A stage IA lung cancer patient with anaplastic lymphoma kinase (ALK) and minimal residual disease (MRD) positive | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A stage IA lung cancer patient with anaplastic lymphoma kinase (ALK) and minimal residual disease (MRD) positive Cheng Shen, Weikang Shao, Hu Liao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6810084/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Recurrence is infrequently seen in early-stage non-small cell lung cancer (NSCLC), particularly in IA stage. For patients with resectable anaplastic lymphoma kinase (ALK) positive NSCLC, platinum-based chemotherapy is the advised adjuvant therapy. However, currently there is no definitive adjuvant treatment plan for NSCLC patients in stage IA who are ALK positive, both in clinical studies and retrospective analysis. We report a case who was adenocarcinoma with ALK positive and we continued to follow up with minimal residual disease (MRD) after surgery. In early stage lung cancer especially in patient with ALK positivity, MRD positivity may help patients assess the possibility of recurrence for cancer as early as possible and receive early medication treatment. non-small cell lung cancer anaplastic lymphoma kinase minimal residual disease Figures Figure 1 Figure 2 Figure 3 Background Recurrence is infrequently seen in early-stage non-small cell lung cancer (NSCLC), particularly in IA stage. For patients with resectable anaplastic lymphoma kinase (ALK) positive NSCLC, platinum-based chemotherapy is the advised adjuvant therapy[ 1 ]. However, currently there is no definitive adjuvant treatment plan for NSCLC patients in stage IA who are ALK positive, both in clinical studies and retrospective analysis[ 2 ]. The use of circulating tumor DNA (ctDNA) has become a non-invasive method to stratify patients based on their risk of recurrence following curative intent therapy[ 3 ]. Additionally, liquid biopsy can enhance therapeutic strategies by addressing tumor heterogeneity, identifying minimal residual disease (MRD) through the detection of tumor-specific ctDNA after surgery[ 4 ]. We report a case who was adenocarcinoma with ALK positive and we continued to follow up with MRD after surgery. Case presentation A 53 years old male presented to our hospital with cough for 5 months. He denied the following symptoms including the presence of chest pain, hoarseness, hemoptysis and dyspnea. Physical examination revealed normal breath sounds in both of the lung fields. Laboratory findings were within normal limits. He had smoked one pack of cigarettes per day for the past 10 years and quit smoking for 20 years. Plain and contrast-enhanced chest and computed tomography (CT) showed a 1.1×0.8 cm anomalous soft tissue mass is located at the junction of the upper and middle lobes of the right lung (Fig. 1 A and 1 B). Informed written consent and institutional review board approval were both obtained from West China Hospital Ethics Committee (No. 202365) and affiliation of ethics committee for the surgery and the publication of the study. As diagnosis was established, surgery was scheduled. Under general anesthesia with selective intubation, the patient lay on the operating table with supine position. We approached the tumor by using video-assisted thoracic surgery (VATS). Systemic mediastinal lymph node dissection was performed, with stations 2, 4, 7, 10 and 11 lymph nodes removed. After complete resection of the lesion, tissue of the nodule was taken out from the tumor for quick frozen pathology. Intraoperative frozen section pathologic examination documented an adenocarcinoma. The operation time was 40 min, and the intraoperative blood loss was 10 ml. The postoperative course was uneventful, and the patient was discharged on postoperative day 2 after the operation with no complication. The final pathologic examination documented Infiltrating non mucinous adenocarcinoma, pT1bN0M0. Immunostaining for CK7, thyroid transcription factor-1 (TTF-1), Napsin A and ALK were positive (Fig. 2 ). P40, Syn, CgA and ROS-1 were negative. Patient was regularly monitored for MRD. The ctDNA for MRD was negative one month after the surgery. However, five months after surgery, we found a recurrence in the patient during follow-up chest CT examination with MRD positive. Contrast-enhanced chest CT scan showed that station 3 lymph node showed significant enhancement. Then, PET-CT displayed abnormal metabolic elevation, which meant the occurrence of lymph node metastasis (Fig. 1 C, 1 D and 1 E). We then approached