Predicting breast tumor response to neoadjuvant chemotherapy with diffuse optical spectroscopic tomography prior to treatment

Purpose: To determine whether pretreatment biomarkers obtained from diffuse optical spectroscopic tomographic (DOST) imaging predicts breast tumor response to neoadjuvant chemotherapy (NAC), which would have value to potentially eliminate delays in prescribing definitive local regional therapy that may occur from a standard complete 6- to 8-month course of NAC. Experimental Design: Nineteen patients undergoing NAC were imaged with DOST before, during, and after treatment. The DOST images of total hemoglobin concentration (Hb_T), tissue oxygen saturation (StO₂), and water (H₂O) fraction at different time points have been used for testing the abilities of differentiating patients having pathologic complete response (pCR) versus pathologic incomplete response (pIR). Results: Significant differences (P < 0.001, AUC = 1.0) were found between pCR patients versus pIR in outcome, based on the percentage change in tumor HbT within the first cycle of treatment. In addition, pretreatment tumor Hb_T (pretreatment Hb_T) relative to the contralateral breast was statistically significant (P = 0.01, AUC = 0.92) in differentiating pCR from pIR. Conclusions: This is the first clinical evidence that DOST Hb_T may differentiate the two groups with predictive significance based on data acquired before NAC even begins. The study also demonstrates the potential of accelerating the validation of optimal NAC regimens through future randomized clinical trials by reducing the number of patients required and the length of time they need to be followed by using a validated imaging surrogate as an outcome measure.