Changes in the tumor oxygenation but not in the tumor volume and tumor vascularization reflect early response of breast cancer to neoadjuvant chemotherapy (original) (raw)
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Clinical cancer research : an official journal of the American Association for Cancer Research, 2014
To determine whether pretreatment biomarkers obtained from diffuse optical spectroscopic tomographic (DOST) imaging predicts breast tumor response to neoadjuvant chemotherapy (NAC), which would have value to potentially eliminate delays in prescribing definitive local regional therapy that may occur from a standard complete 6- to 8-month course of NAC. Nineteen patients undergoing NAC were imaged with DOST before, during, and after treatment. The DOST images of total hemoglobin concentration (HbT), tissue oxygen saturation (StO2), and water (H2O) fraction at different time points have been used for testing the abilities of differentiating patients having pathologic complete response (pCR) versus pathologic incomplete response (pIR). Significant differences (P < 0.001, AUC = 1.0) were found between pCR patients versus pIR in outcome, based on the percentage change in tumor HbT within the first cycle of treatment. In addition, pretreatment tumor HbT (pretreatment HbT) relative to t...
Multimodal approach in assessment of the response of breast cancer to neoadjuvant chemotherapy
Journal of biomedical optics, 2018
The ability for noninvasive visualization of functional changes of a tumor's oxygenation and circulatory system offers new advantages for prognosis and monitoring of the treatment efficacy. The results of breast cancer oxygen state study under chemotherapy action obtained by diffuse optical spectroscopy (DOS) in combination with Doppler ultrasonic imaging are presented. Complex use of optical and ultrasound methods gives complementary information about the size of the tumor node, peculiarities of its vascular bed, rate of its blood flow as well as oxygenation, and provide a picture of the tumor response to treatment. Comparison with tumor pathologic response allowed to identify differences in the changes of these parameters depending on the degree of pathological tumor response to chemotherapy. It was demonstrated that fourth and fifth degrees of therapeutic pathomorphism may be predicted by the increase of oxygen saturation level after the first cycle of chemotherapy. If the re...
Journal of biomedical optics, 2018
Ideally, neoadjuvant chemotherapy (NAC) assessment should predict pathologic complete response (pCR), a surrogate clinical endpoint for 5-year survival, as early as possible during typical 3- to 6-month breast cancer treatments. We introduce and demonstrate an approach for predicting pCR within 10 days of initiating NAC. The method uses a bedside diffuse optical spectroscopic imaging (DOSI) technology and logistic regression modeling. Tumor and normal tissue physiological properties were measured longitudinally throughout the course of NAC in 33 patients enrolled in the American College of Radiology Imaging Network multicenter breast cancer DOSI trial (ACRIN-6691). An image analysis scheme, employing z-score normalization to healthy tissue, produced models with robust predictions. Notably, logistic regression based on z-score normalization using only tissue oxygen saturation (StO2) measured within 10 days of the initial therapy dose was found to be a significant predictor of pCR (AU...
2012
Tissue hemoglobin oxygen saturation (i.e., oxygenation) is a functional imaging endpoint that can reveal variations in tissue hypoxia, which may be predictive of pathologic response in subjects undergoing neoadjuvant chemotherapy. In this study, we used diffuse optical spectroscopic imaging (DOSI) to measure concentrations of oxyhemoglobin (ctO2Hb), deoxy-hemoglobin (ctHHb), total Hb (ctTHb 1⁄4 ctO2Hb þ ctHHb), and oxygen saturation (stO2 1⁄4 ctO2Hb/ctTHb) in tumor and contralateral normal tissue from 41 patients with locally advanced primary breast cancer. Measurements were acquired before the start of neoadjuvant chemotherapy. Optically derived parameters were analyzed separately and in combination with clinical biomarkers to evaluate correlations with pathologic response. Discriminant analysis was conducted to determine the ability of optical and clinical biomarkers to classify subjects into response groups. Twelve (28.6%) of 42 tumors achieved pathologic complete response (pCR) ...
