The Influence of Diet and Lifestyle on Patients with Advanced Colorectal Cancer

描述(申请人提供)：流行病学和科学研究表明，饮食和其他生活方式因素对患结直肠癌的风险有重大影响。新出现的数据表明，其中一些因素会影响早期结肠癌患者的预后。然而，没有关于饮食、生活方式和其他宿主因素对更晚期结直肠癌患者预后的影响的数据。在初步诊断时，20%的结直肠癌患者有转移的证据，另有15%-20%的患者在最初诊断的几年内会因转移而复发。在过去的10年里，这些患者的化疗方案有了很大的改善，中位生存期超过2年，存活4年或更长时间的患者越来越多。患者经常试图了解，如果有的话，饮食和生活方式将改善他们的结果，包括存活率和治疗的耐受性。此外，饮食和生活方式对预后的影响可能部分取决于肿瘤的分子特征。针对NIH计划宣布的PA-09-148“能量平衡与人类癌症研究”，我们建议利用美国国立癌症研究所赞助的2项针对新诊断IV期结直肠癌患者的化疗试验(CALGB 80203和80405)的数据，解决这些知识空白问题，这些试验提供：a)饮食、药物、生活方式和合并症的前瞻性评估；b)石蜡包埋肿瘤标本，以检查这些因素与特定分子改变的相互作用；c)用于研究目的的血液样本；以及d)关于癌症进展、死亡率和化疗相关毒性的全面数据。由于在本试验中对分期、表现状态、联合化疗的使用和随访进行了仔细的定义，因此应最大限度地减少因疾病特征和化疗使用而造成的残留混淆。该数据库将提供独特的机会来检验能量平衡(目标1)、饮食和维生素D(目标2)以及阿司匹林/非类固醇抗炎药(目标3)对晚期结直肠癌患者预后的影响。除了上述假设之外，这一队列将允许在未来假设出现时对其进行快速检查。最终，这个数据库将使我们能够确定许多因素对结直肠癌存活率的影响，提高我们对结直肠癌生物学的理解，并有可能为患者和医疗保健提供者提供实质性的饮食和生活方式建议。 公共卫生相关性：癌症患者经常寻求饮食和生活方式的信息作为他们治疗的一部分。这项应用产生的数据将有助于了解这些因素是否会影响患者的结果。这些数据可能会影响对未来患者的治疗建议，或者导致发展一项随机试验，以进一步了解这一领域的情况。

DESCRIPTION (provided by applicant): Epidemiologic and scientific research indicates that diet and other lifestyle factors have a significant influence on the risk of developing colorectal cancer. Emerging data suggest some of these factors impact on the outcomes of patients with early stage colon cancer. However, there are no data on the influence of diet, lifestyle and other host factors on the outcomes of patients with more advanced colorectal cancer. At the time of initial diagnosis, 20% of colorectal cancer patients have evidence of metastases and another 15- 20% will recur with metastatic disease within a few years of initial diagnosis. In the past 10 years, there have been substantial improvements in chemotherapy options for these patients, with median survival exceeding 2 years and increasing number of patients living 4 or more years. Patients often seek to understand what, if any, diet and lifestyle will improve their outcomes, both survival and tolerability of therapy. Moreover, how diet and lifestyle influence prognosis may depend, in part, on molecular characteristics of the tumor. In response to a NIH Program Announcement, PA-09-148, "Studies of Energy Balance and Cancer in Humans," we propose to address these gaps in knowledge by utilizing data from 2 National Cancer Institute-sponsored chemotherapy trials in newly diagnosed patients with stage IV colorectal cancer (CALGB 80203 and 80405) which provide a) prospective assessments of diet, medication, lifestyle and comorbidities; b) paraffin-embedded tumor specimens to examine how such factors interact with specific molecular alterations; c) blood samples for research purposes; and d) comprehensive data on cancer progression, mortality, and chemotherapy-related toxicity. Since stage, performance status, use of combination chemotherapy and follow-up were carefully defined in this trial, residual confounding by disease characteristics and use of chemotherapy should be minimized. This database will provide the unique opportunity to examine the influence of energy balance (Aim 1), diet and vitamin D (Aim 2) and aspirin/NSAIDs (Aim 3) on the outcomes of patients with advanced colorectal cancer. Beyond the aforementioned hypotheses, this cohort will allow for the rapid examination of future hypotheses as they emerge. Ultimately, this database will permit us to ascertain the influence of numerous factors on colorectal cancer survival, improve our understanding of colorectal cancer biology, and potentially offer substantive diet and lifestyle recommendations for patients and health care providers. PUBLIC HEALTH RELEVANCE: Patients with cancer often seek information of diet and lifestyle as part of their therapy. Data generated from this application will help understand whether such factors influence the outcomes of patients. These data may influence treatment recommendations to future patients or lead to the development of a randomized trial to further knowledge in this area.