Abstract
BackgroundDiffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC).MethodsParticipants 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).ResultsTumour 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.ConclusionsFollowing 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 registrationClinicalTrials.gov NCT01505829.
Highlights
Diffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC)
Of the 40/52 participants with pre- and post-NAC DW-MRI, 7/40 participants did not have interval debulking surgery (IDS), and a further 8/40 had no analysable lesions on pathology that were matched to the imaging, leaving 25/40 participants with matched lesions on imaging and pathology (Supplementary Fig. 1)
This study shows that in EOC/fallopian tube/primary peritoneal cancer lesions responding to NAC, there is a differential increase in Apparent diffusion coefficient (ADC) by anatomic site of the lesion despite a similar volume reduction of >80%
Summary
Diffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC). Epithelial ovarian cancer (EOC) of tubo-ovarian origin and primary peritoneal cancer often present at an advanced stage when multiple metastatic deposits in the pelvis and abdomen are commonly seen.[1] When primary debulking surgery is not feasible, platinum-based neoadjuvant chemotherapy (NAC) is recommended prior to interval debulking surgery (IDS) with the aim of reducing the burden of disease and enabling complete macroscopic (R0) resection, as this is strongly linked to favourable prognosis.[2,3] it is recognised that lesions may show a differential response[4], which is related to the tissue site at which the deposits occur[5] and the local microenvironment which may promote development of resistant metastatic clones.[6] If it were possible to identify lesions that are likely to be poorly responsive to neoadjuvant chemotherapy, these lesions could be targeted at surgical resection. Response evaluation criteria in solid tumours (RECIST) criteria[8] are well-established and widely used including in ovarian cancer.[9]
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