Breast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedback about treatment response at the earliest stages of therapy to identify patients likely to benefit from changing treatment. Diffuse optical spectroscopic imaging (DOSI) has emerged as a promising functional imaging technique for NAC monitoring. DOSI uses non-ionizing near-infrared light to provide non-invasive measures of absolute concentrations of tissue chromophores such as oxyhemoglobin. In 2011, we reported a new DOSI prognostic marker, oxyhemoglobin flare: a transient increase in oxyhemoglobin capable of discriminating NAC responders within the first day of treatment. In this follow-up study, DOSI was used to confirm the presence of the flare as well as to investigate whether DOSI markers of NAC response are regimen dependent. This dual-center study examined 54 breast tumors receiving NAC measured with DOSI before therapy and the first week following chemotherapy administration. Patients were treated with either a standard of care maximum tolerated dose (MTD) regimen or an investigational metronomic (MET) regimen. Changes in tumor chromophores were tracked throughout the first week and compared to pathologic response and treatment regimen at specific days utilizing generalized estimating equations (GEE). Within patients receiving MTD therapy, the oxyhemoglobin flare was confirmed as a prognostic DOSI marker for response appearing as soon as day 1 with post hoc GEE analysis demonstrating a difference of 48.77% between responders and non-responders (p < 0.0001). Flare was not observed in patients receiving MET therapy. Within all responding patients, the specific treatment was a significant predictor of day 1 changes in oxyhemoglobin, showing a difference of 39.45% (p = 0.0010) between patients receiving MTD and MET regimens. DOSI optical biomarkers are differentially sensitive to MTD and MET regimens at early timepoints suggesting the specific treatment regimen should be considered in future DOSI studies. Additionally, DOSI may help to identify regimen-specific responses in a more personalized manner, potentially providing critical feedback necessary to implement adaptive changes to the treatment strategy.

中文翻译：

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漫射光谱成像揭示了对节律和最大耐受剂量方案的早期乳腺肿瘤血流动力学反应

患有早期疾病的乳腺癌患者越来越多地接受新辅助化疗（NAC），以在手术前降低其肿瘤的转移率。在这种情况下，大约31％的患者对治疗无效。这表明需要能够在治疗的最早阶段就治疗反应提供个性化反馈的技术，以识别可能受益于改变治疗方法的患者。漫射光谱成像（DOSI）已经成为一种有前途的NAC监测功能成像技术。DOSI使用非电离的近红外光提供组织生色团（如氧合血红蛋白）的绝对浓度的非侵入性测量。在2011年，我们报告了一种新的DOSI预后指标：氧合血红蛋白耀斑：在治疗的第一天，氧合血红蛋白的瞬时增加能够区分NAC应答者。在此后续研究中，使用DOSI确认耀斑的存在，并调查NAC反应的DOSI标记是否依赖于治疗方案。这项双中心研究检查了54例接受NAC治疗的乳腺肿瘤，在治疗前和化疗后的第一周接受了DOSI测量。使用标准护理最大耐受剂量（MTD）方案或研究性计量学（MET）方案治疗患者。在第一周内追踪肿瘤生色团的变化，并利用广义估计方程（GEE）将其与特定天的病理反应和治疗方案进行比较。在接受MTD治疗的患者中，氧合血红蛋白耀斑被确认为反应的预后DOSI标记，并在事后进行GEE分析后证明，反应者和未反应者之间的差异为48.77％（p <0.0001）。接受MET治疗的患者未观察到耀斑。在所有反应患者中，特异性治疗是氧合血红蛋白第1天变化的重要预测指标，显示接受MTD和MET方案的患者之间相差39.45％（p = 0.0010）。DOSI光学生物标记物在早期时间点对MTD和MET方案具有不同的敏感性，因此建议在将来的DOSI研究中考虑具体的治疗方案。此外，DOSI可能有助于以更个性化的方式识别特定于治疗方案的反应，