Cancer Research, 2012
Tissue hemoglobin oxygen saturation (i.e., oxygenation) is a functional imaging endpoint that can reveal variations in tissue hypoxia, which may be predictive of pathologic response in subjects undergoing neoadjuvant chemotherapy. In this study, we used diffuse optical spectroscopic imaging (DOSI) to measure concentrations of oxyhemoglobin (ctO 2 Hb), deoxy-hemoglobin (ctHHb), total Hb (ctTHb ¼ ctO 2 Hb þ ctHHb), and oxygen saturation (stO 2 ¼ ctO 2 Hb/ctTHb) in tumor and contralateral normal tissue from 41 patients with locally advanced primary breast cancer. Measurements were acquired before the start of neoadjuvant chemotherapy. Optically derived parameters were analyzed separately and in combination with clinical biomarkers to evaluate correlations with pathologic response. Discriminant analysis was conducted to determine the ability of optical and clinical biomarkers to classify subjects into response groups. Twelve (28.6%) of 42 tumors achieved pathologic complete response (pCR) and 30 (71.4%) were non-pCR. Tumor measurements in pCR subjects had higher stO 2 levels (median 77.8%) than those in non-pCR individuals (median 72.3%, P ¼ 0.01). There were no significant differences in baseline ctO 2 Hb, ctHHb, and ctTHb between response groups. An optimal tumor oxygenation threshold of stO 2 ¼ 76.7% was determined for pCR versus non-pCR (sensitivity ¼ 75.0%, specificity ¼ 73.3%). Multivariate discriminant analysis combining estrogen receptor staining and stO 2 further improved the classification of pCR versus non-pCR (sensitivity ¼ 100%, specificity ¼ 85.7%). These results show that elevated baseline tumor stO 2 are correlated with a pCR. Noninvasive DOSI scans combined with histopathology subtyping may aid in stratification of individual patients with breast cancer before neoadjuvant chemotherapy. Cancer Res; 72(17); 4318-28. Ó2012 AACR.
Oncotarget, 2016
This study evaluated pathological response to neoadjuvant chemotherapy using quantitative ultrasound (QUS) and diffuse optical spectroscopy imaging (DOSI) biomarkers in locally advanced breast cancer (LABC). The institution's ethics review board approved this study. Subjects (n = 22) gave written informed consent prior to participating. US and DOSI data were acquired, relative to the start of neoadjuvant chemotherapy, at weeks 0, 1, 4, 8 and preoperatively. QUS parameters including the mid-band fit (MBF), 0-MHz intercept (SI), and the spectral slope (SS) were determined from tumor ultrasound data using spectral analysis. In the same patients, DOSI was used to measure parameters relating to tumor hemoglobin and composition. Discriminant analysis and receiver-operating characteristic (ROC) analysis was used to classify clinical and pathological response during treatment and to estimate the area under the curve (AUC). Additionally, multivariate analysis was carried out for pairwise...
Cancer research, 2016
The prospective multi-center ACRIN 6691 trial was designed to evaluate whether changes from baseline to mid-therapy in a Diffuse Optical Spectroscopic Imaging (DOSI)-derived imaging endpoint, the Tissue Optical Index (TOI), predict pathologic complete response (pCR) in women undergoing breast cancer neoadjuvant chemotherapy (NAC). DOSI instruments were constructed at the University of California, Irvine and delivered to 6 institutions where 60 subjects with newly-diagnosed breast tumors (at least 2 cm in the longest dimension) were enrolled over a 2-year period. Bedside DOSI images of the tissue concentrations of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctHbO2), water (ctH2O), lipid, and TOI (ctHHb x ctH2O/lipid) were acquired on both breasts up to 4 times during NAC treatment: baseline, one-week, mid-point, and completion. Of the 34 subjects (mean age 48.4 {plus minus} 10.7 years) with complete, evaluable data from both normal and tumor-containing breast, 10 (29%) achieved pCR as ...
