radiologic criteria. Radiology 1990;177(2):379–84. [16] Castelijns JA, van den Brekel MW. Imaging of lymphadenopathy in the neck. Eur Radiol 2002;12(4):727–38. [17] Torigian DA, Lopez RF, Alapati S, et al. Feasibility and performance of novel software to quantify metabolically active volumes and 3D partial volume corrected SUV and metabolic volumetric products of spinal bone marrow metastases on 18F-FDG-PET/CT. Hell J Nucl Med 2011;14(1):8–14. [18] Stuckensen T, Kovacs AF, Adams S, Baum RP. Staging of the neck in patients with oral cavity squamous cell carcinomas: a prospective comparison of PET, ultrasound, CT and MRI. J Craniomaxillofac Surg 2000;28(6):319–24. [19] Ft Branstetter B, Blodgett TM, Zimmer LA, et al. Head and neck malignancy: is PET/CT more accurate than PET or CT alone? Radiology 2005;235(2):580–6. [20] Boss A, Stegger L, Bisdas S, et al. Feasibility of simultaneous PET/MR imaging in the head and upper neck area. Eur Radiol 2011;21(7):1439–46. [21] Platzek I, Beuthien-Baumann B, Schneider M, et al. PET/MRI in head and neck cancer: initial experience. Eur J Nucl Med Mol Imaging 2013;40(1):6–11. [22] Nakamoto Y, Tamai K, Saga T, et al. Clinical value of image fusion from MR and PET in patients with head and neck cancer. Mol Imag Biol 2009;11(1):46–53.
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FDG PET/MR for lymph node staging in head and neck cancer Ivan Platzek a,∗ , Bettina Beuthien-Baumann b , Matthias Schneider c , Volker Gudziol d , Hagen H. Kitzler e , Jens Maus f , Georg Schramm f , Manuel Popp b , Michael Laniado a , Jörg Kotzerke b , Jörg van den Hoff f a
Dresden University Hospital, Department of Radiology, Fetscherstr. 74, 01307 Dresden, Germany Dresden University Hospital, Department of Nuclear Medicine, Fetscherstr. 74, 01307 Dresden, Germany Dresden University Hospital, Department of Oral and Maxillofacial Surgery, Fetscherstr. 74, 01307 Dresden, Germany d Dresden University Hospital, Department of Otolaryngology, Fetscherstr. 74, 01307 Dresden, Germany e Dresden University Hospital, Department of Neuroradiology, Fetscherstr. 74, 01307 Dresden, Germany f Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstr. 400, 01328 Dresden, Germany b c
a r t i c l e
i n f o
Article history: Received 24 February 2014 Received in revised form 16 March 2014 Accepted 19 March 2014 Keywords: PET/MR Head and neck cancer Lymph node metastasis Staging
a b s t r a c t Objective: To assess the diagnostic value of PET/MR (positron emission tomography/magnetic resonance imaging) with FDG (18F-fluorodeoxyglucose) for lymph node staging in head and neck cancer. Materials and methods: This prospective study was approved by the local ethics committee; all patients signed informed consent. Thirty-eight patients with squamous cell carcinoma of the head and neck region underwent a PET scan on a conventional scanner and a subsequent PET/MR on a whole-body hybrid system after a single intravenous injection of FDG. The accuracy of PET, MR and PET/MR for lymph node metastases were compared using receiver operating characteristic (ROC) analysis. Histology served as the reference standard. Results: Metastatic disease was confirmed in 16 (42.1%) of 38 patients and 38 (9.7%) of 391 dissected lymph node levels. There were no significant differences between PET/MR, MR and PET and MR (p > 0.05) regarding accuracy for cervical metastatic disease. Based on lymph node levels, sensitivity and specificity for metastatic involvement were 65.8% and 97.2% for MR, 86.8% and 97.0% for PET and 89.5% and 95.2% for PET/MR. Conclusions: In head and neck cancer, FDG PET/MR does not significantly improve accuracy for cervical lymph node metastases in comparison to MR or PET. © 2014 Published by Elsevier Ireland Ltd.
