Inflammatory Cytokines Associated Symptom Burden in NSCLC Patients Receiving CXRT

接受 CXRT 的 NSCLC 患者中炎症细胞因子相关的症状负担

• 批准号: 7532023
• 负责人: Xin Shelley Wang
• 金额: $ 20.79万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7532023
• 关键词: Acute; Affect; Affective Symptoms; Animals; Anorexia; Antibodies; Appendix; Area Under Curve; Behavior; Biological Markers; Biology; Cancer Cluster; Cancer Patient; Characteristics; Chest; Clinical; Clinical Trials; Clinical Trials Design; Common Terminology Criteria for Adverse Events; Condition; Conformal Radiotherapy; Data; Depressed mood; Desire for food; Development; Disease; Distress; Dose; Enrollment; Fatigue; Foundations; Funding; Generations; Goals; Hyperalgesia; Immune System Diseases; Inflammation; Inflammatory; Intensity-Modulated Radiotherapy; Interleukin-1; Interleukin-6; Interleukins; Intervention; Knowledge; Lead; Learning; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Measurable; Measurement; Measures; Mental Depression; Methods; Modeling; Monitor; NIH Program Announcements; Non-Small-Cell Lung Carcinoma; Normal tissue morphology; Outcome; Pain; Parents; Pathway interactions; Patient Outcomes Assessments; Patients; Personal Satisfaction; Phase; Pilot Projects; Play; Pneumonia; Prevalence; Prevention; Production; Proteomics; Protocols documentation; Public Health; Qualifying; Quality of life; Radiation; Radiation Oncology; Radiation therapy; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Reporting; Research; Research Personnel; Risk Factors; Role; Sampling; Sampling Biases; Science; Score; Serum; Severities; Sleep; Sleep disturbances; Sore Throat; Standards of Weights and Measures; Statistical Methods; Statistical Models; Structure of parenchyma of lung; Symptoms; TNF gene; Techniques; Technology; Testing; Therapeutic Effect; Thinking; Time; Tissues; Toxic effect; Treatment-Related Cancer; Tumor Burden; Tumor Necrosis Factor Receptor; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Tumor Volume; University of Texas M D Anderson Cancer Center; Upper arm; Variant; Work; biobehavior; cancer therapy; chemotherapy; cytokine; driving force; experience; human TNF protein; improved; improved functioning; novel; prevent; response; soluble TNF receptor type I; symptom management; tool; trend; tumor

DESCRIPTION (provided by applicant): The objective of the proposed study is to examine whether the Intensity-Modulated Radiation Therapy (IMRT), which modulates the intensity of radiation administered to normal tissue, will result in less cytokine- driven symptom burden in patients with non-small cell lung cancer (NSCLC) compared with standard concurrent chemoradiation therapy (3-Dimensional Conformal Radiation Therapy, or 3DCRT). SPECIFIC AIM 1: To identify the difference between 3DCRT and IMRT chemoradiation therapy in the development of multiple symptoms and serum levels of inflammatory cytokines in patients with NSCLC. Our working hypothesis is that, in a 2-arm, phase II randomized adaptive clinical trial of patients with NSCLC and with the same gross tumor volume (GTV), radiation dose (66 Gy), and concurrent chemotherapy in each arm, less-severe nonspecific symptoms (e.g., fatigue, poor sleep, poor appetite, pain, and sore throat) and lower levels of inflammatory cytokines (mainly IL-6 and soluble TNF receptor type I (sTNF-RI)) will occur in patients in the tissue-protective IMRT arm than in the standard 3DCRT arm. SPECIFIC AIM 2: To establish the association between the parameters for normal-tissue sparing and the serum levels of inflammatory cytokines and symptom severity in patients with NSCLC undergoing chemoradiation. Our working hypothesis is that significantly reduced serum levels of proinflammatory cytokines during chemoradiation will be associated with both significantly decreased symptom severity and reduced median volumes of normal lung being irradiated (evidenced by radiation dose-volume histogram (DVH) and mean lung dose (MLD)) in patients treated with either IMRT or 3DCRT. The unique features of this study are: (a) use of a valid tool to make simultaneous, repeated measurements of cytokines and symptom burden over time of chemoradiation for NSCLC, demonstrated by our descriptive study; (b) use of comprehensive statistical modeling methods to analyze longitudinal data; and (c) comparison of tissue-protective radiotherapy for symptom reduction and prevention with standard radiotherapy in a randomized trial. Validating the role of inflammation as a pathophysiologic mechanism of treatment-induced symptom clusters may suggest avenues for development of aggressive cancer treatment that minimizes symptom burden without compromising tumor control, and will enhance survival by improving the tolerability of aggressive cancer treatments. PUBLIC HEALTH RELEVANCE: Patients undergoing chemoradiation suffer from multiple symptoms, including fatigue, pain, disturbed sleep, poor appetite, and sadness, that often are not monitored by common toxicity criteria yet may cause severe distress and limit the tolerability of the treatment. There is therefore a need for better understanding of the mechanisms underlying symptom burden. The proposed study aims to investigate whether improved normal-tissue sparing from Intensity-Modulated Radiation Therapy (IMRT) may lower serum cytokines and thus control and possibly even prevent treatment-related symptoms, compared with standard chemoradiation treatment. Finding mechanisms to relieve symptom burden and improve the function of the many patients undergoing curative aggressive cancer treatment such as chemoradiation has immense public health significance.

