MONITORING CHEMOTHERAPY RESPONSE BY PHOTON MIGRATION SPECTROSCOPY

通过光子迁移光谱监测化疗反应

• 批准号: 7374255
• 负责人: DAVID HSIANG
• 金额: $ 0.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374255
• 关键词: breast neoplasms; chemotherapy; electromagnetic radiation; mammary gland; measurement; neoplasm /cancer; tissues

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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护治疗。LABC新辅助化疗的最佳强度和持续时间仍然存在争议，因为难以评估对治疗的反应。目前，对治疗的反应通过身体检查、乳房X线摄影和/或超声来测量。几项研究表明，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。类似的研究表明，达到病理性肉眼完全缓解的患者的预后优于那些在手术时留下残留肉眼疾病的患者。因此，确定LABC患者局部手术治疗的最佳时机是非常重要的。目标是防止新辅助化疗患者的过度治疗和治疗不足。 许多成像模式正在研究这个特定的问题，如正电子发射断层扫描（PET）和对比增强磁共振成像（MRI），但这些模式是昂贵的，复杂的，并有有限的访问一般公众。使用非侵入性技术光子迁移光谱（PMS）对正常志愿者和接受化疗的患者进行的初步结果显示，对乳腺组织功能变化具有出色的敏感性。这些变化与LABC受试者的总体肿瘤尺寸减小相关。 光子迁移光谱是一种非侵入式光学技术，利用强度调制的近红外（NIR）光定量测量厚组织中的光学特性。从PMS测量导出的光学特性（吸收、us和散射us'参数）可用于构建组织血红蛋白（总、氧合和脱氧形式）、氧饱和度、血容量分数、水含量、脂肪含量和细胞结构的低分辨率（0.5- 1cm）功能图像。与传统的近红外透照不同，PMS能够在单一的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表征厚组织中的肿瘤。使用非侵入性、多波长、二极管激光PMS设备进行测量。一些初步结果表明，代谢变化是检测局部晚期乳腺癌肿瘤接受新辅助化疗，使用光子迁移技术。测量提供反映组织灌注、耗氧量和细胞/基质发育变化的定量光学特性值。 我们的初步研究将对接受新辅助化疗的乳腺癌患者的肿瘤进行序贯光子迁移光谱（PMS）。将在每个化疗周期之前和之后获得PMS读数。同时，还将收集乳腺肿瘤的基线体格检查、常规实验室检查、脉搏血氧测定和超声测量结果。将对接受新辅助化疗的患者在常规标准治疗中获得的新辅助化疗前和手术后肿瘤样本进行免疫组织病理学检查。所有这些数据将通过统计模型进行分析，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仍然存在的残留疾病的数量。