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Diffusion-weighted MRI in Advanced Epithelial Ovarian Cancer: Apparent Diffusion Coefficient as a Response Marker
Jessica M Winfield1, Jennifer C Wakefield1, David Dolling1
1From the Cancer Research UK Cancer Imaging Centre, Division of Radiation Therapy and Imaging, The Institute of Cancer Research, London, England (J.M.W., J.C.W., E.P., D.J.C., N.M.d.S.); MRI Unit, Institute of Cancer Research and Royal Marsden Hospital, Royal Marsden NHS Foundation Trust, Downs Road, Sutton SM2 5PT, England (J.M.W., J.C.W., E.P., D.J.C., N.M.d.S.); Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, England (D.D., E.H.); Mount Vernon Cancer Centre, Mount Vernon Hospital, Northwood, England (M.H.); Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England (S.F., A.N.P.); Cancer Research UK Cambridge Institute, Cambridge, England (J.D.B.); Addenbrooke's Hospital, Cambridge, England (J.D.B.); Department of Oncology, University of Cambridge, Cambridge, England (J.D.B.); Department of Gynaecological Oncology, Abertawe Bro Morgannwg Health Board, Morriston Hospital, Swansea, Wales (K.L.S.); Imaging Department, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, England (R.A.Q.); Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, England (N.J.T.); Imperial College London Hammersmith Campus, London, England (H.G.); Clinical Discovery Unit, Early Clinical Development, IMED Biotech Unit, Astrazeneca, Cambridge, England (H.G.); Department of Radiology, Abertawe Bro Morgannwg Health Board, Morriston Hospital, Swansea, Wales (L.M.); and Gynaecology Unit, Royal Marsden NHS Foundation Trust, Sutton, England (S.B.).
Abstract:
Background Treatment of advanced epithelial ovarian cancer results in a relapse rate of 75%. Early markers of response would enable optimization of management and improved outcome in both primary and recurrent disease. Purpose To assess the apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI, as an indicator of response, progression-free survival (PFS), and overall survival. Materials and Methods This prospective multicenter trial (from 2012-2016) recruited participants with stage III or IV ovarian, primary peritoneal, or fallopian tube cancer (newly diagnosed, cohort one; relapsed, cohort two) scheduled for platinum-based chemotherapy, with interval debulking surgery in cohort one. Cohort one underwent two baseline MRI examinations separated by 0-7 days to assess ADC repeatability; an additional MRI was performed after three treatment cycles. Cohort two underwent imaging at baseline and after one and three treatment cycles. ADC changes in responders and nonresponders were compared (Wilcoxon rank sum tests). PFS and overall survival were assessed by using a multivariable Cox model. Results A total of 125 participants (median age, 63.3 years [interquartile range, 57.0-70.7 years]; 125 women; cohort one, n = 47; cohort two, n = 78) were included. Baseline ADC (range, 77-258 × 10-5mm2s-1) was repeatable (upper and lower 95% limits of agreement of 12 × 10-5mm2s-1 [95% confidence interval {CI}: 6 × 10-5mm2s-1 to 18 × 10-5mm2s-1] and -15 × 10-5mm2s-1 [95% CI: -21 × 10-5mm2s-1 to -9 × 10-5mm2s-1]). ADC increased in 47% of cohort two after one treatment cycle, and in 58% and 53% of cohorts one and two, respectively, after three cycles. Percentage change from baseline differed between responders and nonresponders after three cycles (16.6% vs 3.9%; P = .02 [biochemical response definition]; 19.0% vs 6.2%; P = .04 [radiologic definition]). ADC increase after one cycle was associated with longer PFS in cohort two (adjusted hazard ratio, 0.86; 95% CI: 0.75, 0.98; P = .03). ADC change was not indicative of overall survival for either cohort. Conclusion After three cycles of platinum-based chemotherapy, apparent diffusion coefficient (ADC) changes are indicative of response. After one treatment cycle, increased ADC is indicative of improved progression-free survival in relapsed disease. Published under a CC BY 4.0 license. Online supplemental material is available for this article.
