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Intratumoral Metabolic Heterogeneity of Cervical Cancer

Authors' Affiliations: ¹ Department of Radiation Oncology, ² Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, ³ Department of Obstetrics and Gynecology, and ⁴ the Alvin J. Siteman Cancer Center, Washington University Medical Center, St. Louis, Missouri

Requests for reprints: Perry W. Grigsby, Washington University School of Medicine, Department of Radiation Oncology, Campus Box 8224, Mallinckrodt Institute of Radiology, 4921 Parkview Place, CAM Lower Level, St. Louis, MO 63110. Phone: 314-362-8502; Fax: 314-747-9557; E-mail: pgrigsby{at}wustl.edu.

Purpose: Previous research has shown that the intertumoral maximum standardized uptake value (SUV_Max) of F-18 fluorodeoxyglucose (FDG)–positron emission tomography (PET) for cervical cancer predicts disease outcome. The purpose of this study was to evaluate the pretreatment intratumoral metabolic heterogeneity of FDG.

Experimental Design: This is a prospective cohort study of 72 patients with International Federation of Gynecology and Obstetrics stages Ib1 to IVa cervical cancer treated with chemoradiation. Three-dimensional FDG-PET threshold tumor volumes were calculated using image segmentation and an adaptive thresholding method for the primary cervix tumor from the pretreatment FDG-PET/computerized tomography. Intratumor heterogeneity was obtained for each patient's cervical tumor by taking the derivative (dV/dT) of the volume-threshold function from 40% to 80%. The association between intratumoral heterogeneity and tumor-specific factors and patient outcomes were determined.

Results: The mean cervix tumor SUV_Max was 12.4 (range, 3.0-38.4). The mean differential tumor heterogeneity was –1.074 (range, –0.107 to –5.623). There was no association between dV/dT and SUV_Max (R² = 0.069), but there was a relationship with dV/dT and tumor volume (R² = 0.881). There was no correlation of dV/dT with tumor histology (P = 0.4905). Heterogeneity was significantly associated with the risk of lymph node metastasis at diagnosis (P = 0.0009), tumor response to radiation as evaluated by FDG-PET obtained 3 months after completing treatment (P = 0.0207), risk of pelvic recurrence (P = 0.0017), and progression-free survival (P = 0.03).

Conclusions: Cervical intratumoral FDG metabolic heterogeneity on the pretreatment FDG-PET predicts risk of lymph node involvement at diagnosis, response to therapy, and risk of pelvic recurrence.