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Dynamic contrast-enhanced MRI in the differentiation of posttreatment fibrosis from recurrent carcinoma of the head and neck

Dynamic contrast-enhanced MRI in the differentiation of posttreatment fibrosis from recurrent carcinoma of the head and neck
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  Dynamic contrast-enhanced MRI in the differentiation of posttreatment fibrosis from recurrent carcinoma of the head and neck  Aslihan Semiz Oysu a, T , Elif Ayanoglu  b , Nihat Kodalli c , Cagatay Oysu d ,Cuneyt Uneri e , Canan Erzen c a   Department of Radiology, Hospital Turk, Istanbul, Turkey  b  Department of Otorhinolaryngology, Acibadem Hospital, Istanbul, Turkey c  Department of Radiology, Marmara University Hospital, Istanbul, Turkey d  Department of Otorhinolaryngology, Haydarpasa Numune Hospital, Istanbul, Turkey e  Department of Otorhinolaryngology, Marmara University Hospital, Istanbul, Turkey Received 20 December 2004; received in revised form 2 January 2005; accepted 24 January 2005 AbstractObjective:  The aim of this study was to investigate the value of dynamic contrast-enhanced magnetic resonance imaging (MRI) inthe differentiation of posttreatment fibrosis from recurrent carcinoma, by comparing the dynamic contrast-enhancement characteristics of the lesions.  Materials and methods:  Twenty-six patients with previously treated carcinoma of the head and neck are studied byconventional and dynamic contrast-enhanced MRI at least 6 months after treatment by radiotherapy and/or surgery. Patients are dividedinto tumor-positive or -negative groups according to the radiological and clinical follow-up and biopsy. Lesion enhancement ratios at eachdynamic sequence are calculated.  Results:  The tumor-positive group consisted of 11 patients, while the tumor-negative group included15 patients. Between the two groups, lesion enhancement ratios are found to be significantly different (  P  b .05).  Conclusion:  Dynamiccontrast-enhanced MRI may be a valuable modality in the differentiation of recurrent tumor from posttreatment fibrotic changes of thehead and neck. D  2005 Elsevier Inc. All rights reserved.  Keywords:  Magnetic resonance imaging; Head and neck neoplasms; Neoplasm recurrence, local; Fibrosis; Diagnosis, differential 1. Introduction Magnetic resonance imaging (MRI) is a valuable modal-ity in the diagnosis and follow-up of patients with head andneck carcinoma. The role of MRI for differentiatingrecurrent tumor from fibrosis after treatment  of head andneck carcinoma was previously investigated [1–5]. Recur-rent tumors were found to demonstrate higher signalintensity (SI) on T2-weighted images than fibrotic benignchanges do. However, further studies have shown that nonneoplastic inflammation or edema may also be respon-sible for  T2 hyperintersity and that this finding is non-specific [3]. In some cases, the identification of a suspiciouslesion is still a challenge.Dynamic contrast-enhanced MRI is valuable for thedifferentiation of tumor recurrence and posttreatment fibrosis in regions such as the breast, pelvis, gastrointestinaland musculoskeletal system [6–11]. To the best of our knowledge, there is no dynamic contrast-enhanced MRIstudy regarding such differentiation in the head and neck region. In this study, we aimed to compare the dynamicenhancement characteristics of benign fibrotic and recurrent tumoral lesions and, therefore, to investigate the value of dynamic contrast-enhanced MRI in the differentiation of  posttreatment fibrotic changes from recurrent carcinomaof the head and neck. 0899-7071/05/$ – see front matter   D  2005 Elsevier Inc. All rights reserved.doi:10.1016/j.clinimag.2005.01.024 T  Corresponding author. Sinan Ercan Sokak Kutlutas Hurriyet Sitesi, ABlok D:30 Erenk  f y Istanbul 34736, Turkey. Tel.: +90 542 3255453; fax:+90 216 3773711.  E-mail address: (A. Semiz Oysu). . Journal of Clinical Imaging 29 (2005) 307–312  2. Materials and methods Twenty-six patients aged 23–72 years (mean: 55 years),with a history of head and neck carcinoma and a radio-logically detectable lesion at the site of treatment, wereincluded in the study. All patients had received a curativetreatment as radiotherapy and/or surgery. The numbers of  patients are shown in Table 1 according to the type of treatment received and location of primary tumor. Patientswho have received any type of treatment during the last 6 months were not included in the study, to eliminate theacute changes. The interval of time between treatment and the study ranged