Background: Optical based imaging modalities have shown promise for monitoring tumor response to neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC). Patients with triple negative BC (TNBC) who achieve a pathologic complete response (pCR) have improved disease free and overall survival after NAC. In this study, we evaluated whether early changes in diffuse optical tomography breast imaging system (DOTBIS) parameters can predict a pCR. In particular, we studied total hemoglobin concentration (ctHbT) in the tumor region.

Methods: This is a retrospective evaluation of 105 stage II-III BC patients enrolled in a prospective cohort study between 2011 and 2019. All patients received standard taxane-based chemotherapy in the neoadjuvant setting and pCR was defined as no invasive tumor cells from the breast and axillary tissue at surgery (ypT0 ypN0). Residual Cancer Burden (RCB) score was also calculated. By imaging the whole breast volume using low intensity near infrared light, we measured tissue concentration of oxy-hemoglobin (ctO2Hb) and deoxy-hemoglobin (ctHHb). After tumor volume segmentation, the mean ctHbT (ctO2Hb+ ctHHb) extracted from the region of interest was normalized by the non-tumor region ctHbT mean value. We conducted an independent-samples t-test to determine if there was a difference in changes in the normalized ctHbT levels at week 4 (w4) between patients with a pCR and non-pCR. A Pearson's correlation assessed for correlation between RCB score and changes in the normalized ctHbT level at w4 compared to baseline.

Results: In total, 77 patients had complete data for the analysis. Of these, TNBC accounted for 18% (14/77) of BC cases. DOTBIS data was acquired at baseline for all patients. Twelve patients received weekly paclitaxel x 12, followed by dose-dense adriamycin/cyclophosphamide every 2 weeks x 4, and two received docetaxel/cyclophosphamide every 3 weeks x 6. Ten of 14 TNBC patients were imaged after four weeks of taxane-based NAC (w4). Of the 14 TNBC patients, 6 (43%) achieved pCR. Two patients were classified as RCB-I, 5 as RCB-II, and 1 non-pCR patient without an available RCB. After comparing normalized ctHbT levels at w4 to baseline, NAC was associated with an overall decrease of 28% for the pCR group (n=5) as opposed to an increase of 67% for non-pCR (n=5). The normalized ratio between ctHbT levels measured at w4 and baseline was statistically lower in the pCR group (0.72 ± 0.28) than non-pCR (1.67 ± 0.83) (95% CI, 0.17 to 2.09), p = .043. Changes in the normalized ctHbT levels after 4 weeks of NAC were strongly correlated to RCB score (r = .833, p = .005).

Conclusions: This study demonstrates that changes as early as 4 weeks in DOTBIS-measured ctHbT levels in patients with TNBC receiving NAC correlate strongly with pathologic response. If further validated on a larger set, these data could potentially be used to optimize treatment outcomes or improve personalized therapeutic strategies.

Citation Format: Mirella L Altoe, Kevin Kalinsky, Hua Guo, Hanina Hibshoosh, Mariella Tejada, Katherine D Crew, Melissa K Accordino, Meghna S Trivedi, Alessandro Marone, Hyun K Kim, Andreas H Hielscher, Dawn L Hershman. Early changes in diffuse optical tomography predicts pathologic complete response to neoadjuvant chemotherapy in triple-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-01-02.