1. Introduction Malignant head and neck tumors are predominantly squamous cell carcinoma [1]. Head and neck cancer is among the malignancies with the highest worldwide incidence [2,3]. Both the choice of therapy and prognosis in head and neck cancer are influenced
∗ Corresponding author. Tel.: +49 351 458 18223/+49 174 164 3356; fax: +49 351 458 5758. E-mail addresses: [email protected] (I. Platzek), [email protected] (B. Beuthien-Baumann), [email protected] (M. Schneider), [email protected] (V. Gudziol), [email protected] (H.H. Kitzler), [email protected] (J. Maus), [email protected] (G. Schramm), [email protected] (M. Popp), [email protected] (M. Laniado), [email protected] (J. Kotzerke), j.van den [email protected] (J. van den Hoff).
by tumor location, tumor invasion of adjacent structures and the presence of metastases [4,5]. Magnetic resonance imaging [6] is widely used in head and neck imaging due to its excellent soft tissue contrast, which can improve tumor detection and delineation in comparison to CT. However, the sensitivity of MR for metastatic lymph node disease is rather low, as it relies on morphological criteria for lymph node evaluation [7]. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been shown to have better sensitivity for cervical lymph node metastases in comparison to both computed tomography (CT) and MR [8,9]. Because of its relatively low spatial resolution [10,11] and low soft tissue contrast, PET is not suited as a standalone imaging modality in head and neck cancer. Hybrid PET/MR systems combine the unique metabolic imaging capabilities of PET with the superb soft tissue contrast of MR. Combined PET/MR thus appears to be a promising modality for head and neck imaging. The aim of this study was to prospectively assess the diagnostic value of PET/MR (positron
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emission tomography/magnetic resonance imaging) with FDG (18F-fluorodeoxyglucose) for lymph node staging in patients with head and neck cancer. 2. Materials and methods 2.1. Patients The prospective study was approved by the institutional ethics committee and all patients signed a written informed consent form. Between January 2011 and February 2012, 61 patients with squamous cell carcinoma of the upper aerodigestive tract were prospectively enrolled and underwent FDG PET/MR. Inclusion criteria were as follows: histologically proven squamous cell carcinoma of the upper aerodigestive tract, no treatment prior to PET/MR, and lymph node histology available after surgery. Twenty-three patients had to be excluded as they did not receive surgical treatment and thus no histological correlation for lymph node findings was available. Consequently, 38 patients (30 men and 8 women) who received surgical treatment were included in the study. The mean age of these patients was 63 yr (age range, 43–82 yr). Tumor locations included the floor of the mouth (n = 10), tongue (n = 9), mandible (n = 7), maxilla (n = 3), larynx (n = 2), piriform sinus (n = 2), lower lip (n = 1), hypopharynx (n = 1), soft palate (n = 1), buccal plane (n = 1) and the palatoglossal arch (n = 1). All patients included in the study had surgery after the PET/MR exam described below. Histology was available for all patients and served as standard of reference. In total, 67 (88.1%) of 76 neck sides were dissected (391 lymph nodes levels, 1289 lymph nodes). Neck dissection specimens were marked by the surgeon to identify lymph node levels in analogy to the classification introduced by the American Academy Committee for Head and Neck surgery and Oncology [12] and thus to allow correlation between histology results and imaging findings. Cervical lymph nodes were assigned to the following groups: Level Ia: submental lymph node group; Level Ib: submandibular lymph node group; Level IIa: upper jugular group, anterior, lateral or medial to the internal jugular vein; Level IIb: upper jugular group, posterior to the internal jugular vein; Level III: middle jugular group; Level IV: lower jugular group; Level V: posterior triangle group; Level VI: anterior compartment group. The surgeons were not blinded to PET/MR findings. 2.2. PET All patients underwent standalone PET and combined PET/MR on the same day after a single FDG injection. The patients were instructed to restrain from food intake for at least 6 h before FDG injection, while fluid intake (water or non-sugar added tea) was encouraged. PET imaging was performed with a dedicated PET scanner (ECAT EXACT HR+, Siemens, Erlangen, Germany, axial field of view of 15.5 cm, reconstructed isotropic spatial resolution ≈6.5 mm). 4.5 MBq FDG/kg body weight were applied intravenously before the examination (263–411 MBq FDG/patient, 345 MBq on average). Blood glucose level at the time of the injection varied between 4.2 and 9.2 mmol/l (average 5.7 mmol/l). Time between the tracer application and the start of the PET scan varied between 53 and 110 min (average 64 min). Emission and transmission scanning (68Ge/68Ga rod sources) covered the body from the proximal femora to the base of the skull. 2.3. PET/MR After the first PET scan the patient was transferred to the adjacent PET/MR scanner (Ingenuity TF PET/MR, Philips Medical Systems, Best, The Netherlands). The PET component of the system features time-of-flight technology, an axial field of view of 18 cm,
