Clinical Significance of Perioperative Minimal Residual Disease Detected by Circulating Tumor DNA in Patients With Lung Cancer With a Long Follow-up Data: An Exploratory Study
Introduction: Molecular residual disease detected by circulating tumor DNA (ctDNA) has been reported to be predictive of patients’ outcomes in various types of cancers after curative intent treatment. Nevertheless, additional detailed information regarding the association of longitudinal ctDNA detec...
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Elsevier
2025-03-01
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| author | Shuta Ohara, MD, PhD Kenichi Suda, MD, PhD Sumedha Sudhaman, PhD Akira Hamada, MD, PhD Masato Chiba, MD, PhD Masaki Shimoji, MD, PhD Toshiki Takemoto, MD, PhD Ekaterina Kalashnikova, PhD Samantha K. Cheung, PhD Michael Krainock, MD, PhD Jordan Feeney, BS Himanshu Sethi, MPH Minetta C. Liu, MD Junichi Soh, MD, PhD Yasuhiro Tsutani, MD, PhD Tetsuya Mitsudomi, MD, PhD |
| author_facet | Shuta Ohara, MD, PhD Kenichi Suda, MD, PhD Sumedha Sudhaman, PhD Akira Hamada, MD, PhD Masato Chiba, MD, PhD Masaki Shimoji, MD, PhD Toshiki Takemoto, MD, PhD Ekaterina Kalashnikova, PhD Samantha K. Cheung, PhD Michael Krainock, MD, PhD Jordan Feeney, BS Himanshu Sethi, MPH Minetta C. Liu, MD Junichi Soh, MD, PhD Yasuhiro Tsutani, MD, PhD Tetsuya Mitsudomi, MD, PhD |
| author_sort | Shuta Ohara, MD, PhD |
| collection | DOAJ |
| description | Introduction: Molecular residual disease detected by circulating tumor DNA (ctDNA) has been reported to be predictive of patients’ outcomes in various types of cancers after curative intent treatment. Nevertheless, additional detailed information regarding the association of longitudinal ctDNA detection with long-term follow-up in lung cancer is needed. Here, we report on a cohort of patients with NSCLC who underwent definitive surgery and ctDNA analysis in the pre-operative, adjuvant, and surveillance settings. Method: Plasma samples were collected from 46 patients with clinical stage II-III NSCLC before surgery (n = 46), after surgery (n = 45), and every six months until two years thereafter (n = 78). A clinically validated, personalized, tumor-informed 16-plex polymerase chain reaction–next-generation sequencing assay was used for the detection and quantification of ctDNA in retrospectively analyzed plasma samples. Results: Circulating tumor DNA was detected in the first postoperative (within 51 days after surgery) plasma samples in 13% (6/45) of patients (landmark analysis). All of them had disease recurrence within a median of 9.1 months. These patients had shorter recurrence-free and overall survivals than those without detectable ctDNA at a landmark time point (p < 0.01) and in multivariate analyses (p < 0.03). Longitudinally (considering all postoperative follow-up time points), ctDNA was detected in 13 patients, all of whom experienced disease recurrence (positive predictive value = 100%). Three patients who had central nervous system–only metastases did not have detectable ctDNA. Conclusions: The presence of ctDNA post-surgery or during surveillance identifies patients with NSCLC at high risk of recurrence. Serial testing is important to detect disease recurrence earlier (lead-time: 3.2 months). |
| format | Article |
| id | doaj-art-458ada9aa9934c089fa2a69cbc4bc95e |
| institution | Kabale University |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | JTO Clinical and Research Reports |
| spelling | doaj-art-458ada9aa9934c089fa2a69cbc4bc95e2025-02-06T05:12:51ZengElsevierJTO Clinical and Research Reports2666-36432025-03-0163100762Clinical Significance of Perioperative Minimal Residual Disease Detected by Circulating Tumor DNA in Patients With Lung Cancer With a Long Follow-up Data: An Exploratory StudyShuta Ohara, MD, PhD0Kenichi Suda, MD, PhD1Sumedha Sudhaman, PhD2Akira Hamada, MD, PhD3Masato Chiba, MD, PhD4Masaki Shimoji, MD, PhD5Toshiki Takemoto, MD, PhD6Ekaterina Kalashnikova, PhD7Samantha K. Cheung, PhD8Michael Krainock, MD, PhD9Jordan Feeney, BS10Himanshu Sethi, MPH11Minetta C. Liu, MD12Junichi Soh, MD, PhD13Yasuhiro Tsutani, MD, PhD14Tetsuya Mitsudomi, MD, PhD15Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, JapanNatera, Inc., Austin, TexasDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, JapanNatera, Inc., Austin, TexasNatera, Inc., Austin, TexasNatera, Inc., Austin, TexasNatera, Inc., Austin, TexasNatera, Inc., Austin, TexasNatera, Inc., Austin, TexasDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan; Department of Thoracic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, JapanDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, JapanDivision