Functional imaging-directed adaptive therapy of head and neck cancer

描述(申请人提供)：虽然预后良好的头颈癌(HNC)的治疗取得了很高的治愈率，但目前对预后较差的HNC(如不能切除的癌症)的治疗并不令人满意，化疗后的局部区域(LR)控制率约为50%，这是这些患者的主要失败模式。多项研究表明，动态增强磁共振成像(DCE-MRI)观察到的肿瘤缺乏血流灌注，弥散加权磁共振成像(DW-MRI)观察到的低扩散，既代表肿瘤膜缺乏破坏，又代表肿瘤细胞密度高，两者都与治疗后较高的LR失败率相关。我们建议使用这些功能成像方式来指导对预测为耐药的肿瘤亚体积进行放射治疗，以克服耐药性并改善LR肿瘤的控制，这将提高这些患者的无病生存率和潜在的总体生存率。目的1是进行一项随机的II期研究，比较放疗剂量的强化与化疗开始后早期表现为灌注不良的肿瘤的亚体积。目的2是研究DW-MRI和DCE-MRI在确定耐药肿瘤亚体积方面的最佳结合，目的3是研究功能MRI作为预测吞咽器官晚期损害的指标，以便根据每个患者对放射的敏感性来个体化这些器官的保留，以减少与治疗相关的吞咽困难。如果成功，AIMS 2和AIMS 3的结果将在未来几年纳入临床研究。影响：由于DCE-MRI和DW-MRI在社区中广泛可用，拟议的研究将导致未来的多机构研究，评估拟议的概念和调查承诺的晚期HNC在LR控制率和DFS方面的改善。

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.