9 cm overlap between bed positions and a reconstructed isotropic spatial resolution of ≈5.5 mm. The PET/MR exam consisted of a low-resolution nondiagnostic “attenuation MR scan” (atMR) of the head, neck, and thorax, followed by a PET scan and a diagnostic MR scan of the head and neck region. atMR is a nondiagnostic T1-weighted gradient echo scan used for PET attenuation correction. As recommended by the manufacturer, it covers head, neck, and thorax. Although the patient is positioned in a 16-channel phased array neurovascular coil from the start of the PET/MR exam, atMR scans are acquired with the integrated quadrature body coil. The acquisition time for the atMR was 2:20 min. The effects of the phased array coil on the PET attenuation are taken into account via a corresponding vendor provided template which is included into the final attenuation image. Average time between the tracer injection and start of the second PET scan was 177 min (143–225 min). Three bed positions were used to cover the complete head and neck region. Emission time was 6 min for each bed position and PET data were acquired in 3D mode. Attenuation correction in the Philips Ingenuity TF PET/MR is based on segmentation of the atMR scan mentioned above in three tissue classes (air, lung tissue, soft tissue) [13]. Subsequently, corresponding linear attenuation coefficients (0 cm−1 for air, 0.022 cm−1 for lung tissue, 0.096 cm−1 for soft tissue) are assigned to the tissue classes. The position of the patient on the scanner table remains unchanged during the whole exam in order to achieve the best possible image overlay of both imaging modalities. Diagnostic MR images were acquired with a 16-channel phased array neurovascular coil. A transverse short tau inversion recovery (STIR) turbo spin echo (TSE) sequence was acquired with 4354 ms/30 ms(repetition time/echo time), 30 slices, 4 mm slice thickness, a field of view of 250 × 180 mm and a 512 × 370 matrix. The acquisition time was 4:21 min. A coronal STIR TSE sequence was performed with 4354 ms/60 ms, 30 slices, 3 mm slice thickness, a field of view of 250 × 199 mm and a matrix of 512 × 407. The acquisition time was 4:47 min. A transverse T1-weighted TSE sequence was performed with 450 ms/9.2 ms, 24 slices, 4 mm slice thickness, a field of view of 250 × 159 mm and a matrix of 512 × 325. Acquisition time was 3:50 min. 0.2 ml/kg body weight Gd-DTPA (Magnevist® , Bayer Schering Pharma, Berlin, Germany) were administered intravenously, followed by 20 ml saline flush. A transverse T1-weighted TSE sequence with spectral presaturation with inversion recovery [14] was performed after contrast injection with 656 ms/9.2 ms, 25 slices, 4 mm slice thickness, a field of view of 250 × 159 mm and a matrix of 512 × 325. Acquisition time was 5:31 min. A coronal T1-weighted high-resolution isotropic volume examination (THRIVE) gradient echo sequence with fat saturation was performed after contrast injection with 7.5 ms/3.6 ms, 2 mm slice thickness, 150 slices, a field of view of 250 × 199 mm and a matrix of 256 × 203. Acquisition time was 3:17 min. Total imaging time for the PET/MR exam was 38 min, including 18 min PET scan time. Fused PET/MR images were created using vendor provided fusion software (Philips Fusion Viewer). 2.4. Image interpretation MR images were evaluated by two board certified radiologists (with seven and eight years experience in head and neck MR, respectively) without access to the PET data. MR image evaluation was performed on a Philips Extended MR Workspace (EWS) console. Lymph nodes with a minimal transverse diameter of 10 mm or more were considered metastatic [15,16]. Lymph node necrosis and contour irregularities were also considered a sign of metastatic
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Fig. 1. A small, histologically proven squamous cell carcinoma adjacent to the mandible. The tumor is easily recognized on the hybrid PET/MR image (C, arrow). The lesion was not visible using MR alone: (A) short tau inversion recovery (STIR) image; (B) corresponding contrast enhanced T1 turbo spin echo (TSE) image with fat saturation.