Journal of Biomedical Optics, 2007
We combine diffuse optical spectroscopy ͑DOS͒ and diffuse correlation spectroscopy ͑DCS͒ to noninvasively monitor early hemodynamic response to neoadjuvant chemotherapy in a breast cancer patient. The potential for early treatment monitoring is demonstrated. Within the first week of treatment ͑day 7͒ DOS revealed significant changes in tumor/normal contrast compared to pretreatment ͑day 0͒ tissue concentrations of deoxyhemoglobin ͑rctHHb T/N = 69± 21% ͒, oxyhemoglobin ͑rctO 2 Hb T/N = 73± 25% ͒, total hemoglobin ͑rctTHb T/N = 72± 17% ͒, and lipid concentration ͑rctLipid T/N = 116± 13% ͒. Similarly, DCS found significant changes in tumor/ normal blood flow contrast ͑rBF T/N =75±7% on day 7 with respect to day 0͒. Our observations suggest the combination of DCS and DOS enhances treatment monitoring compared to either technique alone. The hybrid approach also enables construction of indices reflecting tissue metabolic rate of oxygen, which may provide new insights about therapy mechanisms. © 2007 Society of Photo-Optical Instrumentation Engineers.
Vascularity Change and Tumor Response to Neoadjuvant Chemotherapy for Advanced Breast Cancer
Ultrasound in Medicine & Biology, 2008
For advanced breast cancer with severe local disease (ABC) (stage III/IV), neoadjuvant chemotherapy improves local control and surgical outcome. However, about ϳ20 to 30% of advanced cancers show either no or poor response to chemotherapy. To prevent unnecessary treatment, a capability of predicting clinical response to neoadjuvant chemotherapy of ABC is highly desirable. Vascularity index (VI) of breast cancers was derived from the quantification results in 30 ABC patients by using power Doppler sonography. Power Doppler sonography evaluation was performed every one to two weeks during chemotherapy. The overall response rate for 30 advanced patients tested was 70%, when 50% or more reduction in tumor size was the objective clinical response. Chemotherapy response was unrelated to the original tumor size (p ؍ 0.563) or chemotherapy agents used (p ؍ 0.657). The median VI for all 30 patients was 4.99%. The response rates for hypervascular tumors vs. hypovascular tumors, based on initial median value, were 86.7% and 53.3%, respectively (p ؍ 0.109). The average VIs in responders and nonresponders were 7.67 ؎ 4.77% and 4.01 ؎ 3.82% (p ؍ 0.052). There was a tendency for responders who have a relatively high initial vascularity. The VI change in responder group shows a pattern of initial increasing in vascularity followed by decreasing in vascularity. All patients (17/17) with a VI increment of >5% during chemotherapy had good chemotherapy response, whereas in patients with a VI increment of <5%, the response rate was 30.8% (4/13) (p < 0.001). For patients with a peak VI of >10% during chemotherapy, the response rate was 94.1% (16/17). However, in patients with a peak VI of <10%, the response rate was 38.5% (5/13) (p ؍ 0.001). This prediction was made mostly within one month (25.47 ؎ 12.96 d for VI increments >5% and 25.44 ؎ 12.41 d for VI increased to >10%). In the meantime, the differences in size reduction shown in B-mode sonography were insignificant between responders and nonresponders (patient group with VI increment >5%, p ؍ 0.308; patient group with peak VI >10%, p ؍ 0.396). In conclusion, we propose that VI as determined by using power Doppler sonography is a good and inexpensive clinical tool for monitoring vascularity changes during neoadjuvant chemotherapy in ABC patients. Two parameters-VI increment >5% and peak VI >10%-are potential early predictors for good responses to neoadjuvant chemotherapy within one month in patients with ABC. (