Changes in Diffuse Optical Tomography Images During Early Stages of Neoadjuvant Chemotherapy Correlate with Tumor Response in Different Breast Cancer Subtypes

Purpose: This study's primary objective was to evaluate the changes in optically derived parameters acquired with a diffuse optical tomography breast imaging system (DOTBIS) in the tumor volume of patients with breast carcinoma receiving neoadjuvant chemotherapy (NAC). Experimental Design: In this analysis of 105 patients with stage I-III breast cancer, normalized mean values of total hemoglobin (ctTHb(N)), oxyhemoglobin (ctO(2)Hb(N)), deoxy-hemoglobin concentration (ctHHb(N)), water, and oxygen saturation (StO(2N)) percentages were collected at different timepoints during NAC and compared with baseline measurements. This report compared changes in these optical biomarkers measured in patients who did not achieve a pathologic complete response (non-pCR) and those with a pCR. Differences regarding molecular subtypes were included for hormone receptor-positive and HER2-negative, HER2-positive, and triple-negative breast cancer. Results: At baseline, ctHHb(N) was higher for pCR tumors (3.97 +/- 2.29) compared with non-pCR tumors (3.00 +/- 1.72; P = 0.031). At the earliest imaging point after starting therapy, the mean change of ctHHb(N) compared with baseline (Delta(TP1)ctHHb(N)) was statistically significantly higher in non-pCR (1.23 +/- 0.67) than in those with a pCR (0.87 +/- 0.61; P < 0.0005), and significantly correlated to residual cancer burden classification (r = 0.448; P < 0.0005). Delta(TP1)ctHHb(N) combined with HER2 status was proposed as a two-predictor logistic model, with AUC = 0.891; P < 0.0005; and 95% confidence interval, 0.812-0.969. Conclusions: This study demonstrates that DOTBIS measured features change over time according to tumor pCR status and may predict early in the NAC treatment course whether a patient is responding to NAC.