ASNR 2015 Scientific Paper (Electronic Poster) Hirofumi Kuno, MD, PhD1; Kotaro Sekiya, DDS, PhD1; Satoshi Fujii, MD, PhD2; Hiroaki Onaya, MD, PhD3; Katharina Otani, PhD4; Mitsuo Satake, MD, PhD1; Masahiko Kusumoto MD, PhD1 1. Department of Diagnostic Radiology, 2. Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan 3. Department of Diagnostic Radiology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan 4. Imaging & Therapy Systems Division, Siemens Japan K.K., Shinagawa-ku, Tokyo, Japan Disclosures • Kuno H, Sekiya K, Fujii S, Onaya H, Satake M, Kusumoto M – None • Otani K – Employee, Siemens Japan K.K. • The treatment of laryngeal and hypopharyngeal squamous cell carcinoma (SCC) depends on the presence or absence of cartilage invasion. • When the tumor extends through the cartilage into the soft tissue of the neck, the patient often requires aggressive treatment such as total laryngectomy1-3. • Both computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used for the detection of subtle cartilage invasion, although the modality that can most accurately detect cartilage invasion remains controversial4-10. Furthermore, both modalities have shortcomings. • Recently, dual-energy CT was shown to have higher diagnostic performance than conventional CT 11,12, although its efficiency has not been compared with that of MRI. • To compare the effectiveness of dual-energy CT and MRI in the detection of cartilage invasion by laryngeal and hypopharyngeal SCC. • Study design – Retrospective cross-sectional study with institutional review board approval. • Study population – Between September 2010 and September 2014, 605 consecutive patients diagnosed with laryngeal or hypopharyngeal SCC were scheduled for a contrast-enhanced CT examination for cancer staging using 128 slice dual-source CT. – Among these, 115 underwent 3T-MRI – Eight (7%) patients were excluded because of the below mentioned reasons: • • • Poor general condition Non contrast MRI study MR images showed severe artifacts that rendered the image non-diagnostic – Eventually, 107 patients (98 men, 9 women; 45 – 82 years; median age, 66 years) were enrolled in the final analysis. • Dual-energy CT protocol and postprocessing – 128-slice Dual-Source CT (SOMATOM Definition Flash, Siemens) • Dual-energy mode (100 kV, 140 kV), 200/200 mAs, 32 × 0.6 mm, 0.33 s, p0.6, 1-mm thickness, 0.7-mm increments, D30f. • Contrast medium, Ioverin300, 2. 5mL/s; scan start, 70 s. – Three-material-decomposition analysis (Syngo Dual Energy, Brain Hemorrhage; Siemens Healthcare) • Weighted-average (WA) images were generated by fusing datasets acquired with different tube voltages. These appear similar to 120-kV CT images. • Iodine overlay (IO) images were generated by fusing virtual noncontrast images and iodine images. • MR protocol and sequences – All studies were performed using a 3T MRI system (Ingenia 3.0T or Achieva 3.0T TX, Philips Medical Systems, Best, Netherlands). • Two-dimensional sequences [T2-weighted (T2W), T1-weighted (T2W), and contrast-enhanced fatsaturated T1W), parallel and vertical to the vocal cords, were obtained with a slice thickness of 3 mm and a 1-mm intersection gap. • Three-dimensional sequences (T2W, unenhanced T1W, and enhanced T1W) were additionally performed in regions of interest that included the laryngeal component from 1.0 cm above the hyoid bone to the inferior margin of the cricoid cartilage. • Image interpretation – Two radiologists blinded to the clinical history and the image obtained using the other modality independently analysed the MRI and dualenergy CT images. – The images were presented in random order in two sessions, one with only MR images and one with only dual-energy CT images. – The invasion of each laryngeal were evaluated according to diagnostic criteria and five-point scale (cut