Data documento
02/05/2024

Título
ERBB2 exon 20 insertions are rare in Brazilian non-small cell lung cancer

Autor(es)
Cavagna, R.O. - Zaniolo, B. G. - Paula, F.E. - Berardinelli, G.N. - Santana, I. - Silva, E.C.A. - Dias, J. M. - Jacinto, A.A. - Oliveira, R.E.N.N. - Marchi, P. - Leal, L.F. - Reis, R.M.

Palavras chave
Brazil - ERBB2 - exon 20 insertions - non-small cell lung cancer

Resumo
ERBB2 exon 20 insertions may impact the clinical management of lung cancer patients. However, the frequency of ERBB2 exon 20 insertions in lung cancer patients in Brazil is scarce. Here, we analyzed 722 Brazilian non-small cell lung cancer (NSCLC) patients from Barretos Cancer Hospital that were indicated to require routine lung cancer molecular testing. ERBB2 exon 20 insertions were evaluated by a targeted panel using next-generation sequencing (NGS). Clinicopathological and molecular data were collected from patient medical records. Among the 722 NSCLC patients, 85.2% had lung adenocarcinomas, 53.9% were male, 66.8% were quitter or current smokers, and 63.2% were diagnosed at an advanced stage of the disease. We identified 0.8% (6/722) of patients who harbored the insertion p. (Tyr772_Ala775dup) at exon 20 of the ERBB2 gene. All ERBB2 mutated patients were diagnosed with lung adenocarcinoma, were never smokers, and wild-type for EGFR, KRAS, and ALK hotspot alterations. Less than 1% of Brazilian NSCLC patients harbor ERBB2 exon 20 insertions, yet they could benefit in future from the new drugs in development.

Citação
de Oliveira Cavagna R, Zaniolo BG, de Paula FE, Berardinelli GN, Santana I, da Silva ECA, Dias JM, Jacinto AA, da Nóbrega Oliveira REN, de Marchi P, Leal LF, Reis RM. ERBB2 exon 20 insertions are rare in Brazilian non-small cell lung cancer. Thorac Cancer. 2022 Dec;13(23):3402-3407. doi: 10.1111/1759-7714.14605. Epub 2022 Oct 17. PMID: 36251951; PMCID: PMC9715798.

Data documento
18/10/2024

Título
Gene expression profiles (GEPs) of immuno-oncologic pathways as predictors of response to checkpoint inhibitors in advanced NSCLC

Autor(es)
Pedro De Marchi - Leticia Ferro Leal - Luciane Sussuchi da Silva - Rodrigo de Oliveira Cavagna - Flavio Augusto Ferreira da Silva - Vinicius Duval da Silva - Eduardo Ca da Silva - Augusto O Saito - Vladmir C Cordeiro de Lima - Rui Manuel Reis.

Palavras chave
GEP; Gama interferon; Immunotherapy; Lung-tumor signature; NSCLC; Non-small cell lung cancer; PD-L1; TIS; anti-CTLA-4; anti-PD-(L)1; gene expression profile.

Resumo
Background: Immune checkpoint inhibitors (ICIs) revolutionized non-small-cell lung cancer (NSCLC) treatment. However, improving patients selection for this therapy is needed. Gene expression profile (GEP) is a promising biomarker tool. We assessed the predictive value of 48 onco-immune GEPs in an NSCLC real-world scenario. Methods: Retrospective cohort of Brazilian NSCLC patients treated with ICIs in any line. GEP was assessed in FFPE tumor tissue using the nCounter PanCancer IO360 panel, comprising 770 cancer immune genes. Results: The median age of the 135 patients was 61 years old, most male (57.8 %), history of smoking (83.6 %), ECOG-PS 0-1 (88.7 %), clinical stage IV (91.9 %) and adenocarcinoma (65.1 %). First-line ICI in 40 % of cases, alone or in combination with chemotherapy. The median follow-up was 28 months, overall survival after starting immunotherapy (post-immunotherapy survival - PIS) was 17.8 months, and real-world progression-free survival was 5.5 months. The GEP analysis was possible in 66 patients. We found that 14 different GEPs associated with PIS, namely IDO1, PD-L2, Cytotoxicity, Cytotoxic Cells, IFN Downstream, CTLA4, PD-L1, TIGIT, Lymphoid, Immunoproteasome, Exhausted CD8, IFN Gamma, TIS and APM. TIS and IFN-γ were the most significant GEPs associated with favorable outcomes. The median PIS for patients with high TIS expression was 29.2 versus 15.5 months (HR 0.42; 95 %CI; 0.17-0.67; p<0.05) for those with low expression. Similar results were observed for IFN-γ. Conclusions: The TIS (tumor inflammation signature) and IFN-γ signatures constitute predictive biomarkers to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

Citação
Gene expression profiles (GEPs) of immuno-oncologic pathways as predictors of response to checkpoint inhibitors in advanced NSCLC. De Marchi P, Leal LF, da Silva LS, Cavagna RO, da Silva FAF, da Silva VD, da Silva EC, Saito AO, de Lima VCC, Reis RM.Transl Oncol. 2024 Jan;39:101818. doi: 10.1016/j.tranon.2023.101818. Epub 2023 Oct 31.PMID: 37918166

Data documento
03/05/2024

Título
Liquid Biopsy for Lung Cancer: Up-to-Date and Perspectives for Screening Programs

Autor(es)
Casagrande GMS, - Silva MO, - Reis RM, - Leal LF.

Palavras chave
biomarkers - liquid biopsy - lung cancer - precision medicine

Resumo
Lung cancer is the deadliest cancer worldwide. Tissue biopsy is currently employed for the diagnosis and molecular stratification of lung cancer. Liquid biopsy is a minimally invasive approach to determine biomarkers from body fluids, such as blood, urine, sputum, and saliva. Tumor cells release cfDNA, ctDNA, exosomes, miRNAs, circRNAs, CTCs, and DNA methylated fragments, among others, which can be successfully used as biomarkers for diagnosis, prognosis, and prediction of treatment response. Predictive biomarkers are well-established for managing lung cancer, and liquid biopsy options have emerged in the last few years. Currently, detecting EGFR p.(Tyr790Met) mutation in plasma samples from lung cancer patients has been used for predicting response and monitoring tyrosine kinase inhibitors (TKi)-treated patients with lung cancer. In addition, many efforts continue to bring more sensitive technologies to improve the detection of clinically relevant biomarkers for lung cancer. Moreover, liquid biopsy can dramatically decrease the turnaround time for laboratory reports, accelerating the beginning of treatment and improving the overall survival of lung cancer patients. Herein, we summarized all available and emerging approaches of liquid biopsy-techniques, molecules, and sample type-for lung cancer.

Citação
Casagrande GMS, Silva MO, Reis RM, Leal LF. Liquid Biopsy for Lung Cancer: Up-to-Date and Perspectives for Screening Programs. Int J Mol Sci. 2023 Jan 28;24(3):2505. doi: 10.3390/ijms24032505. PMID: 36768828; PMCID: PMC9917347.