the lymph node by using uniportal VATS. Intraoperative frozen section pathologic examination of the lymph node showed epithelioid cells were found in the lymph node, distributed in clusters and nests meant adenocarcinoma. ALK was also positive. The patient started taking alectinib orally. The ctDNA for MRD was negative 16 months after the surgery (Fig. 3 ). Discussion This is, to our knowledge, a rare report of a case presence of adenocarcinoma with ALK positive in stage IA and MRD positive after five months postoperatively. Although ALK tyrosine kinase inhibitors (TKIs) are the standard treatment for metastatic ALK-positive NSCLC, their efficacy in earlier stages of the disease remains uncertain [ 5 ]. Liquid biopsy, which involves analyzing tumor-derived materials circulating in body fluids like blood, is gaining recognition as a valuable and non-invasive biomarker[ 6 ]. Although the incidence of ALK positive NSCLC patients is relatively low, these cases are highly malignant and prone to recurrence and brain metastasis. The prognosis for such patients is poor, and both chemotherapy and immunotherapy tend to be ineffective. For early-stage ALK-positive patients, the ALINA study suggest that these patients might benefit from targeted therapy alone, without the chemotherapy[ 1 ]. However, this recommendation currently applies only for patients in stage IB. Perioperative ctDNA analysis can reliably detect MRD and pinpoint patients at high risk of recurrence [ 7 ]. Following successful resection of early-stage non-small cell lung cancer, a positive MRD status signifies a heightened recurrence risk. It is advisable to monitor MRD status every 3–6 months after the surgery. In conclusion, patient with stage IA lung cancer have a relatively poor prognosis if ALK positivity is detected. liquid biopsy can potentially improve patient selection for adjuvant therapy (e.g., by the detection of MRD) and aid in selecting optimal treatment regimens. Longitudinal MRD surveillance will enable early detection of disease relapse during follow-up, allowing for earlier directed therapeutically interventions. Declarations Ethics approval and consent to participate Informed written consent and institutional review board approval were both obtained from West China Hospital Ethics Committee (No. 202335) and affiliation of ethics committee for the surgery and the publication of the study. Availability of data and materials All data for this study are publicly available and are ready for the public from database of hospital. Funding Not applicable Consent for publication All the authors consent to publish the paper. Competing interests The authors declare that they have no competing interests. Authors' contributions CS was involved in drafting the manuscript. CS was made contributions to the concepts, acquisition and analysis of the data. WS was involved in acquisition of data and preparing the Tables. HL designed and revised the manuscript. All authors have read and approved the final manuscript. Acknowledgements We greatly appreciate the assistance of the staff of the Department of Thoracic Surgery, West-China Hospital, Sichuan University, and thank them for their efforts. References Wu, Y.L.; Dziadziuszko, R.; Ahn, J.S.; Barlesi, F.; Nishio, M.; Lee, D.H.; Lee, J.S.; Zhong, W.; Horinouchi, H.; Mao, W.; et al. Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. The New England journal of medicine 2024 , 390 , 1265-1276, doi:10.1056/NEJMoa2310532. Lee, J.M.; McNamee, C.J.; Toloza, E.; Negrao, M.V.; Lin, J.; Shum, E.; Cummings, A.L.; Kris, M.G.; Sepesi, B.; Bara, I.; et al. Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2023 , 18 , 1458-1477, doi:10.1016/j.jtho.2023.07.006. Tan, A.C.; Lai, G.G.Y.; Saw, S.P.L.; Chua, K.L.M.; Takano, A.; Ong, B.H.; Koh, T.P.T.; Jain, A.; Tan, W.L.; Ng, Q.S.; et al. Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer. Cancer 2024 , 130 , 1758-1765, doi:10.1002/cncr.35263. Vandekerckhove, O.; Cuppens, K.; Pat, K.; Du Pont, B.; Froyen, G.; Maes, B. Liquid Biopsy in Early-Stage Lung Cancer: Current and Future Clinical Applications. Cancers 2023 , 15 , doi:10.3390/cancers15102702. Li, Y.; Jiang, G.; Wu, W.; Yang, H.; Jin, Y.; Wu, M.; Liu, W.; Yang, A.; Chervova, O.; Zhang, S.; et al. Multi-omics integrated circulating cell-free DNA genomic signatures enhanced the diagnostic performance of early-stage lung cancer and postoperative minimal residual disease. EBioMedicine 2023 , 91 , 104553, doi:10.1016/j.ebiom.2023.104553. Reyes, R.; Reguart, N. Neoadjuvant treatment of stage IIIA-N2 in EGFR-Mutant/ALK-rearranged non-small cell lung cancer. Translational lung cancer research 2021 , 10 , 607-621, doi:10.21037/tlcr-20-780. Xia, L.; Mei, J.; Kang, R.; Deng, S.; Chen, Y.; Yang, Y.; Feng, G.; Deng, Y.; Gan, F.; Lin, Y.; et al. Perioperative ctDNA-Based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1). Clinical cancer research : an official journal of the American Association for Cancer Research 2022 , 28 , 3308-3317, doi:10.1158/1078-0432.Ccr-21-3044. