Assessing tumor hypoxia in cervical cancer by positron emission tomography with 60Cu-ATSM: Relationship to therapeutic response—a preliminary report

Abstract

Purpose Tumor hypoxia is associated with poor response to therapy. We have investigated whether pretreatment tumor hypoxia assessed by positron emission tomography (PET) with Cu-60 diacetyl-bis(N 4-methylthiosemicarbazone) ( 60Cu-ATSM) predicts responsiveness to subsequent therapy in cervical cancer. Methods and materials Fourteen patients with biopsy-proved cervical cancer were studied by PET with 60Cu-ATSM before initiation of radiotherapy and chemotherapy. 60Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M) and peak slope index of tumor tracer uptake. All patients also underwent clinical PET with F-18 fluorodeoxyglucose (FDG) before institution of therapy. The PET results were correlated with follow-up evaluation (14–24 months). Results Tumor uptake of 60Cu-ATSM was inversely related to progression-free survival and overall survival (log–rank p = 0.0005 and p = 0.015, respectively). An arbitrarily selected T/M threshold of 3.5 discriminated those likely to develop recurrence; 6 of 9 patients with normoxic tumors (T/M < 3.5) are free of disease at last follow-up, whereas all of 5 patients with hypoxic tumors (T/M > 3.5) have already developed recurrence. Similar discrimination was achieved with the peak slope index. The frequency of locoregional nodal metastasis was greater in hypoxic tumors ( p = 0.03). Tumor FDG uptake did not correlate with 60Cu-ATSM uptake ( r = 0.04; p = 0.80), and there was no significant difference in tumor FDG uptake between patients with hypoxic tumors and those with normoxic tumors. Conclusion 60Cu-ATSM-PET in patients with cervical cancer revealed clinically relevant information about tumor oxygenation that was predictive of tumor behavior and response to therapy in this small study.