Health Equity and Inclusiveness Junior Investigator Award

Anti–PD-1 therapy has transformed the management of NSCLC, but only a subset of patients respond to anti–PD-1 therapy, and responses are rarely curative. Understanding the effects of anti–PD-1 therapy on the composition and functional state of tumor-associated immune subsets can identify mechanisms of response and resistance to anti–PD-1 therapy and provide insights into rational combination strategies to improve upon response rates. Although the effects of anti–PD-1 therapy within the tumor immune microenvironment in preclinical and human subjects have been previously reported, we propose to broadly characterize the effects of anti–PD-1 therapy on the tumor draining lymph nodes (TDLN). Studying the TDLN is particularly valuable because it is the primary sites at which the tumor antigen exposure and the main site of immune T-cell differentiation. To determine the effect of ICI response in the lymph node, we have created an immunocompetent murine model that recapitulates early-stage treatment and outcomes in patients. Additionally, we have characterized TDLN T cells from early-stage cancer patients and have been able to recapitulate our preclinical findings of unique memory T-cell subsets. Our preliminary results of the immune cell type composition, checkpoint expression, and cytokine expression within TDLNs suggest that there are major remodeling events within the TDLN mediated by anti–PD-1 therapy that are critical for conferring effective antitumor long-term immune responses. We demonstrate that unique memory T cell subsets undergo significant activation, expansion, and maturation in response to anti–PD-1 therapy, to shape antitumor programming in TDLNs. Importantly, our proposed study will provide a methodological demonstration in both a murine model and human TDLN that simultaneous uses Flowcytometry, functional immune assays and single cell sequencing that will enable deep interrogation of the immune profile to PD-1 inhibition resistant and responsive patients.

Despite significant progress in the development of novel biomarkers and therapies for lung cancer, such progress has not equitably benefitted all population groups in the United States (US). Racial and ethnic minorities, low income, uninsured, and underinsured individuals with non-small cell lung cancer (NSCLC) continue to experience disparate access to diagnostics tests and treatments, and experience inferior outcomes. These disparities are, at least, partially driven by social context (i.e., social determinants of health). Patients with NSCLC experience high rates of financial hardship and unmet supportive needs, making them a population likely to have high rates of health-related social needs. The prevalence of social needs in patients with NSCLC and their impact on healthcare utilization, cancer outcomes, and quality of life (QOL) remains unknown. To fill this important knowledge gap, we propose an observational, prospective cohort study of 150 patients with unresectable lung cancer receiving first-line systemic therapy. Our study has two primary goals (Aims): 1) Prospectively quantify the prevalence of social needs and determine the associations between social needs, acute care utilization, and QOL; 2) investigate how patient’s social needs influence oncology providers’ clinical decisions for outpatient cancer care of adults with unresectable NSCLC. To achieve these goals, we will conduct serial survey assessments of 150 patients with unresectable NSCLC and conduct semi-structured interviews with 30 oncology providers. This study is significant as it is the first study longitudinally evaluating social needs during cancer therapy in patients with NSCLC. This study will fill a key knowledge gap and inform interventions focused on identifying and supporting patients at risk of social adversity during cancer treatment.

Hispanics/LatinX comprise the largest-growing minority group in the United States (U.S.). They account for 18.5% of the total U.S. population1 and are projected to become the largest group in the U.S. by 2045, surpassing NHW. Despite large national representation in the U.S., data demonstrates that this population faces barriers to healthcare access. These barriers are often due, but not limited to socioeconomic status, lack of health insurance, limited medical literacy, language barriers, structural racism, and perceived discrimination. Studies show that Hispanics/LatinX have the highest uninsured rates compared to any other ethnic/racial group, thus limiting their ability to receive equitable health care. This lack of equitable care often leads to Hispanics/LatinX forgoing or delaying medical care, avoiding screening, placing them at elevated risk of an advanced stage of cancer diagnosis. Unlike NHW, cancer remains the most common cause of death in the Hispanic/LatinX population.

