Frequent optical imaging during breast cancer neoadjuvant chemotherapy reveals dynamic tumor physiology in an individual patient

Abstract

Rationale and objectives: Imaging tumor response to neoadjuvant chemotherapy in vivo offers unique opportunities for patient care and clinical decision-making. Detailed imaging studies may allow oncologists to optimize therapeutic drug type and dose based on individual patient response. Most radiologic methods are used sparingly because of cost; thus, important functional information about tumor response dynamics may be missed. In addition, current clinical standards are based on determining tumor size changes; thus, standard anatomic imaging may be insensitive to early or frequent biochemical responses. Because optical methods provide functional imaging end points, our objective is to develop a low-barrier-to-access bedside approach that can be used for frequent, functional assessment of dynamic tumor physiology in individual patients.

Materials and methods: Diffuse Optical Spectroscopic Imaging (DOSI) is a noninvasive, bedside functional imaging technique that quantifies the concentration and molecular state of tissue hemoglobin, water, and lipid. Pilot clinical studies have shown that DOSI may be a useful tool for quantifying neoadjuvant chemotherapy response, typically by comparing the degree of change in tumor water and deoxy-hemoglobin concentration before and after therapy. Patient responses at 1 week and mid-therapy have been used to predict clinical outcome. In this report, we assess the potential value of frequent DOSI monitoring by performing measurements on 19 different days in a 51-year-old subject with infiltrating ductal carcinoma (initial tumor size 60 x 27 mm) who received neoadjuvant chemotherapy (anthracyclines and bevacizumab) over an 18-week period.

Results: A composite index, the Tissue Optical Index (TOI), showed a significant ( approximately 50%) decrease over the nearly 18 weeks of chemotherapy. Tumor response was sensitive to the type of chemotherapy agent, and functional indices fluctuated in a manner consistent with dynamic tumor physiology. Final pathology revealed 4 mm of residual disease, which was detectible by DOSI at the conclusion of chemotherapy before surgery.

Conclusion: This case study suggests that DOSI may be a bedside-capable tool for frequent longitudinal monitoring of therapeutic functional response to neoadjuvant chemotherapy.

Figure 1. Current DOSI instrument

The DOSI instrument measures tissue complete absorption and scattering spectra from 650 to 1000 nm through the use of a handheld probe (seen on top of system). Spectroscopic images are generated by translating the handheld probe along a rectilinear grid on the surface of the breast.

Figure 2. Measured Areas

Dots represent DOSI-measured locations on each breast for the study. At each spatial location, broadband NIR absorption and scattering spectra were obtained. The tumor location and orientation is identified by the oval in the Figure.

Figure 3. DOSI-measured near infrared absorption spectra

Sample near-infrared absorption spectra from normal and malignant breast tissues prior to neoadjuvant chemotherapy for both case study patients.

Figure 4. Serial DOSI images: before Bevacizumab

Serial images of ctHHb taken prior to all treatment (−8 days), as well as on day 3, 4, 5, and 7 after the initial A/C chemotherapy treatment. Each image is scaled independently, with the scale bar immediately to the right of the image. The maximum ctHHb value of the tumor dropped significantly after the treatment (days 3 & 4) but quickly returned to pre-treatment levels shortly thereafter (days 5 & 7). Note that the entire tumor volume was not imaged in this example.

Figure 5. Serial DOSI images: after Bevacizumab

Day −7 refers to a week prior to the initiation of a treatment stage featuring Bevacizumab. The number in parentheses is the day count with respect to the start of all therapy. This patient received Bevacizumab on days 27 and 41. We observed an initial decrease in ctHHb, yet the peak values of ctHHb returned to the day −7 values after approximately 2 weeks.

Figure 6. Long-Term tumor response

Tissue optical index (TOI) ratio (tumor/normal) is plotted over the entire course of treatment.