MR-predictive-assay in pre-operative lung cancer therapy: response/resectability

术前肺癌治疗中的 MR 预测分析：反应/可切除性

• 批准号: 7679489
• 负责人: John C Grecula
• 金额: $ 33.75万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7679489
• 关键词: Address; Algorithms; Biological Assay; Cancer Etiology; Cancer Patient; Cessation of life; Characteristics; Clinical; Cluster Analysis; Complement; Data; Disease; Disease-Free Survival; Effectiveness; Excision; Failure; Future; Hypoxia; Image; Image Analysis; Imaging Techniques; Incidence; Institution; Life; Logistic Regressions; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of lung; Malignant neoplasm of thyroid; Mediastinal Diseases; Metabolic; Metastatic Neoplasm to the Liver; Methodology; Methods; Modality; Monitor; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; Outcomes Research; Oxygen; Patients; Pattern; Perfusion; Population; Positron-Emission Tomography; Predictive Factor; Predictive Value; Primary Neoplasm; Protocols documentation; Radiation therapy; Reaction Time; Reporting; Reproducibility; Research; Resectable; Residual Tumors; Resistance; Resolution; Staging; Survival Rate; Testing; Therapeutic; Time; Time Study; Translational Research; Treatment Failure; Treatment Protocols; Treatment outcome; Tumor Volume; Unresectable; base; cancer imaging; cancer therapy; cancer type; chemotherapy; experience; improved; in vivo; lung imaging; malignant breast neoplasm; melanoma; mortality; novel strategies; response; therapy resistant; treatment response; treatment strategy; tumor

DESCRIPTION (provided by applicant): Surgical resectability of lung cancer remains a critical factor influencing survival, but approximately 50% of patients present with unresectable stage III disease due to mediastinal disease. With 5 weeks of preoperative neoadjuvant chemo/radiotherapy (PNT) to reduce the mediastinal disease, 67- 85% of Stage III lung cancers become eligible for surgical resection with reported 33% improvement in 5-year survival. The decision for surgical resection depends upon CT evidence of mediastinal disease responding favorably to PNT. However, 10-20% of the patients becoming eligible for surgical resection are later found unresectable intraoperatively with devastating outcome. The ability to identify those patients who may show excellent PNT response as judged by CT but fail in surgical resection can have profound impact to the treatment strategy and outcome. This imaging-based outcome research is to test the hypothesis that tumor perfusion status during treatment, reflected by the dynamic contrast enhanced (DCE) MR, influences the resectability of stage III lung cancer treated with PNT. This translational research applies a novel approach to in vivo monitoring of PNT response by assessing (1) directly the efficiency in delivery of chemotherapy or oxygen (hypoxia) to the tumor during treatment that critically influence the effectiveness of chemo- or radiation therapy respectively, and (2), indirectly the tumor shrinkage rate that reflects the response of the tumor to the ongoing treatment. Specific Aim 1: To develop, refine, and test MR imaging protocol and analysis methodologies for assessing response of PNT in lung cancer. Specific Aim 2: To apply sequential MR studies and imaging analysis in a clinical population during the course of PNT and assess PNT response with CT, surgical and pathological findings. Specific Aim 3: To determine the added predictive value and best timing of the MR predictive assay. On completion, a MR based early predictive assay for stage III lung cancer treated with PNT will be developed, tested and refined with limited patients in a clinical setting, and the preliminary assessment of the added predictive value of MR parameters will be made by the CT, surgical and pathological findings. We will further discern the differences between favorable and unfavorable responders to PNT and refine the imaging-based predictive algorithm with (1) multi-spectral pixel-by-pixel analysis and cluster analysis by characterizing those low-DCE pixels within a heterogeneous tumor mass which likely represent poorly-perfused tumor regions contributing to treatment failure; and with (2) multi-temporal imaging analysis (sequential MR studies) by identifying the best timing for response assessment.Project Narrative Even a modest (e.g., 10%) improvement in lung cancer survival rates through this study may result in thousands of lives saved or prolonged every year in the U.S and we believe even with marginal improvement, the overall impact of this proposed study can be enormous considering the high incidence and mortality of lung cancer.

描述（由申请人提供）：肺癌的手术可切除性仍然是影响生存的关键因素，但大约50%的患者因纵膈疾病而患有不可切除的III期疾病。通过5周的术前新辅助化疗/放疗（PNT）来减少纵隔疾病，67- 85%的III期肺癌适合手术切除，据报道5年生存率提高了33%。手术切除的决定取决于纵隔疾病对PNT反应良好的CT证据。然而，10-20%的患者成为手术切除资格，后来发现无法切除手术中毁灭性的结果。识别那些通过CT判断可能表现出良好PNT反应但手术切除失败的患者的能力对治疗策略和结果具有深远的影响。 这项基于成像的结局研究旨在验证治疗期间肿瘤灌注状态（由动态对比增强（DCE）MR反映）影响PNT治疗的III期肺癌可切除性的假设。这项转化研究应用了一种新的方法来体内监测PNT反应，通过评估（1）直接评估治疗期间向肿瘤输送化疗或氧气（缺氧）的效率，这分别严重影响化疗或放疗的有效性，和（2），间接反映肿瘤对正在进行的治疗的反应的肿瘤缩小率。 具体目标1：开发、完善和测试用于评估肺癌PNT反应的MR成像方案和分析方法。具体目标二：在临床人群中应用PNT过程中的序列MR检查和影像学分析，并结合CT、手术和病理结果评估PNT反应。具体目标3：确定MR预测试验的附加预测值和最佳时机。 完成后，将在临床环境中对有限的患者开发、测试和完善基于MR的PNT治疗III期肺癌的早期预测分析，并将通过CT、手术和病理结果对MR参数的附加预测值进行初步评估。我们将进一步辨别对PNT的有利和不利应答者之间的差异，并通过（1）多光谱逐像素分析和聚类分析来改进基于成像的预测算法，所述聚类分析通过表征异质肿瘤块内的那些低DCE像素来进行，所述低DCE像素可能代表导致治疗失败的灌注不良的肿瘤区域;以及（2）通过确定缓解评估的最佳时机进行多时间成像分析（序列MR研究）。 即使是一个温和的（例如，通过这项研究，肺癌生存率的改善可能导致美国每年挽救或延长数千人的生命，我们相信即使有微小的改善，考虑到肺癌的高发病率和死亡率，这项拟议研究的总体影响也是巨大的。