Evaluation of genetic, clinical and environmental risk factors to establish effective screening strategies for second primary lung cancer

评估遗传、临床和环境危险因素，建立有效的第二原发性肺癌筛查策略

• 批准号: 10517865
• 负责人: Summer S Han
• 金额: $ 64.85万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10517865
• 关键词: Address; Adoption; Assessment tool; Behavioral; Calibration; Cancer Etiology; Cancer Patient; Cancer Survivor; Cessation of life; Characteristics; Clinical; Cohort Studies; Colorectal; Consensus; Consensus Development; Cost Savings; Data; Diagnosis; Environmental Risk Factor; Evaluation; Exclusion; Genetic; Genetic Risk; Goals; Healthcare Systems; Individual; Life; Long-Term Survivors; Lung; Malignant neoplasm of lung; Measures; Medical History; Meta-Analysis; Modeling; Morbidity - disease rate; Ovarian; Parents; Patients; Performance; Pharmacotherapy; Population; Predictive Cancer Model; Preventive measure; Prospective, cohort study; Prostate; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Public Health; Risk; Risk Assessment; Risk Factors; Role; Sample Size; Smoker; Smoking; Smoking History; Survivors; Time; Translating; Uncertainty; Update; Validation; biobank; cancer risk; clinical risk; cohort; computed tomography screening; follow-up; hazard; high risk; improved; low dose computed tomography; lung cancer screening; models and simulation; mortality; multi-ethnic; parent grant; predictive modeling; programs; risk prediction model; screening; screening guidelines; smoking cessation; standard of care; tool; tumor

Lung cancer (LC) is the leading cause of cancer deaths in the U.S. The widespread adoption of low dose computed tomography (LDCT) screening enables the early detection of LC and is expected to increase the number of long-term LC survivors. While recent studies show that LC survivors have a high risk of developing second primary lung cancer (SPLC), no consensus screening guidelines exist for SPLC among LC survivors. The long-term goal of the parent R37 is to reduce the overall LC mortality in the U.S. by focusing on SPLC. The overall objectives of the parent R37 are (i) to identify the genetic, clinical, and environmental determinants for SPLC, (ii) to assess an individual’s risk of SPLC, and (iii) to evaluate efficient LDCT screening strategies for SPLC for LC survivors. During Years 1- 3 of the parent R37 study, we made substantial progress in achieving these objectives. We developed a risk prediction model for SPLC that incorporates smoking history (measured before IPLC diagnosis), IPLC tumor characteristics, and medical history that is implemented in an open access application, called Second Primary Lung Cancer Risk Assessment Tool (SPLC-RAT). Despite this progress, we observed several major challenges, including the lack of validation of SPLC-RAT using diverse LC patients including heavy smokers and long-term LC survivors. Another major challenge is how to incorporate smoking behavioral changes after IPLC diagnosis (e.g., smoking cessation) into risk-assessment of SPLC. To address these major challenges from the existing R37 study, our aims of this extension R37 study are: (AIM 1) To validate SPLC-RAT using diverse LC patients with a wide range of smoking histories and to re-calibrate the parameters of SPLC-RAT for long-term survivors; (AIM 2) To determine the impact of smoking cessation after IPLC diagnosis on SPLC risk and LC mortality; (AIM 3) To evaluate optimal LDCT screening strategies for SPLC that integrates smoking cessation programs for LC survivors. We will extend a microsimulation model for risk-based LDCT screening for SPLC that integrates smoking cessation programs (e.g., pharmacotherapy) for LC survivors. This proposed extension study is within scope of the parent R37 because these aims are a logical extension of the parent grant (i) by validating and refining the existing SPLC prediction model using more comprehensive data and (ii) by incorporating the temporal changes of the key risk factors (e.g., smoking) for SPLC. We expect that adding these aims will help improve the existing prediction model for SPLC and help understand the role of smoking cessation on SPLC risk and LC mortality. By completing this extension study, we expect to provide a set of optimal screening strategies for SPLC by evaluating the potential harms and benefits of screening under various strategies combined with smoking cessation programs. These results will reduce clinician and patient uncertainty about the potential role of screening and smoking cessation in LC survivors, and thus will likely translate into increased implementation of this life-saving preventive measure.

