Monitoring of neoadjuvant chemotherapy through time domain diffuse optics: Breast tissue composition changes and collagen discriminative potential

TL;DR

This study demonstrates that broadband time domain diffuse optical spectroscopy can monitor breast tissue composition changes during neoadjuvant chemotherapy, with collagen potentially serving as an early biomarker for treatment response.

Contribution

It is the first systematic analysis of tissue composition, including collagen, during NAC using broadband diffuse optical spectroscopy in breast cancer patients.

Findings

Significant reduction in oxy-hemoglobin, collagen, and water in responsive patients.

Increase in lipids observed during therapy.

Collagen levels distinguish between complete and partial responders early in treatment.

Abstract

The purpose of this clinical study is to test broad spectral range (635-1060 nm) time domain diffuse optical spectroscopy in monitoring the response of breast cancer patients to neoadjuvant chemotherapy (NAC). The broadband operation allows us to fully analyze tissue composition in terms of hemoglobin, water, lipids and collagen concentration, which has never been systematically studied until now during the course of therapy. Patients are subjected to multiple breast optical imaging sessions, each one performed at different stages of NAC, both on tumor-bearing and contralateral healthy breast. We correlate the optical results with conventional imaging techniques and pathological response. Preliminary outcomes on data of 10 patients show an average significant reduction in the concentrations of oxy-hemoglobin (-53%, p = 0.0020), collagen (-36%, p = 0.0039) and water (-15%, p = 0.0195), and increase in lipids (+39%, p = 0.0137) from baseline to the end of therapy in the tumor-bearing breast of patients who responded to therapy at least partially. With respect to scattering, the scattering amplitude, a, increases slightly by the end of the therapy compared to the baseline, while the scattering slope, b, shows no significant change. Some change in concentrations of constituents was noticed also in the contralateral healthy breast, even though it was significant only for oxy-hemoglobin concentration. Collagen seems to be the only component distinguishing between complete (p = 0.0423) and partial responders (p = 0.1012) by the end of 2-3 weeks after the start of therapy, suggesting that it could serve as a potential biomarker to measure NAC effectiveness early during treatment. These initial results are consistent with those of standard medical modalities and highlight the sensitivity of the technique to changes that occur in breast composition during NAC.