Biomarkers for site-specific response to neoadjuvant chemotherapy in epithelial ovarian cancer: relating MRI changes to tumour cell load and necrosis

Br J Cancer. 2021 Mar;124(6):1130-1137. doi: 10.1038/s41416-020-01217-5. Epub 2021 Jan 4.

Abstract

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers / metabolism*
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Carcinoma, Ovarian Epithelial / metabolism
  • Carcinoma, Ovarian Epithelial / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Middle Aged
  • Necrosis*
  • Neoadjuvant Therapy / methods*
  • Neoplasm, Residual / drug therapy
  • Neoplasm, Residual / metabolism
  • Neoplasm, Residual / pathology*
  • Prognosis
  • Prospective Studies
  • Tumor Burden

Substances

  • Biomarkers

Associated data

  • ClinicalTrials.gov/NCT01505829