Mutational Portrait of Lung Adenocarcinoma in Brazilian Patients: Past, Present, and Future of Molecular Profiling in the Clinic

Abstract

Objectives: Approximately 60% of lung adenocarcinomas (LAs) carry mutations that can guide treatment with tyrosine-kinase inhibitors (TKI) and other targeted therapies. Data on activating mutations in EGFR and other tyrosine-kinase receptor (TKR) genes in highly admixed populations, such as that of Brazil, are scarce. In this study, we comprehensively analyzed the actionable alteration profile of LA in Brazilian patients. Materials and Methods: EGFR driver mutation data were collected from a large Brazilian LA cohort covering an 8-year period of molecular testing in a single institution. Tests were performed using three distinct methods, and demographic and histopathological data were analyzed. For a subset of patients, driver mutations in KRAS, NRAS, and BRAF and gene fusions involving TKR genes (before TKI treatment) and EGFR T790M (after TKI treatment) were assessed. Results: EGFR mutations were detected in 25% of 1,316 LAs evaluated, with exon 19 deletions and exon 21 L858R TKI sensitizing mutations representing 72.5% of all mutations. Mutation rates were higher in women and non-smokers (p < 0.001). Next-generation sequencing was very sensitive, with a lower rate of inconclusive results compared with Sanger sequencing and pyrosequencing. EGFR/RAS/BRAF hotspot gene panels were applied in 495 LA cases and detected oncogenic mutations in 51.3% of samples, most frequently in EGFR (22.4%) and KRAS (26.9%). In subgroups of 36 and 35 patients, gene fusions were detected in 11.1% of tumors and EGFR T790M resistance mutations were detected in 59% of plasma samples from patients previously treated with TKI, respectively. Conclusion: This report provides the first comprehensive actionable alteration portrait of LA in Brazil. The high rate of actionable alterations in EGFR and other driver genes in LA reinforces the need to incorporate TKI guided by molecular diagnostics into clinical routines for patients in both public and private healthcare systems.

Non–Small-Cell Lung Cancer With CNS Metastasis: Disparities From a Real-World Analysis (GBOT-LACOG 0417)

“…Unfortunately, access, affordability, and incorporation strategies remain relevant challenges in the public health care. 26,27 Because of the relatively high prevalence of occult CNS metastasis in patients with stage III or IV NSCLC, it is suggested that brain MRI should be routinely performed in most cases. In symptomatic patients, brain MRI is the standard test, whereas CT scan is an alternative when MRI is not available.…”

Testing for EGFR Mutations and ALK Rearrangements in Advanced Non-Small-Cell Lung Cancer: Considerations for Countries in Emerging Markets

“…Although no formal surveys exist, an estimated 70% of all AdC NSCLC cases in Brazil undergo molecular testing. 124,162,163 There are no national outcome or survival statistics, as local data collection is variable or simply not performed across several states. In addition, testing practices vary between centers: several laboratories have adopted reflex testing policies, whereas others approach molecular testing as an on-demand service.…”

“…In addition, testing practices vary between centers: several laboratories have adopted reflex testing policies, whereas others approach molecular testing as an on-demand service. Similarly, some laboratories prefer NGS technologies, [162][163][164] sequencing 14-20 genes at one time, 124,162,165 whereas others have adopted strategies to improve TAT by using RT-PCR assays for EGFR and BRAF mutations, 162,[164][165][166] and IHC/FISH for ALK, ROS1 and PD-L1 rearrangements. 163,164,167 In the absence of government reimbursement for molecular testing, several pharmaceutical companies have recently established a national "Lung Mapping" consortium.…”

Predicting EGFR mutation status in lung adenocarcinoma presenting as ground-glass opacity: utilizing radiomics model in clinical translation

“…All extracted features were classified into three categories include (1) first-order features; (2) shape-and size-based features; (3) textural features. Specifically, the textural features were computed based on four kinds of the matrix: 1) gray-level co-occurrence matrix (GLCM), 2)…”

“…[1] In lung adenocarcinoma patients, more than 60% carry driver mutations that could guide treatment strategies and the epidermal growth factor receptor (EGFR) mutation is one of the most frequent genetic alterations among them. [2; 3] EGFR-mutant lung adenocarcinoma patients were proved to be highly sensitive to EGFR-tyrosine kinase inhibitors (TKIs) and achieve significant survival benefit from EGFR-TKIs as the first-line treatment,[4; 5] hence it is much valuable for lung adenocarcinoma patients to confirm the EGFR mutation status in clinical practice, for treatment guidance.…”