Fewer actionable mutations but higher tumor mutational burden characterizes NSCLC in black patients at an urban academic medical center

Noura J Choudhury; Mansooreh Eghtesad; Sabah Kadri; John Cursio; Lauren Ritterhouse; Jeremy Segal; Aliya Husain; Jyoti D Patel

doi:10.18632/oncotarget.27212

Fewer actionable mutations but higher tumor mutational burden characterizes NSCLC in black patients at an urban academic medical center

Oncotarget. 2019 Oct 8;10(56):5817-5823. doi: 10.18632/oncotarget.27212.

Authors

Noura J Choudhury¹, Mansooreh Eghtesad², Sabah Kadri³, John Cursio⁴, Lauren Ritterhouse⁵, Jeremy Segal⁵, Aliya Husain⁶, Jyoti D Patel¹

Affiliations

¹ Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
² Department of Pathology, Advocate Illinois Masonic Medical Center, Chicago, Illinois, USA.
³ Department of Pathology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
⁴ Department of Public Health Sciences, The University of Chicago, Chicago, Illinois, USA.
⁵ Division of Genomic and Molecular Pathology, Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
⁶ Department of Pathology, The University of Chicago, Chicago, Illinois, USA.

Abstract

Background: Black patients have been historically underrepresented in studies investigating molecular patterns in non-small cell lung cancer (NSCLC). We aimed to investigate differences in actionable mutations among patients at our urban, diverse medical center. Results: 146 patients were included (59 black, 76 white, 7 Asian, 3 Hispanic, 1 mixed). 35 patients had a targetable mutation. Seven black patients (11.8%) had a targetable mutation compared to 28 non-black patients (32.2%, p = 0.005). 15 black patients had PD-L1 expression ≥50% compared to 19 non-black (25.4% vs 21.8%, p = 0.69). Black patients had a higher TMB compared to non-black (15.3 mutations/Mb compared to 11.5 mutations/Mb, p = 0.001). In a multivariate analysis, TMB was driven by smoking (p < 0.01), without any additive interaction in black patients who smoke (p = 0.8). Conclusion: NSCLC tumors from black patients had a higher TMB and were less likely to carry a targetable mutation. The higher TMB seen was driven by a higher prevalence of smoking among black patients in our study, which may not reflect nationwide trends. Our results serve as a proof of concept that differences in molecular markers exist between black and non-black patients, and that these differences may impact the treatment options available to black patients. Methods: Retrospective chart review of patients with a diagnosis of NSCLC who underwent both PD-L1 testing and massively parallel sequencing (UCM-OncoPlus) was conducted. We examined whether high PD-L1 expression, tumor mutational burden (TMB), and presence of targetable mutations (EGFR, BRAF, ERBB2, RET or ALK translocations, ROS1 rearrangements) occur at different frequencies in tumors from black patients compared to non-black patients.

Keywords: biomarkers; healthcare disparities; immunotherapies; non-small cell lung cancer; targeted therapies.