Hypoxia Image-Guided Radiation Therapy

缺氧影像引导放射治疗

• 批准号: 8519383
• 负责人: Nancy Y Lee
• 金额: $ 41.13万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8519383
• 关键词: Acute; Adverse effects; Applications Grants; Biological Markers; Biopsy; Biopsy Specimen; Clinical; Core Biopsy; Data; Development; Disease; Distant; Distant Metastasis; Dose; Early treatment; Epigenetic Process; Evolution; Failure; Functional Imaging; Genomics; Goals; Grant; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; High Dose Chemotherapy; Human Papillomavirus; Hypoxia; Image; Imagery; Individual; Intensity-Modulated Radiotherapy; Knowledge; Lead; Link; Low Dose Radiation; Malignant Neoplasms; Methods; Metric; Misonidazole; Neck; Neck Dissection; Nodal; Outcome; Outpatients; Pathologic; Patients; Phenotype; Physicians; Population; Positron-Emission Tomography; Primary Neoplasm; Probability; Prognostic Marker; Protein-Lysine 6-Oxidase; Radiation; Radiation therapy; Recording of previous events; Regimen; Reporting; Resolution; Sampling Errors; Signal Transduction; Site; Spatial Distribution; Staging; Staining method; Stains; Stratification; Surgical Management; Survival Rate; Systemic Therapy; Techniques; Testing; Therapeutic; Time; Toxic effect; Treatment Failure; Treatment outcome; Tumor Markers; Validation; aggressive therapy; base; chemoradiation; chemotherapy; cohort; combat; experience; human study; image guided radiation therapy; improved; molecular marker; novel; outcome forecast; prognostic; response; therapeutic target; treatment response; tumor; uptake; Acute; Adverse effects; Applications Grants; Biological Markers; Biopsy; Biopsy Specimen; Clinical; Core Biopsy; Data; Development; Disease; Distant; Distant Metastasis; Dose; Early treatment; Epigenetic Process; Evolution; Failure; Functional Imaging; Genomics; Goals; Grant; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; High Dose Chemotherapy; Human Papillomavirus; Hypoxia; Image; Imagery; Individual; Intensity-Modulated Radiotherapy; Knowledge; Lead; Link; Low Dose Radiation; Malignant Neoplasms; Methods; Metric; Misonidazole; Neck; Neck Dissection; Nodal; Outcome; Outpatients; Pathologic; Patients; Phenotype; Physicians; Population; Positron-Emission Tomography; Primary Neoplasm; Probability; Prognostic Marker; Protein-Lysine 6-Oxidase; Radiation; Radiation therapy; Recording of previous events; Regimen; Reporting; Resolution; Sampling Errors; Signal Transduction; Site; Spatial Distribution; Staging; Staining method; Stains; Stratification; Surgical Management; Survival Rate; Systemic Therapy; Techniques; Testing; Therapeutic; Time; Toxic effect; Treatment Failure; Treatment outcome; Tumor Markers; Validation; aggressive therapy; base; chemoradiation; chemotherapy; cohort; combat; experience; human study; image guided radiation therapy; improved; molecular marker; novel; outcome forecast; prognostic; response; therapeutic target; treatment response; tumor; uptake

DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) is a debilitating and lethal disease. Despite significant advances in radiotherapy and surgical management, the 5-year survival rates have remained suboptimal. To improve therapeutic outcomes, better biomarkers and targeted therapeutic approaches are needed. Novel biomarkers can provide guidance for patient stratification and can optimize therapeutic strategy by improving patient survival and/or decreasing treatment-related toxicities. Although the recent focus on biomarkers for HNSCC has been on the human papilloma virus (HPV) status, additional efforts in improving the efficacy of individualized therapy have lead to the discovery of a number of promising epigenetic or genomic based markers as well as non-invasive functional imaging. One known cause of locoregional failure or distant metastasis after radiotherapy for HNSCC is tumor hypoxia. We propose that in tumors with positive HPV status and no hypoxia before radiotherapy or rapid resolution of tumor hypoxia (depicted by fluoromisonidazole positron emission tomography or 18F- FMISO PET) during treatment, a less intensive and less toxic regimen will yield the same tumor control as the standard 70Gy approach (intensity reduction or non- inferiority approach in Aim 1). To perform dose de-escalation in a safe manner, we propose to limit de-escalation to the node(s) of HPV+ HNSCC. All of these patients who underwent dose de-escalation to the node(s) will also undergo neck dissection as part of their treatment. On the other hand, HPV negative tumors with the presence of hypoxia before radiotherapy and with persistent hypoxia during treatment may require more aggressive therapy (intensity escalation or superiority approach). In Aim 2, we will determine using quantitative metrics between hypoxia 18F-FMISO image findings versus tumor treatment response in a HPV negative cohort. In Aim 3, we will conduct an imaging-pathological study to detail the spatial and temporal correlation between the evolution of 18F-FMISO imaging signal and change in hypoxia biomarker expression. Obtaining longitudinal profile of any given hypoxia biomarker will require repeated biopsies of tumors during a course of radiotherapy which in general has not been received well by the patient. Therefore, a priori using noninvasive 18F-FMISO PET is more appealing and practical. Confirmation of 18F-FMISO-biomarker correlation in Aim 3 will provide physicians a noninvasive avenue in selecting tumors likely to spread distantly for more intensive or novel therapy.

描述（由申请人提供）：头部和颈部鳞状细胞癌（HNSCC）是一种令人衰弱的致命疾病。尽管放疗和手术治疗取得了重大进展，但5年的存活率仍然是最佳的。为了改善治疗结果，需要更好的生物标志物和靶向治疗方法。新型生物标志物可以为患者分层提供指导，并可以通过改善患者生存和/或降低与治疗相关的毒性来优化治疗策略。尽管最近对HNSCC生物标志物的重点是人类乳头状瘤病毒（HPV）状态，但在提高个性化疗法的疗效方面的额外努力导致发现了许多有希望的表观遗传学或基因组标记物以及非侵入性功能成像。 HNSCC放射疗法后，局部区域衰竭或远处转移的一个已知原因是肿瘤缺氧。我们提出，在放射疗法前呈阳性HPV状态且无缺氧或肿瘤缺氧的快速分辨率（通过荧光症甲唑唑次唑次座位发射断层扫描或18F-FMISO PET）在治疗过程中，在强度较小且毒性较低的治疗方案中会产生相同的肿瘤控制，因为标准的70GY方法将产生相同的肿瘤控制（强度下降或非次要地下性，目标是1）。为了以安全的方式执行剂量降级，我们建议将降级限制为HPV+ HNSCC的节点。所有这些接受剂量降低到节点的患者也将作为治疗的一部分进行颈部解剖。另一方面，放射治疗前缺氧和治疗期间持续性缺氧的HPV阴性肿瘤可能需要更具侵略性的治疗（强度升级或优越性方法）。在AIM 2中，我们将确定使用HPV阴性队列中缺氧18F-FMISO图像发现与肿瘤治疗反应之间的定量指标。在AIM 3中，我们将进行一项成像病理学研究，以详细说明18F-FMISO成像信号的演变与缺氧生物标志物表达的变化之间的空间和时间相关性。在放射治疗过程中，获得任何给定的低氧生物标志物的纵向轮廓将需要重复的肿瘤活检，这通常不受患者的良好接受。因此，先验使用非侵入性18F-Fmiso PET更具吸引力和实用性。 AIM 3中18F-Fmiso-Biomarker相关性的确认将为医生提供无创的途径，以选择可能远距离扩散以进行更深入或新颖的疗法的肿瘤。