Improving Screening for Second Primary Lung Cancer in High-Risk Veterans

Background: Meeting the unique medical needs of cancer survivors – set to rise from 18 million currently to 26 million in the US by 2040 – presents a growing challenge for the Veterans Affairs (VA) system. Lung cancer, the second most common diagnosis at the VA, is expected to accelerate this growth, driven by increased screening uptake and advances in treatment. Significance: Lung cancer survivors who develop second primary lung cancer, a new cancer distinct from recurrence, experience twice the mortality of those who do not, stressing the need for surveillance protocols for early detection. While established lung cancer risk factors, such as smoking, impact the risk of second cancers, current guidelines on screening for survivors exclude these factors. Lacking clear guidelines, both over- and underscreening may occur. Underscreening may miss early second cancer diagnoses, while overscreening risks radiation exposure and unnecessary biopsies. Screening based on individual risk can minimize harms (false positives) while maximizing benefits (true positives). While we've previously developed and validated a risk prediction model for second primary lung cancer in non-Veterans, the unique risks of Veterans necessitate a new, tailored model. Also, before starting a trial of risk-stratified screening, we need a feasible intervention to ensure that screening effectiveness is not limited by uptake. Here we aim to develop a Veteran-specific risk model and adapt existing risk stratification interventions in initial primary lung cancer screening to second primaries. Innovation & Impact: Our study will be the first to develop and pilot a risk stratification intervention for second primary lung cancer screening in clinic. This work will set the stage for an IIR application for a future multi-site Hybrid III trial, evaluating the implementation and effectiveness of risk-stratified screening on survivor outcomes and ultimately improve survivor mortality. Specific Aims: Aim 1: Develop and validate a Veteran-specific second primary lung cancer risk prediction model and assess its potential benefit over current guideline recommendations. The objective is to develop a comprehensive risk model and evaluate the net benefit of using the risk model to guide screening. Aim 2: Understand key stakeholder perspectives on current screening workflows to inform the future incorporation of risk-stratified screening for survivors. The objective is to identify barriers and facilitators to the proposed risk stratification intervention in current initial and second primary lung cancer screening workflows. Aim 3: Develop and pilot modifications of existing lung cancer screening workflows to optimize screening for Veteran survivors at high risk of second primary lung cancer. Using the risk model from Aim 1 and stakeholder insights from Aim 2, the objective is to develop and pilot a risk-stratification intervention for screening survivors. Methodology: In Aim 1, we will develop a second primary lung cancer risk prediction model using electronic health record data, incorporating known lung cancer risk factors and cancer-specific information from the VA Cancer Registry. We will validate the model and evaluate the impact of risk-stratified screening on the balance between true and false positives (net benefit) compared to current guidelines. In Aim 2, we will interview clinical providers and screening coordinators on A) risk stratified screening for initial primary cancer and B) survivor imaging workflows to adapt initial primary risk stratification interventions to meet survivor needs. In Aim 3, we will design and pilot the risk stratified survivor screening intervention and intervention strategies. We will iteratively adapt our strategies to local needs at each individual pilot site. Upon completing the pilot, we'll interview site staff to assess acceptability and identify strategies to address potential barriers to scaling the intervention. Next Steps/Implementati Project Number: 1IK2HX003949-01A1 | Fiscal Year: 2025 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: Julie Wu | Institution: VA GREATER LOS ANGELES HEALTHCARE SYSTEM, LOS ANGELES, CA | Activity Code: IK2 | Study Section: Research Career Scientist[MRA0] View on NIH RePORTER: https://reporter.nih.gov/project-details/11112851