Clinical trial NCT03923335: The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer
Official title: The Predictive Value of Guangzhou Panel for Recurrence in Early-stage Colorectal Cancer
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Colorectal Neoplasms
Keywords: colorectal cancer
prognostic biomarkers
DNA Methylation
gene panel
recurrence
disease free survival
Lead sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-04-22
Enrollment: 287
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients that had pathologically verified stage I-II CRC and underwent surgical resection in Sixth Affiliate Hospital of Sun Yat-sen University

Brief summary: This study aims to evaluate the predictive value of a four-gene methylation assay called Guangzhou Panel in early-stage colorectal cancer. Patients will be divided into two groups: high risk group and low risk group. The primary endpoint is 5 year disease free survival (DFS).

Detailed description: The current risk stratification system defined by clinicopathological features does not identify the risk of disease recurrence in patients with early-stage colorectal cancer (CRC) with optimal accuracy. The investigators aimed to investigate whether the epigenetic alterations could serve as novel prognostic biomarkers that would improve the accuracy of the current primary tumor, regional nodes, metastasis (TNM) staging system.

In the current study, the Investigators have analyzed the genome-wide methylation status of cytosine-phosphate-guanosine (CpG) sites using Infinium MethylationEPIC array in primary tumor and adjacent normal samples from 23 recurrent and 22 recurrence-free stage I and II CRC patients to identify potential methylation markers for disease-free survival (DFS). The prognostic value of the candidate biomarkers has been evaluated in a training cohort (n=174) and an independent validation cohort (n=267), and is to be validated in a prospective cohort (estimated n=287).

Comprehensive data analysis identified a subset of methylated CpG loci that associated with a high risk of recurrence. Methylated CpGs in four genes were significantly associated with DFS in multivariate analysis in both training and validation cohort. Moreover, Hypermethylated Genes Counts panel using these four markers showed a higher prognostic value than any clinicopathological factor, current molecular biomarkers or single methylated CpG marker alone in the training and validation cohorts. This four-gene methylation assay is defined as Guangzhou Panel.

The investigators aim to conduct a prospective observational study to evaluate the predictive value of Guangzhou Panel in early-stage colorectal cancer. A total of 287 patients with pathologically verified stage I-II CRC and underwent surgical resection are expected to be recruited in our study. These patients will be divided into high-risk group and low-risk group and will be followed up at least 5 years. The primary endpoint is 5-year disease free survival (DFS). The prognostic strength of candidate biomarkers was adjusted in multivariate Cox regression models including multiple biomarkers and clinicopathologic variables.

Eligibility criteria: Inclusion Criteria:

1. TNM stage I-II (T1-4N0M0) colorectal cancer cases
2. receive radical surgical resection
3. have completed data of tumor location, histological type, behavioral characteristics or TNM staging
4. have tumor specimens and either a valid microsatellite instability (MSI) or immuno-histochemistry (IHC) data
5. have valid V-raf murine sarcoma viral oncogene homolog B1 (BRAF), kirsten rat sarcoma viral oncogene (KRAS), CpG island methylator phenotype (CIMP) results
6. have at least 4 years of follow-up
7. have valid time to local recurrence/metastasis in follow-up
8. have clinical/treatment record data and valid preoperative status of intestinal obstruction or perforation (IOP), counts of lymph node removed in surgical resection.

Exclusion Criteria:

1. have had a previous diagnosis of any cancer or presence of any tumor other than the CRC
2. have had inflammatory bowel disease
3. have had hereditary colorectal cancer syndromes, including Familial adenomatous polyposis, mutyh (MYH)-associated polyposis, Peutz-Jeghers syndrome, Juvenile polyposis coli, phosphate and tension homology deleted on chromosome ten (PTEN) tumor-hamartoma syndromes, Lynch Syndrome, and Familial Colorectal Cancer Type X.

Primary outcomes:
measure: disease free survival
timeFrame: From date of operation until the date of first recurrence or date of death from any cause, whichever came first, assessed up to 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Sixth Affiliate Hospital of Sun Yat-Sen University
state: Guangdong
Study officials:
affiliation: The Sixth Affiliated Hospital, Sun Yat-sen University
name: Yanxin Luo, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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