Clinical characteristics of EGFR-ctDNA shedders in EGFR-mutant NSCLC patients
Background: Circulating tumor DNA (ctDNA) revolutionized the molecular diagnostics of lung cancer by enabling non-invasive, sensitive identification of actionable mutations. However, ctDNA analysis may be challenging due to tumor shedding variability, leading to false negative results. This study ai...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003541 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832591862614982656 |
|---|---|
| author | Martina Ruglioni Iacopo Petrini Stefania Crucitta Andrea Sbrana Giovanna Irene Luculli Leila Sadeghi Gol Carola Forte Antonio Chella Christian Rolfo Romano Danesi Marzia Del Re |
| author_facet | Martina Ruglioni Iacopo Petrini Stefania Crucitta Andrea Sbrana Giovanna Irene Luculli Leila Sadeghi Gol Carola Forte Antonio Chella Christian Rolfo Romano Danesi Marzia Del Re |
| author_sort | Martina Ruglioni |
| collection | DOAJ |
| description | Background: Circulating tumor DNA (ctDNA) revolutionized the molecular diagnostics of lung cancer by enabling non-invasive, sensitive identification of actionable mutations. However, ctDNA analysis may be challenging due to tumor shedding variability, leading to false negative results. This study aims to understand the determinants for ctDNA shedding based on clinical characteristics of lung cancer patients, for a better interpretation of false negative results to be considered when ordering ctDNA analysis for clinical practice. Methods: Blood samples were collected from patients with stage IV EGFR-mutated (mEGFR) NSCLC before treatment and monitored until disease progression. EGFR was assessed on tissue by standard procedures, while EGFR status on ctDNA was tested using dPCR at baseline and at the first reassessment. NGS was used to evaluate patients mutational status at the progression of the disease. Results: A total of 40 mEGFR tissue samples were collected. Plasma samples were analyzed for mEGFR before starting the first line, 65 % of patients had detectable mEGFR in ctDNA (“shedders”). Higher ECOG PS (p = 0.04), bilateral localization of primary tumor (p = 0.04), and the presence of intrathoracic/extrathoracic disease (p = 0.05), were associated to mEGFR shedding. Shedders had shorter PFS compared to non-shedders (p = 0.03). Patients with detectable mEGFR in ctDNA at the first radiological assessment exhibited worse PFS compared to patients with ctDNA clearance (p = 0.05). Conclusion: Our preliminary data demonstrate that specific clinical characteristics predict mEGFR shedding in ctDNA of NSCLC, suggesting a potential clinical applicability for understanding potential false negative results and appropriate reporting in clinical practice. |
| format | Article |
| id | doaj-art-a8f32e6bba2d4b7f91781e22bc7ed6f3 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-a8f32e6bba2d4b7f91781e22bc7ed6f32025-01-22T05:41:23ZengElsevierTranslational Oncology1936-52332025-02-0152102228Clinical characteristics of EGFR-ctDNA shedders in EGFR-mutant NSCLC patientsMartina Ruglioni0Iacopo Petrini1Stefania Crucitta2Andrea Sbrana3Giovanna Irene Luculli4Leila Sadeghi Gol5Carola Forte6Antonio Chella7Christian Rolfo8Romano Danesi9Marzia Del Re10Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, ItalyUnit of Pneumology, Department of Translational Research and New Technologies in Medicine, University Hospital of Pisa, Pisa, ItalyUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, ItalyUnit of Pneumology, Department of Translational Research and New Technologies in Medicine, University Hospital of Pisa, Pisa, ItalyUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, ItalyUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, ItalyUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, ItalyUnit of Pneumology, Department of Translational Research and New Technologies in Medicine, University Hospital of Pisa, Pisa, ItalyDepartment of Internal Medicine, Division of Medical Oncology, The Arthur G. James Comprehensive Cancer Center, Columbus, OH, USADepartment of Oncology and Hemato-Oncology, University of Milan, Italy; Corresponding author.Saint Camillus International University of Medical and Health Sciences, Rome, Italy; Direzione Scientifica Fondazione Policlinico A. Gemelli IRCCS, Rome, ItalyBackground: Circulating tumor DNA (ctDNA) revolutionized the molecular diagnostics of lung cancer by enabling non-invasive, sensitive identification of actionable mutations. However, ctDNA analysis may be challenging due to tumor shedding variability, leading to false negative results. This study aims to understand the determinants for ctDNA shedding based on clinical characteristics of lung cancer patients, for a better interpretation of false negative results to be considered when ordering ctDNA analysis for clinical practice. Methods: Blood samples were collected from patients with stage IV EGFR-mutated (mEGFR) NSCLC before treatment and monitored until disease progression. EGFR was assessed on tissue by standard procedures, while EGFR status on ctDNA was tested using dPCR at baseline and at the first reassessment. NGS was used to evaluate patients mutational status at the progression of the disease. Results: A total of 40 mEGFR tissue samples were collected. Plasma samples were analyzed for mEGFR before starting the first line, 65 % of patients had detectable mEGFR in ctDNA (“shedders”). Higher ECOG PS (p = 0.04), bilateral localization of primary tumor (p = 0.04), and the presence of intrathoracic/extrathoracic disease (p = 0.05), were associated to mEGFR shedding. Shedders had shorter PFS compared to non-shedders (p = 0.03). Patients with detectable mEGFR in ctDNA at the first radiological assessment exhibited worse PFS compared to patients with ctDNA clearance (p = 0.05). Conclusion: Our preliminary data demonstrate that specific clinical characteristics predict mEGFR shedding in ctDNA of NSCLC, suggesting a potential clinical applicability for understanding potential false negative results and appropriate reporting in clinical practice.http://www.sciencedirect.com/science/article/pii/S1936523324003541Circulating-tumor DNANSCLCTumor sheddingPredictive biomarkersmEGFR |
| spellingShingle | Martina Ruglioni Iacopo Petrini Stefania Crucitta Andrea Sbrana Giovanna Irene Luculli Leila Sadeghi Gol Carola Forte Antonio Chella Christian Rolfo Romano Danesi Marzia Del Re Clinical characteristics of EGFR-ctDNA shedders in EGFR-mutant NSCLC patients Translational Oncology Circulating-tumor DNA NSCLC Tumor shedding Predictive biomarkers mEGFR |
| title | Clinical characteristics of EGFR-ctDNA shedders in EGFR-mutant NSCLC patients |
| title_full | Clinical characteristics of EGFR-ctDNA shedders in EGFR-mutant NSCLC patients |
| title_fullStr | Clinical characteristics of EGFR-ctDNA shedders in EGFR-mutant NSCLC patients |
| title_full_unstemmed | Clinical characteristics of EGFR-ctDNA shedders in EGFR-mutant NSCLC patients |
| title_short | Clinical characteristics of EGFR-ctDNA shedders in EGFR-mutant NSCLC patients |
| title_sort | clinical characteristics of egfr ctdna shedders in egfr mutant nsclc patients |
| topic | Circulating-tumor DNA NSCLC Tumor shedding Predictive biomarkers mEGFR |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003541 |
| work_keys_str_mv | AT martinaruglioni clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients AT iacopopetrini clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients AT stefaniacrucitta clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients AT andreasbrana clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients AT giovannaireneluculli clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients AT leilasadeghigol clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients AT carolaforte clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients AT antoniochella clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients AT christianrolfo clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients AT romanodanesi clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients AT marziadelre clinicalcharacteristicsofegfrctdnasheddersinegfrmutantnsclcpatients |