[F-18] FMISO PET hypoxia imaging in cervical cancer: Pretherapy uptake in predicting survival. Free

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Objectives: Hypoxia has been recognized as a significant problem in cancer of the uterine cervix. The genetic instability and molecular changes secondary to hypoxic stress promote an aggressive tumor phenotype that imparts resistance to both radiotherapy and chemotherapy, resulting in poor patient outcome. PET imaging with [F-18] fluoromisonidazole (FMISO) takes advantage of increased tracer retention in hypoxic tissues and is a non-invasive method to characterize and quantify hypoxia in cancer. We report our early experience with FMISO PET as a predictor of survival in patients with cervical cancer. Methods: Eighteen patients with cancer of the uterine cervix were enrolled in an FMISO-PET imaging protocol through 2005. PET images were obtained 90 min following the injection of 0.1 mCi/Kg of FMISO. All patients had bladder catheterization with irrigation to reduce bladder uptake. Tissue to blood (T:B) FMISO ratio was calculated using venous blood samples obtained during the emission part of the scan and a cutoff T:B ratio of 1.2 was used to signify hypoxia. Hypoxic volume (HV) is the sum of all pixels with a T:B ratio ≥ 1.2 and is expressed in mL. These patients also had whole body FDG scans that enabled measurement of glucose metabolism (SUVmax). Survival was analyzed using Cox proportional hazard model for FMISO and FDG. Results: Clinical Stage I - 4; Stage II - 4 and Stage III - 10. Histopathology: 6 adenocarcinoma and 12 squamous cell carcinoma. There were 4 deaths, 5 progressions and 9 with NED during the period. The mean hypoxic volume (HV): 16 mL (0.4 -68.4) and the mean FMISO Tissue:Blood max: 1.9 (1.33 - 3.8). The mean FDG SUVmax: 15.5 (2.1 - 28.8). Hypoxic Volume (HV), Tumor to Blood ratio (T:Bmax) and FDG (SUVmax) were each assessed using univariate Cox proportional hazards regression to measure their significance in relation to overall survival and progression-free survival. HV was highly prognostic for both endpoints (p=0.036 and 0.025 respectively) but FDG was not (p= 0.79 and 0.76). Similarly, the survival analysis shows a significant role for ict survival with grea han FDG in these patients. Conclusions: FMISO PET is a useful and non-invasive way to characterize and quantify hypoxia in cervical cancer. In a small group of patents with cervical cancer, pre-therapy FMISO uptake is able to predict survival after therapy with confidence. (This study was supported by Seattle Cancer Consortium Pilot Grant and in part by NIH P01 CA42045).