MONITORING CHEMOTHERAPY RESPONSE BY PHOTON MIGRATION SPECTROSCOPY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。局部晚期乳腺癌（LABC）患者的最佳管理仍然是一个复杂的治疗问题。LABC占美国所有新诊断乳腺癌的5-20%，在医疗服务不足的地区发病率更高。多年来，LABC的治疗已经从接受根治性乳房切除术发展到使用新辅助化疗，然后进行乳房切除术或乳房保留治疗。由于难以评估治疗效果，LABC新辅助化疗的最佳强度和持续时间仍存在争议。目前，对治疗的反应是通过体检、乳房x光检查和/或超声来衡量的。几项研究表明，在新辅助化疗的临床评估或反应与治疗后手术标本中发现的反应的病理评估之间存在显著差异。类似研究表明，达到病理宏观完全缓解的患者比手术时遗留宏观病变的患者预后更好。因此，确定LABC患者局部手术治疗的最佳时机非常重要。目的是防止新辅助化疗患者治疗过度或治疗不足。许多成像方式正在研究这一特定问题，如正电子发射断层扫描（PET）和对比增强磁共振成像（MRI），但这些方式昂贵、复杂，并且对公众的使用有限。光子迁移光谱（PMS）非侵入性技术的初步结果显示，正常志愿者和接受化疗的患者对乳腺组织功能变化具有良好的敏感性。这些变化与LABC受试者的总体肿瘤尺寸减小有关。光子迁移光谱是一种非侵入性光学技术，利用强度调制的近红外（NIR）光定量测量厚组织的光学特性。从PMS测量得到的光学性质（吸收、散射和散射参数）可用于构建低分辨率（0.5-1 cm）的组织血红蛋白（总、含氧和脱氧形式）、氧饱和度、血容量分数、含水量、脂肪含量和细胞结构的功能图像。与传统的近红外透照不同，PMS可以在一次非侵入性测量中定量分析组织吸收和散射参数。PMS提供的独特功能信息使其非常适合于表征厚组织中的肿瘤。测量使用非侵入性，多波长，二极管激光PMS设备进行。一些初步结果表明，在局部晚期乳腺癌肿瘤中，使用光子迁移技术进行新辅助化疗可以检测到代谢变化。测量提供定量光学特性值，反映组织灌注、耗氧量和细胞/基质发育的变化。我们的试点研究将对接受新辅助化疗的乳腺癌患者的肿瘤进行连续光子迁移光谱（PMS）。在每个化疗周期之前和之后将获得经前质谱读数。同时，基线体检，常规实验室，脉搏血氧仪和乳腺肿瘤的超声测量也将被收集。对新辅助化疗患者术前和术后常规护理标准中获得的肿瘤样本进行免疫组织病理学检查。然后，所有这些数据将用统计模型进行分析，以确定PMS是否可以准确地确定和量化接受化疗的乳腺癌肿瘤的生理参数以及手术标本中残留疾病的数量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Optimal management of patients with locally advanced breast cancer (LABC) remains a complex therapeutic problem. LABC represents 5-20% of all newly diagnosed breast cancers in the United States with a higher incidence in medically underserved areas. Over the years, treatment for LABC has been evolving from undergoing a radical mastectomy to the use of neoadjuvant chemotherapy followed by a mastectomy or breast conservation therapy. The optimal intensity and duration of neoadjuvant chemotherapy for LABC still remains controversal due to the difficulty of evaluating response to therapy. Presently, response to treatment is measured by physical exam, mammography, and/or ultrasound. Several studies have showed significant discrepancies between the clinical assessment or response to neoadjuvant chemotherapy and the pathologic assessment of response found in post-therapy surgical specimens. Similar studies have shown that patients achieving pathologic macroscopic complete response have a better prognosis that those patients left with residual macroscopic disease at the time of surgery. Consequently, it is very important to determine the optimal timing of the local surgical treatment of LABC patients. The goal would be to prevent over and under treatment of patients with neoadjuvant chemotherapy. Many imaging modalities are investigating this specific problem such as positron emission tomography (PET) and contrast enhanced magnetic resonance imaging (MRI) but these modalities are expensive, complex, and have limited access to the general public. Preliminary results with a non-invasive technique, Photon Migration Spectroscopy (PMS), on normal volunteers and patients receiving chemotherapy have shown excellent sensitivity to breast tissue functional changes. These changes were correlated with a decrease in overall tumor dimensions in the cases of LABC subjects. Photon Migration Spectroscopy is a non-invasive optical technique that utilizes intensity-modulated, near-infrared (NIR) light to quantitatively measure optical properties in thick tissues. Optical properties (absorption, us and scattering us' parameters) derived from PMS measurements can be used to construct low-resolution (0.5-1 cm) functional images of tissue hemoglobin (total, oxy, and deoxy forms), oxygen saturation, blood volume fraction, water content, fat content, and cellular structure. Unlike conventional NIR transillumination, PMS enables quantitative analysis of tissue absorption and scattering parameters in a single non-invasive measurement. The unique functional information provided by PMS makes it well suited to characterizing tumors in thick tissues. Measurements are performed using a non-invasive, multi-wavelength, diode-laser PMS device. Some preliminary results show that the metabolic changes are detectable in locally advanced breast cancer tumors undergoing treatment with neoadjuvant chemotherapy using photon migration techniques. The measurements provide quantitative optical property values that reflect changes in tissue perfusion, oxygen consumption, and cell/matrix development. Our pilot study will be to perform sequential Photon Migration Spectroscopy (PMS) on tumors of breast cancer patients undergoing neoadjuvant chemotherapy. PMS readings will be obtained prior to and subsequent to each chemotherapy cycle. Concurrent, baseline physical exams, routine labs, pulse oximetry, and ultrasound measurements of the breast tumor will also be collected. Immunohistopathology will be performed on both the pre-neoadjuvant chemotherapy and the post-surgical tumor samples which are obtained in the routine standard of care for patients undergoing neoadjuvant chemotherapy. All this data will be then analyzed with statistical models to see whether PMS can determine accurately and quantify the physiological parameters of breast cancer tumors undergoing chemotherapy and the amount of residual disease still present in the surgical specimen.