Functional imaging-directed adaptive therapy of head and neck cancer

描述（由申请人提供）：对于预后良好的头颈癌（HNC）的治疗达到了很高的治愈率，但目前对于预后较差的头颈癌（如不可切除的癌症）的治疗并不令人满意，化疗后局部区域控制率（LR）约为50%，是这些患者的主要失败模式。多项研究表明，动态对比增强MRI （DCE-MRI）观察到的肿瘤灌注不足，以及弥散加权MRI （DW-MRI）观察到的低弥散，既表明肿瘤膜破坏不足，又表明肿瘤细胞密度高，这两者都与治疗后LR失败率较高有关。我们建议使用这些功能成像方式来指导对预测耐药的肿瘤亚体积进行强化放疗，以克服耐药并改善LR肿瘤控制，这将提高这些患者的无病生存期和潜在的总生存期。目的1是进行一项随机II期研究，比较放射剂量对化疗开始后早期显示灌注不良的肿瘤亚体积的增强。目的2是研究DW-MRI与DCE-MRI在确定耐药肿瘤亚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指标，以便根据每个患者对放疗的敏感性，个体化保留这些器官，以减少治疗相关的吞咽困难。如果成功，目标2和目标3的结果将在以后的几年纳入临床研究。影响：由于DCE-MRI和DW-MRI在社会上广泛使用，建议的研究将导致未来的多机构研究，以评估建议的概念和调查所承诺的先进HNC的LR控制率和DFS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.