Longitudinal monitoring of tumor physiology following cyclophosphamide treatment using diffuse reflectance spectroscopy and diffuse correlation spectroscopy

Monitoring early physiological changes during neoadjuvant chemotherapy (NAC) is important for treatment assessment, as conventional anatomical assessments often lag behind underlying physiological changes. This study utilized diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) to longitudinally monitor tumor physiology in a preclinical rat model of breast cancer. Daily measurements of tissue oxygen saturation (StO₂), relative blood flow index (rBFi), and a derived relative tissue metabolic rate of oxygen (rtMRO₂) were obtained in tumors treated with a single dose of cyclophosphamide (CTX) and in untreated controls. Following CTX administration on day 9, treated tumors exhibited a pronounced increase in rBFi and rtMRO₂ on day 11, preceding the onset of tumor volume reduction on day 12; the rise in rtMRO₂ exceeded that of rBFi and was statistically significant ( p < 0.05). The rBFi/rtMRO₂ ratio declined during early growth and increased between the selected early and late intervals in seven of the eight CTX-treated animals with late observations. The present findings support the use of integrated DRS-DCS for early detection and longitudinal monitoring of physiological changes associated with single-agent CTX treatment in this preclinical model. Changes in rBFi and rtMRO₂ were observed prior to the detection of tumor volume reduction by caliper measurements.