Hypoxia and Treatment Response in Head and Neck Cancer

头颈癌的缺氧和治疗反应

• 批准号: 7236108
• 负责人: Joseph G Rajendran
• 金额: $ 11.71万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7236108
• 关键词: bioimaging /biomedical imaging; biomarker; cell proliferation; glucose metabolism; head /neck neoplasm; human subject; human therapy evaluation; hypoxia; image guided surgery /therapy; neoplasm /cancer radiation therapy; neoplasm /cancer therapy; patient oriented research; positron emission tomography; prognosis

The primary goal of this project is to extend the established role of FMISO PET in evaluating hypoxia in head and neck cancer and to assess its ability to predict response to therapy. In spite of advances in the diagnosis of head and neck cancer, a vast majority of patients are still diagnosed in advanced stages and show poor response to treatment. The clinical course of these neoplasms is difficult to predict based on current prognostic criteria. Current management modalities involve surgery and radiation therapy in different combinations; with nearly half the patients receiving radiotherapy. Advanced head and neck cancer frequently exhibits hypoxia that imparts resistance, negatively affecting treatment response and outcome. Advances in radiation treatment planning and delivery promise the ability to deliver higher radiation dose to a small volume of tissue at high risk of failure (such as hypoxic tissue) without increasing morbidity. Our experiments are designed to non-invasively quantify regional hypoxia in head and neck cancer by [F-18] fluoromisonidazole (FMISO) PET. The specific aims are: (1a) Correlate FMISO measures of hypoxia with treatment outcomes; and investigate the best image metric that describes tissue hypoxia and clinically useful predictors of disease course and treatment; (1b) Test the change in FMISO uptake as a predictor of treatment outcome; (2a & b) Correlate pre-treatment FMISO uptake with biological markers of hypoxia, angiogenesis, glucose metabolism and cellular proliferation to establish its role as a prognostic variable. FMISO PET images will be correlated with biomarkers and genomic expression on microarray in tissue specimens to create a prognostic profile. Coregistered FMISO PET and CT images will be used to direct sampling of resected specimens. (3) Fusion of FMISO PET/CT images to treatment planning CT using validated coregistration techniques to project hypoxic tissue on anatomic imaging. FMISO PET images will be aligned to our treatment planning systems to evaluate the feasibility of incorporating hypoxic regions in treatment planning and delivering 'boost' radiotherapy to these regions. This information will not be used to alter patient treatment, but will evaluate the synergy between FMISO PET + IMRT, in producing clinically optimal treatment plans. We will also analyze failure patterns in FMISO-avid regions that could have undergone dose escalation. Successful completion of this project will result in a better understanding of the problem of hypoxia in head and neck cancer and the role of FMISO PET as a prognostic variable laying the foundation for large scale studies and more rational treatments based on tumor microenvironment.

该项目的主要目标是扩展FMISO PET在评估头颈癌缺氧中的确定作用，并评估其预测治疗反应的能力。尽管在诊断头颈癌方面取得了进步，但绝大多数患者仍被诊断为高级阶段，并且对治疗的反应不佳。这些肿瘤的临床过程很难根据当前的预后标准来预测。当前的管理方式涉及不同组合中的手术和放射治疗；近一半的患者接受了放疗。晚期头颈癌经常表现出缺氧，会赋予抗药性，对治疗反应和结果产生负面影响。辐射治疗计划和交付的进步有望将较高辐射剂量输送到 少量的组织高衰竭风险（例如低氧组织）而不会增加发病率。我们的实验旨在通过[F-18]氟甲唑嗪（FMISO）PET非侵入性地量化头颈癌的区域缺氧。具体目的是：（1a）将缺氧的FMISO度量与治疗结果相关；并研究描述组织缺氧和临床上有用的疾病病程和治疗预测指标的最佳图像指标； （1B）测试FMISO摄取的变化，作为治疗结果的预测指标； （2a＆b）与缺氧，血管生成，葡萄糖代谢和细胞增殖的生物学标志物相关的FMISO摄取前，以确立其作为预后变量的作用。 fmiso宠物 图像将与组织样品中微阵列上的生物标志物和基因组表达相关，以创建预后曲线。将使用核心的FMISO PET和CT图像来指导切除的样品的采样。 （3）FMISO PET/CT图像融合使用经过验证的Corecistration技术在解剖成像上投射低氧组织的治疗计划CT。 FMISO PET图像将与我们的治疗计划系统保持一致，以评估将低氧区域纳入治疗计划中的可行性，并将“增强”放射疗法交付给这些区域。该信息将不会用于改变患者治疗，而是会评估FMISO PET + IMRT之间的协同作用，以制定临床上最佳的治疗计划。我们还将分析可能经历剂量升级的FMISO-AVID区域的故障模式。该项目的成功完成将使人们更好地了解头颈癌缺氧问题，以及FMISO PET作为预后变量的作用，为大规模研究奠定了基础，并基于肿瘤微环境的更多合理处理。