Using Physiological Age to Predict Chemotherapy Toxicity

描述(申请人提供)：癌症现在是美国最主要的死亡原因，乳腺癌是美国女性的主要癌症之一。随着老年人口的急剧增长，预计到2030年，65岁及以上妇女(“老年”)中每年确诊的乳腺癌病例绝对数将几乎翻一番。尽管专业人士建议考虑对所有患有浸润性乳腺癌的女性进行化疗，但针对不断增长的老年人口的治疗决策仍然很复杂，这主要是因为这一群体在临床试验中的代表性不足，以及存在相互竞争的死亡原因，导致对化疗利弊平衡的持续不确定性。不幸的是，年龄、合并症和临床判断无法预测哪些老年女性会耐受化疗。我们组建了一支由肿瘤学家、老年病学家、癌症流行病学家、卫生服务研究人员、人口学家、决策科学家和消费者组成的跨学科团队，以填补我们对老年女性化疗知识的空白。我们建议开发并验证“生理年龄”指标，该指标定义为对化疗等应激源的反应能力。这项拟议的研究将嵌套在北加州凯撒永久医院(KPNC)登记的新诊断乳腺癌患者(n=5021)的大型5年期NCI资助的前瞻性队列中。KPNC拥有自动化的、高质量的数据库，允许收集与化疗相关的详细信息。我们将从队列研究中招募所有65岁及以上的女性，并从访谈和计算机记录中测量“生理年龄”，专注于在日常实践中容易获得的变量。我们将使用样本的一部分数据来开发该指数，然后测试该指数在独立样本中正确预测观察到的毒性结果的能力。我们还将测试该指数预测12个月生活质量和全因死亡率的能力。然后，结果将被用于增强一个广泛使用的基于网络的临床决策工具(辅助！)。我们的方法利用现有资源，以具有成本效益的方式解决重要的新科学问题。该项目的创新之处在于，它把重点放在老年妇女身上--这是一种研究不足但不断增加的乳腺癌风险人群--并将“生理年龄”作为一种根据老年妇女个人潜在健康状况和耐受化疗能力量身定制治疗方法的应用。我们的方法可以用来提高将患乳腺癌的不断扩大的老年人口及其提供者之间共享治疗决策的质量。我们开发的范例也应该广泛适用于影响老年人群的其他常见癌症的化疗决定。

DESCRIPTION (provided by applicant): Cancer is now the leading cause of death in the US, and breast cancer is one of the leading cancers among US women. With the dramatic growth in the older population, the absolute number of breast cancer cases diagnosed each year among women 65 and older ("older") is expected to almost double by the year 2030. Despite professional recommendations to consider chemotherapy for all women with invasive breast cancer, treatment decision making for the growing older population remains complex, largely as a result of under- representation of this group in clinical trials and the presence of competing causes of mortality, leading to persistent uncertainty about the balance of chemotherapy benefits and harms. Unfortunately, age, comorbidity and clinical judgement fail to predict which older women will tolerate chemotherapy. We have assembled a trans-disciplinary team of oncologists, geriatricians, cancer epidemiologists, health services researchers, demographers, decision scientists and consumers to fill gaps in our knowledge about chemotherapy in older women. We propose to develop and validate an index of "physiological age", defined as capacity to respond to stressors such as chemotherapy. The proposed study will be nested in a large 5- year NCI-funded prospective cohort of newly diagnosed breast cancer patients (n=5,021) enrolled in Kaiser Permanente of Northern California (KPNC). KPNC has automated, high quality databases that allow for collection of detailed chemotherapy-related information. We will enroll all women 65 and older from the cohort study and measure "physiological age" from interview and computerized records, concentrating on variables that can be readily obtained in routine practice. We will develop the index using data from a portion of the sample, then test the ability of the index to correctly predict observed toxicity outcomes in an independent sample. We will also test the ability of the index to predict 12-month quality of life and all-cause mortality. Results will then be used to enhance a widely used web-based clinical decision tool (Adjuvant!). Our approach leverages existing resources to address important new scientific questions in a cost efficient manner. This project is innovative in its focus on older women - an under-studied but growing population at risk for breast cancer - and the application of "physiological age" as a method of tailoring treatment to an individual older woman's underlying health and ability to tolerate chemotherapy. Our approach could be used to enhance the quality of shared treatment decision making between the expanding older population that will develop breast cancer and their providers. The paradigm we develop should also be broadly portable to chemotherapy decisions for other common cancers affecting older populations.