肺癌（LC）是美国癌症死亡的主要原因。 计算机断层扫描（LDCT）筛查能够早期发现LC，并有望增加 LC长期存活者的数量。虽然最近的研究表明，LC幸存者有很高的风险发展 第二原发性肺癌（SPLC），没有共识的筛选指南存在SPLC中LC幸存者。 母公司R37的长期目标是通过专注于SPLC来降低美国的总体LC死亡率。的 亲本R37的总体目标是：（i）确定遗传、临床和环境决定因素， SPLC，（ii）评估个体的SPLC风险，以及（iii）评估有效的LDCT筛查策略， LC幸存者的SPLC。在母研究R37的第1- 3年，我们在以下方面取得了实质性进展： 这些目标。我们开发了一个SPLC的风险预测模型，该模型结合了吸烟史（测量 IPLC诊断前）、IPLC肿瘤特征和病史， 第二原发性肺癌风险评估工具（SPLC-RAT）。尽管取得了这些进展，但我们 观察到几个主要挑战，包括缺乏使用不同LC患者的SPLC-RAT验证 包括重度吸烟者和长期LC幸存者。另一个主要挑战是如何将吸烟 IPLC诊断后的行为变化（例如，戒烟）纳入SPLC的风险评估。解决 这些主要挑战来自现有的R37研究，我们的目的是扩大R37研究：（目的1）为了验证 SPLC-RAT使用具有广泛吸烟史的不同LC患者并重新校准参数 SPLC-RAT的长期存活者;（目的2）确定IPLC诊断后戒烟的影响 SPLC风险和LC死亡率;（目的3）评估SPLC的最佳LDCT筛查策略， 为LC幸存者提供戒烟计划。我们将扩展基于风险的LDCT微观仿真模型 筛查整合戒烟计划的SPLC（例如，药物治疗）。这 拟议的扩展研究在母R37的范围内，因为这些目标是 （i）通过使用更全面的数据验证和改进现有的SPLC预测模型， 以及（ii）通过纳入关键风险因素的时间变化（例如，吸烟）。我们预计 增加这些目标将有助于改进现有的SPLC预测模型，并有助于理解 戒烟对SPLC风险和LC死亡率的影响。通过完成这项扩展研究，我们希望提供一个 通过评估SPLC筛查的潜在危害和益处， 各种策略结合戒烟计划。这些结果将减少临床医生和患者 筛查和戒烟在LC幸存者中的潜在作用的不确定性，因此可能 转化为加强执行这一拯救生命的预防措施。

项目成果

Response to Letter to the Editor: Caution Needed for Analyzing the Risks of Second Cancers.

对给编辑的信的回应：分析第二种癌症的风险需要谨慎。

• DOI: 10.1016/j.jtho.2018.05.007
• 发表时间: 2018
• 期刊: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
• 作者: Wozniak,AntoinetteJ;Schwartz,AnnG
• 通讯作者: Schwartz,AnnG

Second Primary Lung Cancer Among Lung Cancer Survivors Who Never Smoked.

• DOI: 10.1001/jamanetworkopen.2023.43278
• 发表时间: 2023-11-01
• 期刊: JAMA NETWORK OPEN
• 影响因子: 13.8
• 作者: Choi, Eunji;Su, Chloe C.;Wu, Julie T.;Aredo, Jacqueline V.;Neal, Joel W.;Leung, Ann N.;Backhus, Leah M.;Lui, Natalie S.;Le Marchand, Loic;Stram, Daniel O.;Liang, Su-Ying;Cheng, Iona;Wakelee, Heather A.;Han, Summer S.
• 通讯作者: Han, Summer S.

Overall Survival Among Patients With De Novo Stage IV Metastatic and Distant Metastatic Recurrent Non-Small Cell Lung Cancer.

• DOI: 10.1001/jamanetworkopen.2023.35813
• 发表时间: 2023-09-05
• 期刊: JAMA NETWORK OPEN
• 影响因子: 13.8
• 作者: Su, Chloe C.;Wu, Julie T.;Choi, Eunji;Myall, Nathaniel J.;Neal, Joel W.;Kurian, Allison W.;Stehr, Henning;Wood, Douglas;Henry, Solomon M.;Backhus, Leah M.;Leung, Ann N.;Wakelee, Heather A.;Han, Summer S.
• 通讯作者: Han, Summer S.

Risk Model-Based Lung Cancer Screening and Racial and Ethnic Disparities in the US.

• DOI: 10.1001/jamaoncol.2023.4447
• 发表时间: 2023-12-01
• 期刊: JAMA ONCOLOGY
• 影响因子: 28.4
• 作者: Choi, Eunji;Ding, Victoria Y.;Luo, Sophia J.;ten Haaf, Kevin;Wu, Julie T.;Aredo, Jacqueline V.;Wilkens, Lynne R.;Freedman, Neal D.;Backhus, Leah M.;Leung, Ann N.;Meza, Rafael;Lui, Natalie S.;Haiman, Christopher A.;Park, Sung-Shim Lani;Le Marchand, Loic;Neal, Joel W.;Cheng, Iona;Wakelee, Heather A.;Tammemaegi, Martin C.;Han, Summer S.
• 通讯作者: Han, Summer S.

Software Application Profile: dynamicLM-a tool for performing dynamic risk prediction using a landmark supermodel for survival data under competing risks.

• DOI: 10.1093/ije/dyad122
• 发表时间: 2023-12-25
• 期刊: INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
• 影响因子: 7.7
• 作者: Fries, Anya H.;Choi, Eunji;Wu, Julie T.;Lee, Justin H.;Ding, Victoria Y.;Huang, Robert J.;Liang, Su-Ying;Wakelee, Heather A.;Wilkens, Lynne R.;Cheng, Iona;Han, Summer S.
• 通讯作者: Han, Summer S.