Abstract

Abstract Background: Optical based imaging modalities have shown promise for monitoring tumor response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. In this study, we evaluate whether changes in deoxy-hemoglobin concentration values acquired by a Diffuse Optical Tomography Breast Imaging System (DOTBIS) over different time points are associated with tumor response. Methods: This is a retrospective evaluation of 55 stage II-III BC patients in the neoadjuvant setting who received weekly paclitaxel x 12, followed by dose-dense adriamycin/cyclophosphamide every 2 weeks x 4. The patients were enrolled in this cohort study between 2011 and 2019, and DOTBIS images were acquired from the patient whole breast volume at 6 different time points: at baseline (TP0); two weeks after the first taxane infusion (TP1); after four infusions of taxane (TP2); at the end of the taxane regimen and before starting AC cycle (TP3); after two AC infusions (TP4); and at the end of NAC and before surgery (TP5). ctHHb tumor concentration was measured using low-intensity near-infrared light and normalized by the non-tumor region ctHHb mean value (ctHHbN). In order to evaluate whether pCR status, menopausal status, and molecular subtype classification influence the change of ctHHbN over time, we designed a multilevel mixed-effect statistical model. pCR was defined as no invasive tumor cells from the breast and axillary tissue at surgery (ypT0 ypN0). Results: 20 patients had pCR and 35 were classified as non-pCR. The estimate average ctHHbN for pCR tumors at baseline was 4.02. There was a significant reduction in ctHHbN levels for pCR group at TP1 (-1.31, p = .0001) and TP2 (-1.36, p = .0416). Changes in ctHHbN levels compared to baseline (TP0) values were statistically significant different between pCR and non-pCR at all time points except at the end of the taxane cycle (TP3), Table 1. No significant changes over time were identified between molecular subtypes groups, or between pre- and post-menopausal status. Conclusions: Our study adds to the body of evidence reported for diffuse optical imaging methods applied to breast cancer treatment response. These results show that DOTBIS measured features, such as ctHHbN, change in accordance with pCR status after 2 weeks under NAC, and there are differences in time evolution between the pCR groups. Reduction in ctHHbN levels represents the chemotherapeutic- induced changes in the tumor microvasculature: lower ctHHbN values associate with the reduction in tumor cell proliferation, and consequently in oxygen consumption. Future studies are warranted to evaluate whether early response prediction might determine if earlier treatment changes alter patient outcome. Table 1 - Changes in ctHHbN levels compared to baseline (TP0) values between pCR and non-pCR at all imaging time points. Bold values indicate statistical significance at p <.05 level.Time PointMean Difference ± Std. Errorp-valueTP11.92 ± 0.400.0000TP22.04 ± 0.820.0145TP30.83 ± 1.030.4198TP42.71 ± 0.870.0021TP52.63 ± 0.900.0037 Citation Format: Mirella L Altoe, Kevin Kalinsky, Hua Guo, Hanina Hibshoosh, Mariella Tejada, Katherine D Crew, Melissa K Accordino, Meghna Trivedi, Alessandro Marone, Hyun K Kim, Andreas H Hielscher, Dawn L Hershman. Monitoring neoadjuvant chemotherapy using diffuse optical tomography breast imaging system [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-10.

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