Lingual Strength & Dysphagia after Oropharynx Cancer: Proton vs. Photon Radiation

 描述(申请人提供)：吞咽困难是放射治疗口咽鳞状细胞癌(OPSCC)的一种剂量限制性毒性，也是当代口咽癌试验(例如，RTOG-1221，ECOG-3311)的主要功能终点。适形放射传递方法通过最大限度地减少吞咽困难-吸入相关结构(DARS)的剂量，有望减轻吞咽困难的负担。最近的工作集中在咽缩肌和喉部的剂量作为吞咽困难的驱动因素，但新出现的数据表明口腔剂量对吞咽结果的重要性。在健康受试者和吞咽困难患者中，舌力与吸入和吞咽终点相关，我们发表的数据显示，口腔前部的辐射剂量预示着口咽调强光子治疗(通常称为调强放疗)后的长期吞咽困难。我们的合作者已经证明，在调强放射治疗计划中使用光子束所需的剂量权衡会导致口腔前部的剂量增加。这被认为会导致更严重的急性粘膜炎，并容易导致慢性吞咽困难，尽管IMRT有其他剂量优势。质子辐射(IMPT)被认为是一种降低口咽放疗的新方法，它通过减少靶区附近未受影响的正常结构的附带辐射剂量，而传统的调强放疗使用光子束在很大程度上是不可避免的。我们的初步数据支持质子疗法(IMPT)对口腔前部区域的特定剂量优势。我们假设质子疗法(IMPT)的口腔剂量优势转化为在舌力和最终吞咽结果方面优于光子疗法(IMRT)的功能优势。因此，这项应用的主要目的是确定放疗技术(IMPT和IMRT)、前口腔剂量和舌力之间的关系，因为它们对OPSCC术后放射性相关的吞咽困难有贡献。在这项申请中，我们建议在参加父母随机放射治疗临床试验的患者子组中进行相关研究。研究小组已经开发了一项IRB批准的、激活的口咽癌IMPT和IMRT的II/III期随机试验，该试验将检查初级毒性和生存终点。在这项R03的应用中，我们建议前瞻性地在这项试验的第二阶段登记的一组患者中检查三个相关的问题：1)IMPT比IMRT后的舌力更好，2)前部的 口腔剂量与高适形口咽放疗后的舌力相关，以及3)高适形口咽放疗后的吞咽困难与舌力相关吗？

 DESCRIPTION (provided by applicant): Dysphagia is a dose-limiting toxicity of radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC), and is the primary functional endpoint of contemporary oropharyngeal cancer trials (e.g., RTOG-1221, ECOG-3311). Conformal methods of radiation delivery hold promise to lessen the burden of dysphagia by minimizing dose to dysphagia-aspiration related structures (DARS). Recent work has focused on dose to the pharyngeal constrictors and larynx as a driver of dysphagia, but emerging data suggest the importance of oral cavity dose to swallowing outcomes. Lingual strength correlates with aspiration and swallowing endpoints in healthy subjects and patients with dysphagia, and our published data show that radiation dose to the anterior oral cavity predicts for long-term dysphagia after oropharyngeal intensity modulated photon therapy (commonly referred to as IMRT). Dose trade-offs required in IMRT plans using photon beams have been shown by our collaborators to result in elevated doses to the anterior oral cavity. This is thought to contribut to a greater degree of acute mucositis and predispose to chronic dysphagia despite other dose advantages of IMRT. Proton radiation (IMPT) is proposed as a novel method to de-escalate oropharyngeal RT by reducing collateral radiation dose to uninvolved normal structures adjacent to target volumes that are largely unavoidable with traditional IMRT using photon beams. Our preliminary data support a specific dose advantage with proton therapy (IMPT) to the region of the anterior oral cavity. We hypothesize that the oral cavity dose advantage with proton therapy (IMPT) translates to functional advantages over photon therapy (IMRT) in lingual strength, and ultimately in swallowing outcome. Thus, the primary objective of this application is to establish the relationship between RT technique (IMPT versus IMRT), anterior oral cavity dose, and lingual strength as they contribute to radiation-associated dysphagia after OPSCC. In this application, we propose to conduct correlative studies in a subgroup of patients enrolled on a parent randomized radiotherapy clinical trial. The investigative team has developed an IRB-approved, activated randomized phase II/III trial of IMPT versus IMRT for oropharyngeal cancer that will examine primary toxicity and survival endpoints. In this R03 application, we propose to prospectively examine three correlative questions in a subgroup of patients enrolled in the phase II portion of this trial: 1) is lingual strength better after IMPT vs. IMRT, 2) does anterior oral cavity dose correlate with lingual strength after highly conformal oropharyngeal RT, and 3) does lingual strength correlate with dysphagia after highly conformal oropharyngeal RT?