LC is the leading cause of cancer-related death for Hispanic/LatinX men and the second most common cause of death for Hispanic/LatinX women. LC carries a 5-year overall survival rate of less than 20%, mainly due to advance stage at diagnosis. Survival rates are even lower for Hispanics/LatinX (13% vs 17%), who are more likely to be diagnosed at advanced stages of LC than their NHW counterparts (59% vs 52%). To increase the rates of early detection, different organizations have supported the use of LDCT as a screening modality in eligible individuals, after results from the NLST showed a 20% mortality reduction in LC with the use of LDCT for screening. Currently, The U.S. Preventive Services Task Force (USPSTF) recommends annual screening for LC in adults 50–80 years of age with at least a 20-pack year smoking history who are current smokers or have quit within the last 15 years. This criterion was extrapolated from the high-risk features in subjects that participated in the NLST that ultimately led to the LC screening recommendations. Unfortunately, the population in the NLST is not an accurate representation of the U.S population, as 95% of the participants were white and only 1.8% were Hispanics. Additionally, studies have shown that LatinX individuals are less aware of LC screening than NHW, but when informed, they are more LatinX interested in pursuing screening (90.7%) compared with non-LatinX (67%).

Besides tobacco use, having a previous malignancy is a risk factor for LC. HNC survivors are at increased
risk of second primary lung cancer compared to the general population, largely due to their heavy smoking history. Patients with tobacco related HNC have up to a 13% risk of developing second primary LC. Currently, the guidelines recommend performing a 3-month post treatment for subjects with head and neck malignancies treated with curative intent. However, NCCN does not advise performing imaging surveillance beyond 6 months in this patient population, unless there are signs and/or symptoms to suggest cancer recurrence. In reference to LC screening, The NCCN recommends annual screening with LDCT for HNC survivors with a smoking history of 20 pack years or more. However, no prospective studies have been performed to assess the risk of second primary LC in this high-risk population. Of the few studies that have been completed, one study completed a post hoc secondary analysis of the NLST to evaluate the incidence of second primary lung cancer in HNC survivors screened with low dose CT (LDCT) versus chest x-ray (CXR). Out of X participants, 171 HNC survivors had undergone screening. Of these, 90.1% identified as White, 4.1% as Black, and 0% as Hispanic or LatinX and lung cancer was identified in 20 (12%) of the HNC survivors screened. A total of 15% (12/82) and 9% (8/89) of the HNC survivors screened with LDCT and CXR, respectively, were diagnosed with LC. The study found a higher LC incidence in HNC survivors compared to participants without head and neck cancer, with an adjusted rate ratio of 2.54 (95% CI, 1.63-3.95). Additionally, the study found an average smoking history of 80 pack years amongst HNC survivors compared to 48 pack years in the rest of the study population.

The study proposed here will fill an important gap and assess the awareness and eligibility of lung cancer
screening in Hispanic/LatinX HNC survivors via a survey questionnaire and understand the barriers to
screening via qualitative interviews. We will create the first lung cancer screening program tailored for and focused exclusively on Hispanic/LatinX HNC survivors.

Background: In recent years, an increasing incidence of lung cancer among young patients (<50 years) has been reported in Europe, Asia, and the United States. Young patients with lung cancer are more likely to be women, of Asian or Hispanic descent, have adenocarcinoma histology, and are more likely to present with distant metastases at diagnosis. Although young patients with lung cancer are more likely to be diagnosed at a disruptive time in their lives and face greater mental health and financial challenges than older patients with lung cancer, we lack data regarding their specific psychosocial needs. The lack of inclusion of young patients in survivorship studies has created a knowledge gap that we propose to remedy with the proposed study.

Aim and Hypothesis: The overarching aim of this study is to define the psychosocial needs of young patients with lung cancer and evaluate important cancer care delivery factors, including financial toxicity, gender and racial differences and study participants’ experiences with the healthcare system. We hypothesize that young patients will have greater unmet psychosocial needs and financial toxicity than older patients with lung cancer.

