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.

 DESCRIPTION (provided by applicable): 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是局部晚期非小细胞肺癌（NSCLC）患者的主要治疗选择，但是当前的治疗可导致次优肿瘤对照，局部衰竭，同时承受着毒性的实质性风险，而在20％的患者中则具有3+ Grad 3+肺毒性。在此提案中，我们将探讨有关功能性肺部辐射剂量是否更好地预测临床毒性的基本问题，而不是对解剖肺的辐射剂量，以及对处于局部衰竭高风险的患者的选择性剂量升级是否可以改善肿瘤控制，同时限制毒性。具体目的是：（1）评估局部晚期NSCLC患者队列中功能性肺避免和反应自适应升级（FLARE）RT的毒性； （2）将基线灌注成像参数与治疗后辐射肺炎相关联； （3）预测区域RT剂量诱导的灌注成像参数变化的肺功能测试的变化。为了支持上述目的，在RT和RT后3个月内，在基线时，患有局部晚期NSCLC接收RT的患者将接受肺功能测试（PFTS）和灌注/通风SPECT/CT/CT和PET/CT。高精度放射疗法将通过结合差异避免计划，以将平均剂量降低到SPECT/CT定义的灌注肺中，并在3周中期治疗的FDG PET/CT中定义的差异性肿瘤剂量升级，分类为归类为FDG PET早期的精选患者。 SPECT/CT灌注图像直方图和肺功能异质性的纹理特征将与基于CT的剂量 - 体积参数进行比较，以与肺毒性相关。 SPECT/CT灌注图像吸收的空间映射变化将建模为二分法剂量反应，功能完全损失高于剂量阈值，这是每个剂量箱中的binned剂量反应，每个剂量bin中的部分损失，并且在Voxel尺度上连续剂量反应。该项目将精确地将功能性肺部回避和选择性剂量升级与创新方法相结合，该方法可以使异构患者群体患有局部晚期肺癌的每个细分市场受益。成功完成将为II / III阶段多中心试验中的效率评估效率评估铺平道路，并有可能显着改善局部晚期NSCLC患者的结果。