| Research BackgroundCervical cancer is the most common malignance in female genital system with a high incidence in recent years. Local recurrence and distant metastasis is the leading cause of death in patients with cervical cancer, and their prognosis is correlated closely with early diagnosis, accurate staging and the choice of treatment methods. Generally speaking, the diagnosis of cervical cancer is mainly based on medical history, symptom, gynecological examination and cervical biopsy. FIGO classification is usually acquired in the clinical staging, and the staging would be judged according to clinical examination before treatment, with the intraoperative and postoperative findings not changed the final results yet. Because lymph node metastasis is a very important prognostic factor, and traditional FIGO classification does not refer to the status of lymph node and lymph-vascular space invasion, and thus, the accuracy of FIGO staging is relatively low, which would produce incorrect guidance on the choice of treatment for the patients. While selecting appropriate therapeutic way is the prerequisite of lowering the incidence of recurrence and death in such patients, therefore, early judgment of lymph node status, accurately detecting the recurrence and metastasis of cervical cancer and formulating individualized therapeutic schedule as soon as possible would prolong the survival time of these patients and improve their survival rate.With the extensive use of F-FDG PET/CT imaging in the diagnosis and treatment of various tumors, it also provided a more objective and accurate criterion for the diagnosis, staging and clinical evaluation of cervical cancer and then produced a profound impact on improving the prognosis, increasing the recovery rate and survival rate of these patients. As a new type of molecular imaging technology, 18F-FDG PET/CT could early provide the function and metabolic information of the tumors. The SUV, a very important semi-quantitative parameter, which is derived from 18F-FDG PET/CT, is able to reflect the degree of invasion and prognosis of the malignancy; its value is closely correlated with metabolic activity, proliferation rate, grading, pathological subtype and the level of glucose transport protein, and thus, it is helpful in differentiating the malignancy from the benign and judging the dangerous degree of the tumors. On the one hand, we observed and recorded the variation trend of SUV in different pathological subtype, differentiated degree, FIGO staging, tumor size and whether the local invasion or lymph node metastasis occurred or not through calculating the SUV of primary lesion of cervical cancer, and explored the its cut-off value in predicting the local invasion, lymph node metastasis and distant metastasis in these patients, on the other hand, we discussed the diagnostic efficacy of PET/CT in detecting pelvic lymphatic metastasis in patients with early-stage cervical cancer on the basis of local imaging and whole body scan. Finally we summarized the applied value of 18F-FDG PET/CT in the clinical management of patients with cervical cancer.We took advantage of following two parts in this study emphatically to analyze the applied value of 18F-FDG PET/CT imaging in the clinical diagnosis and treatment and prognosis assessment of patients with cervical cancer:1. The diagnostic value of 18F-FDG PET/CT in the primary lesion of cervical cancer. 2. The comparative studies of F-FDG PET/CT and MRI in the diagnosis of pelviclymph-node metastases in patients with early-stage cervical cancer.PARTIThe diagnostic value of 18F-FDG PET/CT in the primary lesion of cervical cancerObjective This study retrospectively analyzed the PET/CT results of 162 cervical cancer patients who were confirmed by pathological examination, and probed the applied value of 18F-FDG PET/CT in the diagnosis of primary lesion of cervical cancer. The histopathological results were considered as the reference standard.Materials and Methods This study was approved by our hospital’s institutional review board. Between October,2009 and December,2013,162 cervical cancer patients aged 26-76 years (mean age:52.56±13.84 years) who were all confirmed by the results of pathological examination were enrolled into our study. The histological subtypes of the patients were as follows:squamous cell carcinoma in 123 patients, adenocarcinoma in 25, small cell neuroendocrine carcinoma in eight, clear cell carcinoma in seventeen and adenosquamous carcinoma in fourteen patients, respectively. The initial FIGO stage was Ial in three patients, Ia2 in 7, Ibl in 21, Ib2 in 29, Ha in 22, Ⅱb in 24, Ⅲa in 29, Ⅲb in 15, Iva in 4 and IVb in 8 patients. Each patient was gave an 18F-FDG PET/CT scan before treatment, and the imaging results and SUVmax of the primary lesion were recorded accordingly after the scan. The treatment pattern included surgery (radical hysterectomy with pelvic lympha-denectomy), chemotherapy and radiotherapy. All patients were followed up for at least half a year. SPSS for windows 17.0 statistical software was used for statistical correlation analysis, and Statistical significance was set at P<0.05.Results Among 162 cases,78 cases were under the age of 50 years, and 84 cases were more than 50 years old; 82 cases were found in early FIGO stage (stage Ⅰa-Ⅱa), and the other 80 cases found in middle-advanced FIGO stage (stage IIb-IVb); in 123 cases with squamous cell carcinoma,69 cases were well differentiated, while 54 cases were poorly differentiated; the tumor size of 37 cases was less than 4cm, and