disease. In case of differing results the final decision was met together in consensus. PET scans were evaluated by two nuclear medicine physicians (with 20 years and 6 years of experience in PET, respectively) without access to other imaging modalities, including MR images. In case of differing results the final decision was met together in consensus. The ROVER® software package (ABX advanced biochemical compounds, Radeberg, Germany) [17] was used for PET evaluation. Lesions which appeared to have increased tracer uptake in comparison to the salivary glands or muscles were considered suggestive for malignancy [18]. PET/MR images were evaluated by a board-certified radiologist (with seven years experience with head and neck MR) and a boardcertified nuclear-medicine physician (with 20 years of experience in PET) in consensus. The readers were blinded for earlier results from PET and MR readings. The time interval between evaluation sessions for PET/MR and evaluation sessions for PET and MR was at least four weeks in order to eliminate bias from earlier consensus readings. Lymph node levels were rated according to a five-point scale: 0 = benign, 1 = probably benign, 2 = equivocal, 3 = probably malignant, 4 = malignant. Neck sides received a score identical to the highest rating of any lymph node level located on this side.
3. Results 3.1. Primary tumors The primary tumor was detected by PET/MR in 33 (86.8%) of 38 patients, by PET in 33 (86.8%) of 38 cases, and by MRI in 28 (74.7%) of 38 cases (Fig. 1). Tumors missed by MRI (10 of 38, 26.3%) included seven pT1 stage tumors (floor of the mouth: n = 3; mandible: n = 2; tongue: n = 1; palatoglossal arch: n = 1), two stage pT2 tumors (maxilla: n = 1, floor of the mouth: n = 1) and one pT3 tumor (located in the soft palate). All five tumors not diagnosed by PET and PET/MR were stage pT1 cases (floor of the mouth: n = 3; tongue: n = 1; mandible: n = 1). Among the five (13.1%) of 38 patients whose primary tumor was detected by PET/MR but not by MR, two had T1-, two had T2and one had T3-stage disease. 3.2. Cervical lymph node metastases Histopathology detected metastatic disease in 16 (42.1%) of 38 patients or 21 (31.3%) of 67 dissected neck sides. Eleven (28.9%) of 38 patients had unilateral and 5 (13.1%) of 38 patients had bilateral lymph node metastases. Thirty-eight (9.7%) of 391 lymph node levels contained metastatic lymph nodes. Seventy metastatic lymph nodes were identified using histopathology. The maximal diameter of metastases varied between 3 and 35 mm.
2.5. Statistical analysis Receiver operating characteristic (ROC) analysis was used to compare the accuracy of the three modalities. Sets of ROC curves were generated for the likelihood of malignancy in each lymph node level and for the likelihood of malignancy in each neck side. ROC analysis for the likelihood of malignancy in each neck side was included both because of possible clinical implications and to reduce possible clustering effects [19], which are more pronounced in lymph node level analysis because of the larger number of lymph node levels per patient. Sensitivity and specificity were also calculated, with equivocal cases considered positive. Cohen’s kappa was used to evaluate interrater agreement. MedCalc 12.0 (MedCalc Software, Ostend, Belgium) was used for ROC analysis and evaluation of interrater agreement. A pvalue < 0.05 was considered statistically significant.
Fig. 2. ROC curve generated for the detection of malignancy in a lymph node level. There was no significant difference between the AUCs (areas under the curve), representing the accuracy of the three imaging methods (PET/MR, PET and MR).
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Fig. 3. Cervical lymph node metastasis (arrow) in a patient with a squamous cell carcinoma of the right piriform sinus. (A) Nonenhanced T1-weighted turbo spin echo (TSE) image; (B) short tau inversion recovery (STIR) image; (C) fused PET/MR image. The metastasis was recognized on PET and PET/MR images because of the increased FDG uptake, but not on MR images, as the lymph node is not enlarged.
