Functional imaging-directed adaptive therapy of head and neck cancer

功能成像引导的头颈癌适应性治疗

• 批准号: 9212122
• 负责人: Yue Cao
• 金额: $ 48.71万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9212122
• 关键词: Aftercare; Cellular Membrane; Cellularity; Cetuximab; Clinical Research; Combined Modality Therapy; Communities; Complication; Conformal Radiotherapy; Data; Decision Making; Deglutition; Deglutition Disorders; Diffusion; Disease; Disease Progression; Disease-Free Survival; Dose; Evaluable Disease; Extracellular Space; Failure; Functional Imaging; Future; Head and Neck Cancer; High-LET Radiation; Investigation; Local Therapy; Localized Malignant Neoplasm; Magnetic Resonance Imaging; Malignant Neoplasms; Membrane; Methods; Modality; Mucositis; Organ; Outcome; Patient risk; Patients; Pattern; Perfusion; Physiological; Prognostic Marker; Radiation; Radiation therapy; Randomized; Resistance; Safety; Site; Structure; Survival Rate; Testing; Therapeutic; Time; Tissues; Toxic effect; Translating; Treatment-related toxicity; Water; arm; base; chemoradiation; chemotherapy; contrast enhanced; high risk; hypoperfusion; imaging modality; improved; improved outcome; individual patient; individualized medicine; irradiation; magnetic resonance imaging biomarker; metabolic imaging; molecular imaging; outcome forecast; phase 2 study; population based; prognostic; prognostic value; public health relevance; response; targeted agent; therapy resistant; tumor

DESCRIPTION (provided by applicant): While therapy for good-prognosis head and neck cancer (HNC) achieves a high rate of cure, current therapy for poor prognosis HNC such as non-resectable cancer is unsatisfactory with local-regional (LR) control rates around 50% after chemo-irradiation, representing the major failure pattern in these patients. Multiple studies have demonstrated that lack of tumor perfusion observed by dynamic contrast-enhanced MRI (DCE-MRI), and low diffusion observed on diffusion-weighed MRI (DW-MRI), representing both lack of tumor membrane disruption and high tumor cellularity, are each associated with higher rates of LR failure rates following therapy. We propose to use these functional imaging modalities to guide intensifying of radiotherapy to tumor sub-volumes predicted to be resistant to therapy, in order to overcome resistance and improve LR tumor control, which will improve disease-free and potentially overall survival in these patients. Aim 1 is to conduct a randomized phase II study comparing intensification of the radiation doses to the tumor sub-volumes demonstrating poor perfusion early after the start of chemo-radiation. Aim 2 is to investigate the optimal integration of DW-MRI with DCE-MRI in determining the resistant tumor sub-volumes, and Aim 3 is to investigate functional MRI as a predictor of late damage of the swallowing organs, in order to individualize the sparing of these organs aiming to reduce treatment-related dysphagia based on each patient's sensitivity to radiotherapy. If successful, the results of Aims 2 and 3 wil be incorporated in the clinical study in later years. IMPACT: As DCE-MRI and DW-MRI are widely available in the community, the proposed studies will lead to future multi- institutional study which will assess the improvements in LR control rates and DFS in advanced HNC promised by the proposed concepts and investigations.

描述（由申请人提供）：虽然预后良好的头颈癌（HNC）的治疗达到了高治愈率，但目前预后不良的HNC（如不可切除的癌症）的治疗不令人满意，化疗-放疗后局部区域（LR）控制率约为50%，代表了这些患者的主要失败模式。多项研究表明，通过动态对比增强MRI（DCE-MRI）观察到的肿瘤灌注不足和在扩散加权MRI（DW-MRI）上观察到的低扩散（代表肿瘤膜破裂不足和高肿瘤细胞构成）均与治疗后LR失败率较高相关。我们建议使用这些功能成像模式来指导对预测对治疗有抵抗力的肿瘤子体积的放射治疗的强化，以克服抵抗力并改善LR肿瘤控制，这将改善这些患者的无病生存率和潜在的总生存率。目的1是进行一项随机II期研究，比较化疗-放疗开始后早期灌注不良的肿瘤子体积的放射剂量强化。目的2是研究DW-MRI与DCE-MRI在确定耐药肿瘤子体积方面的最佳整合，目的3是研究功能性MRI作为吞咽器官晚期损伤的预测因子，以便根据每个患者对放疗的敏感性对这些器官进行个体化保留，旨在减少治疗相关的吞咽困难。如果成功，目标2和3的结果将在以后几年纳入临床研究。影响：由于DCE-MRI和DW-MRI在社区中广泛使用，因此拟议的研究将导致未来的多机构研究，该研究将评估拟议概念和研究所承诺的晚期HNC的LR控制率和DFS的改善。