Socioeconomic Disparities in Diagnostic Testing Among Patients with Diffuse Large B-Cell Lymphoma in the US
Authors: Yang Fei , Abraham Anup , Zhang Ju , Xiao Yan , Hammer Richard D. , Doll Donald C. , Prime Matthew S. 
Published: November 2020

Background
A better understanding of diffuse large B-cell lymphoma (DLBCL) subtypes characterized by cell of origin (COO), molecular and immunophenotypic features is associated with more accurate prognosis and may guide treatment selection to achieve better outcomes. Current World Health Organization (WHO) and National Comprehensive Cancer Network (NCCN) guidelines recommend for all patients with DLBCL, immunohistochemistry (IHC, such as Hans algorithm) as a surrogate of gene expression profiling to identify COO, and molecular testing by fluorescence in situ hybridization (FISH) or karyotype to identify molecular/cytogenetic features. Despite advances in treatment and increasing knowledge of clinical importance of DLBCL subtype classification, socioeconomic disparities persist in the treatment of DLBCL in the US (Shenoy PJ, et al. Cancer 2011;117(11):2530-2540) and the use of guideline-recommended diagnostic testing in clinical practice remains unclear. Understanding whether test utilization varies by socioeconomic determinants is important to enable all patients to achieve better/equal access to health care and optimal outcomes.
Methods
To understand guideline-recommended diagnostic testing utilization in real-world settings and to assess socioeconomic disparities in relation to test utilization among patients with DLBCL in the US, this retrospective cohort study leveraged data from the Flatiron Health electronic health record (EHR)-derived de-identified database. Patients above 18 years old with a diagnosis of DLBCL between Jan-2011 and Dec-2019 were included in the study. Information on IHC, FISH and karyotype analysis was abstracted from pathology reports or clinical visit notes, where available. Utilization of guideline-recommended diagnostic testing was defined as patients with documentation of a confirmed known result on: 1) expression of MYC, BCL2, BCL6, CD10 or MUM1 protein for IHC; and 2) rearrangement of oncogene MYC, BCL2 or BCL6 by FISH or karyotype analysis for molecular testing. 'Not tested' was defined as patients with no evidence/documentation of diagnostic testing for all of the aforementioned markers.
Socioeconomic determinants included age, gender, type of insurance plan, race/ethnicity group and geographic location of residency. We assessed changes in rates of IHC and molecular testing during the study follow-up period using Cochran-Armitage trend tests. To assess the impact of socioeconomic determinants on test utilization, multivariable logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for IHC and molecular testing separately, while adjusting for several demographic and clinical characteristics.
Results
In total 5387 patients with DLBCL were included in the study. Guideline-recommended diagnostic testing rates increased between 2011 and 2019 (66.9 to 85.6% for IHC and 49.5 to 67.0% for molecular testing, both P-values &lt;0.001). In the multivariable-adjusted analysis, no association was found between any socioeconomic determinants and test utilization throughout the study follow-up years for IHC. For molecular testing, however, patients who were older (OR: 0.97, 95% CI: 0.96-0.98), female (OR: 0.77, 95% CI: 0.64-0.93), living in the northeast (OR: 0.75, 95% CI: 0.58-0.97) and without an insurance plan (OR: 0.65, 95% CI: 0.51-0.82) had lower odds of having the test, compared to those who were younger, male, living in the south and with a commercial insurance plan. Regarding racial/ethnic perspective, compared to white patients, Asians were more likely to be associated with having molecular testing (OR: 4.06, 95% CI: 1.81-10.84); no association was found for other racial/ethnic groups.
Discussion
Although the results of this study showed a significant increase in the adoption of guideline-recommended diagnostic testing for patients with DLBCL in the US between 2011-2019, socioeconomic disparities appeared to still exist in the access to molecular testing. Providing equitable access to diagnostic testing would be a critical parameter for patients' clinical benefit. It should be noted that findings about test utilization need cautious interpretation, as patients with DLBCL might have been tested but not documented in the EHR or might have the test performed at sites outside of the Flatiron Health network.

Disclosures
Yang: F. Hoffmann-La Roche: Current Employment. Zhang:F. Hoffmann-La Roche: Current Employment. Xiao:F. Hoffmann-La Roche: Current Employment. Hammer:PER Med education: Honoraria; PathEdEx: Current equity holder in private company; Caris Lifesciences: Honoraria; Roche: Consultancy, Honoraria, Research Funding. Prime:F. Hoffmann-La Roche: Current Employment.