3.3. Level-based evaluation ROC curves based on the level-by-level accuracy of PET/MR, PET and MR are shown in Fig. 2. In the assessment of lymph node levels, the area under the ROC curve was 0.96 for PET/MR (95% CI: 0.94–0.98), 0.95 for PET (95% CI: 0.92–0.97) and 0.9 (95% CI: 0.86–0.92) for MR. There was no statistically significant difference for lymph node level assessment between PET/MR and MR (p = 0.07), PET and MR (p = 0.16), and PET/MR and PET (p = 0.29). On a level basis, sensitivity and specificity for metastatic involvement were 65.8% (25/38; 95% CI: 48.6–80.4%) and 97.2% (343/353; 95% CI: 94.9–98.6%) for MR, 86.8% (33/38; 95% CI: 72.0–95.6%) and 97.0% (343/353; 95% CI: 93.4–97.8%) for PET and 89.5% (34/38; 95% CI: 75.2–97.1%) and 95.2% (338/353; 95% CI: 93.1–97.6%) for PET/MR, respectively. An example for a lymph node metastasis recognized by PET/MR (and PET) but missed by MR is shown in Fig. 3. Scores assigned by the two nuclear medicine physicians who performed the evaluation were identical for 331 lymph node levels and different for 60 lymph node levels ( = 0.82). The radiologists who evaluated the MR images assigned identical scores for 340 (86.9% of 391 lymph node levels and different scores for 51 (13%) of 391 levels ( = 0.92). In the assessment of neck sides, the area under the ROC curve was 0.91 (95% CI: 0.82–0.97) for PET/MR, 0.9 (95% CI: 0.8–0.96) for PET and 0.82 (95% CI: 0.7–0.9) for MR. There were no significant differences between MR and PET/MR (p = 0.08), MR and PET (p = 0.18) and between PET and PET/MR (p = 0.25) regarding accuracy for metastatic lymph node involvement per neck side (Fig. 4). Sensitivity and specificity for neck side involvement in metastatic lymph node disease were 90.5% (19/21; 95% CI: 69.6–98.8%) and 84.8% (39/46; 95% CI: 80.2–94.5%) for PET/MR, 85.7% (18/21; 95% CI: 63.7–97.0%) and 84.8% (39/46: 95% CI: 71.1–93.7%) for PET and 66.7% (14/21; 95% CI: 48.0–85.4%) and 87.0% (40/46; 95% CI: 73.7–95.1%) for MR, respectively. Four neck sides classified as benign or rather benign (scores 0 or 1) by MR were rated as equivocal or rather malignant by PET/MR (scores 2 or 3). These included two neck sides contralateral to the primary tumor.
4. Discussion The results of the current study indicate that FDG PET/MR, MR alone, and PET alone have similar accuracy for lymph node staging
Fig. 4. ROC curve generated for the detection of malignancy in a neck side. In analogy to the ROC analysis of lymph node levels, the accuracy of PET/MR, PET and MR for metastatic lymph node disease per neck side does not differ significantly.
in head and neck cancer, regarding both individual lymph node levels and neck sides. While the sensitivity of PET/MR was higher than the sensitivity of MR, the difference was not pronounced enough to significantly affect accuracy. The study did not confirm our initial hypothesis that the use of FDG PET/MR would result in improved accuracy in comparison to MR. While PET/MR was able to identify metastatic disease in four neck sides classified as benign or rather benign by MR, including two contralateral neck sides, on the whole there was no statistically significant difference between the three methods. Our results imply that the additional cost and scan time of a PET/MR examination in comparison to MR are not justified in initial staging of head and neck cancer. To our knowledge, this is the first study which evaluated the role of FDG PET/MR for lymph node staging in head and neck cancer. Boss et al. [20] and Platzek et al. [21] have already demonstrated the feasibility of FDG PET/MR for evaluation of head and neck tumors. These initial reports did not include a comparison with lymph node histology. Our results show parrallels to a study by Nakamoto et al. [22], who found no significant advantage of software image fusion (FDG PET and MR) over MR for initial staging of head and neck cancer. However, this study did not include an evaluation based on lymph node-levels or neck sides. Image fusion is also not wholly comparable to hybrid PET/MR examinations, as the latter is performed without patient repositioning, thus reducing possible mismatch of PET and MR findings.
