| [Objective]1. To assess the value of18F-FDG PET/CT in the diagnosis of preoperative non-small cell lung cancer.2. To assess the clinical value of multiple18F-FDG PET/CT in the surveillance and prediction of postoperative recurrence and metastasis in patients with non-small cell lung cancer.[Materials and Methods]1. Study objective1.1Patients with non-small cell lung cancer before surgery Form July2004to October2013, a total of229patients with clinical suspected or already established diagnosis of non-small cell lung cancer were enrolled in this study, including179men and75women, aged from30to87years old, with a mean age of59.5years old. Lung carcinoma was diagnosed by histopathology examination of surgical or biopsy samples in175patients.31cases by the percutaneous needle aspiration,17cases by bronchoscopy,6cases by sputum cytology. This group of patients was used to assess the value of18F-FDG PET/CT for diagnosing the primary tumor of lung cancer.1.2Lymph node metastasis of non-small cell lung cancer One hundred fifty patients were selected from those of group1.1for assessing the value of18F-FDG PET/CT in the diagnosing the lymph node metastasis. All of the patients underwent the lobectomy and lymph node dissection, including105men and45women, aged from34to80years old, with a mean age of59.0years old.1.3Multiple18F-FDG PET/CT examinations for the postoperative tumor surveillanceForm July2004to October2011, a total of106patients with the postoperative non-small cell lung cancer were enrolled in this study, including79men and27women, with a mean age of58.4years old. All of the patients underwent multiple18F-FDG PET/CT scans within one week before the operation and3months after the operation. The median number of examinations is3(2to16) times.The diagnosis of recurrent tumor and metastasis was established by pathologic examination, ulti-modality imaging 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 PET tracer (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. Imaging methods and conditionsAll of the patients underwent PET/CT scans after fasting at least6hours prior to examination, detect blood sugar, weighed, measuring height are required before injection imaging agent.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, if necessary, add to sweep the lower limbs, collection of6to8beds. Patients with suspected intracranial metastases should be collected by the method of three-dimensional model of cerebral, emission scanning3min/beds; for solitary pulmonary nodules less than3cm conduct thin-section CT scans, thickness of1.25mm.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.5.1.1Diagnostic criteria for primary tumors of lung cancer On the CT images, the lesion was diagnosed to be lung cancer acoording to whether it has following image presentations or not, such as the lobulation, speculation, the think walled hollow, bronchiolograms, ground-glass opacification, or vascular convergence sign and pleural indentation. On the PET images, if the uptake of lesion was higher than that of the mediastinal blood pool, it was dignosed to be lung cancer.5.1.2Diagnostic criteria for regional lymph node metastasis(1) When the lymph node which had18F-FDG uptake higher than that of the mediastinal blood pool and has not significantly increased density or calcification, no matter how large it is,it is diagnosed to be lymph node metastasis.(2) When the lymph node which had18F-FDG uptake similar to or lower than that of the mediastinal blood pool, the diagnosis of lymph node was determined by the lesion size presenting on the CT images, if the short diameter of the regional lymph is smller than1.0cm, it was diagnosed to be negative of metastasis, if the short diameter of the regional lymph nodes was larger than1.0cm, it was diagnosed to be positive of metastasis.5.1.3Diagnostic criteria for recurrence and metastasis of postoperative lung carcinoma(1) After excluding the physiological uptake, typical inflammation or postoperative changes, PET showed localized concentration shadow in pulmonary or extrapulmonary, if the lesion was higher than the surrounding normal tissue significantly, CT also showed the soft tissue nodules and masses in the corresponding parts, it was diagnosed to be recurrence or metastasis. If the lesion was appeared in bone, mainly based on the18F-FDG uptake to determine the tumor lesion, except that the surgical trauma, fractures and post-treatment change up by the drug which can make leukocyte up, in this case, we must combine CT to decide the bone metastasis;(2) If CT images showed a new lesion in thes pulmonary, if the nodules were rounded, soft tissue density, smooth edges. it was diagnosed to be recurrence or metastasis no matter the 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 staging criteria of lung cancerIt was used seventh edition of American Joint Committee on Cancer (AJCC) about TNM staging of lung cancer.7. Statistical analysisStatistical Package for the Social Sciences (SPSS)17.0(SPSS Inc., Chicago, IL) was used for statistical analysis. The size and SUVmax of the primary lesion was expressed as mean±standard deviation (X±S), the primary was18F-FDG high uptake and combination with CT diagnosis of lung cancer to compare the sensitivity of PET/CT using Pearson Chi-square; the relationship of size and SUVmax of the non-small cell lung cancer patients primary lesion, using partial correlation