Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy
Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy
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DOI：
10.1073/pnas.0611058104
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发表时间：
2007-03-06
影响因子：
11.1
通讯作者：
Tromberg, Bruce J.
中科院分区：
文献类型：
--
作者：
Cerussi, Albert;Hsiang, David;Tromberg, Bruce J.
扩散光学光谱（DOS）和成像是新兴的诊断技术，其定量测量cm厚组织中的脱氧血红蛋白（ctHHb）、氧合血红蛋白（ctO（2）Hb）、水（ctH（2）O）和脂质的浓度。在早期临床研究中，弥散光学成像和DOS已被用于表征乳腺肿瘤的生化成分，并监测II/III期新辅助化疗患者的治疗反应。我们研究了阿霉素/环磷酰胺新辅助化疗方案3个月前和1周后的DOS测量值是否可以预测最终的术后病理反应。治疗前11例患者的基线DOS测量结果显示，与正常乳腺组织相比，肿瘤ctHHb、CtO（2）Hb、ctH（2）O和光谱散射斜率显著增加，体积脂质减少。在首次治疗后1周（6.5 ± 1.4天）内，病理学证实的应答者（n = 6）的ctHHb、CtO（2）Hb和ctH（2）O的肿瘤浓度分别下降27 ± 15%、33 ± 7%和11 ± 15%，而无应答者（n = 5）和正常侧对照显示这些参数无显著变化。治疗后1周治疗反应的最佳单一预测因子是ctHHb（敏感性为83%，特异性为100%），而基于ctHHb和ctH（2）O变化的判别分析将反应者与无反应者分类，敏感性和特异性均为100%。此外，治疗前肿瘤与正常ctO（2）Hb比值在应答者（2.82 +/- 0.44）中显著高于无应答者（1.82 +/- 0.49）。这些结果突出了DOS对肿瘤细胞代谢和生化组成的敏感性，并证明了其预测和监测个体对治疗的反应的潜力。
Diffuse optical spectroscopy (DOS) and imaging are emerging diagnostic techniques that quantitatively measure the concentration of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctO(2)Hb), water (ctH(2)O), and lipid in cm-thick tissues. In early-stage clinical studies, diffuse optical imaging and DOS have been used to characterize breast tumor biochemical composition and monitor therapeutic response in stage II/III neoadjuvant chemotherapy patients. We investigated whether DOS measurements obtained before and 1 week into a 3-month adriamycin/cytoxan neoadjuvant chemotherapy regimen can predict final, postsurgical pathological response. Baseline DOS measurements of 11 patients before therapy revealed significant increases in tumor ctHHb, CtO(2)Hb, ctH(2)O, and spectral scattering slope, and decreases in bulk lipids, relative to normal breast tissue. Tumor concentrations of ctHHb, CtO(2)Hb, and ctH(2)O dropped 27 +/- 15%, 33 +/- 7%, and 11 +/- 15%, respectively, within 1 week (6.5 +/- 1.4 days) of the first treatment for pathology-confirmed responders (n = 6), whereas nonresponders (n = 5) and normal side controls showed no significant changes in these parameters. The best single predictor of therapeutic response 1 week posttreatment was ctHHb (83% sensitivity, 100% specificity), while discrimination analysis based on combined ctHHb and ctH(2)O changes classified responders vs. nonresponders with 100% sensitivity and specificity. In addition, the pretreatment tumor-to-normal ctO(2)Hb ratio was significantly higher in responders (2.82 +/- 0.44) vs. nonresponders (1.82 +/- 0.49). These results highlight DOS sensitivity to tumor cellular metabolism and biochemical composition and demonstrate its potential for predicting and monitoring an individual's response to treatment.