Evaluation of Somatic Mutation Spectrum as Biomarker for Survival Outcome in Chinese CRC


By analyse the tissue/blood variant spectrum model using NGS, the present clinical trial aims to elucidate the genetic basis of CRC in Chinese; to establish of CRC genetic map in Chinese patients; to identification new genetic biomarkers, drug and pathways; and to subtyping for precision treatment and management for Chinese CRC patients.

Full Title of Study: “A Cohort Study Evaluating the Effectiveness of the Somatic Mutation Spectrum Model in CRC Prognosis and Prediction Stratification”

Study Type

  • Study Type: Observational [Patient Registry]
  • Study Design
    • Time Perspective: Other
  • Study Primary Completion Date: February 1, 2020

Detailed Description

Colorectal cancer (CRC), as one of the common malignant tumors with high morbidity and mortality, is a major health threat in China. Surgical resection is the conventional treatment for early and intermediate stage CRC, chemotherapy is the main treatment for late stage CRC.

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA with an average size of 170bp, mixed with cell free DNA (cfDNA) of other sources in blood circulation. Although the mechanisms of its release have not been fully addressed, apoptosis and/or necrosis of tumor cells and serum exosome are considered as its main source, which makes it a genomic reservoir of different tumor clones. Also, as its half-life is up to hours, ctDNA is reflecting the most up-to-date status of tumor genome. Hence, it allows for noninvasive molecular characterization of tumors,which can be qualitative, quantitative and used for disease monitoring. The possibility of that ctDNA could be used to detect micrometastatic disease in patients received surgical resection was suggested in several studies. Using Next Generation Sequencing (NGS), Newman et al. have shown that the serum level of ctDNA was correlated with tumor progress and prognosis in NSCLC. Isaac et al. demonstrated the postoperative ctDNA level was associated with breast cancer progression, and it was more sensitive compared to CT scan for predicting the early relapse. Tie et al. examined the postoperative ctDNA level of 1046 plasma samples from a prospective cohort of 230 patients with resected stage II CRC by NGS, and their results demonstrated that recurrence happened in 79% of the patients with positive postoperative ctDNA at median follow-up of 27 months, versus 9.8% in the negative postoperative ctDNA group.

Arms, Groups and Cohorts

  • Retrospective cohort
    • Whole exome sequencing of 2500 retrospective tissue sample.
  • Prospective cohort
    • Whole exome sequencing of 500 prospectively collected tissue samples. Panel sequencing of 451 genes of prospectively collected blood samples.

Clinical Trial Outcome Measures

Primary Measures

  • prediction accuracy of survival rate
    • Time Frame: through study completion, an average of 5 years
    • We will use the gene mutation data and follow-up data of the patients to construct a prediction model,the accuracy of model to anticipating the 5 year survival rate of patients is the primary endpoint
  • prediction accuracy of recurrent rate
    • Time Frame: through study completion, an average of 3 years
    • We will use the gene mutation data and follow-up data of the patients to construct a prediction model,the accuracy of model to anticipating the 3 year recurrent rate of patients is the primary endpoint

Secondary Measures

  • Mutation Consistency of tissue and blood sample
    • Time Frame: through study completion, an average of 3 years
    • We do NGS sequencing of both the tissue sample and blood sample of the CRC patients. The gene mutation data will be analysis, and the percentage of same and different mutation of tissue and blood sample will be reported.

Participating in This Clinical Trial

Inclusion Criteria

Retrospective cohort:

1. The patient had no previous history of tumor prior to the diagnosis of colorectal cancer.

2. The tissue samples of patients were obtained from the radical(stage I-III) or palliative (stage IV) resection of colorectal cancer.

3. The clinical data of patients are complete.

4. The treatment record of the patients after surgery are complete, and the fellow-up data are available.

Prospective cohort:

1. Patients who were diagnosed as stage IV colorectal cancer and planed to received palliative systematic chemotherapy.

2. Paired 10 ml blood and tissue samples should be available

3. The clinical informations of patients and definite pathological diagnosis of colorectal cancer should be obtained

4. Patients agree with the group to follow-up them and provide follow-up informations

5. Performance status ECOG(Eastern Cooperative Oncology Group) score ≤2

6. Informed consent must be obtained from the patient

Exclusion Criteria

Retrospective cohort:

1. The patient had previous history of tumor prior to colorectal cancer surgery

2. The clinical data of patients are not available

4. The date of treatment after surgery are not integrity, outcome data are not available

Prospective cohort:

1. The patient received a blood transfusion within three months;

2. The patient has active HIV, hepatitis B or hepatitis C infection;

3. pregnant patients;

4. Alcohol or drug users;

5. Other situation that researchers considered might affect the results of the experiment or violate the ethics.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sun Yat-sen University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Ruihua Xu, Clinical Professor – Sun Yat-sen University
  • Overall Official(s)
    • Ruihua Xu, MD.,PhD, Study Director, Sun Yat-sen University
  • Overall Contact(s)
    • Feng Wang, MD.,PhD., +862087343795, wangfeng@sysucc.org.cn


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