Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico

Abstract

Targeted therapy has changed the paradigm of advanced NSCLC management by improving the survival rate of patients carrying actionable gene alterations using specific inhibitors. The epidemiologic features of these alterations vary among races. Understanding the racial differences benefits drug development, clinical trial design, and health resource allocation. Compared to Caucasian and Asian populations, current knowledge on Hispanic patients is less and no data of Hispanic patients from Puerto Rico have been reported. We retrieved and analyzed the demographic, clinical, and molecular data of Hispanic NSCLC patients from Puerto Rico with molecular tests performed in the Genoptix Medical Laboratory in Carlsbad, CA, USA between 2011 and 2018. The majority of the NSCLC patients in our study had either adenocarcinoma (75.4%) or squamous cell carcinoma (15.1%). The incidence of EGFR mutations was 24%. They were more common in female and younger patients (<60 years). The deletion of Exon 19 and Exon 21 L858R comprised 55.1% and 31.0% of all EGFR mutations, respectively. The frequency of the T790M mutation was lower compared to that of Hispanic patients reported in the literature (0.5% vs. 2.1%). In addition, 18.7% of the patients were positive for KRAS mutations, which was at the high end of that reported in Hispanic patients. Other driver gene alterations, ALK, MET, RET, ROS1, KRAS, ERBB2, etc., demonstrated similar incidences, as well as gender and age distributions to those previously reported. The KRAS/TP53 and KRAS/STK11 co-mutations were of very low frequencies (3.6%), which could potentially affect the responsiveness to PD1/PD-L1 immunotherapy. Our study demonstrated that the prevalence of NSCLC gene alterations in Hispanic patients from Puerto Rico was comparable to the reported average prevalence in Latin American countries, supporting the intermediate NSCLC gene alteration rate of Hispanic patients between Asian and Caucasian patients. Novel information of the frequencies of KRAS mutation subtypes, driver gene alterations in ROS1, BRAF, and ERBB2, and passenger gene alterations including a rare case with the FGFR2-TACC2 translocation in Hispanic NSCLC patients from Puerto Rico were also described.

Evaluating Real World Mutational Differences Between Hispanics and Asians in NSCLC at a Large Academic Institution in Los Angeles

“…36 , 37 , 40 , 41 In particular, a retrospective analysis of 951 Puerto Rican patients from 2011 to 2018 showed an incidence of 18.7% KRAS mutations along with 3.6% co-mutation with both tumor protein p53 (TP53) and Serine/threonine kinase 11 (STK11). 36 This study also showed a 3.9% ALK rearrangement prevalence rate. Another study involving multiple Latin American countries showed an ALK rearrangement prevalence of 6.8%.…”

An effective prognostic model for assessing prognosis of non-small cell lung cancer with brain metastases

“…As early as 2006, TACC3 was reported as a prognostic marker for NSCLC (Jung et al, 2006). In two independent epidemiological genetic characterization surveys in all locations, the incidence of FGFR-TACC gene fusions was extremely high in NSCLC (Zheng et al, 2020). Survival analysis was an excellent method to verify the validity of model predictions (Han et al, 2021;Jiang et al, 2021).…”

Molecular Biology and Therapeutic Perspectives for K-Ras Mutant Non-Small Cell Lung Cancers

“…Two relevant observations come from analyses of Puerto Rican and Brazilian cohorts [ 49 , 50 ]. In Puerto Rico, lung ACs present with KRAS mutations in 18.7% of the cases, a rate that is significantly higher than in the aforementioned general Hispanic populations [ 48 , 50 ]; in Brazil, 14.6% of lung ACs harbour KRAS mutations, with a higher prevalence in non-Asian patients [ 49 ]: in both populations, c.34G > T (p.G12C) is the most diffused type of alteration.…”