The Association Between Neighborhood Socioeconomic Status (SES) and Tumor Differentiation in Surgically Resected Non-Small Cell Lung Cancer (NSCLC) Patients

Purpose: Although neighborhood socioeconomic status (SES) is known to impact non-small cell lung cancer (NSCLC) outcomes, it is unclear whether neighborhood SES influences tumor biology in surgically resected NSCLC patients. We evaluated the association between neighborhood SES and tumor differentiation in pathologic stage I-III NSCLC patients who underwent definitive resection.

Methods: We identified NSCLC patients who underwent resection of their primary tumor without neoadjuvant therapy at a comprehensive cancer center between 2013 and 2021. We abstracted patient data from the cancer registry and electronic medical record. Patient residential addresses were geocoded and neighborhood disadvantage scores (0 [least] – 10 [most disadvantaged]) were assigned using the Regional Opportunity Index (ROI): people and place variables, which measure a neighborhood’s educational, economic, housing, transportation, health, and civic assets. Histologic grade was classified in categories: well/moderately differentiated (Grade 1/2) and poorly differentiated/undifferentiated (Grade 3/4). We examined univariate distributions of all covariates and utilized the Pearson Chi-Squared, Wilcoxon Rank Sum, and Fisher’s Exact Tests to examine the bivariate distributions of covariates by tumor grade. We utilized a logistic regression model to estimate the odds of a poorly differentiated tumor based on neighborhood SES, controlling for age at surgery, sex, smoking, race/ethnicity, education, cancer stage, and histology.

Results: One hundred and six patients met criteria and were included in this analysis. Fifty-five patients (52%) identified as female, seventy-one patients (67%) currently or had formally smoked, sixty patients (62%) were non-Hispanic White, eighty-two patients (77%) had Adenocarcinoma, thirty-eight patients (36%) had a poorly or undifferentiated (Grade 3 or 4) tumor, and sixty-four patients (60%) had pathologic stage I disease, while 25% had stage II and 15% had stage III disease. Those with Grade 3/4 tumors were significantly more likely to reside in a low SES neighborhood, compared to patients with Grade 1/2 tumors, defined by ROI people (3.15 vs 2.35, p-value = 0.012) and ROI place (4.32 vs 3.56, p-value = 0.005). In a crude logistic regression, we found that both ROI indices were associated with tumor differentiation. For both ROI: people and ROI: place, each unit increase (i.e., more disadvantaged) was associated with greater risk for poor tumor differentiation (OR = 1.46, 95% CI: 1.10, 1.99; OR = 1.57, 95% CI: 1.12, 2.25). After controlling for confounders, including individual level SES and smoking, both associations persisted (OR = 1.58, 95% CI: 1.05, 2.45; OR = 1.56, 95% CI: 1.03, 2.44).

Conclusion: Adverse neighborhood-level socioeconomic status is associated with increased odds of higher tumor grade among surgically resected NSCLC patients, after controlling for confounding factors such as, race/ethnicity, individual-level SES, and smoking status. Analysis revealed an independent association between neighborhood-level disadvantage and poorly differentiated tumors. These preliminary findings suggest a potential mechanism linking individuals with low SES to worse NSCLC outcomes. Further investigations are warranted to clarify the pathways between neighborhood context and tumor biology.

Identify the source of the funding for this research project: City of Hope Cancer Control and Population Sciences Program Pilot Award, Innovative Health Equity Research Pilot Award from the Beckman Research Institute of City of Hope, NIH Clinical Scientist Institutional Career Development Program Award 5K12CA001727-25