| [Objective]1. To assess the value of18F-FDG PET/CT in the diagnosis and staging of larynx carcinoma.2. To assess the clinical value of18F-FDG PET/CT in the surveillance of postoperative recurrence and metastasis in patients with larynx carcinoma.[Materials and Methods]1. Study objective1.1Patients with established diagnosis or suspected larynx carcinomaForm July2003to June2012, a total of49patients with clinical suspected or already established diagnosis of larynx carcinoma were enrolled in this study, including45men and4women, aged from33to78years old, with a mean age of58years old, all of patients underwent whole body18F-FDG PET/CT examination within a week before therapy. Larynx carcinoma was diagnosed by histopathology examination of surgical or biopsy samples. Regional lymph node metastasis was established based on pathological examination in19patients treated with surgery and based on imaging and clinical follow-up in26cases treated with routine radiotherapy or chemotherapy. The diagnosis of distant metastases was identified Based on all clinical information including laparoscopy, operative exploration, histopathology, imaging examination (X-Rays, B-ultrasound, CT, MRI, Whole body bone SPECT, PET/CT), clinical examination, and laboratory tests. All of patients were followed-up for more than6months.1.2Patients with larynx carcinoma after surgeryForm July2003to June2012, a total of65patients with larynx carcinoma after surgery were enrolled in this study, including62men and3women, aged from34to79years old, with a mean age of62.4years old, all patients were treated by surgery, Among them,23patients also received additional postoperative radiotherapy and (or) chemotherapy. Recurrent and/or metastasis tumors were dignosed by histopathology, multi-imaging studies including B-ultrasound, CT, MRI, PET/CT and clinical follow-up for more than six months.2. Imaging modality and imaging agentThe examinations were carried out using a GE Discovery LS PET/CT scanner (GE, Healthcare, and Waukesha, WI). The positron emitter was produced using the cyclotron of PETtracer (GE, Healthcare, Waukesha, WI).The tracer18F-FDG, was manufactured automated by the tracer synthesis system of FDG Microlab (GE, Healthcare, Waukesha, WI), with a radiochemical purity>95%.3. PET/CT imagingAll of the patients and healthy subjects underwent PET/CT scans after fasting at least6hours prior to examination. Patients also received orally600ml and200ml of1.5%diatrizoate meglumine at an hour and5minute before the scans.18F-FDG with the dose of5.5MBq/kg was administrated intravenously via a T tube. After about60minutes of relaxed rest in a supine position in dark rooms without visual or acoustic stimulations, the patients were asked to void and were then placed into the PET/CT scanner for image acquisition. The image acquisition included non-enhanced CT scan and PET scan covered the range from the head to the middle thigh. 4. Image reconstruction and fusionPET images were reconstructed by using a standard iterative algorithm (ordered subset expectation maximization) with CT data being used for attenuation correction. The CT images were reconstructed by using a standard method.The thickness of each slice of PET and CT after reconstruction was4.25mm. The acquired images of PET and CT were sent to the Xeleris (GE Medical Systems) workstation for image registration and fusion.5. PET/CT Image analysis5.1Qualitative analysisPET, CT and PET/CT images were interpreted independently by three experienced senior physicians of nuclear medicine and three experienced senior physicians of CT diagnosis. After visually examining all images on the workstation, the reviewers reached a final diagnosis based mainly on fusion images of PET and CT. Any initial difference of opinion was resolved by consensus.5.1.1Primary TumorA lesion in larynx showing18F-FDG uptake that exceeded that of the surrounding normal tissue was considered as positive of malignancy. The syn-modality CT was used to determine morphologic location, and used to exclude physiology accumulation and typical inflammation.5.1.2Regional lymph node metastasesIt was defined as positive of lymph node metastasis if the lymph node was larger than1.0cm, or central liquefaction necrosis showed in the lymph node, or18F-FDG uptake showed in the lymph node even although it was smaller than1.0cm.5.1.3Distant metastasesAfter excluding the physiological uptake, it was defined as positive of distant metastases if the radioactivity uptake in lesion was higher than the surrounding normal tissue.5.1.4Diagnostic criteria for recurrence and metastasis of postoperative larynx carcinoma(1) After excluding the physiological uptake, typical inflammation or postoperative changes, it was defined as positive of recurrence and metastasis if the radioactivity uptake of a nodule or mass lesion was higher than the surrounding normal tissue.