that of 125 cases was more than 4cm; the numbers of patients with SUVmax of primary lesion <8.35 and≥8.35 were all 81 cases. The findings of 18F-FDG PET/CT showed that the local invasion of cervical cancer was found in 78 cases, pelvic and paraaortic lymph node metastases found in 53 cases, and distant metastases in 9 cases. The mean SUVmax of primary tumor in all patients was equal to 9.49±4.78 (range:2.5～23.5); the SUVmax of squamous carcinoma group was higher than that of non-squamous carcinoma group (10.01±4.75 vs.7.83±4.54, P<0.05), and yet, the SUVmax of high differentiation group was lower than that of low differentiation group (7.93±4.04 vs. 12.68±4.27, P<0.05). The significant difference of mean SUVmax was found in different FIGO staging, tumor size, whether the local invasion and lymph node or distant metastasis occurred or not; the SUVmax of early stage group (stage Ⅰa-Ⅱa) was lower than that of middle-advanced stage group (stage Ⅱb～Ⅳb) (7.22±3.56 vs. 11.81±4.77, P<0.05), and the Pearson test showed that the SUVmax of primary tumor was positively correlated with FIGO staging (r=0.679, P=0.000); the SUVmax was higher in group of tumor size≥4cm than in that of tumor size<4cm(10.41±4.75 vs. 6.36±3.41, P<0.05), the larger the tumor size, the higher the SUVmax (Z=-4.906, P=0.000); the SUVmax in groups with local invasion, positive lymph node and distant metastasis was higher respectively than that in corresponding negative group (11.63±4.70 vs.7.50±3.93,8.55±4.46 vs.11.42±4.87,9.06±4.43, vs.16.72±4.95, P<0.05). If we took SUVmax=8.35 for critical value, all the patients then were divided into two groups:low uptake group (SUVmax<8.35) and high uptake group (SUVmax≥8.35), with the significant difference confirmed between two groups (5.60±1.70 vs.13.37±3.55, P=0.000); the SUVmax of primary tumor in patients with local invasion and distant metastasis was obviously higher than that in corresponding negative patients, and in high uptake group,53 cases were found with local invasion, 33 cases found with pelvic and paraaortic lymph node metastasis, and 8 cases with distant metastasis, which were higher than the corresponding values of 25 cases,20 cases,1 case respectively in low uptake group, with the significant difference found by comparing to the incidence between two groups (P<0.05).Conclusion Our study showed that the SUVmax of primary tumor of cervical cancer was obviously diverse in different histological subtypes and differentiated degree, FIGO staging, tumor size, and whether the local invasion and distant metastasis occurred or not; its value had a certain relationship with histological subtypes, differentiated degree, FIGO staging, tumor size, and the occurrence of local and distant metastasis, and yet, it is not correlated with the age of patients; the SUVmax of primary tumor in cervical cancer patients can predict the occurrence rate of local invasion, lymph node and distant metastasis, with the cut-off value equal to 8.35. 18F-FDG PET/CT scan before treatment had a more and more great value in clinical staging and the evaluation of curative effect and prognosis of patients with cervical cancer, and would play an important role in the clinical management of these patients.PART ⅡThe comparative studies of 18F-FDG PET/CT and MRI in the diagnosis of pelvic lymph-node metastases in patients with early-stage cervical cancerObjective Cervical cancer is a common gynecologic malignant tumor in women with the five-year overall survival rate only about 50%. Local recurrence and distant metastasis is the leading cause of cancer-related death in these patients. Generally we would make the diagnosis on the basis of medical history, clinical symptom, gynecological examination and cervical biopsy and delineate approximately the local extent of primary tumor by CT or MRI imaging. FIGO (International Federation of Gynecology and Obstetrics, FIGO) stage is commonly used for clinical staging of cervical cancer and its accuracy is relatively low by comparing with surgical staging mainly due to the indifference to lymph node metastasis. As a matter of fact, lymph node involvement is not only closely correlated with local recurrence and distant metastasis, but also a vital impact factor to prognosis. Once the lymph nodes metastases occur, the prognosis would be poor. Treatment of early-stage cervical cancer is mainly based on radical hysterectomy with pelvic and para-aortic lymph node dissection, supplemented by radiotherapy and chemotherapy; however, about 90% of conventionally resected lymph nodes are not metastatic, and indiscriminately pelvic lymphadenectomy would lead to some complications, such as pelvic lymphocyst, neurovascular injury, and adhesion, etc; as a result, clarifying the preoperative status of lymph nodes in early-stage cervical cancer is very important; it can help us to determine the scope of the operation as well as reduce the concurrent injury and its influence on quality of life which is caused by pelvic lymphadenectomy. 