Functional hemodynamic imaging markers for the prediction of pathological outcomes in breast cancer patients treated with neoadjuvant chemotherapy.

Significance: Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes.

Aim: We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT.

Approach: Twenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers.

Results: Normalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles ($p=0.042$). In addition, the change in normalized tumor ${\mathrm{StO}}_2$ upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle ($p=0.038$). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI.

Conclusions: These findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens.