Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study
Abstract Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations. Methods A series of 1282 consecutive Sardinian LAC patie...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | BMC Pulmonary Medicine |
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| Online Access: | https://doi.org/10.1186/s12890-021-01803-0 |
| _version_ | 1819007124402864128 |
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| author | Panagiotis Paliogiannis Maria Colombino Maria Cristina Sini Antonella Manca Milena Casula Grazia Palomba Marina Pisano Valentina Doneddu Angelo Zinellu Davide Santeufemia Sardinian Lung Cancer (SLC) Study Group Giovanni Sotgiu Antonio Cossu Giuseppe Palmieri |
| author_facet | Panagiotis Paliogiannis Maria Colombino Maria Cristina Sini Antonella Manca Milena Casula Grazia Palomba Marina Pisano Valentina Doneddu Angelo Zinellu Davide Santeufemia Sardinian Lung Cancer (SLC) Study Group Giovanni Sotgiu Antonio Cossu Giuseppe Palmieri |
| author_sort | Panagiotis Paliogiannis |
| collection | DOAJ |
| description | Abstract Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations. Methods A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline). Results The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18–21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) agents, had a significantly longer survival in comparison to those without (p < 0.0001); conversely, KRAS mutations were associated with a significantly lower survival (p = 0.0058). Among LAC patients with additional tissue section available for next-generation sequencing (NGS)-based analysis, 26/193 (13.5%) patients found positive for even low-rate EGFR-T790M mutated alleles at baseline were associated with a highly significant lower survival in comparison to those without (8.7 vs. 47.4 months, p < 0.0001). Conclusions In addition to its predictive value for addressing targeted therapy approaches, the assessment of as more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced LAC patients. |
| first_indexed | 2024-12-21T00:19:35Z |
| format | Article |
| id | doaj.art-7029413aa581422290dbd6c1d3035618 |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-12-21T00:19:35Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-7029413aa581422290dbd6c1d30356182022-12-21T19:22:07ZengBMCBMC Pulmonary Medicine1471-24662022-01-012211810.1186/s12890-021-01803-0Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life studyPanagiotis Paliogiannis0Maria Colombino1Maria Cristina Sini2Antonella Manca3Milena Casula4Grazia Palomba5Marina Pisano6Valentina Doneddu7Angelo Zinellu8Davide Santeufemia9Sardinian Lung Cancer (SLC) Study GroupGiovanni Sotgiu10Antonio Cossu11Giuseppe Palmieri12Department of Medical, Surgical and Experimental Sciences, University of SassariUnit of Cancer Genetics, Institute of Biomolecular Chemistry (ICB), National Research Council (CNR)Unit of Cancer Genetics, Institute of Biomolecular Chemistry (ICB), National Research Council (CNR)Unit of Cancer Genetics, Institute of Genetic and Biomedical Research (IRGB), National Research Council (CNR)Unit of Cancer Genetics, Institute of Biomolecular Chemistry (ICB), National Research Council (CNR)Unit of Cancer Genetics, Institute of Biomolecular Chemistry (ICB), National Research Council (CNR)Unit of Cancer Genetics, Institute of Genetic and Biomedical Research (IRGB), National Research Council (CNR)Department of Medical, Surgical and Experimental Sciences, University of SassariDepartment of Biomedical Sciences, University of SassariMedical Oncology, Civil HospitalDepartment of Biomedical Sciences, University of SassariDepartment of Medical, Surgical and Experimental Sciences, University of SassariUnit of Cancer Genetics, Institute of Genetic and Biomedical Research (IRGB), National Research Council (CNR)Abstract Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations. Methods A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline). Results The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18–21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) agents, had a significantly longer survival in comparison to those without (p < 0.0001); conversely, KRAS mutations were associated with a significantly lower survival (p = 0.0058). Among LAC patients with additional tissue section available for next-generation sequencing (NGS)-based analysis, 26/193 (13.5%) patients found positive for even low-rate EGFR-T790M mutated alleles at baseline were associated with a highly significant lower survival in comparison to those without (8.7 vs. 47.4 months, p < 0.0001). Conclusions In addition to its predictive value for addressing targeted therapy approaches, the assessment of as more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced LAC patients.https://doi.org/10.1186/s12890-021-01803-0Lung adenocarcinomaMutation analysisEGFRKRASBRAFALK and MET rearrangements |
| spellingShingle | Panagiotis Paliogiannis Maria Colombino Maria Cristina Sini Antonella Manca Milena Casula Grazia Palomba Marina Pisano Valentina Doneddu Angelo Zinellu Davide Santeufemia Sardinian Lung Cancer (SLC) Study Group Giovanni Sotgiu Antonio Cossu Giuseppe Palmieri Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study BMC Pulmonary Medicine Lung adenocarcinoma Mutation analysis EGFR KRAS BRAF ALK and MET rearrangements |
| title | Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study |
| title_full | Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study |
| title_fullStr | Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study |
| title_full_unstemmed | Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study |
| title_short | Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study |
| title_sort | global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma a real life study |
| topic | Lung adenocarcinoma Mutation analysis EGFR KRAS BRAF ALK and MET rearrangements |
| url | https://doi.org/10.1186/s12890-021-01803-0 |
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