Early Therapeutic Prediction Based on Tumor Hemodynamic Response Imaging: Clinical Studies in Breast Cancer with Time-Resolved Diffuse Optical Spectroscopy

Shigeto Ueda,Toshiaki Saeki

doi:10.3390/app9010003

Shigeto Ueda, Toshiaki Saeki

Open Access

https://doi.org/10.3390/app9010003

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Journal: Applied sciences	Publication Date: Dec 20, 2018
Citations: 4	License type: CC BY 4.0

Affiliation: Saitama Medical University

Abstract

This study reports data from three clinical studies using the time-resolved diffuse optical spectroscopy (TRS) system among breast cancer patients. The parameters of oxy-hemoglobin (O2Hb), deoxy-hemoglobin (HHb), total hemoglobin (tHb), and oxygen saturation (SO2) were evaluated using TRS, and its efficacy was tested in three trials. In trial 1, we recruited 118 patients with primary breast cancer to estimate the tumor detection rate. The cumulative detection rate was 62.7%, while that in T stage 0 was 31.3% and in T stage 1 was 44.7%. These were lower than those of T stage 2 (78.9%) and T stage 3 (100%). Next, we used TRS to monitor tumor hemodynamic response to neoadjuvant chemotherapy (n = 100) and found that pathological complete response (pCR) tumors had significantly lower tumor tHb than non-pCR tumors; a similar result was observed in estrogen receptor (ER)-negative tumors, but not in ER-positive tumors. The third trial monitored hemodynamic response to antiangiogenic therapy, bevacizumab (n = 28), and we demonstrated that sequential optical measurement of tumor SO2 might be useful for detecting acute hypoxia 1–3 days after bevacizumab initiation. Next, response monitoring of neoadjuvant endocrine therapy (n = 30) suggested that changes in tumor tHb during treatment can predict and distinguish between responsive and non-responsive tumors early in letrozole therapy. In conclusion, our results show that hemodynamic monitoring of tumors by TRS could pair the unique features of tumor physiology to drug therapy and contribute to patient-tailored medicine. We recently established a platform for performing TRS in patients with breast cancer.

Highlights

Breast cancer is one of the most common causes of death worldwide
We present findings obtained from three clinical studies and discuss the usefulness and limitations of time-resolved diffuse optical spectroscopy (TRS) in breast cancer treatment
All three were prospective clinical studies: (1) clinical study of in vivo optical imaging of breast cancer using diffuse optical spectroscopy (UMIN000011888); (2) value of usefulness of diffuse optical spectroscopic imaging for monitoring the efficacy of bevacizumab followed by paclitaxel in breast cancer patients (UMIN000015837); (3) early prediction of tumor response using imaging and molecular biomarkers of hormone sensitive breast cancer in a neoadjuvant hormonal therapy setting (UMIN000013815), and were registered at the UMIN Clinical trials registry

Summary

Introduction

Screening and recent advances in adjuvant therapy for primary breast cancer have reduced its mortality rate by approximately 10–16% in Japan [1]. As data suggest that one in fourteen Japanese women will develop breast cancer in their lifetimes, screening, diagnosis, and adjuvant therapy are essential strategies. X-ray mammography is the current gold standard screening modality, and ultrasonography is considered an adjunct therapy to mammography in premenopausal women [2]. DOSI uses near-infrared light, in the 600–1000 nm wavelength range, to measure the concentrations of oxy-hemoglobin (O2 Hb), deoxy-hemoglobin (HHb), water (water), lipid (lipid), and oxygen saturation (SO2 ) in breast tissue [3]. DOSI is a non-invasive, non-ionizing, cost-effective modality that provides functional quantification of tumor angiogenesis, hypoxia, edema, and adipose tissue [4,5,6]

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