Abstract P6-01-02: Spatial heterogeneity of response on whole-body MRI to first line hormonal therapy predicts progression-free survival in metastatic breast cancer
Authors: M Kosmin, A Makris, H Sokhi, T Thijssen, A Padhani
Journal: Cancer Research (2018)

Abstract Background Whole-body magnetic resonance imaging (WB-MRI) reliably identifies types of response to systemic therapy in metastatic breast cancer (MBC) through analysis of changes in water diffusivity, cellularity and cell variability. We adapted a novel methodology that uses WB-MRI to capture spatial response heterogeneity data via the METastasis Response Assessment Diagnostic System (MET-RADS). This study evaluates whether the extent of spatial heterogeneity seen at initial response assessment is predictive of progression-free survival (PFS) in patients on first line hormonal therapy for MBC. Methods Patients on first line hormonal therapy for MBC who had undergone baseline and on-treatment response assessment WB-MRI scans were identified. All scans were performed using a published WB-MRI protocol. Patients with disease progression at their first WB-MRI response assessment were excluded from further analysis. Criteria for response assessment utilised the methodology described by MET-RADS. A Likert five-point Response Assessment Category (RAC) score (1=response highly likely; 2=response likely; 3=no change; 4=progression likely; 5=progression highly likely) was applied separately to 14 defined anatomic regions. Within each region, two RAC scores were recorded to reflect both the dominant and the next most common pattern of response behaviour. Data were therefore captured on inter- and intra-regional response heterogeneity. A novel Response Heterogeneity Index (RHI) was calculated from the regional RAC scores. The RHI value summarised the overall response heterogeneity seen across all involved regions, with higher scores indicative of greater heterogeneity of response. Depth of overall response to treatment was defined as the mean RAC score for all involved regions, with lower scores indicative of a greater depth of treatment response. RHI and mean RAC score data were separated by median values into two groups for analysis. Results Thirty-three patients were suitable for analysis. Patients with higher levels of response heterogeneity (defined as RHI≥4; n=16) had significantly shorter PFS than those with RHI &amp;lt;4 (n=17; median PFS: 12 vs 24 months; log rank test p=0.006). Depth of initial response, as defined by mean RAC score, and PFS were unrelated (mean RAC ≤2.5 (n=17) vs mean RAC &amp;gt;2.5 (n=16); median PFS: 27 vs 23 months; log rank test p=0.699). There was no correlation between RHI score and mean RAC score (r2=0.002). Conclusions Lower variability of response behaviour at first treatment assessment is predictive of longer treatment duration in patients receiving first line hormonal therapy for MBC. The spatial heterogeneity of response evident on WB-MRI may represent the genetic heterogeneity and clonal evolution of MBC, which are key factors in the development of treatment resistance. Citation Format: Kosmin M, Makris A, Sokhi H, Thijssen T, Padhani A. Spatial heterogeneity of response on whole-body MRI to first line hormonal therapy predicts progression-free survival in metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-01-02.