Diffuse Optical Monitoring of Head and Neck Tumor Therapy

描述（由申请人提供）：放射或化学-放射治疗是头颈癌的标准治疗，但众所周知，这种治疗在缺氧肿瘤患者中效果较差。此外，癌症治疗可能会改变肿瘤的生理状态，从而影响治疗效果。调节肿瘤氧合的因素包括血流、血氧合、氧代谢和尼古丁水平（即，烟草使用）。然而，由于缺乏适当的技术，肿瘤血流动力学和代谢在癌症治疗期间没有常规测量。计算机断层扫描（CT）和磁共振成像（MRI）是目前最好的和可重复的方法来测量目标病变选择客观反应评估，但这些方式需要大型和昂贵的仪器，严重限制了他们在临床上的常规使用。我们的初步研究已经证明了漫射光学在临床床边治疗期间连续监测肿瘤血流动力学和代谢的能力。本项目的目标是开发和优化一种无创多功能多模态临床光学仪器，以帮助在最早的阶段评估和预测肿瘤反应。更具体地说，这种光学仪器将监测和预测头颈部肿瘤化疗-放疗的血流动力学和代谢反应。我们假设，功能评估肿瘤的生理状态和治疗过程中的动态变化将提供信息，为长期治疗结果的早期预测，从而使临床医生能够优化治疗的每一个病人在一个时间敏感的方式。为了实现这一目标，我们将组装一个混合的流量和氧气系统，结合了新开发的扩散相关光谱（DCS）流量计与商业组织血氧计，用于同时测量肿瘤血流，氧合和氧代谢（来自流量和氧合数据）。将对包括光学探头和软件平台在内的仪器进行测试和优化，以连续和纵向监测包括吸烟者和非吸烟者（n=125）在内的患者在治疗前、治疗期间和治疗后的肿瘤生理状态和血流动力学/代谢变化。预期在治疗结果之间将观察到显著的相关性（例如，肿瘤体积变化、肿瘤毒性、疾病复发时间、存活）和肿瘤生理状态和变化以及尼古丁水平。不同类型的生理参数可能显示出每个患者对癌症治疗的不同敏感性，这可能揭示影响个体治疗结果的主要因素。我们的新型混合光学系统将提供与CT和MRI互补的血流动力学和代谢成像对比，并具有早期评估和预测癌症治疗反应的独特潜力。我们的长期目标是发展强大的科学合作，利用非侵入性光学技术在早期阶段优化和个性化癌症治疗。 公共卫生相关性：单独使用放射治疗或与化疗联合使用是头颈癌的标准治疗，但众所周知，这种治疗在血管化不良/缺氧肿瘤患者中效果较差。该项目的目标是开发和测试一种低成本的临床级光学仪器，可以快速评估肿瘤的血液动力学和代谢状态以及早期对癌症治疗的反应。这种对肿瘤血流动力学和代谢特性的深入评估将为早期预测和评估治疗结果提供重要信息，从而使临床医生能够优化个体化治疗。

DESCRIPTION (provided by applicant): Treatment with radiation or chemo-radiotherapy is the standard therapy for head and neck cancers but this treatment is well known to be less efficacious in patients with hypoxic tumors. Furthermore, cancer therapy may alter tumor physiological status, thus impacting treatment efficacy. Factors that modulate tumor oxygenation include blood flow, blood oxygenation, oxygen metabolism, and nicotine levels (i.e., tobacco use). Tumor hemodynamics and metabolism, however, are not routinely measured during cancer therapy due to the lack of appropriate technologies. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are the best currently available and reproducible methods to measure target lesions selected for objective response assessment, but these modalities require large and costly instrumentation that severely limits their routine use in clinics. The capabilities of diffuse optics for continuously monitoring tumor hemodynamics and metabolism during therapy at the clinical bedside have recently been demonstrated in our preliminary studies. The objective of this project is to develop and optimize a noninvasive versatile multi-modality clinical optical instrument to aid in evaluating and predicting tumor responses at the most early stage possible. More specifically, this optical instrument will monitor and predict hemodynamic and metabolic responses to chemo- radiotherapy in head and neck tumors. We hypothesize that functional assessment of tumor physiological status and dynamic changes during therapy will provide information for early prediction of long-term treatment outcomes, thus enabling clinicians to optimize therapy for each patient in a time sensitive fashion. To achieve this goal, we will assemble a hybrid flow and oxygen system that combines a newly developed diffuse correlation spectroscopy (DCS) flowmeter with a commercial tissue-oximeter for simultaneous measurement of tumor blood flow, oxygenation, and oxygen metabolism (derived from the flow and oxygenation data). The instrument including optical probes and a software platform will be tested and optimized for continuous and longitudinal monitoring of tumor physiological status and hemodynamic/metabolic changes before, during and after therapy in patients including smokers and nonsmokers (n=125). It is anticipated that significant correlations will be observed between therapy outcomes (e.g., tumor volume change, tumor toxicity, time to disease recurrence, survival) and tumor physiological status and changes as well as nicotine levels. Different types of physiological parameters may show different sensitivities to cancer therapy in each patient, which could reveal the primary factor(s) affecting individual therapy outcomes. Our novel hybrid optical system will provide hemodynamic and metabolic imaging contrasts complementary to those of CT and MRI, and holds unique potential for early evaluating and predicting cancer therapy responses. Our long-term goal is to develop robust scientific collaborations to optimize and individualize cancer therapy at early stages with noninvasive optical technologies. PUBLIC HEALTH RELEVANCE: Treatment with radiation alone or in combination with chemotherapy is standard therapy for the head and neck cancers, but this treatment is well known to be less efficacious in patients with poorly-vascularized/hypoxic tumors. The objective of this project is to develop and test a low-cost clinical-level optical instrument that can quickly assess tumor hemodynamic and metabolic status and responses to cancer therapy in the early stages. This in depth assessment of tumor hemodynamic and metabolic properties will provide essential information for the early prediction and evaluation of treatment outcomes, thus enabling clinicians to optimize individual treatment.