Liquid Biopsy-Based Novel Modality for Postoperative Management of Lung Cancer

Development and Validation of Non-Invasive Monitoring Techniques for Postoperative Recurrence and Novel Adjuvant Therapeutic Strategies in Lung Cancer

The goal of this study is to develop new techniques for minimal residual disease(MRD) monitoring and to confirm the efficacy and safety of MRD-guided postoperative management for early stage non-small cell lung cancer. The main questions this study aims to answer are:

• How to develop multi-omics-based high-sensitivity detection methods to accurately capture MRD and monitor postoperative recurrence in lung cancer?
• Is adaptive treatment guided by ctDNA-MRD for lung cancer patients superior to traditional clinical management and effectively improves survival?
• Do heterogeneous patient populations (grouped by stages, histopathological subtypes, driver mutations, and treatment histories) show differences in effects under ctDNA-MRD guided postoperative management strategies?

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer; Minimal Residual Disease; Adaptive Treatment
• Intervention / Treatment: Other: Adaptive postoperative management based on minimal residual disease

Detailed Description

Approximately 30% of early-stage lung cancer patients experience recurrence after curative surgery. However, the clinical utility of routine chest CT surveillance remains limited. Emerging evidence has demonstrated that liquid biopsy-based minimal residual disease (MRD) detection may serve as a more sensitive monitoring strategy. Longitudinal ctDNA dynamics analysis further enables real-time assessment of tumor progression and early detection of molecular relapse.

This study aims to develop a novel multidimensional approach for non-invasive postoperative recurrence monitoring in lung cancer and establish an MRD-guided adjuvant therapy model to optimize precision treatment and MRD-stratified follow-up protocols for lung cancer patients. This study will evaluate the sensitivity and specificity of novel monitoring methods and further compare emerging non-invasive recurrence monitoring approaches with conventional ctDNA-based techniques, driving continuous advancements in lung cancer research.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kezhong Chen, MD; Phone Number: +86-010-88325983; Email: mdkzchen@163.com
• Study Contact Backup: Name: Xiaoqiu Yuan; Phone Number: +86-010-88325983; Email: YuanXQ_pkuphxw@foxmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Kezhong Chen, MD; Phone Number: +86-010-88325983; Email: mdkzchen@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Non-small cell lung cancer with stage IA-IIIA (8th edition TNM classification) planning to undergo curative surgery or to undergo neoadjuvant therapy
• Solid nodules >1 cm or ground-glass nodules >1.5 cm on imaging
• No history of malignancies other than non-small cell lung cancer in the past 5 years
• Specimens are well preserved and imaging documents are accessible.

Exclusion Criteria:

• Age<18 years old
• Non-small cell lung cancer with pathologic stage IIIB-IV (8th edition TNM classification)
• Pathology results confirmed not to be non-small cell lung cancer
• History of malignancies other than non-small cell lung cancer in the past 5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: adaptive postoperative management group; For those who don't receive neoadjuvant therapy, if the MRD testing results after surgery keep negative, postoperative adjuvant therapy will be waived. For those who receive neoadjuvant therapy, if the efficacy reaches pathological complete response(pCR) and MRD testing results keep negative, postoperative adjuvant therapy will be waived. Otherwise, participants will receive a customized treatment plan based on Multi-disciplinary Treatment (MDT).	Other: Adaptive postoperative management based on minimal residual disease; participants will not receive postoperative treatment if (neoadjuvant therapy efficacy reaches pCR and) MRD results keep negative.
No Intervention: standard clinical postoperative management group; These participants will receive standard postoperative adjuvant therapy and routine follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Two-year recurrence-free survival rate	The difference in the proportion of patients with (suspected) relapse or metastasis between the intervention group and the control group within two years.	Time from curative surgery to confirmation of clinical progression (recurrence or metastasis) within two years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The difference in overall survival between the intervention group and the control group.	Time from curative surgery to confirmation of death (any cause)，assessed up to 60 months.
Incremental cost effectiveness ratio	The cost of lung cancer-related treatment, including the cost of drugs, follow-up treatment, drug management costs (consultation fees, anti-tumor drug allocation fees, intravenous infusion fees, nursing fees, etc.), follow-up costs, laboratory tests and imaging examination costs, and the management costs of adverse reactions (1 cycle is counted as 1 time), and the per capita standard expenses calculated according to the Checkmate816 study protocol and China's expenses were used to calculate ICER.	24 months after surgery
Timely diagnosis rate by the novel MRD monitoring technique	The proportion of patients with recurrence signals detected by non-invasive methods prior to clinical confirmation of recurrence/metastasis, and quantify the mean lead time.	two years
Sensitivity of the novel MRD monitoring approach	Evaluate the sensitivity of the novel MRD-based assay against previous ctDNA-MRD-only approaches. Use receiver operating characteristic (ROC) curves and limit of detection (LoD) analyses for cross-platform comparison.	two years

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Peking University; Peking University First Hospital; Shanghai Zhongshan Hospital; National Institute for Occupational Safety and Health (NIOSH/CDC); Shandong Cancer Hospital and Institute; Guangdong Provincial People's Hospital; Shanghai Chest Hospital; Jiangsu Cancer Institute & Hospital; Wuhan Union Hospital, China; Second Xiangya Hospital of Central South University; Shenzhen Third People's Hospital
• Investigators: Study Chair: Kezhong Chen, MD, Peking University People's Hospital; Study Director: Guangxi Wang, PhD, Peking University; Study Director: Jiatao Zhang, MD, Guangdong Provincial People's Hospital; Study Director: Rong Yin, MD, Jiangsu Cancer Institute & Hospital; Study Director: Ziming Li, MD, Shanghai Chest Hospital; Principal Investigator: Yintao Li, MD, Shandong Cancer Hospital and Institute; Principal Investigator: Zizi Zhou, MD, Shenzhen Third People's Hospital; Principal Investigator: Fang Wu, MD, Second Xiangya Hospital of Central South University; Principal Investigator: Jun Yin, MD, Shanghai Zhongshan Hospital; Principal Investigator: Yuan Cheng, MD, Peking University First Hospital; Principal Investigator: Quanfu Huang, MD, Wuhan Union Hospital, China; Principal Investigator: Xiaojun Zhu, PhD, China National Institute for Occupational Safety and Health (NIOSH/CDC)

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: March 25, 2025
• First Submitted That Met QC Criteria: April 8, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Neoplasm, Residual
• Other Study ID Numbers: 2023ZD0501900

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No