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

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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.