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

 描述（由申请人提供）：吞咽困难是口咽鳞状细胞癌（OPSCC）放疗的剂量限制性毒性，是当代口咽癌试验的主要功能终点（例如，RTOG-1221，ECOG-3311）。适形放射治疗方法有望通过最小化吞咽困难-抽吸相关结构（DARS）的剂量来减轻吞咽困难的负担。最近的研究集中在咽缩肌和喉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，舌强度与误吸和吞咽终点相关，我们发表的数据显示，口咽强度调制光子治疗（通常称为IMRT）后，前口腔的辐射剂量可预测长期吞咽困难。我们的合作者已经证明，使用光子束的调强放射治疗计划中所需的剂量权衡会导致口腔前部剂量升高。尽管IMRT有其他剂量优势，但这被认为会导致更大程度的急性粘膜炎和慢性吞咽困难。质子放射（IMPT）被提出作为一种新的方法，以降低口咽RT通过减少附带辐射剂量的未涉及的正常结构附近的目标体积，这在很大程度上是不可避免的与传统的IMRT使用光子束。我们的初步数据支持质子治疗（IMPT）对前口腔区域的特定剂量优势。我们假设质子治疗（IMPT）的口腔剂量优势转化为在舌强度和最终吞咽结果方面优于光子治疗（IMRT）的功能优势。因此，本申请的主要目的是确定RT技术（IMPT与IMRT）、前口腔剂量和舌强度之间的关系，因为它们会导致OPSCC后放射相关性吞咽困难。在本申请中，我们建议在参加父随机放疗临床试验的患者亚组中进行相关研究。研究小组已经开发了一项IRB批准的，激活的IMPT与IMRT治疗口咽癌的随机II/III期试验，将检查主要毒性和生存终点。在该R 03申请中，我们建议在本试验II期部分入组的患者亚组中前瞻性地检查三个相关问题：1）IMPT与IMRT相比，舌强度更好，2） 口腔剂量与高度适形口咽放疗后舌强度相关，3）舌强度与高度适形口咽放疗后吞咽困难相关吗？

 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?