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The sensitivity and specificity of FDG PET and MR calculated in our study are similar to the results of previous studies which evaluated these imaging modalities [8,23–25]. However, while the current study did not find significant differences between FDG PET/MR and standalone MR, previous studies reported PET/CT to have superior accuracy for metastatic lymph node disease when compared to MR. For example, Ng et al. [9] found that FDG PET/CT has better sensitivity than CT and MR for metastatic lymph node involvement in carcinoma of the oral cavity. In contrast, Yoon et al. [25] found no significant differences between PET/CT, MR and CT regarding accuracy for metastatic lymph node disease in head and neck cancer, which is similar to our study. These differences may in part be caused by different patient selection criteria, as Ng et al. included only patients with no palpable metastatic neck disease, while this was not the case in our study. The inclusion of patients with palpable neck disease may minimize differences in outcome between imaging modalities, as it may be assumed that palpable lymph nodes are large enough to be detected by MR. Another possible contributing factor for the high accuracy of MR in our study may be the readers’s experience with head and neck MR. While Ng et al. state that the radiologists in their study had experience with head and neck MR, the level of experience is not specified. In contrast, Yoon et al. state that the radiologists responsible for the MR reading in their study had 5 and 12 years experience in head and neck MR, which is comparable to our study (7 and 8 years experience, respectively). In our study, the surgeons were not blinded to the results of PET/MR imaging, which is another possible source of bias. Technological differences between the current study and previous studies may also partially explain different results. The PET/MR system used in our study utilizes a 3 T magnet and time-of-flight PET technology. Both have the potential to improve the signal-tonoise-ratio, and thus image quality of MR and PET, respectively. The use of both technologies for head and neck imaging has not been evaluated yet. While time-of-flight PET improves PET image quality, it also may improve the visibility of inflammatory lymph nodes and lead to false positives. Our study has several limitations. The decision to include only patients with histologically proven primary tumors is a limitation of the study design, as it is not possible to provide meaningful data on accuracy for primary tumor detection. This limitation is a consequence of clinical routine, as patients presenting with suspicious findings of the oral cavity, the pharynx or larynx are usually biopsied before MR or CT is performed. The relatively long time between tracer injection and the start of PET/MR may also be a limiting factor. Usually, FDG PET scans start about 60 min after tracer injection, while in our study the time between the injection and the start of the PET component of the combined PET/MR exam was 177 min on average. Tumor FDG uptake increases with time, leading to higher SUVmax values at later time points [26]. This may improve the recognition of lymph node metastases. The longer interval after radiotracer application was a consequence of the preceding conventional PET scan, as described above. The combination of conventional PET and PET/MR in this study was dictated by ethical concerns, as at the beginning of the study, there was virtually no information about extracranial PET/MR available. In contrast, conventional FDG PET is a well established method in head and neck imaging. Thus by performing FDG PET/MR after the stand-alone PET, we were able to evaluate the new modality without additional radiotracer injection and thus avoid potential unnecessary radiation exposure. The study also does not include a comparison to PET/CT, which is more widely available than PET/MR. Comparison with FDG PET/CT is especially important, as some studies were able to show that the accuracy of FDG PET/CT is significantly better when compared to FDG PET [19,27]. As the current study found no significant difference in accuracy