描述（由申请人提供）：拟议的研究的目的是检查与非小all小细胞肺癌（NSCLC）患者的细胞因子驱动的症状负担更少的强度调节放射治疗（IMRT）是否会导致细胞因子驱动的症状负担较小，与标准相关化学疗法相比，是否会导致细胞因子驱动的症状负担较小。具体目的1：确定NSCLC患者的多种症状和血清炎症细胞因子水平的发展中3DCRT和IMRT化学放疗治疗之间的差异。 Our working hypothesis is that, in a 2-arm, phase II randomized adaptive clinical trial of patients with NSCLC and with the same gross tumor volume (GTV), radiation dose (66 Gy), and concurrent chemotherapy in each arm, less-severe nonspecific symptoms (e.g., fatigue, poor sleep, poor appetite, pain, and sore throat) and lower levels of inflammatory cytokines (mainly与标准3DCRT组相比，组织保护IMRT组的患者将发生IL-6和可溶性TNF受体I型（STNF-RI））。具体目的2：建立正常组织隔离的参数与NSCLC患者进行化学辐射患者的炎症细胞因子的血清水平与症状严重程度之间的关联。我们的工作假设是，化学疗法期间促炎细胞因子的血清水平显着降低将与症状严重程度显着降低和炎症的正常肺中位数降低有关（在患者中以imrt或3d Crt的患者中的患者或平均肺剂量图（MLD）和平均肺剂量（MLD）和平均肺剂量（MLD）和平均肺剂量（MLD）和平均肺剂量（MLD剂量（MLD））相关（证明是证明的。这项研究的独特特征是：（a）使用有效的工具来对NSCLC进行化学放疗的同时，重复测量细胞因子和症状负担，并通过我们的描述性研究证明； （b）使用全面的统计建模方法来分析纵向数据； （c）在一项随机试验中比较组织保护放射疗法与标准放射疗法的症状减轻和预防疗法。验证炎症作为治疗诱发的症状簇的病理生理机制可能表明开发了侵略性癌症治疗的途径，从而在不损害肿瘤控制的情况下最大程度地减轻了症状负担，并通过提高积极癌症治疗的耐受性来提高存活率。公共卫生相关性：接受化学放疗的患者患有多种症状，包括疲劳，疼痛，睡眠不足，食欲不振和悲伤，这些症状通常不会受到常见毒性标准但可能导致严重困扰并限制治疗的耐受性。因此，需要更好地了解症状负担的机制。拟议的研究旨在研究与标准化学放疗治疗相比，对强度调节的放射治疗（IMRT）（IMRT）的改善是否可以降低血清细胞因子，从而可以降低血清细胞因子，从而可以控制甚至可以防止治疗相关的症状。找到减轻症状负担并改善许多接受治愈性侵袭性癌症治疗（例如化学放疗）的机制具有巨大的公共卫生意义。