Abstract P5-01-05: Early optical tomography changes correlate with residual cancer burden scores in women receiving neoadjuvant chemotherapy
Authors: Lim Emerson A , Gunther Jacqueline E , Flexman Molly , Kim Hyun K , Hibshoosh Hanina , Kalinsky Kevin , Crew Katherine , Maurer Matthew , Feldman Sheldon , Taback Bret , Ananthakrishnan Preya , Chen Margaret , Refice Susan , Hielscher Andreas , Hershman Dawn L 
Published: May 2015

Background: The Residual Cancer Burden (RCB) score predicts survival in patients (pts) with breast cancer (BC) treated with neoadjuvant chemotherapy (NACT). Predicting tumor response early during NACT may allow for treatment optimization. Diffuse optical tomography (DOT) is an imaging modality that measures the distribution of water (H2O), oxy- (HbO), and deoxy-hemoglobin (Hb) concentrations as a surrogate for vascularity and architecture. We hypothesize that the 2-week change in DOT parameters will correlate with the RCB score. We also explored the association between DOT parameters and tissue biomarkers: Ki-67 change and microvessel density (MVD).

Methods: Women with stage II-IIIc invasive BC scheduled to receive 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 NACT and after 2 weeks on treatment. 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), RCB class (0, 1, 2, 3), and a dichotomized RCB score (RCB class 0 or 1: responders; RCB class 2 or 3: non-responders). Ki-67 was measured on baseline tumor biopsies and surgical specimens. MVD was assessed on baseline tumor biopsies. 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 change. Correlation was assessed between MVD and baseline DOT measures.

Results: Since July 2011, we have recruited 28 pts of a total planned accrual of 40. 25 pts have had surgery and complete data are available for 23. Of the 23 pts, 6 had a pCR (RCB 0), 2 had RCB 1, 10 had RCB 2, and 5 had RCB 3. The Pearson correlations (r) between the 2-week change in HbO, Hb, and H2O with the continuous RCB index were 0.65 (p=0.002), 0.70 (p=0.0006), and 0.70 (p=0.0006), 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). There was an association in Ki-67 change and 2-week H2O change (r=0.43 p=0.059). A subset of 15 pts had MVD assessments, but these did not correlate with baseline DOT parameters (r ≤0.18, p&gt;0.5).

2-week DOT % change by dichotomized RCB score HbOHbH2OResponder (RCB 0/1)-31.0%-22.3%-5.5%Non-Responder (RCB 2/3)-4.4%-2.3%-0.3%P value0.020.010.015

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 with 2-week changes in HbO, Hb, and H2O. Significantly different changes in DOT parameters were associated with the other RCB classifications. Ki-67 changes and baseline MVD were not statistically significantly associated with DOT parameters. We are analyzing static and dynamic DOT data on the remaining pts. Additional pts are being recruited to evaluate DOT's predictive ability by tumor subtype.

Citation Format: Emerson A Lim, Jacqueline E Gunther, Molly Flexman, Hyun K Kim, Hanina Hibshoosh, Kevin Kalinsky, Katherine Crew, Matthew Maurer, Sheldon Feldman, Bret Taback, Preya Ananthakrishnan, Margaret Chen, Susan Refice, Andreas Hielscher, Dawn L Hershman. Early optical tomography changes correlate with residual cancer burden scores in women receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-01-05.