between 6 and 74 months (mean:30 months). Informed consent was taken from all patients inthe study, and the study protocol was approved by the localethical committee.MRI was performed with a 1.5-Tesla unit (Signa HorizonGE Medical Systems, Milwaukee, WI, USA) by use of ahead or neck coil according to thelesion site. Axial spin-echoT1-weighted (TR/TE/NEX: 420-500/9/2), T2-weighted(TR/TE/NEX: 6000/99/2), dynamic contrast-enhanced fast multiplanar spoiled gradient-echo (FMSPGR) and contrast-enhanced spin-echo T1-weighted (TR/TE/NEX: 420-500/ 9/2) sequences were obtained from all patients. The parameters for dynamic scans fat saturated two-dimensionalFMSPGR with TR/TE are the following: 250/1.8, oneexcitation, 90 8  flip angle. All sequences were performedusing 4-mm section thickness with a 1-mm intersectiongap, 256  160 matrix and 20  20 or 18  18 field of viewfor neck and head imaging, respectively.The contrast agent used was 0.1 mmol/kg gadolinium-DTPA, given intravenously via an automatic injector (Medrad, Pittsburgh, PA, USA), at a rate of 1 ml/s andfollowed by a 10-ml saline flush. Dynamic scans wereobtained following the preparation of the intravenous lineand the automatic injector. After the first unenhancedFMSPGR scan, the second scan was begun simultaneouslywith the injection, and a total of 11 scans, including the first unenhanced scan, were obtained. At each scan, 16 sectionswere obtained at 34 s.The radiologically detectable lesions, i.e., mass or asymmetrical soft tissue thickening at the primary site,were evaluated on spin-echo images by two radiologistswith consensus. All images were compared with the previous pre- and posttreatment imaging studies of the patient. All patients were divided into either the tumor- positive or -negative group according to the followingcriteria. The patients without a mass lesion and showing nochange in findings during the follow-up were included inthe tumor-negative group. The patients who had a masslesion or progressive change in findings were accepted to besuspicious for tumor. Computed tomography guided fineneedle aspiration biopsy was performed for these lesions,and these patients were included in either the tumor- positive or -negative group according to the biopsy results.The analysis of the dynamic scans was performed by aradiologist, at the site that showed a mass lesion, asymmetryor pathologic signal change at qualitative analysis. Anelliptic region of interest (ROI) was chosen, the size of which differed according to the size of the lesion, to includeas much of the lesion as possible and to exclude extraneoustissues. The size of the ROIs ranged between 20 and74 mm 2 . Adjustment of the location of the ROI was made at each image to compensate minor movements of the patient.The mean SI value of the ROI was recorded at each scan of the dynamic sequence and on two consecutive sections.Measurements were made at two consecutive sections, andthe mean SI value is used for each lesion.To achieve standardization between patients, enhance-ment ratios are used for comparison. Enhancement ratios(  E  ) are calculated for each lesion and a normal muscle at the same slice with the lesion (  E  =SI at any time/SI at  precontrast sequence  100). For each patient, enhancement ratio versus time curves were established.Statistical analyses were performed using SPSS statisticalsoftware, Version 10.01, running on an IBM-compatiblePC. Student’s  t   test was used to compare the enhancement ratios at each dynamic sequence and the maximumenhancement ratio of lesions between the two groups. 3. Results The analysis of the images revealed mass lesion in 9and asymmetrical soft tissue thickening in 17 primarylesion sites. All patients with a mass and four patients with progression in the size of the radiologic lesion underwent  biopsy. Biopsy results were consistent with tumor in Table 1Types of treatment and locations of primary tumorsLocation Surgery RT a  Surgery+RTSurgery+RT+CT  b RT+CTLarynx 2 1 10 – 1 Nasopharynx – – – – 3Paranasal sinus 1 – 1 – – Oral cavity 1 – 2 – 1Hypopharynx 1 – – – – External ear canal – – – 1 – Parotid gland 1 – – – –  a  Irradiation therapy.  