(2) Multiple nodules in lungs showed on CT images were suggested as pulmonary metastases, no matter these lesions had or had not18F-FDG uptake.5.2Semi-quantitative AnalysisLesion with abnormal18F-FDG uptake was identified by three experienced senior physicians of PET/CT. The maximum standardized uptake value (SUVmax) was calculated automatically by the workstation by setting the regions of interest (ROI) on the lesion.6. The diagnostic criteria of unenhanced contrast CT6.1Primary Tumor(1) Soft tissue mass or significant soft tissue thickening in larynx;(2) The thickness of the anterior commissure of larynx was greater than2mm;(3) Low density fats shadow in preepiglottic space and paraglotic space was replaced by soft tissue density mass;(4) The boundary of the laryngeal cartilages and tumor was unclear, or cartilages were violated, dissolved, hardened.6.2Regional lymph node metastasesIt was defined as positive of lymph node metastasis if the lymph node was larger than1.0cm, or central liquefaction necrosis showed in the lymph node.6.3Distant metastasesThe morphologic change was seen in the syn-modality CT, and the imaing findings ruled out primary lesions. 7. The staging criteria of larynx carcinomaAccording to UICC cancer staging manual8. Statistical analysisStatistical Package for the Social Sciences (SPSS)13.0(SPSS Inc., Chicago, IL) was used for statistical analysis. SUVmax was expressed as mean±standard deviation (X±S). Differences in sensitivity of PET/CT and unenhanced contrast CT in diagnosis of primary tumor and regional lymph node were tested by McNemar’s test (two-tailed). The pathologic differentiation and T stage of primary tumor were tested by Pearson Chi-square or Fisher in regional lymph node metastasis group and no regional lymph node metastasis group. The size and SUVmax of primary tumor were tested by Independent-Samples T test in regional lymph node metastasis group and no regional lymph node metastasis group. Age, carcinoma site, the pathologic differentiation, T stage, node metastasis and postoperative irradiation therapy were tested by Pearson Chi-square in no recurrence or metastasis group and recurrence or metastasis group within2years after surgery of65patients with larynx carcinoma. PO.05was considered statistically significant.[Results]1. In the patients with established diagnosis or suspected larynx carcinoma1.1The value of18F-FDG PET/CT in the diagnosis of larynx carcinoma1.1.1The diagnosis of the primary tumorIn the total of49patients enrolled,45patients of them were proved to be larynx carcinoma, while3of them were inflammation, and one was physiological uptake. In44patients with positive of PET/CT finding,43were proved to be larynx carcinoma.18F-FDG uptake in these lesions was intense (SUVmax=12.83±6.6). PET/CT showed false-positive in one patients and false-negative in two cases. The sensitivity, specificity and accuracy of PET/CT for diagnosing larynx carcinoma were95.6%, 75%and93.9%, respectively. However unenhanced contrast CT showed false-positive in two patients and false-negative in12cases. The sensitivity, specificity and accuracy of unenhanced contrast CT for diagnosing primary tumor were73.3%,50%and71.4%, respectively. Compared to unenhanced contrast CT PET/CT has a significantly higher sensitivity (95.6%vs.73.3%, P=0.002). In13patients with advanced infiltrated disease, PET/CT identified all of the tumor infiltrations clearly, while unenhanced contrast CT only identified clearly in5cases.1.1.2The diagnosis of regional lymph node metastases1.1.2.1On the patient-basedIn45patients with larynx carcinoma, regional lymph node metastases were diagnosed in28of them. The ipsilateral neck regional lymph node metastases were showed in22cases, the bilateral neck regional lymph node metastases were showed in5cases, and the contralateral neck regional lymph node metastases was showed in one case.18F-FDG PET/CT detected cervical lymph node metastases<1.0cm in10patients. PET/CT found positive lymph nodes in30patients with26of ture-positive and4of false-positive. PET/CT showed false-negative in two patients. The sensitivity, specificity and accuracy of PET/CT for diagnosing regional lymph node metastases were92.9%,76.5%and86.7%, respectively. Unenhanced contrast CT detected positively in19patients, including1of false-positive and18of true-positive. Unenhanced contrast CT showed false-negative in10patients. The sensitivity, specificity and accuracy of unenhanced contrast CT for diagnosing regional lymph node metastases were64.3%,94.1%and5.6%, respectively. On the patient-based, PET/CT show a more sensitivity than unenhanced contrast CT for detecting regional lymph node metastases.1.1.2.2On the lesion-basedOf the46excised lymph nodes from19patients,25were positive of metastasis. The diameter of regional lymph nodes was larger than1.0cm in16lesions. PET/CT found positive lymph nodes in27lesions with23of