Impact of Body Composition and Related Inflammatory and Immune States on Prognosis of Non-Muscle Invasive Bladder Cancer

身体成分及相关炎症和免疫状态对非肌肉浸润性膀胱癌预后的影响

• 批准号: 10674401
• 负责人: Marilyn L Kwan
• 金额: $ 88.14万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-14 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674401
• 关键词: Address; Adipose tissue; Adverse effects; Adverse event; Affect; Age; BCG Live; Bacillus Calmette-Guerin Therapy; Biological Markers; Body Composition; Body mass index; Cancer Patient; Cancer Prognosis; Cancer Survivor; Chronic; Clinical; Clinical Data; Data; Diagnosis; Diet; Disease; Disease Outcome; Environment; Failure; Fatty acid glycerol esters; Genetic; Immune; Immune response; Immunity; Immunologic Markers; Immunosuppression; Immunotherapy; Infiltration; Inflammation; Inflammatory; Intravesical Administration; Investigation; Life Style; Link; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Managed Care; Measures; Mediating; Modeling; Muscle; Newly Diagnosed; Obesity; Outcome; Patients; Performance; Phenotype; Physical activity; Prognosis; Prognostic Factor; Prognostic Marker; Prospective Studies; Prospective cohort; Prospective, cohort study; Recurrence; Recurrent Malignant Neoplasm; Recurrent disease; Research; Risk; Role; Scanning; Sex Differences; Shapes; Skeletal Muscle; Smoking; System; Testing; Time; Treatment Failure; Treatment outcome; Visceral; X-Ray Computed Tomography; age related; age-related muscle loss; cancer diagnosis; cancer epidemiology; cancer recurrence; clinical care; disease prognosis; effective therapy; experience; follow-up; high risk; improved; individualized medicine; intravesical; lifestyle factors; mortality; muscle form; muscle invasive bladder cancer; non-muscle invasive bladder cancer; older patient; participant enrollment; patient stratification; prevent; prognostic; progression risk; risk stratification; sarcopenia; sarcopenic obesity; sex; skeletal muscle wasting; subcutaneous; success; survivorship; treatment planning; treatment response; tumor; tumor progression

Abstract Bladder cancer is one of the top ten most common cancers in the U.S., and one of the most expensive to treat. Most cases (75%) are non-muscle-invasive bladder cancer (NMIBC) with high rates of recurrence (70%) and progression (25%). While prognostic factors remain largely unknown, the success of Bacillus Calmette-Guerin (BCG), an intravesical immunotherapy as the most effective therapy for NMIBC for over four decades, highlights the potential of the inflammatory and immune environments in determining treatment response and prognosis. Given the median age of bladder cancer diagnosis is 73 years, patients are commonly faced with age-related loss of muscle mass (sarcopenia), increase of fat accumulation (obesity), or both (sarcopenic obesity), which are all characterized by chronic inflammation and altered immune responses. These body composition phenotypes are associated with tumor progression and increased mortality. Thus, we hypothesize that body composition at diagnosis may shape the host inflammatory and immune milieu and impact bladder cancer prognosis. This hypothesis will be tested in the Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well; R01 CA172855, MPI: Kwan/Tang/Kushi) of newly diagnosed NMIBC patients from 2015-2019 at Kaiser Permanente, one of the largest prospective cohort studies of NMIBC, with 1,472 patients enrolled with rich patient, clinical, and biospecimen data to examine genetic and lifestyle factors in prognosis and survival. We propose to conduct a full investigation of body composition, inflammation, and immunity in bladder cancer outcomes in Be-Well to determine how adiposity, muscle, and inflammatory and immune biomarkers at diagnosis can identify NMIBC patients at high risk for treatment failure and/or disease recurrence and progression. Our aims are: 1) to determine the association of computed tomography (CT)-derived body composition phenotypes (sarcopenia, adiposity, myosteatosis) with NMIBC recurrence (first and multiple) and progression; 2) to determine the association of body composition with BCG immunotherapy outcomes including adverse events and treatment failure; 3) to examine the association of circulating inflammatory and immune biomarkers with body composition and BCG outcomes and NMIBC prognosis; 4) explore if the addition of body composition measures and inflammatory and immune biomarkers improves the performance of current risk stratification models for NMIBC patients. Given the common clinical use of CT, body composition measures could be readily incorporated into the current clinicopathological factor- based risk stratification system to improve the clinical care of NMIBC.

摘要 膀胱癌是美国十大最常见的癌症之一，也是治疗费用最高的疾病之一 大多数病例（75%）为非肌层浸润性膀胱癌（NMIBC），复发率高（70%）， 进展（25%）。虽然预后因素在很大程度上仍然未知，但卡介苗的成功 (BCG)，膀胱内免疫疗法是四十多年来NMIBC最有效的疗法， 强调了炎症和免疫环境在决定治疗反应方面的潜力， 预后鉴于膀胱癌诊断的中位年龄为73岁，患者通常面临 与年龄相关的肌肉质量损失（肌肉减少症），脂肪积累增加（肥胖症），或两者兼而有之（肌肉减少症 肥胖症），这些疾病的特征都是慢性炎症和免疫应答改变。这些身体 组合物表型与肿瘤进展和增加的死亡率相关。因此，我们假设 诊断时的身体成分可能会影响宿主的炎症和免疫环境， 癌症预后这一假设将在膀胱癌流行病学，健康和生活方式中进行测试。 2015 - 2019年新诊断NMIBC患者的研究（Be-Well; R01 CA172855，MPI：Kwan/Tang/Kushi） 在Kaiser Permanente，NMIBC最大的前瞻性队列研究之一，有1，472名患者入组 丰富的患者，临床和生物标本数据，以检查预后中的遗传和生活方式因素， 生存我们建议对身体成分、炎症和免疫力进行全面调查 在Be-Well的膀胱癌结果中，以确定肥胖、肌肉和炎症以及 诊断时的免疫生物标志物可以鉴定处于治疗失败的高风险的NMIBC患者和/或 疾病复发和进展。我们的目标是：1）确定计算的关联 NMIBC的断层扫描（CT）衍生的身体组成表型（肌肉减少症、肥胖症、肌肉脂肪变性） 复发（首次和多次）和进展; 2）确定身体成分与BCG的相关性 免疫治疗结果，包括不良事件和治疗失败; 3）检查 循环炎症和免疫生物标志物与身体成分和BCG结果和NMIBC 预后; 4）探索是否增加身体成分测量以及炎症和免疫生物标志物 改善了NMIBC患者当前风险分层模型的性能。鉴于常见的临床 使用CT，身体成分测量可以很容易地纳入当前的临床病理因素- 基于危险分层系统，以改善NMIBC的临床护理。