Methods: This study will utilize an expert, multi-disciplinary research team aligned with patient advocates to deploy an explanatory sequential mixed methods design to understand the needs of young patients with lung cancer. We will conduct a cross-sectional two-arm survey regarding psychosocial distress and financial toxicity among a diverse patient population utilizing two validated questionnaires, the Psychosocial Screen for Cancer (PSSCAN-R) questionnaire and the COmprehensive Score for financial Toxicity (COST) assessment. After the quantitative data collection is completed, we will conduct a preliminary analysis that will guide the discussion in the next phase, where we will conduct four focus groups with young patients with lung cancer to expand and obtain in-depth answers about the issues discovered in the survey portion of the study. The study team will collaborate with experienced biostatisticians and qualitative data researchers to conduct the appropriate statistical analysis.

Results and Dissemination Plan: The study results will be submitted to an international conference and later be published in a high-impact journal. In addition, we will disseminate the study results to the lung cancer patient community via a series of webinars; these webinars will be recorded and later shared with patient advocacy groups and lung cancer organizations.

Long-term Outcomes: Our data will yield insights to inform the oncology community of the barriers encountered by young patients with lung cancer and will allow us to develop the first clinical and research program for young patients with lung cancer in the nation.

Background: Patients with NSCLC whose tumors harbor a targetable molecular alteration have improved outcomes when they receive targeted therapy. Historically, targetable alterations have been associated with specific patient characteristics such as female gender, young age, non-smokers, and Asians. Given this association, patients with characteristics not commonly associated with targetable mutations do not always receive timely and complete molecular testing. We hypothesize that male gender, age >65, history of smoking, African American race and Hispanic ethnicity will be independently associated with delayed detection and treatment of a targetable alteration. We will evaluate the impact of delayed targeted therapy on overall survival and brain metastasis development.

Methods: We will perform a retrospective cohort study of approximately 2200 patients with EGFR, ALK or ROS1 targetable alterations obtained through multi-institution retrospective chart review. Multivariate logistic regression will be used to evaluate the association of patient characteristics with complete molecular testing prior to first-line therapy, targeted therapy as first-line therapy, and development of brain metastases. Kaplan-Meier methodology will be used to estimate median overall survival. The log rank test will be used to compare median overall survivals. Multivariate Cox Regression will further evaluate interactions between delayed targeted therapy and patient characteristics as well as help control for potential confounders.

Importance: This will be the first study to evaluate the impact of delayed detection and delayed treatment of driver mutations in NSCLC. This information is critical to designing interventions to improve outcomes in patient groups with characteristics not usually associated with driver mutations.

A common source of lung cancer morbidity is presented by incidental pulmonary nodules (IPNs), which can represent missed cancers when incompletely followed. Underrepresented patients are particularly at risk of guidelines discordant care. Our institution cares for a large proportion of these minority communities. We therefore propose to develop a comprehensive program for the identification, risk stratification and management of IPNs identified through imaging in the emergency setting. We first seek to incorporate lung nodule detection and management software into our electronic medical record (EMR). To facilitate recognition of nodules, we will utilize natural language processing to screen and flag imaging. A multidisciplinary ensemble of practitioners will validate findings and participate in management. At the crux of this team will be a patient navigator to communicate with patients and assist in follow-up. We next seek to create an IPN risk prediction algorithm. Clinical and radiographic elements from the EMR will be subjected to artificial intelligence-based review to automatically leverage data towards a machine learning-derived algorithm. The final element of our proposal will investigate a blood-based gene expression assay as a marker for malignancy. Following its evaluation using a cohort of biobanked samples, we will apply this RNA-based detection assay to look for markers of malignancy to facilitate the early detection of lung cancers. We ultimately seek to improve lung cancer care within our largely underserved population through a combination of incorporating patients with IPNs into the health care system and providing appropriate and automated risk stratification to expedite care and diagnosis.