ture-positive and4false-positive. Unenhanced contrast CT detected17groups, including16true-positive and one false-positive.18F-FDG PET/CT showed a diagnostic sensitivity of92%, significant higher than that64%of unenhanced contrast CT (P=0.016).1.1.3The correlation of primary tumor with the regional lymph node metastasis of larynx carcinomaIn45patients with larynx carcinoma, regional lymph node metastases were diagnosed in28of them. The regional lymph node metastasis of larynx carcinoma was related with the pathologic differentiation, T stage, the size and SUVmax of primary tumor according to the Univariate Analysis(P=0.009,0.023,0.015and0.006, respectively).1.2The value of18F-FDG PET/CT in staging of larynx carcinomaIn45patients with larynx carcinoma, The staging were raised in15patients by PET/CT because PET/CT detected more tumor infiltration in9cases, and also detected more positive lymph node metastases in6cases. One patient was downstaged the clinical stage because of being ruled out contralateral neck lymph node metastasis. In addition, PET/CT detected a synchronous tumor in one case.2. In the patients with postoperative larynx carcinoma2.1The value of18F-FDG PET/CT in the surveillance of postoperative recurrence and metastasis2.1.1The value of18F-FDG PET/CT in the surveillance of postoperative recurrenceOf65postoperative larynx carcinoma,17patients has recurrent tumor. PET/CT detected positive lesion in17patients, including16true-positive and one false-positive. There was also one false-negative. The sensitivity, specificity and accuracy of PET/CT in detecting recurrent tumor were94.1%,97.9%and96.9%, respectively.2.1.2The value of18F-FDG PET/CT in the surveillance of postoperative metastasis2.1.2.1On the patient-basedIn the65postoperative patients, PET/CT showed true positive in26cases, false positive in one case, true negative in37cases and false negative in one case. On the patient-based, the sensitivity, specificity and accuracy of PET/CT in detecting metastasis were96.3%,97.4%and96.9%, respectively.2.1.2.2On the lesion-basedOf75positive lesions were detected in65postoperative larynx carcinoma by18F-FDG PET/CT,72were proved to be malignant. There were43lymph node metastases including15in neck,14in mediastinal,7in hilar,4in supraclavivular or subclavian fossa,1in retroperitoneal,1in pelvic and1in groin. There were29distant metastasis including6in lungs,6in bones,6in muscles,3in adrenals,2in pericardials,2in pleuras,1in liver,1in infratemporal fossa,1in chest wall and1in abdominal wall metastasis. PET/CT also had3false-positive and2false-negative. On the lesion-based, the sensitivity, specificity and accuracy of PET/CT in detecting metastasis were97.3%,88.0%and95.0%, respectively.2.2Influencing factors of recurrence and (or) metastasis in the patients with larynx carcinoma within2years after surgeryIn36patients with recurrence and (or) metastasis.18F-FDG PET/CT detected34cases correctly. The lesions were detected by PET/CT in16.7%of patients in half a year,27.8%in6months to1year,36.1%in1～2year and13.9%after2years, respectively. However, two patients were negative. In the total,18F-FDG PET/CT detected29cases correctly within2years after surgery, and two patients were negative. The pathologic differentiation, T stage of primary tumor and lymph node metastasis were found to be the important influence factors of tumor recurrence and (or) metastasis within two years after operation according to the Univariate Analysis(P=0.000,0.005and0.014, respectively). However, age, carcinoma site, and postoperative irradiation therapy had no significant impact on tumor recurrence and (or) metastasis (P=0.73,0.901and0.292respectively).[Conclusions]1. The present study reveals the vast majority of larynx carcinoma have intense uptake of18F-FDG and18F-FDG PET/CT is a sensitivity imaging modality for detecting larynx carcinoma;2. The regional lymph node metastasis of larynx carcinoma was related with the pathologic differentiation, T stage, the size and SUVmax of primary tumor.3. The present study reveals the metastases of larynx carcinoma also have intense uptake of18F-FDG PET/CT has obvious advantages for detecting the distant metastases in the whole body and plays a great role in the staging of larynx carcinoma.4.18F-FDG PET/CT has an important role in the surveillance of postoperative recurrent tumor and (or) metastasis in the patients with larynx carcinoma.5. The pathologic differentiation, T stage of primary tumor and node metastasis were important influence factors of tumor recurrence and (or) metastasis within two years after operation.6. The early-staged larynx carcinoma with smaller lesions would be ignored in PET/CT scans because of low18F-FDG uptake. In the meanwhile, inflammation is usually misdiagnosed, so, in some special case, the diagnosis must be made carefully. |
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