Dual PETOvac - Dual Time PET/CT in the Preoperative Assessment of Ovarian Cancer

Overview

The investigators want to compare the use of MRI with PET/CT preformed after 1 hour and 3 hours in preoperative assessment of resectability. The investigators' hypothesis is that dual time PET/CT performed at 60 and 180 minutes will increase the diagnostic accuracy of conventional PET (performed at 60 minutes) in preoperative assessment of resectability. Further more the investigators suggest that the GLUT/G6Pase index correlates to the SUVmax. And retention index (RI, see Methods - PET protocol) is a prognostic marker in ovarian cancer.

The use of PET/CT in ovarian cancer has not been well-established. The diagnosis usually includes physical examination (incl. pelvic examination), blood test incl. CA-125 and transvaginal ultrasound. Furthermore imaging includes CT of thorax/abdomen and/or MR of pelvic. Ninety per cent of the ovarian cancers are epithelial carcinoma (EOC), which can be divided into serous (45%), mucinous (4%), endometrioid (5%), clear cell, undifferentiated and mixed types. All EOC are treated equally. Treatment of ovarian cancer involves surgery and chemotherapy. The decision of operability is made at the multidisciplinary conference. Prognosis depends not only in the stage and histological type of the tumor but also at the end result of surgery. Residual disease after initial surgery is a strong prognostic factor for survival, with improvement on both overall and progression free survival being greatest in women with no or minimal (tumor \< 1 cm) visible disease at the end surgery. Supra radical surgery is a radical procedure plus e.g. extensive peritonectomy, resection of liver metastases, splenectomy, resection of the tail of pancreas and bowel resection. Only 60% of patients in advanced stage ovarian cancer are deemed optimal debulked peroperative. Patients with optimal debulking have a 5 year survival of 42% versus patients not possible of achieve radical operation with 5 year survival of 15%, resulting in a hazard rate of 2,12 for optimal vs. not optimal debulking. A correct preoperative assessment is important in planning of operation and to avoid futile operation in patients not resectable. Preoperative CT has shown to have a predictive value in assessment of the completeness of cytoreduction. But also PET/CT is has shown to be a independent predictor of resectability. Currently MR is standard in evaluating patient operability. Studies has shown PET/CT to be particularly useful in distinguishing patients with stages I-IIIB and IIIC-IV, with an accuracy of 98% compared to 88% with CT alone. The latter group is important to identify because optimal debulking often is not possible and they will benefit from preoperative chemotherapy. Currently the use of PET/CT in staging ovarian cancer is controversial, mainly because of the relatively low specificity, due to FDG-uptake in inflammatory cells and benign lesions. The concordance of PET/CT and surgical staging of ovarian cancer have been reported to range from 69% to 78%.8,9, And a recent study found good correlation between PET/CT findings and laparoscopy but a high rate of false negative results in lesions \< 5 mm. But dual time point imaging is maybe the solution to this problem. Today it is standard to perform PET/CT scan 60-90 minutes after injection of tracer. Theoretically, you should get increased tumor/background ratio by performing a late scan, thus better being able to distinguish between malignant and benign. Dual time imaging studies in head and neck cancers, breast cancer and lung cancer suggests improvement in diagnostic accuracy of PET. But the use of delayed imaging in ovarian cancer has not been studied. The tracer used in PET is 18F-fluoro-2-deoxy-d-glucose. Generally cancer cells are thought to have low or absent G6Pase expression compared to normal cells and cancer cells have increased expression of GLUT (especially GLUT1) and hexokinase (especially HK2), which further leads to intracellular trapping of FDG-6-phosphate in malignant cells and there by yielding high maximum standardized uptake value (SUVmax). But ovarian cancers have found to have a relatively low ratio of hexokinase/phosphatase maybe explaining the low/absent rise in FDG-uptake. The amounts of GLUT, hexokinase and G6Pase are responsible for the FDG trapping intracellular and the retention on the late scans.

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