INDIVIDUALIZING IMRT TREATMENT IN BRAIN AND HEAD/NECK CA

脑部和头颈 CA 的个体化 IMRT 治疗

• 批准号: 7560569
• 负责人: Avraham Eisbruch
• 金额: $ 33.05万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7560569
• 关键词: Blood; Blood - brain barrier anatomy; Brain; Brain Neoplasms; Clinical; Clinical Research; Clinical Trials; Complication; Condition; Conformal Radiotherapy; Daily; Data; Deglutition; Deglutition Disorders; Deoxycytidine; Diffusion; Diffusion Magnetic Resonance Imaging; Dose; Failure; Gadolinium; Glioblastoma; Glioma; Goals; Head and Neck Cancer; Head and neck structure; Image; Intensity-Modulated Radiotherapy; Magnetic Resonance Imaging; Malignant Glioma; Metabolic Marker; Methionine; Methods; Neck Cancer; Normal tissue morphology; Outcome; Parotid Gland; Patients; Penetration; Permeability; Pharmaceutical Preparations; Phase I/II Trial; Physiological; Physiology; Positron-Emission Tomography; Principal Investigator; Progressive Disease; Radiation; Radiation-Sensitizing Agents; Range; Rate; Research; Risk; Schedule; Severities; Standards of Weights and Measures; Structure; Techniques; Technology; Testing; Therapeutic Index; Time; Toxic effect; Treatment outcome; Week; Weight; Work; Xerostomia; analog; base; chemotherapy; gemcitabine; improved; innovation; irradiation; pre-clinical; programs; response; size; temozolomide; treatment planning; tumor

In our previous research we developed highly conformal radiation treatment for head/neck and brain tumors using sculpted dose distributions and demonstrated the ability to escalate tumor dose with minimal complications (brain), and maintain high control rates while decreasing a major complication (xerostomia) for head/neck cancers. Our long-term goal is to increase tumor control and reduce complication rates by individualizing the timing and intensity of therapy based on innovative imaging. We propose to intensify treatment for glioblastoma by escalating the daily fraction doses while also utilizing effective chemotherapy (temozolomide). We will test the hypothesis that diffusion MRI (dMRI), which may predict tumor response early after therapy is started, will be a useful basis for re-optimization during the course of treatment, allowing the escalation of dose to non-responding parts of the tumor. We will also make use of our preliminary MRI results which suggest that radiation can open the bloodtumor- barrier (BTB) to chemotherapeutic and radiosensitizing agents (like gemitabine). We will test whether concurrent conformal radiation and gemcitabine (administered after the BTB is opened) will be safer and improve response rates for grade 3 gliomas, and whether we can improve the outcome by escalating the doses to the parts of the tumor demonstrating lack of increased permeability of the BTB early after the start of therapy. In head and neck cancer, we will test strategies that promise to decrease treatment-related late dysphagia and aspiration. We will test if reducing dose to the swallowing structures can reduce the severity of late dysphagia, and test the utility of innovative imaging (FLT-PET, and dMRI) to predict (early after the start of therapy) which tumors are likely to fail treatment, as well as directing individualized dose intensification using re-optimization plans. We expect that the Project will show improving non-complicated tumor control rates in brain and head and neck cancer by customizing treatment intensity following analysis of possible early predictors of response.

在我们以前的研究中，我们开发了高度适形放射治疗头颈部和脑肿瘤， 塑造剂量分布，并证明了以最小并发症增加肿瘤剂量的能力 （脑），并保持高控制率，同时减少头颈癌的主要并发症（口干症）。 我们的长期目标是通过个体化的时机和方法来增加肿瘤控制和降低并发症发生率。 基于创新成像的治疗强度。我们建议加强胶质母细胞瘤的治疗， 每日分次剂量，同时也利用有效的化疗（替莫唑胺）。我们将检验这个假设 弥散磁共振成像（dMRI）可以在治疗开始后早期预测肿瘤反应， 在治疗过程中进行重新优化，允许剂量递增至无反应的部分， 肿瘤我们还将利用我们的初步核磁共振结果，这表明辐射可以打开血液肿瘤- 屏障（BTB）对化疗和放射增敏剂（如吉西他滨）的影响。我们将测试 同时进行适形放疗和吉西他滨（在BTB开放后给药）将更安全， 3级胶质瘤的反应率，以及我们是否可以通过增加剂量来改善结果， 肿瘤在治疗开始后早期表现出缺乏BTB的增加的渗透性。头颈 颈部癌症，我们将测试有希望减少治疗相关的晚期吞咽困难和误吸的策略。我们 将测试减少吞咽结构的剂量是否可以降低晚期吞咽困难的严重程度，并测试 创新成像（FLT-PET和dMRI），以预测（治疗开始后早期）哪些肿瘤可能失败 治疗，以及使用重新优化计划指导个体化剂量强化。我们预计 该项目将通过以下方式提高脑和头颈部癌症的非复杂性肿瘤控制率： 在分析可能的反应早期预测因素后定制治疗强度。