Comprehensive Analysis of Gene Mutation Profile in Chinese NSCLC Patients by Next-generation Sequencing

Tianjin Medical University Cancer Institute and Hospital

In recent years, the development of lung cancer has been improved from pathological level to the molecular level. Research showed that there are many gene mutations in non-small cell lung cancer (NSCLC), and some activating mutations have become the hotspots in target therapy area. With the development of targeted drug research, the molecular classification of NSCLC will be more and more important. But a large number of clinical data showed that gene mutation in Chinese NSCLC patients is significantly different from Caucasian population, which suggesting that it is necessary to identify gene mutation profile in Chinese patients with NSCLC.

Six hundred NSCLC paraffin tissue samples was collected during operation from Tianjin Cancer hospital in 2009-2012, which including lung squamous cell carcinoma and adenocarcinoma. The target area of 295 genes, including lung cancer drive genes, important signal pathway genes, drug resistance genes will be detected by next-generation sequencing deep (average 1000X). We will identify gene mutation profile for Chinese lung squamous cell carcinoma and adenocarcinoma patients. The aim is to find related predictor and prognostic factors by analysing the relationship between these gene mutations and clinical characteristics and follow-up treatment.

Study Overview

• Status: Completed
• Conditions: NSCLC

Detailed Description

The objective of this study is to build NSCLC gene mutation profile in China and find related correlation between gene mutation panel and clinical outcome.

Approximately 600 surgical tissue samples will be collected during operation in Tianjin Cancer hospital from 2009-2012, including lung squamous cell carcinoma and adenocarcinoma. The target area of 295 genes, including lung cancer drive genes, important signal pathway genes, drug resistance genes will be detected by New generation Sequencing (NGS) deep (average 1000X). This genes was selected from Mutations can guide treatment or as prognosis factors in NCCN/FDA/CFDA guideline, related mutations in phase II/III studies and NCCN/FDA/CFDA approved in other type tumors and related mutations in phase I or pre-clinical studies and can not guide treatment or as prognosis factors.

All mutations detected in 600 samples are summarized for statistics, calculating the mutation proportion in overall population. Clustering analysis is performed according to the main drive genes related biological pathways, correlation between gene mutation data and categorical clinical variables is performed by Fisher's Exact Test. The Log-rank test will be used to explore the relationship between the clinical outcomes (DFS and OS, respectively) and gene mutations (present or absent) or each of the clinical features (gender, age, smoking status, TNM staging, histology, tumor location, recurrence, number of lymph node metastasis, tumor size, postoperative adjuvant treatment, DFS and OS). Then a Cox Proportional Hazards model will be constructed to evaluate the effect of multiple variables (genomic and clinical features) on DFS, and OS, respectively. Benjamini-Hochberg false discovery rate (FDR) method is used to adjust the p-value and calculate the statistically differences. All p values were two-sided, and P<0.05 was assumed to be significant.

• Study Type: Observational
• Enrollment (Actual): 513

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

From May 2009 to November 2012, diagnosed lung cancer patients at Tianjin Medical University Cancer Institute & Hospital were enrolled

Description

Inclusion Criteria:

• Patients enrolled from 2009 to 2012. Histological confirmed NSCLC.

Exclusion Criteria:

• Received any systemic or local treatment before surgery. Along with other malignant tumors. Lack up intact follow-up information.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation between gene mutations and survival	The Log-rank test will be used to explore the relationship between the clinical outcomes (DFS and OS, respectively) and gene mutations (present or absent) or each of the clinical features (gender, age, smoking status, TNM staging, histology, tumor location, recurrence, number of lymph node metastasis, tumor size, postoperative adjuvant treatment, DFS and OS). Then a Cox Proportional Hazards model will be constructed to evaluate the effect of multiple variables (genomic and clinical features) on DFS, and OS, respectively. Benjamini-Hochberg false discovery rate (FDR) method is used to adjust the p-value and calculate the statistically differences. All p values were two-sided, and P<0.05 was assumed to be significant.	December 2017

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation between gene mutations and clinical parameters.	Correlation between gene mutation data and categorical clinical variables is performed by Fisher's Exact Test.	December 2017

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Collaborators: Guangzhou Burning Rock Dx Co., Ltd.; AstraZeneca Investment (China) Co., Ltd
• Investigators: Principal Investigator: Changli Wang, Prof., Tianjin Medical University Cancer Institute & Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 27, 2016
• Primary Completion (ACTUAL): September 27, 2017
• Study Completion (ACTUAL): February 1, 2018

Study Registration Dates

• First Submitted: May 23, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (ACTUAL): August 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 7, 2018
• Last Update Submitted That Met QC Criteria: August 5, 2018
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: next-generation sequencing; Chinese NSCLC
• Other Study ID Numbers: E2016060A

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