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) is a molecular imaging technique, and can be used for local imaging and whole body scan, reflect the function of metabolism of local lesion and distant metastasis by visualizing the uptake of 18F-FDG. And thus, it is expected to play an important role in the detection of pelvic lymph node metastasis in cervical cancer patients. In this article, we then probed the role of 18F-FDG PET/CT in the detection of lymph node involvement in patients with early-stage cervical cancer, and evaluated its application value in monitoring recurrence, guiding clinical treatment and judging prognosis, etc. The postoperative histopathological results were considered as the gold standard.Materials and Methods This study was approved by our hospital’s institutional review board and was performed according to the 1964 Declaration of Helsinki and all subsequent revisions. We retrospectively analyzed the results of preoperative 18F-FDG PET/CT and pelvic MRI imaging on 87 patients with cervical cancer, measured simultaneously the maximum standard uptake value (SUVmax) and short-axis diameter of pelvic lymph nodes, and then made a careful node-by-node comparison with the postoperative histopathological findings. All of the patients were scheduled for radical hysterectomy with pelvic lymph node dissection, and some of them had paraaortic node dissection if necessary. Lymphadenectomy involved removing all visible lymph nodes in the surgical fields. To enable a certain region-specific comparison, para-aortic and pelvic lymph nodes were divided into seven regions:the para-aortic area, both common iliac areas, both external iliac areas, and both internal iliac/obturator areas. The location, shape and size of each resected lymph node after surgery were recorded respectively, and we would classified these nodes into three groups afterwards on the basis of previous findings:group normal, reactive and metastasis. And then cases of true-positive, false-positive, true-negative, and false-negative lymph nodes on PET/CT and MRI scan were recorded accordingly. All clinical data, including pathological type, clinical FIGO staging, operation methods, and imaging findings, were reviewed and analyzed. All patients were followed up for at least 6 months. The postoperative histopathological findings was the reference standard for definitive diagnosis.Results 87 patients aged 45-73 years (mean age:55years) who had been confirmed histopathologically as having primary early-stage cervical cancer were enrolled into this study. The initial FIGO stage was Ial in three patients, Ia2 in 14, Ibl in 19, Ib2 in 15, Ⅱa in 26, and Ⅱb in 10 patients, respectively. The histological subtypes of the patients were as follows:squamous cell carcinoma in 69 patients, adenocarcinoma in 12, small cell neuroendocrine carcinoma in two and clear cell carcinoma in four patients. From among the 87 patients,1163 lymph nodes in all were surgically resected and 67 were confirmed histopathologically for metastasis, with 23 in right iliac/obturator area,16 in left iliac/obturator area, nice in right external iliac area, seven in left external iliac area, seven in right common iliac area,four in left common iliac area and one in Para-aortic area. The SUVmax and short-axis diameter of true-positive lymph nodes on PET/CT scan were equal to 4.9±2.1 (range 2.5～12.5) and 2.4cm±1.1cm (range 0.6cm-4.7cm), respectively; the results of Pearson correlation test between SUVmax and short-axis diameter of the true-positive lymph nodes showed that the former was positively correlated with the latter (Pearson correlation coefficient r=0.762, P= 0.000).78 positive lymph nodes were detected by PET/CT imaging, among which 17 were false-positive and 6 false-negative; however, only 41 positive lymph nodes were found by MRI scan, including 16 false-positive and 42 false-negative ones. The overall node-based sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of PET/CT in the diagnosis of lymph node metastasis were 91%(61/67),78.2 (61/78),99.4% (1079/1085),98%(1140/1163), respectively. These values were superior to the corresponding values of MRI, which were 37.3%(25/67),61%(25/41),96.3% (1080/1122), and 95%(1105/1163) (P<0.034). The differences in those values were statistically significant. The specificity of PET/CT (98.4%,1079/1096) was lower than that of MRI (98.5%,1080/1096); the statistically significant differences were not found yet (P-0.861). By ROC analysis, the difference between PET/CT and MRI for identifying overall node-based metastases was statistically significant (AUC PET/CT 0.719, AUC MRI 0.587, p=0.031). Among 87 patients with cervical cancer,34 were diagnosed for lymph node metastases, all of which were detected on PET/CT imaging, while only 15 cases discovered by MRI scan. Patient-based sensitivity, PPV, NPV, accuracy of PET/CT for detection of lymph node involvement were 100%(34/34), 87.2%(34/39),100%(48/48),94.3%(82/87), respectively, which were higher than the corresponding MRI values with sensitivity 44%(15/34), PPV 65%(15/23), NPV 74% (45/61), accuracy 69%(60/87) (P<0.04); however, the specificity (91%,48/53) of PET/CT was higher than that of MRI with specificity of 85%(45/53), without the statistically significant differences confirmed (P=0.374). The difference in diagnostic efficacy in identifying patient-based metastases between PET/CT and MRI was significant (PET/CT versus MRI, AUC 0.974 vs.0.705, p<0.001).Conclusion Compared with MRI, PET/CT which uses metabolism-based criteria proves to be valuable for lymph node metastases with higher sensitivity, specificity and accuracy in patients with early-stage cervical cancer, and becomes a good supplementary examination tool to clinical FIGO staging. It would play an important role in reducing unnecessary surgical resection of lymph nodes and encouraging more and more clinical physicians to recognize the decisive PET/CT imaging, and is expected to exert a profound impact on the subsequent selection of treatment methods and relevant clinical management of these patients. |
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