off: score 3) • • • • • Score 1, definitely negative; Score 2, probably negative; Score 3, possibly positive (erosion); Score 4, probably positive (lysis); score 5, definitely positive (extra). – The final diagnosis was determined by consensus and was used to compare the CT findings with the pathologic results. • Diagnostic criteria – On MRI, cartilage invasion was considered present when the cartilage displayed a signal intensity similar to that of the adjacent tumor on T1W, T2W, and contrast-enhanced T1W images. – With regard to dual-energy CT, combined weighted-average (WA) and iodine overlay (IO) images were used for the evaluation of cartilage invasion, as described in previous reports 11. Diagnostic readings always began with the WA image, followed by additional reading of the IO image when appropriate. The WA image allows the evaluation of the cartilage shape, while the enhancement pattern on the IO image enables the identification of uptake due to the blood vessels of the cancer tissue, as opposed to the avascular cartilage. • Histologic evaluation – Surgical specimens, including all cartilages around the tumor, were fixed in formalin, decalcified in advance, and cut into 3.0–4.0-mmthick slices in the frontal direction, similar to the cross-sectional MR and CT images, and evaluated by a pathologist. • Statistical Analysis – Fifty five of the 107 patients (51%) underwent surgery, and findings from histopathological examination were used as the standard of reference for evaluating the diagnostic performance in terms of sensitivity and specificity using receiver operating characteristic (ROC) curve analysis. Sensitivity and specificity were evaluated using McNemar’s test. – All statistical tests were performed using commercial software (STATA ver. 12). – P-value of <.05 was considered statistically significant. Table 1 Diagnostic Performance for Evaluation of Cartilage Invasion and Extralaryngeal Spreading TP TN FN FP Sensitivity (%) Thyroid cartilage (n=55) MRI 19 23 0 13 100 (19/19) Dual-energy CT 17 36 2 0 89 (17/19) Cricoid cartilage (n=55) MRI 8 41 0 6 100 (8/8) Dual-energy CT 6 46 2 1 75 (6/8) Right Arytenoid cartilage (n=55) MRI 5 43 1 6 83 (5/6) Dual-energy CT 4 47 2 2 67 (4/6) Left Arytenoid cartilage (n=55) MRI 3 48 0 4 100 (3/3) Dual-energy CT 2 51 1 1 67 (2/3) Extralaryngeal spread (n=55) MRI 32 17 2 4 94 (32/34) Dual-energy CT 32 17 2 4 94 (32/34) Specificity (%) PPV (%) NPV (%) 64 (23/36) 100 (23/23)* 59 (19/32) 100 (23/23) 100 (17/17) 95 (36/38) 87 (41/47) 98 (46/47) 57 (8/14) 86 (6/7) 100 (41/41) 96 (46/48) 88 (43/49) 96 (47/49) 45 (5/11) 67 (4/6) 98 (43/44) 96 (47/49) 92 (48/52) 98 (51/52) 43 (3/7) 67 (2/3) 100 (48/48) 98 (51/52) 81 (17/21) 81 (17/21) 89 (32/36) 89 (32/36) 89 (17/19) 89 (17/19) Note.-Numbers in parentheses were used to calculate the percentages. TP = true positive, TN = true negative, FP = false positive, FN = false negative, PPV = Positive Predictive Value, NPV = Negative Predictive Value, * p=0.00009 for comparison between MRI and DECT • The specificity of dual-energy CT was superior to that of MRI (100% vs 64%, respectively; P < .0001) for the evaluation of thyroid cartilage, but no evidence indicated that the sensitivity of dual-energy CT differed from that of MRI (89% vs 100%, respectively; P = .50). 