Personalized radiation therapy through functional lung avoidance and response-adaptive dose escalation: utilizing multimodal molecular imaging to improve the therapeutic ratio

通过功能性肺回避和反应适应性剂量递增进行个性化放射治疗：利用多模态分子成像提高治疗率

• 批准号: 9079185
• 负责人: Stephen R. Bowen
• 金额: $ 45.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9079185
• 关键词: Adverse effects; Affect; Aftercare; Anatomy; Cancer Control; Cancer Patient; Clinical; Clinical Data; Dose; Environmental air flow; Failure; Functional disorder; Heterogeneity; Image; Lung; Malignant neoplasm of lung; Maps; Modeling; Multicenter Trials; Non-Small-Cell Lung Carcinoma; PET/CT scan; Patient-Focused Outcomes; Patients; Perfusion; Phase; Photons; Positron-Emission Tomography; Pulmonary Inflammation; Pulmonary function tests; Radiation; Radiation Pneumonitis; Radiation Therapy Oncology Group; Radiation Toxicity; Radiation therapy; Randomized; Recurrent disease; Regimen; Respiratory physiology; Risk; Risk Assessment; Survival Rate; Therapeutic; Toxic effect; Treatment Protocols; Work; X-Ray Computed Tomography; attenuation; base; chemotherapy; cohort; conventional therapy; efficacy evaluation; fluorodeoxyglucose positron emission tomography; high risk; improved; improved outcome; innovation; loss of function; lung imaging; molecular imaging; patient population; patient stratification; public health relevance; quantitative imaging; randomized trial; response; risk mitigation; single photon emission computed tomography; tumor; uptake

 DESCRIPTION (provided by applicant): We propose to deliver personalized radiation therapy to patients with locally advanced NSCLC that improves the therapeutic ratio by: (1) increasing local control through FDG PET/CT-guided tumor dose escalation in select patients at high risk of local failure, and (2) limiting pulmonary toxicity through radiation dose avoidance of functiona lung defined on perfusion SPECT/CT. RT is a major treatment option for patients with locally advanced non-small cell lung cancer (NSCLC), but current treatments result in suboptimal tumor control with local failures up to 50%, while carrying substantial risk of toxicity, with grad 3+ pulmonary toxicity seen in 20% of patients. In this proposal, we will explore the fundamental questions of whether radiation dose to functional lung better predicts clinical toxicity than radiation dose to anatomic lung, and whether selective dose escalation to patients at high risk of local failure improves tumor control, while limiting toxicity. The specific aims are: (1) to evaluae toxicity of Functional Lung Avoidance & Response-adaptive Escalation (FLARE) RT in a cohort of locally advanced NSCLC patients; (2) to correlate baseline perfusion imaging parameters with post-treatment radiation pneumonitis; and (3) to predict changes in pulmonary function tests from regional RT dose-induced changes in perfusion imaging parameters. In support of the above aims, patients with locally advanced NSCLC receiving RT will undergo pulmonary function tests (PFTs) and perfusion/ventilation SPECT/CT and PET/CT at baseline, during week 3 of RT and 3 months post-RT. High precision radiation therapy will be administered by combining differential avoidance planning to reduce mean dose to SPECT/CT-defined perfused lung, and differential tumor dose escalation defined on 3 week mid-treatment FDG PET/CT in select patients classified as early FDG PET non-responders. SPECT/CT perfusion image histogram and textural features of lung function heterogeneity will be compared against CT-based dose-volume parameters for correlation to pulmonary toxicity. Spatially mapped changes in SPECT/CT perfusion image uptake will be modeled as a dichotomous dose-response with complete loss of function above dose thresholds, a binned dose-response with partial loss of function in each dose bin, and continuous dose-response at the voxel scale. This project will precisely combine functional lung avoidance and selective dose escalation in an innovative approach that can benefit each segment of a heterogeneous patient population with locally advanced lung cancer. Successful completion will pave the way for efficacy evaluation of FLARE RT in a phase II / III multi-center trial with the potential to significantly improve outcome of patients with locally advanced NSCLC.

 描述（由申请人提供）：我们建议为局部晚期 NSCLC 患者提供个性化放射治疗，通过以下方式提高治疗率：(1) 通过 FDG PET/CT 引导的肿瘤剂量递增，对选定的高危患者进行局部控制。 (2) 通过灌注 SPECT/CT 确定的功能性肺的辐射剂量避免来限制肺毒性，这是局部晚期非小细胞肺癌 (NSCLC) 患者的主要治疗选择，但目前的治疗结果是。肿瘤控制不佳，局部失败率高达 50%，同时具有巨大的毒性风险，20% 的患者出现 3 级以上肺部毒性。在本提案中，我们将探讨对功能性肺的辐射剂量是否更好这一基本问题。与解剖肺的辐射剂量相比，可以预测临床毒性，以及对局部失败高风险患者进行选择性剂量递增是否可以改善肿瘤控制，同时限制毒性。具体目的是：（1）评估功能性肺避免和治疗的毒性。对局部晚期 NSCLC 患者进行反应适应性升级 (FLARE) 放疗；(2) 将基线灌注成像参数与治疗后放射性肺炎相关联；(3) 预测局部放疗剂量引起的肺功能测试变化为了支持上述目标，接受 RT 的局部晚期 NSCLC 患者将在第 3 周期间在基线时接受肺功能测试 (PFT) 和灌注/通气 SPECT/CT 和 PET/CT。 RT 期间和 RT 后 3 个月将通过结合差异性避免计划来实施高精度放射治疗，以减少 SPECT/CT 定义的灌注肺的平均剂量，并根据 3 周治疗中期 FDG PET/CT 定义的差异性肿瘤剂量递增。在选定的早期 FDG PET 无反应患者中，将肺功能异质性的 SPECT/CT 灌注图像直方图和纹理特征与基于 CT 的剂量体积参数进行比较，以了解与肺毒性的相关性。在 SPECT/CT 灌注图像摄取中，将建模为二分剂量反应（在剂量阈值以上功能完全丧失）、分档剂量反应（每个剂量仓中部分功能丧失）以及体素尺度的连续剂量反应。该项目将通过一种创新方法精确地将功能性肺避免和选择性剂量递增结合起来，使局部晚期肺癌的异质患者群体的各个部分受益，成功完成将为疗效评估铺平道路。 FLARE RT 在 II/III 期多中心试验中的应用，有可能显着改善局部晚期 NSCLC 患者的预后。