Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection
Introduction: EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR-mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation. Methods: From...
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Elsevier
2025-01-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364324001280 |
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| author | Song Dong, PhD Bingfa Yan, PhD Si-Yang Liu, PhD Xuan Gao, PhD Hui-Zhao Hong, MD Hong-Ji Li, MD Wei Gao, PhD Hong-Hong Yan, PhD Si-Yang Maggie Liu, PhD Hai-Yan Tu, PhD Yi Pan, PhD Qing Zhou, PhD Xue-Ning Yang, PhD Xue-Feng Xia, PhD Xin Yi, PhD Wen-Zhao Zhong, PhD Yi-Long Wu, MD Jia-Tao Zhang, PhD |
| author_facet | Song Dong, PhD Bingfa Yan, PhD Si-Yang Liu, PhD Xuan Gao, PhD Hui-Zhao Hong, MD Hong-Ji Li, MD Wei Gao, PhD Hong-Hong Yan, PhD Si-Yang Maggie Liu, PhD Hai-Yan Tu, PhD Yi Pan, PhD Qing Zhou, PhD Xue-Ning Yang, PhD Xue-Feng Xia, PhD Xin Yi, PhD Wen-Zhao Zhong, PhD Yi-Long Wu, MD Jia-Tao Zhang, PhD |
| author_sort | Song Dong, PhD |
| collection | DOAJ |
| description | Introduction: EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR-mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation. Methods: From January 2019 to December 2022, 71 patients with stages I to III NSCLC and EGFR (exon 19 deletion or L858R) mutations were enrolled in this observational study. A total of 375 blood samples were analyzed using the MRD_Navigator assay. Among them, 27 patients suspended EGFR TKI treatment based on undetectable MRD and were thus included in the adaptive, de-escalation group. Results: Overall, the sensitivity of longitudinal MRD was 86.2%. Only four patients (11.8%) recurred with longitudinal undetectable MRD, indicating a negative predictive value of 88.2%. Of the patients who had detectable MRD after surgery, nine subsequently received EGFR TKI treatment, with only one (11.1%) achieving persistent circulating tumor DNA clearance post–EGFR TKI. Furthermore, 22 patients with stages IB to III disease who had previously suspended their TKI treatment based on undetectable MRD were included in the adaptive group, with an average duration of TKI 3.9 (range: 0–35.0) months. The 2-year disease-free survival rate of these 22 patients was 80.2%, and the median was not reached. Five patients (n = 5 of 22, 22.7%) had disease recurrence during the period of drug cessation but were stable under EGFR TKI treatment until the latest follow-up. Two patients remained in complete remission. Conclusions: Our initial findings underscore the potential of an adaptive, de-escalation approach to adjuvant EGFR TKIs based on circulating tumor DNA-MRD monitoring. |
| format | Article |
| id | doaj-art-53643bd155c048d5bc49ea739a649af6 |
| institution | Kabale University |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | JTO Clinical and Research Reports |
| spelling | doaj-art-53643bd155c048d5bc49ea739a649af62025-01-20T04:17:54ZengElsevierJTO Clinical and Research Reports2666-36432025-01-0161100758Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete ResectionSong Dong, PhD0Bingfa Yan, PhD1Si-Yang Liu, PhD2Xuan Gao, PhD3Hui-Zhao Hong, MD4Hong-Ji Li, MD5Wei Gao, PhD6Hong-Hong Yan, PhD7Si-Yang Maggie Liu, PhD8Hai-Yan Tu, PhD9Yi Pan, PhD10Qing Zhou, PhD11Xue-Ning Yang, PhD12Xue-Feng Xia, PhD13Xin Yi, PhD14Wen-Zhao Zhong, PhD15Yi-Long Wu, MD16Jia-Tao Zhang, PhD17Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaGeneplus-Beijing Institute, Beijing, People's Republic of China; State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaGeneplus-Beijing Institute, Beijing, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaGeneplus-Beijing Institute, Beijing, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaChinese Thoracic Oncology Group (CTONG), Guangzhou, Guangdong, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaGeneplus-Beijing Institute, Beijing, People's Republic of ChinaGeneplus-Beijing Institute, Beijing, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of ChinaGuangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of China; Corresponding author. Address for correspondence: Jia-Tao Zhang, PhD, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of China.Introduction: EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR-mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation. Methods: From January 2019 to December 2022, 71 patients with stages I to III NSCLC and EGFR (exon 19 deletion or L858R) mutations were enrolled in this observational study. A total of 375 blood samples were analyzed using the MRD_Navigator assay. Among them, 27 patients suspended EGFR TKI treatment based on undetectable MRD and were thus included in the adaptive, de-escalation group. Results: Overall, the sensitivity of longitudinal MRD was 86.2%. Only four patients (11.8%) recurred with longitudinal undetectable MRD, indicating a negative predictive value of 88.2%. Of the patients who had detectable MRD after surgery, nine subsequently received EGFR TKI treatment, with only one (11.1%) achieving persistent circulating tumor DNA clearance post–EGFR TKI. Furthermore, 22 patients with stages IB to III disease who had previously suspended their TKI treatment based on undetectable MRD were included in the adaptive group, with an average duration of TKI 3.9 (range: 0–35.0) months. The 2-year disease-free survival rate of these 22 patients was 80.2%, and the median was not reached. Five patients (n = 5 of 22, 22.7%) had disease recurrence during the period of drug cessation but were stable under EGFR TKI treatment until the latest follow-up. Two patients remained in complete remission. Conclusions: Our initial findings underscore the potential of an adaptive, de-escalation approach to adjuvant EGFR TKIs based on circulating tumor DNA-MRD monitoring.http://www.sciencedirect.com/science/article/pii/S2666364324001280Non–small cell lung cancerEpidermal growth factor receptorDe-escalation therapyMolecular residual diseaseCirculating tumor DNA |
| spellingShingle | Song Dong, PhD Bingfa Yan, PhD Si-Yang Liu, PhD Xuan Gao, PhD Hui-Zhao Hong, MD Hong-Ji Li, MD Wei Gao, PhD Hong-Hong Yan, PhD Si-Yang Maggie Liu, PhD Hai-Yan Tu, PhD Yi Pan, PhD Qing Zhou, PhD Xue-Ning Yang, PhD Xue-Feng Xia, PhD Xin Yi, PhD Wen-Zhao Zhong, PhD Yi-Long Wu, MD Jia-Tao Zhang, PhD Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection JTO Clinical and Research Reports Non–small cell lung cancer Epidermal growth factor receptor De-escalation therapy Molecular residual disease Circulating tumor DNA |
| title | Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection |
| title_full | Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection |
| title_fullStr | Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection |
| title_full_unstemmed | Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection |
| title_short | Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection |
| title_sort | monitoring of circulating tumor dna and indication of de escalation adjuvant targeted therapy for egfr mutated nsclc after complete resection |
| topic | Non–small cell lung cancer Epidermal growth factor receptor De-escalation therapy Molecular residual disease Circulating tumor DNA |
| url | http://www.sciencedirect.com/science/article/pii/S2666364324001280 |
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