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6810084","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":495009670,"identity":"aeeca9f7-6f8f-459b-84b7-0b4b8e78a519","order_by":0,"name":"Cheng Shen","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Cheng","middleName":"","lastName":"Shen","suffix":""},{"id":495009671,"identity":"a0c2e7e8-c1f5-467c-9b7b-4fdb241ebdd1","order_by":1,"name":"Weikang Shao","email":"","orcid":"","institution":"Genecast Biotechnology Co., Ltd","correspondingAuthor":false,"prefix":"","firstName":"Weikang","middleName":"","lastName":"Shao","suffix":""},{"id":495009672,"identity":"d008f8fb-cb10-465b-8b95-5f4838f16e99","order_by":2,"name":"Hu Liao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYHACxgMJDAwJDOyNjQ8+EKsHooXncLPhDKK1MIC0SKS3SXMQo1y+/QDDgQc1NnkGNx82SDMw2MnpNhDQYnAmAeiwY2nFBrcTG4wLGJKNzQ4Q0iIB8gvb4cQNQC3JMxgOJG4jpEV+BkjLP6CWmwcbDvMQo4XhBlBLYhtQyw3GxmaitID9ktiXljjzTGIz4wwDIvwCDDHGhz++2ST2HT/+/MeHCjs5gloYGPiRo9yAoPJRMApGwSgYBcQAAGhZSuE3y9lyAAAAAElFTkSuQmCC","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":true,"prefix":"","firstName":"Hu","middleName":"","lastName":"Liao","suffix":""}],"badges":[],"createdAt":"2025-06-03 10:23:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6810084/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6810084/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88416355,"identity":"df068407-8324-4722-beb6-788d10d012a3","added_by":"auto","created_at":"2025-08-06 08:59:01","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":233984,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA and B\u003c/strong\u003e: Chest Contrast-enhanced CT features of the case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC, D and E\u003c/strong\u003e: Chest CT scan and PET-CT showed that station 3 lymph node showed significant enhancement and abnormal metabolic elevation.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6810084/v1/7e85cc67f080350a984cb845.jpg"},{"id":88416358,"identity":"701471a3-0988-4955-8cff-06b1081ab52a","added_by":"auto","created_at":"2025-08-06 08:59:01","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":47621,"visible":true,"origin":"","legend":"\u003cp\u003eALK fusion mutation of the patient.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6810084/v1/56fa56ea3106844b44c577f0.jpg"},{"id":88416360,"identity":"a06755dc-1e33-47fa-97f0-965d9cdfb125","added_by":"auto","created_at":"2025-08-06 08:59:01","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":235436,"visible":true,"origin":"","legend":"\u003cp\u003eA regularly monitored for MRD.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6810084/v1/caa183fdf2095184537e21c3.jpg"},{"id":102747682,"identity":"02a06fd3-7b3f-4cb5-9f3b-03799bbdbe11","added_by":"auto","created_at":"2026-02-16 09:05:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":849894,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6810084/v1/d23dff99-d9e1-434d-bc16-158f54a64fe6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A stage IA lung cancer patient with anaplastic lymphoma kinase (ALK) and minimal residual disease (MRD) positive","fulltext":[{"header":"Background","content":"\u003cp\u003eRecurrence is infrequently seen in early-stage non-small cell lung cancer (NSCLC), particularly in IA stage. For patients with resectable anaplastic lymphoma kinase (ALK) positive NSCLC, platinum-based chemotherapy is the advised adjuvant therapy[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, currently there is no definitive adjuvant treatment plan for NSCLC patients in stage IA who are ALK positive, both in clinical studies and retrospective analysis[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The use of circulating tumor DNA (ctDNA) has become a non-invasive method to stratify patients based on their risk of recurrence following curative intent therapy[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Additionally, liquid biopsy can enhance therapeutic strategies by addressing tumor heterogeneity, identifying minimal residual disease (MRD) through the detection of tumor-specific ctDNA after surgery[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. We report a case who was adenocarcinoma with ALK positive and we continued to follow up with MRD after surgery.