analysis; The relationship of the primary lesion SUVmax and staging using correlation analysis. Among different types of pathology groups non-small cell lung cancer primary lesion size and SUVmax, the comparative analysis of adenocarcinoma SUVmax and pathlological of differentitaion using One-Way ANOVA. The relationship between the lung pathology primary tumor SUVmax, the primary tumor size and SUVmax in the regional lymph node metastasis group and no metastasis group with primary lesion and the primary lesion size and SUVmax in no recurrence or metastasis group and recurrence or metastasis group within2years after surgery with lung carcinoma using two independent samples t test. The primary lesion categor, stage and histological type in the regional lymph node metastasis group and no metastasis group with rimary lesion and age, gender, histological type, staging were tested by Pearson Chi-square in no recurrence or metastasis group and recurrence or metastasis group within2years after surgery with lung carcinoma. P<0.05was considered statistically significant.[Results]1. Patients with non-small cell lung cancer before surgery1.1The manifestion of primary lesions of NSCLC on18F-FDG PET/CT images.Among the229patients, mong229enrolled lung cancer patients, the primary lesions of80.3%(184) patients were positive on PET images, including118cases are adenocarcinoma,45cases are squamous cell carcinoma,9cases are squamous cell carcinoma and12cases are other types of cancer), SUVmax was9.4+6.2, the proportion of this part patients was80.3%; There were19.7%(45) of the primary tumor which were negative on18F-FDG PET,including32case of bronchioloalveolar carcinoma,11cases of adenocarcinoma,1case of medium to poorly differentiated adenocarcinoma, one case of small characinoid), The SUVmax of them was1.8±0.6In184lung cancer lesions with positive18F-FDG PET,91.3%presented as solid nodules,8.7%as mixed nodules. In45patients with negative PET lesions,44.4%of them presented as solid nodules,40.0%as mixed nodules and15.6%as groud-glass nodules.If the lesion with positive PET was diagnosed to be lung cancer, the sensitivity of PET was80.3%.If lesions with positive PET and typical CT manifestions, such as the lobulation, speculation, the think walled hollow, bronchiolograms, ground-glass opacification, or vascular convergence sign and pleural indentation, was diagnosed to be lung cancer, the sensitivity of18F-FDG PET/CT was96.3%.There was significant difference of sensitivity between these two diagnostic criteria(X2=31.325, P=0.000).In the present study, seven lung cancer were misdiagnosed as benign lesions when the second diagnostic criteria. All of these seven lesions were smaller than 1.5cm in diameter. Among them, five lesions are non-calcified solid nodules with one of well-differentiated adenocarcinoma,3of bronchioloalveolar carcinoma and one of carcinoid). In the other two lesions, one presented as patchy shadow, and one as solid nodule with sand-like calcification. Both of them were bronchoalveolar carcinoma.1.2The relationship between the SUVmax, size and staging in the non-small cell lung cancerIn the229patients with NSCLC,the size and SUVmax of the primary lesion were2.8+1.6cm(0.5～11.9cm) and8.4±5.8(0.5～28.6),respectively. Among them,185patients were belong to be stage Ⅰ,27to be stage Ⅱ,17to be stage Ⅲa. The statistical analysis showed that there was positive relationship between the size and the SUVmax (r=0.516, P=0.000), when the disease had the same stage and histopathogy. It also demonstrated that there was a positive relationship between the SUVmax and tumor stage (r=0.370, P=0.000).1.3The relationship between the pathological types and the SUVmax of the primary tumor of NSCLC229patients were divided into4groups:adenocarcinoma group, squamous cell carcinoma group, adeno-squamous cell carcinoma group and other pathological types group including large cell carcinoma, lymphoid epithelial carcinoma, mucoepidermoid carcinoma, carcinoid, etc.The SUV max of the primary lesion in these four groups were6.8±4.6,12.2±6.1,13.3±8.9and12.5±7.3,respectively.The statistical analysis showed SUVmax of adenocarcinoma group was significantly lower than those of other three groups (P valve is0.000,0.000and0.001,respectively). No significant differences were observed between three non-adenocarcinoma groups (all P>0.05).1.4Comparsion of the SUVmax of different types of adenocarcinoma. One hundred and sixty-two patients with adenocarcinoma were divided into4groups:bronchioloalveolar carcinoma group and well differentiated, moderataly differentiated and poorly differentiated adenocarcinoma groups. The statistical analysis showed that the SUVmax of bronchioloalveolar carcinoma group was much lower than those of well differentiated, moderataly differentiated and poorly differentiated (P valve is0.017、0.000、0.000and0.014respective). The SUVmax of well differentiated adenocarcinoma group was singnificantly lower than that of poorly differentiated (P=0.122and0.248respective).2. Lymph node metastasis of non-small cell lung cancer2.1The pathological results of the resected lymph nodes by surgeryIn150patients underwent the surgery,39of them were confirmed to have regional lymph node metastases. There were143lymph node metastases in62groups.Other2042lymph nodes in462groups were proved to be negative of metastasis. Of the62groups, lymph node metastases were commonly found in2rd,4rd,7rd,10rd,llrd group,which occupied84.0%of lesions.The distributions of lymph node metastases were10+1lrd>4rd>7rd>2rd>8rd>6rd>5rd>3rd>1rd.