The Role of ctDNA Testing Plus AI-based Pathology in Resectable LSCC

Circulating Tumor DNA (ctDNA) Dynamic Monitoring Plus Artificial Intelligence (AI)-Based Pathology Predict the Efficacy of Chemoimmunotherapy in Resectable Lung Squamous Cell Carcinoma (LSCC)

The goal of this observational study is to explore whether ctDNA dynamic monitoring plus AI-based pathology can more effectively predict the therapeutic effect of neoadjuvant chemoimmunotherapy for resectable lung squamous cell carcinoma, so as to accurately guide clinical diagnosis and treatment.

Study Overview

• Status: Recruiting
• Conditions: Lung Squamous Cell Carcinoma
• Intervention / Treatment: Diagnostic test: WES and ctDNA detection

Detailed Description

This study is a single-center, observational, non-interventional, prospective study. 50 patients diagnosed with lung squamous cell carcinoma receiving neoadjuvant chemoimmunotherapy (ranging 2 to 4 cycles) will be planned to be enrolled in the study. Pre-treatment biopsy tissues of enrolled patients will be collected for whole exon sequencing (WES) testing, and personalized detection panel will be customized based on WES testing results. Peripheral blood will be collected 1 day before each cycle of neoadjuvant therapy, 1 day before surgery, 3 days after surgery, and 3 weeks after surgery for ctDNA testing. In addition, the prediction model of AI-based pathology will be constructed by AI deep learning based on pathological sections of pre-treatment biopsy tissues. All inclued patients will be regularly followed up for at least 5 years.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Yan Hu, M.D., Ph.D.; Phone Number: 8685296122; Email: yanhu@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • Department of Thoracic Surgery, Second Xiangya Hospital of Central South University, China
      • Contact: Yan Hu, M.D., Ph.D.; Email: yanhu@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Resectable or potentially resectable stage II-IIIb lung squamous cell carcinoma patients receiving neoadjuvant chemoimmunotherapy

Description

Inclusion Criteria:

• Histopathology or cytology confirmed the lung squamous cell carcinoma
• Age ranging from 18 to 75
• Agree to participate in this study and sign an informed consent form
• Treatment-naive tumor
• According to the American Joint Committee on Cancer (AJCC) eighth edition of the Lung Cancer Staging Manual, the clinical stage is stage II-IIIb resectable or potentially resectable tumor
• Sufficient tissue/blood samples are available to meet research requirements
• The ECOG PS score is 0-1

Exclusion Criteria:

• Patients who cannot understand the content of the experiment and cannot cooperate, and those who refuse to sign the informed consent form
• Non-squamous NSCLC
• Unresectable IIIa-IIIb tumor
• Patients with solid organ or blood system transplantation
• Previous use of CTLA-4, PD-1, or PD-L1 immune checkpoint inhibitors
• Patients with interstitial lung disease
• Patients with acute or chronic infectious disease
• Pregnant and lactating women
• Patients who have undergone other clinical drug trials

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with lung Squamous Cell Carcinoma receiving neoadjuvant chemoimmunotherapy	Diagnostic test: WES and ctDNA detection; WES and ctDNA detection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic completet response (pCR) rate	pCR rate is defined as the percentage of participants having an absence of residual tumor cells in resected lung specimens and lymph nodes following completion of neoadjuvant therapy.	Up to 1 year
ctDNA resolution	ctDNA resolution is defined as the change or resolution in tumor-derived DNA found in the bloodstream from diagnosis to after neoadjuvant therapy and after surgery, correlated with pathologic complete response (pCR)	Up to 2 years
Development of computer algorithm to identify pCR features	Development of computer algorithm to identify pCR features	From retrospective data collection to algorithm development (6 month)
Validation of computer algorithm to identify pCR features	Validation of computer algorithm to identify pCR features	From prospective data collection to algorithm validation (6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative complications rate	Number of participants experiencing perioperative complications will be recorded.	Up to 3 years
Major pathological response (MPR) rate	MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and resected lymph nodes following completion of neoadjuvant therapy.	Up to 1 year
Objective response rate(ORR)	The proportion of patients achieved complete or patial remission(Imageological) according to RECIST 1.1 prior to definitive surgery.	Up to 1 year
Adverse events (AEs)	Number of participants experiencing AEs will be recorded. An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 5 years
Health-related Quality of Life	Health-related Quality of Life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0, the EORTC Quality of Life Questionnaire in Lung Cancer (EORTC QLQ-LC13), and the European Quality of Life 5 Dimensions (EQ-5D) questionnaire.	Up to 5 years
Perioperative pain evaluation	Perioperative pain evaluation assessed by a numeric rating scale (NRS)	Up to 3 years
Disease free survival (DFS)	From the date of surgery to any of the following events: disease progression, disease recurrence or death from any cause.	Up to 5 years
Overall survival (OS)	From the date of participated in study to the date of death.	Up to 5 years

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University
• Collaborators: Shanghai OrigiMed Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 23, 2023
• Primary Completion (Anticipated): September 23, 2028
• Study Completion (Anticipated): September 23, 2029

Study Registration Dates

• First Submitted: February 23, 2023
• First Submitted That Met QC Criteria: March 18, 2023
• First Posted (Actual): March 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: March 18, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell
• Other Study ID Numbers: LYF2022198

Drug and device information, study documents

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