Abstract P4-01-14: Two-week change in optical tomography predicts residual cancer burden score in women treated with neoadjuvant chemotherapy
Authors: Lim EA , Gunther JE , Flexman M , Kim HK , Hibshoosh H , Kalinsky K , Crew K , Maurer M , Taback B , Feldman S , Ananthakrishnan P , Refice S , Brown M , Hielscher A , Hershman DL 
Published: August 2014

Background: A low Residual Cancer Burden (RCB) score after neoadjuvant chemotherapy (NACT) predicts an improved survival in patients (pts) with breast cancer (BC). While an early predictor of tumor response to NACT would allow for treatment optimization, no ideal method exists. Diffuse optical tomography (DOT) is a novel, fast, and low-cost imaging approach that assesses the distribution of water (H2O), oxyhemoglobin (HbO), and deoxyhemoglobin (Hb) concentrations, as a measure of tissue vascularity, without the use of ionizing radiation or breast compression, allowing for safe repeated measurements. We hypothesize that changes in DOT parameters will predict the RCB score following NACT.

Methods: Women with stage II-IIIc invasive BC scheduled to undergo NACT with 12 cycles of a weekly taxane followed by 4 cycles of doxorubicin with cyclophosphamide were enrolled. Treatment with biologic therapies was allowed. DOT assessments were made before starting NACT, 2 weeks into treatment, and before surgery. DOT data were reconstructed into 3D images of the tumor region, from which HbO, Hb, and H2O concentrations were extracted. Final pathology specimens were scored for the RCB index (continuous measure), RCB class (0, 1, 2, 3), and a dichotomized RCB score (RCB class 0 or 1: responders to NACT; RCB class 2 or 3: non-responders). Ki-67 was measured on baseline tumor biopsies and surgical specimens. Correlation analysis, ANOVA testing, and two sample t-tests were used to evaluate the relationship between the 2-week changes in DOT parameters and the RCB score and Ki-67 level.

Results: Since July 2011, we have recruited 24 pts of a total planned accrual of 40. 19 pts have undergone surgery and complete data is available for 13 at this time. Of the 13 pts, 4 had a pCR (RCB 0), 2 had RCB 1, 6 had RCB 2, and 1 had RCB 3. The Pearson correlations between the 2-week change in HbO, Hb, and H2O with the continuous RCB index were 0.76 (p = 0.0022), 0.87 (p = 0.0001), and 0.74 (p = 0.0038), respectively. There was a significant difference in the 2-week Hb change for pts with RCB 0 compared to pts with RCB 1, 2, or 3. There were significant differences in the 2-week change in H2O and HbO for pts with RCB 0 compared to pts with RCB 2. There were also significant differences between DOT parameters by the dichotomized RCB score (table 1). Ki-67 change was correlated with 2-week H2O change (Pearson r = 0.61 p = 0.045).

2-week DOT% change by RCB class and dichotomized RCB score HbOHbOH2ORCB 0-38%-28.5%-6.7%RCB 1-3.9%-2.9%-0.2%RCB 2+2.3%-0.6%+0.7%RCB 3+1.0%+10.9%-0.4%    Responders (RCB 0/1)-26.6%-20%-4.5%Non-Responders (RCB 2/3)+2.1%+1%+0.6%P value0.010.00690.014

Conclusions: Two-week DOT change is an early predictor of response to NACT as measured by the RCB score. We found significant associations between the RCB index and Ki-67 with 2-week changes in HbO, Hb, and H2O. Significantly different changes in DOT parameters were associated with the other RCB classifications. We are analyzing DOT data on the remaining pts and will conduct biomarker assessments of microvessel density changes. Additional pts are being recruited to evaluate DOT's predictive ability by tumor subtype.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-14.