(of which group10>11rd group=group4>7group> group2> group8> group6> group5> group3>1group> group9.In39patients with regional lymph node metastasis, the lesions occurred only in the hilar in38.5%(15/39) of the patients, only in mediaste in35.9%(14/39) of patients, in both of hilar and mediaste in the25.6%(10/39) of the patients.2.2The diagnostic capacity of F-FDG PET/CT for the lymph node metastasis based on the groupsIn the62groups of lymph node metastases, the lesion was smaller than1.0cm in5groups and larger than1.0cm in the other57groups18F-FDG PET/CT showed positive in53groups with48groups of true positive and 5groups of false positive. PET/CT demonstrated negative in other538groups. The sensitivity, specificity and accuracy of PET/CT for diagnosing regional lymph node metastases were77.4%,99.1%and96.9%, respectively.2.3The correlation of primary tumor with the regional lymph node metastasis of NSCLC18F-FDG PET/CT showed positive in53groups with48groups of true positive and5groups of false positive. PET/CT demonstrated negative in other538groups. The location and the pathological categories showed no significant effect on the lymph node metastasis (P=0.523and0.560, respectively).3. Multiple18F-FDG PET/CT examinations for the postoperative tumor surveillance3.1The value of18F-FDG PET/CT in the surveillance of postoperative recurrence and metastasis3.1.1The detection rate of18F-FDG PET/CT imaging in detecting non-small cell lung cancer recurrence and metastasisIn106patients,53cases confirmed recurrence or metastasis by histopathology and clinical follow-up,53cases without recurrence. The median time after18F-FDG PET/CT detected tumor recurrence and metastasis was19.3(7.4to75.8) months clinical follow-up. The lesions were detected by PET/CT in0.4%of patients in half a year,20.8%in one year,75.5%in two years,81.1%in three years,90.6%in four years, and98.1%after4years.3.1.2PET/CT results for the detection of the recurrence and metastasis after surgery on the patient-basedIn the106postoperative patients, PET/CT showed true positive in52cases, false positive in4case, true negative in49cases and false negative in1case. On the patient-based, the sensitivity, specificity and accuracy of PET/CT in detecting metastasis were98.1%,92.5%and95.3%, respectively.3.1.3PET/CT results for the detection of the recurrence and metastasis after surgery on t on the lesion-basedOf106positive lesions,99lesions were confirmed metastases after living tissue pathology, surgical pathology or more than6months of clinical follow-up.There were detected in104postoperative by18F-FDG PET/CT,96were proved to be malignant. PET/CT also had8false-positive and3false-negative. On the lesion-based, the sensitivity, specificity and accuracy of PET/CT in detecting metastasis were97.0%,78.9%and92.0%, respectively.3.2The factors for the recurrence and (or) metastasis in the patients with NSCLC within2years after surgeryTo2years after the cutoff point for the study,93patients were enrolled,18F-FDG PET/CT detected40cases correctly within2years after surgery, and53patients were no recurrence or metastasis. The stage,the size and SUVmax of primary tumor 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、0.002and0.010, respectively). However, gender, age and histological type had no significant impact on tumor recurrence and (or) metastasis (P=0.958、0.088and0.292, respectively).[Conclusions]1. The present study reveals the most of NSCLC have intense uptake of18F-FDG and18F-FDG PET/CT is a sensitivity imaging modality for detecting lung cancer.2. It is not enough sensitive to diagnosis the lung cancer only based on the18F-FDG uptake. Some bronchioloalveolar carcinoma, well differentiated adenocarcinoma present as false negative on18F-FDG PET/CT because of low 18F-FDG uptake. Combined analysis of the manifestions showed on the PET and CT is necessary for diganosing the lung cancer.3. With the same stage and histopaological type, the larger lung cancer lesion often has a higher SUVmax.4. The SUVmax of the primary lesion of adenocarcinoma was lower than squamous cell carcinoma, adeno-squamous cell carcinoma and the other type cancer.5. The SUVmax of the bronchioloalveolar carcinoma is lower than those of well differentiated, moderataly differentiated and poorly differentiated adenocarcinoa. The SUVmax of well differentiated adenocarcinoma is lower than that of poorly differentiated adenocarcinoma.6. The regional lymph node metastasis occurs commonly in the10rd,11rd,4rd,7rd,2rd, group regions.7. F-FDG PET/CT imaging has a moderately capacity for diagnosing the regional lymph nodes metastasis in the patients with non-small cell lung cancer.8. The occurrence of regional lymph node metastasis in the NSCLC patients was related with the size and SUVmax of primary tumor.9.18F-FDG PET/CT has an important role in the surveillance of postoperative recurrent tumor and (or) metastasis in the patients with NSCLC.lO.The size and SUVmax of primary tumor 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、0.002and0.010, respectively). However, gender, age and histological type had no significant impact on tumor recurrence and (or) metastasis (P=0.958、0.088and0.292, respectively). |
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