of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan; Kindai Hospital Global Research Alliance Center, Kindai University Hospital, Osaka-Sayama, Japan; Izumi City General Hospital, Izumi, Japan; Corresponding author. Address for correspondence: Tetsuya Mitsudomi, MD, PhD, Kindai Hospital Global Research Alliance Center, and Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.Introduction: Molecular residual disease detected by circulating tumor DNA (ctDNA) has been reported to be predictive of patients’ outcomes in various types of cancers after curative intent treatment. Nevertheless, additional detailed information regarding the association of longitudinal ctDNA detection with long-term follow-up in lung cancer is needed. Here, we report on a cohort of patients with NSCLC who underwent definitive surgery and ctDNA analysis in the pre-operative, adjuvant, and surveillance settings. Method: Plasma samples were collected from 46 patients with clinical stage II-III NSCLC before surgery (n = 46), after surgery (n = 45), and every six months until two years thereafter (n = 78). A clinically validated, personalized, tumor-informed 16-plex polymerase chain reaction–next-generation sequencing assay was used for the detection and quantification of ctDNA in retrospectively analyzed plasma samples. Results: Circulating tumor DNA was detected in the first postoperative (within 51 days after surgery) plasma samples in 13% (6/45) of patients (landmark analysis). All of them had disease recurrence within a median of 9.1 months. These patients had shorter recurrence-free and overall survivals than those without detectable ctDNA at a landmark time point (p < 0.01) and in multivariate analyses (p < 0.03). Longitudinally (considering all postoperative follow-up time points), ctDNA was detected in 13 patients, all of whom experienced disease recurrence (positive predictive value = 100%). Three patients who had central nervous system–only metastases did not have detectable ctDNA. Conclusions: The presence of ctDNA post-surgery or during surveillance identifies patients with NSCLC at high risk of recurrence. Serial testing is important to detect disease recurrence earlier (lead-time: 3.2 months).http://www.sciencedirect.com/science/article/pii/S2666364324001322Circulating tumor DNA (ctDNA)Tumor informed approachNon-small cell lung cancer (NSCLC)Prognostic factorRecurrence-free survival (RFS)Disease monitoring |
| spellingShingle | Shuta Ohara, MD, PhD Kenichi Suda, MD, PhD Sumedha Sudhaman, PhD Akira Hamada, MD, PhD Masato Chiba, MD, PhD Masaki Shimoji, MD, PhD Toshiki Takemoto, MD, PhD Ekaterina Kalashnikova, PhD Samantha K. Cheung, PhD Michael Krainock, MD, PhD Jordan Feeney, BS Himanshu Sethi, MPH Minetta C. Liu, MD Junichi Soh, MD, PhD Yasuhiro Tsutani, MD, PhD Tetsuya Mitsudomi, MD, PhD Clinical Significance of Perioperative Minimal Residual Disease Detected by Circulating Tumor DNA in Patients With Lung Cancer With a Long Follow-up Data: An Exploratory Study JTO Clinical and Research Reports Circulating tumor DNA (ctDNA) Tumor informed approach Non-small cell lung cancer (NSCLC) Prognostic factor Recurrence-free survival (RFS) Disease monitoring |
| title | Clinical Significance of Perioperative Minimal Residual Disease Detected by Circulating Tumor DNA in Patients With Lung Cancer With a Long Follow-up Data: An Exploratory Study |
| title_full | Clinical Significance of Perioperative Minimal Residual Disease Detected by Circulating Tumor DNA in Patients With Lung Cancer With a Long Follow-up Data: An Exploratory Study |
| title_fullStr | Clinical Significance of Perioperative Minimal Residual Disease Detected by Circulating Tumor DNA in Patients With Lung Cancer With a Long Follow-up Data: An Exploratory Study |
| title_full_unstemmed | Clinical Significance of Perioperative Minimal Residual Disease Detected by Circulating Tumor DNA in Patients With Lung Cancer With a Long Follow-up Data: An Exploratory Study |
| title_short | Clinical Significance of Perioperative Minimal Residual Disease Detected by Circulating Tumor DNA in Patients With Lung Cancer With a Long Follow-up Data: An Exploratory Study |
| title_sort | clinical significance of perioperative minimal residual disease detected by circulating tumor dna in patients with lung cancer with a long follow up data an exploratory study |
| topic | Circulating tumor DNA (ctDNA) Tumor informed approach Non-small cell lung cancer (NSCLC) Prognostic factor Recurrence-free survival (RFS) Disease monitoring |
| url | http://www.sciencedirect.com/science/article/pii/S2666364324001322 |
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