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PURPOSETissue inadequacy and operational challenges may limit lung cancer comprehensive biomarker testing. Here, we describe the initial implementation of a tailored tissue molecular journey at Oncoclínicas Precision Medicine Laboratory in Brazil, which includes fast-track (FT) non–next-generation sequencing (NGS) assays combined with a broad NGS panel.METHODSFrom 2021 to 2023, all nonsquamous lung cancer samples eligible for the patient support program “Lung Mapping Consortium” at Oncoclínicas & Co were evaluated using the FT panel (immunohistochemistry for PD-L1 and anaplastic lymphoma kinase [ALK], polymerase chain reaction for EGFR and BRAF, and fluorescence in situ hybridization for ROS1) plus a broad DNA and RNA sequencing panel of 180 genes (custom ARCHER panel).RESULTSFrom 1,272 samples received by the laboratory, 3% had no tissue for any molecular testing, 20% was not eligible for broad NGS panel as per pathologist assessment (tumor purity and quantity), additional 12% did not reach presequencing analytical thresholds (nucleic acid quantity and/or quality), and 3% had postsequencing failure. Most frequent alterations were KRAS mutations (28.4%, KRASG12C 9.7%), EGFR mutations (23.6%, exon20 insertions 2.9%), ALK fusions (6.4%), MET exon 14 skipping (4.4%), ERBB2 mutations (3.4%), ROS1 fusions (3.1%), and BRAFV600E (1.9%). In 35% of the samples, FT non-NGS tests were the only molecular diagnostics: EGFR mutations (14%), ALK fusions (4.4%), ROS1 fusions (1.8%), and BRAFV600E (0.7%). Overall, high PD-L1 expression (≥50%) was found in 12.3%.CONCLUSIONThis study provides data on the molecular epidemiology of lung adenocarcinoma in Brazil, confirming high prevalence of EGFR mutations, ALK fusions, and MET exon 14 skipping alteration. Biomarker detection is largely affected by biospecimen collection and processing, with one third of the patients eligible for non-NGS testing only, which presents reduced coverage and sensitivity for actionable drivers.

INTRODUCTION: Immunotherapy led to increased survival in advanced non-small cell lung cancer; however, it has also increased treatment costs. In this study, real-world data was used to evaluate the average cost of treatment of patients with lung cancer. MATERIAL AND METHODS: This is a retrospective study that extracted patient-level data from a Brazilian Oncology Group database. The inclusion criteria were patients with non-small cell lung cancer from stage I-IV, and that received at least one line of treatment from 2018 to 2019. The primary endpoint was the average cost of treatment according to the disease stage, and secondary endpoints were the average cost of each line of treatment among patients with advanced disease, and the percentage of this amount that was related to immunotherapy acquisition. The study also assessed overall survival and the cost-effectiveness of immunotherapy at first-line versus immunotherapy at second-line or beyond, that was presented as the incremental cost effectiveness ratio per quality-adjusted life years. RESULTS: Fifty patients were included, being four (8%) at early-stage (I and II), 10 (20%) at locally advanced disease (III) and 36 (72%) at advanced-stage (IV). The average costs of treatment for each disease stage were respectively US$30,040, US$52,162, and US$95,607 =0.071). Among patients with advanced disease that received IO, the average cost of the entire treatment was highest with immunotherapy at first line (US$116,623) compared with immunotherapy at second-line (US$112,967) or third-line (US$37,279). Immunotherapy at first-line resulted in an estimated additional 0.26 quality-adjusted life years compared to immunotherapy at second-line (US$19,240). CONCLUSION: The cost of treating non-small cell lung cancer is higher as more advanced is the neoplasm stage at diagnosis. Regarding immunotherapy, the cost of treatment is higher as earlier the treatment is performed, even tough, the cost-effectiveness ratio for first-line treatment seems to be favorable compared to second-line treatment.

PURPOSEThere is a paucity of consistent data concerning genetic mutations in Brazilian patients with lung cancer. The aim of this study was to retrospectively analyze epidermal growth factor receptor (EGFR) mutations detected in a real-world scenario using a large cohort of Brazilian patients with non–small-cell lung cancer (NSCLC).MATERIALS AND METHODSThis was a cross-sectional, observational, descriptive study on the basis of a database of EGFR molecular analysis from tumor samples of patients with a confirmatory histopathological diagnosis of primary lung cancer. Specimens were collected from 2013 to 2017 and were tested using cobas, next-generation sequencing, and Sanger sequencing platforms.RESULTSA total of 7,413 tumor specimens were tested. The patients were predominantly women with a median age of 67.0 years. Patients with at least one mutation represented 24.2% of the total sample. Among the positive patients, the majority had just one mutation, but two or more simultaneous mutations were observed in 1.52% of patients. Exon 19 deletion was the most prevalent alteration in the sample (12.8%), followed by exon 21 L858R (6.9%) and exon 20 insertion (1.6%). All others were considered uncommon mutations and were observed in 18.5% of all mutated patients and 4.0% of the total sample (2.3%-18.7% depending on the sequencing method).CONCLUSIONThis study examined the prevalence of EGFR mutations in Brazilian patients with NSCLC using different technologies, suggesting that the type of method used, directed or nondirected against specific mutations, influences the analysis, particularly for uncommon mutations, which will be missed by mutation-specific approaches such as cobas testing. Our estimates are the largest in Latin America and are consistent with previous reports from other parts of the world. Besides the variability in methods described here as technology incorporation advances in a nonhomogeneous manner, it is probably like the real-world clinical setting Brazilian oncologists face in their daily practice.

Background and Objectives: One of the most frequently mutated oncogenes in cancer belongs to the Ras family of proto-oncogenes, which encode distinct key signaling events. RAS gain-of-function mutations are present in ~30% of all human cancers, with KRAS being the most frequently mutated isoform showing alterations in different cancer types including lung cancer. This study aimed to investigate the incidence of KRAS mutations, and concomitant mutations, in advanced non-small cell lung adenocarcinoma patients. Materials and Methods: This was a retrospective study, where genomic DNA extracted from paraffin-embedded tumor tissues from 121 Brazilian advanced non-small cell lung adenocarcinoma patients were analyzed to evaluate via Next Generation Sequencing (NGS) the incidence of KRAS mutations and co-occurring mutations and correlate, when possible, to clinicopathological characteristics. Statistical analyses were performed to calculate the prevalence of mutations and to investigate the association between mutational status, mutation type, and sex. Results: The results showed a prevalence of male (N = 63; 54.8%) compared to female patients (N = 52, 45.2%), and mutant KRAS was present in 20.86% (24/115) of all samples. Interestingly, 33.3% of the mutant KRAS samples showed other mutations simultaneously. Conclusions: This study revealed the presence of rare KRAS concomitant mutations in advanced lung adenocarcinoma patients. Further investigation on the importance of these genomic alterations in patient prognosis and treatment response is warranted.