b Chemotherapy.Table 2Distribution of patients between groups according to the location of the primary tumor Location Tumor group Fibrosis groupLarynx 7 7 Nasopharynx – 3Paranasal sinus 1 1Oral cavity – 4Hypopharynx 1 – External ear canal 1 – Parotid gland 1 –   A. Semiz Oysu et al. / Journal of Clinical Imaging 29 (2005) 307–312 308  11 and fibrosis in 2 of these 13 lesions, and these patientswere included in the tumor-positive and -negative groups,respectively. The remaining 13 patients that had no massand showed no change in asymmetry at the follow-upwere included in the tumor-negative group. The distribu-tion of patients between groups according to the locationof the primary tumor is given in Table 2.The enhancement ratios of the lesions were significantlydifferent from the third to the seventh series (68–204 s) between the tumor-positive and -negative groups (  P  b .05;Fig. 1). The difference was highly significant from thefourth to the sixth series (102–170 s;  P  b .01). Normalmuscle enhancement was not significantly different betweenthe tumor-positive and -negative groups (  P  N .05; Fig. 1). InFigs. 2 and 3, case examples from the tumor-positive and-negative groups are given. 4. Discussion The early detection of tumor recurrence in cancer  patients is crucial for better prognosis. After a successfulradiation therapy, tumor tissue shows regression and fibrotictissue takes the place of the tumor  [2]. In addition, after  surgery, the early development of granulation tissue at thesurgical site turns out to be a fibrotic scar  [12]. Such benign reactions to treatment may mimic tumor both in physicaland radiological examinations; therefore, the differentiationof tumor from fibrotic changes after therapy is sometimes achallenge in the follow-up of patients.MRI is shown to be a valuable noninvasive modality indistinguishing fibrotic changes from tumor  [1]. Although both tumor and fibrotic tissue can have similar signalintensities on T1-weighted images, fibrosis is shown to bedifferentiated from tumor by low SI on T2-weightedimages, which reflects low water content and decreasedvascularity [6]. However, fibrosis may appear as a masslesion, and especially lesions with mixed signal intensitiescan be difficult to categorize [1]. Early studies havesuggested that recurrent tumors demonstrate higher signalvalues on T2-weighted images than benign fibrotic scars do.The high SI pattern of tumor on T2-weighted images isreported to be nonspecific, and persistent inflammat ion in afibrotic tissue can mimic such signal changes [2,6].The value of contrast enhancement for the qualitativeevaluation of neoplasms in the head and neck is welldocumented [13,14]. The presence of gadolinium enhance-ment is not specific for the characterization of tumor or fibrotic tissue. However, the quantification of contrast material uptake in the lesion can be used for differentiation.Dynamic contrast-enhanced MRI is a method that revealsthe temporal enhancement characteristics of different tissues Fig. 1. Mean lesion (A) and muscle (B) enhancement ratios between tumor-positive and -negative groups are shown.  A. Semiz Oysu et al. / Journal of Clinical Imaging 29 (2005) 307–312  309  (by the use of sequential scans taken through an area of interest following an intravenous injection of a contrast agent  [15]). The change in the amount of contrast material in a lesion versus time is related to the tissue vascularity andangiogenetic characteristics, which is different in benign andmalignant lesions [16–18].Dynamic contrast-enhanced MRI is used previously incancer patients for lesion characterization, to detect earlyrelapse within treated tissues, to predict the success of therapy and to monitor the effects of treatments [17,18]. Dynamic contrast-enhanced MRI is reported to be usefulfor the differentiation of tumor recurrence and posttreatment  ABC Fig. 2. A 75-year-old female patient had received primary radiotherapy for hypopharyngeal carcinoma 16 months ago. Left pharyngeal enhancing lesion isshown in T1, T2, contrast-enhanced T1-weighted images (A) and the dynamic sequence (B). The enhancement ratio vs. time curve of the lesion is shown,together with the mean lesion enhancement ratio vs. time curves of the tumor-positive and -negative groups (C). Tumor was proved at biopsy.  A. Semiz Oysu et al. / Journal of Clinical Imaging 29 (2005) 307–312 310  CBA Fig. 3. A 50-year-old male patient was laryngectomized and received postoperative radiotherapy 18 months ago. T1, T2, contrast-enhanced T1-weightedimages (A) and the dynamic sequence (B) demonstrate the asymmetrical enhancement at the base of the tongue. There was no suspicion of tumor at clinicaland radiological follow-up. The enhancement ratio vs. time curve of the lesion is similar to the mean lesion enhancement ratio vs. time curve of the tumor-negative group (C).  A. Semiz Oysu et al. / Journal of Clinical Imaging 29 (2005) 307–312  311
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