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 53 years old male presented to our hospital with cough for 5 months. He denied the following symptoms including the presence of chest pain, hoarseness, hemoptysis and dyspnea. Physical examination revealed normal breath sounds in both of the lung fields. Laboratory findings were within normal limits. He had smoked one pack of cigarettes per day for the past 10 years and quit smoking for 20 years. Plain and contrast-enhanced chest and computed tomography (CT) showed a 1.1\u0026times;0.8 cm anomalous soft tissue mass is located at the junction of the upper and middle lobes of the right lung (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Informed written consent and institutional review board approval were both obtained from West China Hospital Ethics Committee (No. 202365) and affiliation of ethics committee for the surgery and the publication of the study.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAs diagnosis was established, surgery was scheduled. Under general anesthesia with selective intubation, the patient lay on the operating table with supine position. We approached the tumor by using video-assisted thoracic surgery (VATS). Systemic mediastinal lymph node dissection was performed, with stations 2, 4, 7, 10 and 11 lymph nodes removed. After complete resection of the lesion, tissue of the nodule was taken out from the tumor for quick frozen pathology. Intraoperative frozen section pathologic examination documented an adenocarcinoma. The operation time was 40 min, and the intraoperative blood loss was 10 ml. The postoperative course was uneventful, and the patient was discharged on postoperative day 2 after the operation with no complication. The final pathologic examination documented Infiltrating non mucinous adenocarcinoma, pT1bN0M0. Immunostaining for CK7, thyroid transcription factor-1 (TTF-1), Napsin A and ALK were positive (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). P40, Syn, CgA and ROS-1 were negative. Patient was regularly monitored for MRD.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe ctDNA for MRD was negative one month after the surgery. However, five months after surgery, we found a recurrence in the patient during follow-up chest CT examination with MRD positive. Contrast-enhanced chest CT scan showed that station 3 lymph node showed significant enhancement. Then, PET-CT displayed abnormal metabolic elevation, which meant the occurrence of lymph node metastasis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eC, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eD and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eE). We then approached the lymph node by using uniportal VATS. Intraoperative frozen section pathologic examination of the lymph node showed epithelioid cells were found in the lymph node, distributed in clusters and nests meant adenocarcinoma. ALK was also positive. The patient started taking alectinib orally. The ctDNA for MRD was negative 16 months after the surgery (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is, to our knowledge, a rare report of a case presence of adenocarcinoma with ALK positive in stage IA and MRD positive after five months postoperatively. Although ALK tyrosine kinase inhibitors (TKIs) are the standard treatment for metastatic ALK-positive NSCLC, their efficacy in earlier stages of the disease remains uncertain [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Liquid biopsy, which involves analyzing tumor-derived materials circulating in body fluids like blood, is gaining recognition as a valuable and non-invasive biomarker[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough the incidence of ALK positive NSCLC patients is relatively low, these cases are highly malignant and prone to recurrence and brain metastasis. The prognosis for such patients is poor, and both chemotherapy and immunotherapy tend to be ineffective. For early-stage ALK-positive patients, the ALINA study suggest that these patients might benefit from targeted therapy alone, without the chemotherapy[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, this recommendation currently applies only for patients in stage IB. Perioperative ctDNA analysis can reliably detect MRD and pinpoint patients at high risk of recurrence [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Following successful resection of early-stage non-small cell lung cancer, a positive MRD status signifies a heightened recurrence risk. It is advisable to monitor MRD status every 3\u0026ndash;6 months after the surgery.