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.

抽象的 膀胱癌是美国十大最常见的癌症之一，也是最昂贵的治疗之一。 大多数病例（75％）是非肌肉侵入性膀胱癌（NMIBC），复发率很高（70％）和 进展（25％）。虽然预后因素在很大程度上尚不清楚，但杆状芽孢杆菌的成功 （BCG），一种静脉免疫疗法，是NMIBC多40多年的最有效疗法， 突出了炎症和免疫环境在确定治疗反应和 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），脂肪积累的增加（肥胖）或两者（肌肉减少症） 肥胖），所有这些都以慢性炎症和免疫反应的改变为特征。这些身体 组成表型与肿瘤进展和死亡率增加有关。因此，我们假设 诊断时的身体成分可能会塑造宿主的炎症和免疫环境并撞击膀胱 癌症的预后。该假设将在膀胱癌的流行病学，健康和生活方式中进行检验 从2015 - 2019年开始研究（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 有了丰富的患者，临床和生物测量数据，以检查预后中的遗传和生活方式因素 生存。我们建议对身体组成，炎症和免疫力进行全面研究 在Be-Well中的膀胱癌预后，以确定肥胖，肌肉和炎症性和 诊断时的免疫生物标志物可以鉴定出患有高治疗失败风险和/或的NMIBC患者 疾病复发和进展。我们的目标是：1）确定计算的关联 与NMIBC 复发（第一和多重）和进展； 2）确定身体成分与BCG的关联 免疫疗法结局，包括不良事件和治疗失败； 3）检查 具有身体成分和BCG结局和NMIBC的循环炎症和免疫生物标志物 预后； 4）探索是否增加身体成分措施以及炎症和免疫生物标志物 改善NMIBC患者当前风险分层模型的性能。鉴于常见的临床 使用CT，可以很容易地将人体组成测量纳入当前的临床病理因素 - 基于风险分层系统，以改善NMIBC的临床护理。