Multiparametric MR imaging parameters—apparent diffusion coefficient (ADC) and extravascular extracellular space (v e )—may provide response-to-therapy markers for patients with advanced ovarian cancer, according to a study published in the March issue of Radiology.
Current mechanisms for monitoring response to chemotherapy in ovarian cancer patients include CA-125 serum level measurements and lesion size evaluations via Response Evaluation Criteria in Solid Tumors (RECIST) criteria. However, both measures are imperfect.
Many patients have multiple tumor sites; CA-125 addresses responding and nonresponding tumors. “RECIST can be difficult to assess with adequate reproducibility,” wrote Evis Sala, MD, PhD, from University of Cambridge, England, and colleagues. In addition, there may be gaps between functional response and RECIST changes, and the criteria may not fully assess differential response at different anatomic locations.
“Recent data have shown that ovarian cancer may have substantial molecular heterogeneity at presentation, and this may explain drug resistance in ovarian and other gynecologic cancers,” the researchers wrote.
Sala and colleagues hypothesized that functional 3T MR techniques could help assess response to therapy and thus designed a study to examine multiparametric MR (diffusion-weighted MR, dynamic contrast-enhanced MR and MR spectroscopy) in evaluation of response to chemotherapy among patients with advanced disease and to compare parameters between primary masses and metastatic disease.
The study population was comprised of 22 patients with Stage 3 or higher ovarian cancer who were recommended for neoadjuvant chemotherapy prior to debulking surgery.
Patients first underwent CT imaging to assess the presence and size of lesions in three locations: primary ovarian lesion, omental cake and peritoneal deposits. Three cycles of chemotherapy were administered to all patients before MR scanning.
A radiologist reconstructed the images and created ADC and vascular signal fraction (VSF) maps and compared mean ADC, mean VSF, dynamic-contrast enhanced (DCE) MR parameters and choline concentration between responders and nonresponders. Lesion size using RECIST and CA-125 levels served as the reference standard for evaluating response to chemotherapy.
The baseline analysis showed ADC for peritoneal deposits was significantly lower than those of ovarian or omental lesions. The ADC of ovarian lesions increased significantly after three cycles of chemotherapy. In contrast, pre- and post-therapy ADC for omental lesions and peritonel deposits did not change significantly. Other changes included a significant decrease in k ep and a significant increase in v e values of ovarian lesions after chemotherapy, according to Sala et al.
The researchers suggested that the increases in ADC and v e of ovarian lesions after chemotherapy result from the cytotoxic effect of platinum. They offered that peritoneal disease may be marked by more densely packed cells, which are resistant to chemotherapy.
In the comparison of 11 responders and nine nonresponders by RECIST criteria, the researchers observed a significantly larger increase in ADCs and significantly greater decrease in k ep values of ovarian lesions after treatment among responders.
According to CA-125 criteria, there were nine responders and 11 nonresponders. This analysis showed a significantly higher increase in the v e values of ovarian lesions among responders.
The study demonstrated that each multiparametric imaging technique provided a quantitative parameter that reflects site-specific tumor behavior and possible data on the mechanism of chemotherapy action, according to the researchers. Diffusion-weighted MR could serve “as the most appropriate imaging modality for monitoring response to neoadjuvant platinum-based chemotherapy in patients with advanced ovarian cancer,” they wrote.
“The use of multiparametric MRI, with each technique yielding quantitative parameters that may potentially reflect site-specific tumor behavior and information on the mechanism of action of chemotherapy used, may have potential implications for chemoresistance and hence individualized patient treatment,” Sala and colleagues concluded.