Oncotarget

Research Papers:

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 and Jyoti D. Patel _

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Oncotarget. 2019; 10:5817-5823. https://doi.org/10.18632/oncotarget.27212

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Abstract

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

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

Correspondence to:

Jyoti D. Patel,email: jpatel25@medicine.bsd.uchicago.edu

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

Received: June 19, 2019     Accepted: August 27, 2019     Published: October 08, 2019

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.


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