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between PET/MR and PET, it is possible that PET/CT is superior to PET/MR too. While previous studies which compared the accuracy of CT and MR for cervical lymph node metastases do not support such a hypothesis [28], this issue deserves further investigation. 5. Conclusions The use of FDG PET/MR does not improve accuracy for initial lymph node staging in head and neck cancer in comparison to MR and FDG PET. Further studies are necessary to evaluate the possible role of PET/MR in suspected recurrence of head and neck cancer. Conflict of interest statement There was no conflict of interest. References [1] Curado MP, Hashibe M. Recent changes in the epidemiology of head and neck cancer. Curr Opin Oncol 2009;21(3):194–200. [2] Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA-Cancer J Clin 1999;49(1):33–64, 1. [3] Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010. [4] Johnson JT. A surgeon looks at cervical lymph nodes. Radiology 1990;175(3):607–10. [5] Denis F, Garaud P, Manceau A, et al. Prognostic value of the number of involved nodes after neck dissection in oropharyngeal and oral cavity carcinoma. Cancer Radiother 2001;5(1):12–22. [6] El-Husseiny G, Kandil A, Jamshed A, et al. Squamous cell carcinoma of the oral tongue: an analysis of prognostic factors. Br J Oral Maxillofac Surg 2000;38(3):193–9. [7] Ng SH, Yen TC, Liao CT, et al. 18F-FDG PET and CT/MRI in oral cavity squamous cell carcinoma: a prospective study of 124 patients with histologic correlation. J Nucl Med 2005;46(7):1136–43. [8] Hannah A, Scott AM, Tochon-Danguy H, et al. Evaluation of 18 Ffluorodeoxyglucose positron emission tomography and computed tomography with histopathologic correlation in the initial staging of head and neck cancer. Ann Surg 2002;236(2):208–17. [9] Ng SH, Yen TC, Chang JT, et al. 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 2006;24(27):4371–6. [10] Brambilla M, Secco C, Dominietto M, Matheoud R, Sacchetti G, Inglese E. Performance characteristics obtained for a new 3-dimensional lutetium oxyorthosilicate-based whole-body PET/CT scanner with the National Electrical Manufacturers Association NU 2-2001 standard. J Nucl Med 2005;46(12):2083–91. [11] De Ponti E, Morzenti S, Guerra L, et al. Performance measurements for the PET/CT Discovery-600 using NEMA NU 2-2007 standards. Med Phys 2011;38(2):968–74. [12] Robbins KT, Medina JE, Wolfe GT, Levine PA, Sessions RB, Pruet CW. Standardizing neck dissection terminology. Official report of the Academy’s Committee for Head and Neck Surgery and Oncology. Arch Otolaryngol Head Neck Surg 1991;117(6):601–5. [13] Schulz V, Torres-Espallardo I, Renisch S, et al. Automatic, three-segment, MRbased attenuation correction for whole-body PET/MR data. Eur J Nucl Med Mol Imaging 2011;38(1):138–52. [14] Spiro RH, Morgan GJ, Strong EW, Shah JP. Supraomohyoid neck dissection. Am J Surg 1996;172(6):650–3. [15] van den Brekel MW, Stel HV, Castelijns JA, et al. Cervical lymph node metastasis: assessment of radiologic criteria. Radiology 1990;177(2):379–84. [16] Castelijns JA, van den Brekel MW. Imaging of lymphadenopathy in the neck. Eur Radiol 2002;12(4):727–38. [17] Torigian DA, Lopez RF, Alapati S, et al. Feasibility and performance of novel software to quantify metabolically active volumes and 3D partial volume corrected SUV and metabolic volumetric products of spinal bone marrow metastases on 18F-FDG-PET/CT. Hell J Nucl Med 2011;14(1):8–14. [18] Stuckensen T, Kovacs AF, Adams S, Baum RP. Staging of the neck in patients with oral cavity squamous cell carcinomas: a prospective comparison of PET, ultrasound, CT and MRI. J Craniomaxillofac Surg 2000;28(6):319–24. [19] Ft Branstetter B, Blodgett TM, Zimmer LA, et al. Head and neck malignancy: is PET/CT more accurate than PET or CT alone? Radiology 2005;235(2):580–6. [20] Boss A, Stegger L, Bisdas S, et al. Feasibility of simultaneous PET/MR imaging in the head and upper neck area. Eur Radiol 2011;21(7):1439–46. [21] Platzek I, Beuthien-Baumann B, Schneider M, et al. PET/MRI in head and neck cancer: initial experience. Eur J Nucl Med Mol Imaging 2013;40(1):6–11. [22] Nakamoto Y, Tamai K, Saga T, et al. Clinical value of image fusion from MR and PET in patients with head and neck cancer. Mol Imag Biol 2009;11(1):46–53.
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Please cite this article in press as: Platzek I, et al. FDG PET/MR for lymph node staging in head and neck cancer. Eur J Radiol (2014), http://dx.doi.org/10.1016/j.ejrad.2014.03.023