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Intratumoral Heterogeneity of 64Cu-ATSM Uptake is a Prognostic Indicator in Patients with Cervical Cancer

Albert J Chang, Farrokh Dehdashti, Barry A Siegel, Michael J Welch, Julie K Schwarz and Perry W Grigsby

 Introduction: Intratumoral heterogeneity determined by FDG-PET is a poor prognostic factor in cervical cancer. Cu-

ATSM has been used to evaluate hypoxia in cervical cancer. In this study, FDG and 64Cu-ATSM uptake patterns were compared and the prognostic significance of 64Cu-ATSM heterogeneity was determined. Methods: 15 patients with cervical cancer who underwent pretreatment 64Cu-ATSM- and FDG-PET/CT were included. The 64Cu-ATSM- and FDG-PET/CT images were co-registered and tumor volumes were autocontoured for each image set in 10% increments of the SUVmax ranging from 40% to 80%. The hypoxic fraction defined by 64Cu-ATSM uptake was determined. Concordance between 64Cu-ATSM and FDG uptake was determined by Dice’s coefficient. Heterogeneity of 64Cu-ATSM and FDG uptake was calculated as the variance of the 40-80% isothreshold volumes. The association between heterogeneity of 64Cu-ATSM uptake with tumor-specific factors and outcomes was determined. Results: The hypoxic fraction ranged from 0.773 ± 0.013 to 0.087 ± 0.010 as defined by the 40% to 80% Cu-ATSM isothreshold volumes, respectively. Dice’s similarity coefficients for the FDG and 64Cu-ATSM 40 to 80% isothreshold volumes ranged from 0.476 ± 0.012 to 0.112 ± 0.017. Greater 64Cu-ATSM heterogeneity was associated with increased risk of lymph node metastasis at diagnosis (p<0.01), persistent disease after therapy, (p<0.01), and decreased median progression-free survival (11 months vs. not reached, p=0.03). Conclusion: Significant fractions of cervical tumors are hypoxic. Regions of highest 64Cu-ATSM and FDG uptake were discordant. Elevated 64Cu-ATSM heterogeneity may predict for increased risk of lymph node metastases, decreased responsiveness to treatment, and decreased progression-free survival.