1.00 0.75 Sensitivity 0.50 0.25 0.00 0.00 0.25 0.50 1-Specificity DECT_Th ROC area: 0.9518 Reference 0.75 1.00 MRI_Th ROC area: 0.9379 • No evidence indicated differences in the average areas under the ROC curves between dual-energy CT and MRI (0.952 vs 0.938, respectively; P = .70). Case 1: False-positive findings for thyroid cartilage invasion on MRI (A) (B) (C) False-positive findings for thyroid cartilage invasion on magnetic resonance imaging (MRI) in a 59-year-old man with hypopharyngeal cancer (A) T2-weighted, T1-weighted, and fat-suppressed contrast-enhanced T1-weighted MR images show a tumor mass (T) arising from the right piriform sinus. The adjacent thyroid cartilage has a signal intensity similar to that of the tumor (arrow). (B) A weighted-average (WA) image does not show erosion or lysis at the same level, and an iodine overlay (IO) image is not used for diagnosis. (C) A corresponding axial slice from the surgical specimen at the same level shows that the right thyroid lamina has not been invaded by the tumor (arrow). The posterior part of the right thyroid lamina with enhancement shows moderate infiltration of lymphocytes into the medullary space, accompanied by fibrosis and aggregation of macrophages (shown on click; square). (hematoxylin–eosin stain; original magnification, 200×) Case 2: False-negative findings for thyroid cartilage invasion on DECT (A) (B) ? ? (C) False-negative findings for thyroid cartilage invasion on dual-energy CT (DECT) in a 67-year-old man with laryngeal cancer (A) T2-weighted, T1-weighted, and fat-suppressed contrast-enhanced T1-weighted MR images show the signal intensity similar to that of the tumor in thyroid cartilage has a (arrow). (B) A weighted-average (WA) image shows focal erosion on the left thyroid cartilage (arrows). However, iodine overlay (IO) image shows no corresponding enhancement in the region indicated in the WA image (arrow). (C) The minor invasion of tumor cells into an ossified-right wing of the thyroid cartilage with an extent of 5mmdiameter is observed in the histopathological findings (arrow). Thyroid lamina with extensively enhancement on MRI reflect the moderate infiltration of lymphocytes into the medullary space, accompanied with desmoplastic reaction according to destruction of normal tissue by tumor cell invasion (shown on click; square). (Hematoxylin–eosin stain; original magnification.). • In the current study, we compared the diagnostic performance of dual-energy CT with that of MRI with regard to the evaluation of tumor invasion by laryngeal and hypopharyngeal SCC. • The specificity of dual-energy CT was superior to that of MRI for the evaluation of thyroid cartilage, but no evidence indicated that the sensitivity of dual-energy CT differed from that of MRI. • High specificity could be achieved because the WA and IO images depicted a precise shape of ossified cartilages and iodine distribution in nonossified cartilages, thus preventing the overestimation of invasion that occurred during diagnoses with MRI. • MRI shows great potential for detecting cartilage invasion because of high contrast resolution for images without motion artifacts. However, inflammatory changes in cartilage sometimes resemble cartilage invasion, and high false-positive rates remain an issue. The previously reported specificity of MRI for the detection of thyroid cartilage invasion is only 56%–65% 4,12. • Peritumoral inflammatory changes were shown in both the invaded and noninvaded laryngeal cartilages surrounding the actual tumor borders, and changes were easily observed in many ossified cartilages, particularly in the fatty marrow infiltrated with calcified areas 4,11,12. MRI cannot identify cortical bone, which has no MR signal. Therefore, MRI may be inferior for the evaluation of cortical bone changes, while it can depict fatty marrow changes. • In addition, for advanced laryngeal and hypopharyngeal SCC in particular, MRI seems to be prone to motion artifacts because of the relatively long scan times12. • Dual-energy CT can provide WA images, which are similar to conventional 120-kV images, and IO images with high spatial resolution 13-16. Iodine-enhanced tumors and non-ossified cartilages can be distinguished using IO images, because iodine enhancement is evident in tumor tissue, but not in cartilage11,12. • A preliminary report suggests