Funder: We acknowledge funding from Cancer Research UK BIDD grant C1353/A12762 and Cancer Research UK and Engineering and Physical Sciences Research Council support to the Cancer Imaging Centre at the Institute of Cancer Research and Royal Marsden Hospital in association with the Medical Research Council and Department of Health C1060/A10334, C1060/A16464 and National Health Service funding to the National Institute for Health Research Biomedical Research Centres at Royal Marsden Hospital/Institute of Cancer Research and Cambridge, Experimental Cancer Medicine Centres, the Clinical Research Facility in Imaging, and the Cancer Research Network. We are also grateful for financial support from Addenbrooke’s Charitable Trust. The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health Research or the Department of Health.BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC). METHODS: Participants with newly diagnosed EOC due for platinum-based chemotherapy and interval debulking surgery were recruited prospectively in a multicentre study (n = 47 participants). Apparent diffusion coefficient (ADC) and solid tumour volume (up to 10 lesions per participant) were obtained from DW-MRI before and after NAC (including double-baseline for repeatability assessment in n = 19). Anatomically matched lesions were analysed after surgical excision (65 lesions obtained from 25 participants). A trained algorithm determined tumour cell fraction, percentage tumour and percentage necrosis on histology. Whole-lesion post-NAC ADC and pre/post-NAC ADC changes were compared with histological metrics (residual tumour/necrosis) for each tumour site (ovarian, omental, peritoneal, lymph node). RESULTS: Tumour volume reduced at all sites after NAC. ADC increased between pre- and post-NAC measurements. Post-NAC ADC correlated negatively with tumour cell fraction. Pre/post-NAC changes in ADC correlated positively with percentage necrosis. Significant correlations were driven by peritoneal lesions. CONCLUSIONS: Following NAC in EOC, the ADC (measured using DW-MRI) increases differentially at disease sites despite similar tumour shrinkage, making its utility site-specific. After NAC, ADC correlates negatively with tumour cell fraction; change in ADC correlates positively with percentage necrosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01505829