\u003c/p\u003e\u003cp\u003eIn conclusion, patient with stage IA lung cancer have a relatively poor prognosis if ALK positivity is detected. liquid biopsy can potentially improve patient selection for adjuvant therapy (e.g., by the detection of MRD) and aid in selecting optimal treatment regimens. Longitudinal MRD surveillance will enable early detection of disease relapse during follow-up, allowing for earlier directed therapeutically interventions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed written consent and institutional review board approval were both obtained from West China Hospital Ethics Committee (No. 202335) and affiliation of ethics committee for the surgery and the publication of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data for this study are publicly available and are ready for the public from database of hospital.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors consent to publish the paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCS was involved in drafting the manuscript. CS was made contributions to the concepts, acquisition and analysis of the data. WS was involved in acquisition of data and preparing the Tables. HL designed and revised the manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe greatly appreciate the assistance of the staff of the Department of Thoracic Surgery, West-China Hospital, Sichuan University, and thank them for their efforts.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWu, Y.L.; Dziadziuszko, R.; Ahn, J.S.; Barlesi, F.; Nishio, M.; Lee, D.H.; Lee, J.S.; Zhong, W.; Horinouchi, H.; Mao, W.; et al. Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. \u003cem\u003eThe New England journal of medicine \u003c/em\u003e\u003cstrong\u003e2024\u003c/strong\u003e, \u003cem\u003e390\u003c/em\u003e, 1265-1276, doi:10.1056/NEJMoa2310532.\u003c/li\u003e\n\u003cli\u003eLee, J.M.; McNamee, C.J.; Toloza, E.; Negrao, M.V.; Lin, J.; Shum, E.; Cummings, A.L.; Kris, M.G.; Sepesi, B.; Bara, I.; et al. Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives. \u003cem\u003eJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer \u003c/em\u003e\u003cstrong\u003e2023\u003c/strong\u003e, \u003cem\u003e18\u003c/em\u003e, 1458-1477, doi:10.1016/j.jtho.2023.07.006.\u003c/li\u003e\n\u003cli\u003eTan, A.C.; Lai, G.G.Y.; Saw, S.P.L.; Chua, K.L.M.; Takano, A.; Ong, B.H.; Koh, T.P.T.; Jain, A.; Tan, W.L.; Ng, Q.S.; et al. Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer. \u003cem\u003eCancer \u003c/em\u003e\u003cstrong\u003e2024\u003c/strong\u003e, \u003cem\u003e130\u003c/em\u003e, 1758-1765, doi:10.1002/cncr.35263.\u003c/li\u003e\n\u003cli\u003eVandekerckhove, O.; Cuppens, K.; Pat, K.; Du Pont, B.; Froyen, G.; Maes, B. Liquid Biopsy in Early-Stage Lung Cancer: Current and Future Clinical Applications. \u003cem\u003eCancers \u003c/em\u003e\u003cstrong\u003e2023\u003c/strong\u003e, \u003cem\u003e15\u003c/em\u003e, doi:10.3390/cancers15102702.\u003c/li\u003e\n\u003cli\u003eLi, Y.; Jiang, G.; Wu, W.; Yang, H.; Jin, Y.; Wu, M.; Liu, W.; Yang, A.; Chervova, O.; Zhang, S.; et al. Multi-omics integrated circulating cell-free DNA genomic signatures enhanced the diagnostic performance of early-stage lung cancer and postoperative minimal residual disease. \u003cem\u003eEBioMedicine \u003c/em\u003e\u003cstrong\u003e2023\u003c/strong\u003e, \u003cem\u003e91\u003c/em\u003e, 104553, doi:10.1016/j.ebiom.2023.104553.\u003c/li\u003e\n\u003cli\u003eReyes, R.; Reguart, N. Neoadjuvant treatment of stage IIIA-N2 in EGFR-Mutant/ALK-rearranged non-small cell lung cancer. \u003cem\u003eTranslational lung cancer research \u003c/em\u003e\u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e10\u003c/em\u003e, 607-621, doi:10.21037/tlcr-20-780.\u003c/li\u003e\n\u003cli\u003eXia, L.; Mei, J.; Kang, R.; Deng, S.; Chen, Y.; Yang, Y.; Feng, G.; Deng, Y.; Gan, F.; Lin, Y.; et al. Perioperative ctDNA-Based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1). \u003cem\u003eClinical cancer research : an official journal of the American Association for Cancer Research \u003c/em\u003e\u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e28\u003c/em\u003e, 3308-3317, doi:10.1158/1078-0432.Ccr-21-3044.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
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