that the specificity of combined WA and IO image analysis is significantly superior to that of WA image analysis alone (96% vs. 70%), with no compromise on sensitivity (86% vs. 86%)11. • Furthermore, combined WA and IO images can evaluate the erosion or loss of ossified cartilages and judge the iodine distribution in the corresponding area at the same time. When the WA image does not show cartilage destruction, regardless of inflammatory changes in the fatty marrow, cartilage invasion is considered absent. • The specificity of dual-energy CT is higher than that of MRI for the evaluation of thyroid cartilage invasion by SCC, and it may be as useful as MRI during treatment decisionmaking for laryngeal and hypopharyngeal SCC. 1. Hartl DM, Landry G, Hans S, Marandas P, Brasnu DF. Organ preservation surgery for laryngeal squamous cell carcinoma: low incidence of thyroid cartilage invasion. Laryngoscope 2010;120(6):1173-1176. 2. Pfister DG, Laurie SA, Weinstein GS, et al. American Society of Clinical Oncology clinical practice guideline for the use of larynx-preservation strategies in the treatment of laryngeal cancer. J Clin Oncol 2006;24(22):3693-3704. 3. Rodriguez CP, Adelstein DJ, Rybicki LA, et al. Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy. Head Neck 2008;30(12):1535-1542. 4. Becker M, Zbaren P, Casselman JW, Kohler R, Dulguerov P, Becker CD. Neoplastic invasion of laryngeal cartilage: reassessment of criteria for diagnosis at MR imaging. Radiology 2008;249(2):551-559. 5. Li B, Bobinski M, Gandour-Edwards R, Farwell DG, Chen AM. Overstaging of cartilage invasion by multidetector CT scan for laryngeal cancer and its potential effect on the use of organ preservation with chemoradiation. Br J Radiol 2011;84(997):64-69. 6. Castelijns JA, Becker M, Hermans R. Impact of cartilage invasion on treatment and prognosis of laryngeal cancer. Eur Radiol 1996;6(2):156-169. 7. Beitler JJ, Muller S, Grist WJ, et al. Prognostic Accuracy of Computed Tomography Findings for Patients With Laryngeal Cancer Undergoing Laryngectomy. J Clin Oncol 2010;28(14):2318-2322. 8. Becker M, Zbaren P, Delavelle J, et al. Neoplastic invasion of the laryngeal cartilage: reassessment of criteria for diagnosis at CT. Radiology 1997;203(2):521-532. 9. Zbaren P, Becker M, Lang H. Pretherapeutic staging of laryngeal carcinoma. Clinical findings, computed tomography, and magnetic resonance imaging compared with histopathology. Cancer. 1996;77:1263-1273 10. Becker M, Zbaren P, Laeng H, Stoupis C, Porcellini B, Vock P. Neoplastic invasion of the laryngeal cartilage: comparison of MR imaging and CT with histopathologic correlation. Radiology 1995;194(3):661-669. 11. Kuno H, Onaya H, Iwata R, Kobayashi T, Fujii S, Hayashi R, Otani K, Ojiri H, Yamanaka T, Satake M. Evaluation of cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinoma with dual-energy CT. Radiology. 2012;265(2):488-96 12. Kuno H, Onaya H, Fujii S, Ojiri H, Otani K, Satake M. Primary staging of laryngeal and hypopharyngeal cancer: CT, MR imaging and dual-energy CT. Eur J Radiol. 2014 Jan;83(1):e23-35 13. Graser A, Johnson TR, Hecht EM, et al. Dual-energy CT in patients suspected of having renal masses: can virtual nonenhanced images replace true nonenhanced images? Radiology 2009;252(2):433-440. 14. Gupta R, Phan CM, Leidecker C, et al. Evaluation of Dual-Energy CT for Differentiating Intracerebral Hemorrhage from Iodinated Contrast Material Staining. Radiology 2010;257(1):205-211. 15. Johnson TR, Krauss B, Sedlmair M, et al. Material differentiation by dual energy CT: initial experience. Eur Radiol 2007;17(6):1510-1517. 16. Krauss B, Schmidt B, Flohr TG. Dual Source CT. In: Johnson TRC, Fink C, Schönberg SO, Reiser MF, eds. Dual Energy CT in Clinical Practice. 1st ed. Heidelberg, Dordrecht, London, New York, Springer, 2011; 11-20.