Shihe Gene's major achievements: the first multi-center prospective colorectal cancer MRD study data published in China

Introduction:

MRD monitoring based on ctDNA is currently an important research direction in the field of early and mid-term tumor precision treatment.
Compared with traditional imaging and tumor marker detection, this technology has the advantages of high sensitivity, convenience, and low risk, but there is still a lack of large-scale clinical research.
Proof of verification
.

The team of Professor Ruihua Xu from the Cancer Center of Sun Yat-sen University and the team of Professor Cai Sanjun from Fudan University Cancer Hospital and the team of Professor Ding Kefeng from the Second Affiliated Hospital of Zhejiang University carried out a prospective multi-center cohort study (NCT03312374), using Shihe gene ctDNA liquid biopsy Technology, dynamic assessment of early and mid-stage colorectal cancer postoperative MRD status, exploring the value of MRD status in colorectal cancer recurrence risk stratification and recurrence monitoring, the latest research results were published in Journal of Hematology & Oncolology (IF=11.
06, real-time impact factor 17) Magazine
.

research content:

A total of 276 patients with colorectal cancer in clinical stage II/III were enrolled in this study, of which 240 patients received radical surgery and were included in the study
.

Collect surgical tissue samples of the enrolled patients, dynamic plasma samples within one week before surgery, 3-7 days after surgery, and 6-24 months after surgery (blood sampling every three months).

Research highlights:

① The first domestic multi-center prospective large-scale cohort study of ctDNA MRD for colorectal cancer, with large sample size and long follow-up time

This research was jointly completed by three domestic first-class research centers, Sun Yat-sen University Cancer Center, Fudan University Affiliated Cancer Hospital, and Zhejiang University Second Affiliated Hospital
.

From 2017 to 2020, a total of 276 patients with early and mid-stage bowel cancer surgery were enrolled, and a complete follow-up was carried out.

② The research design is perfect, the implementation is solid, the results are remarkable, and it is widely valued by the field, and the real-time IF of the journal is 17 points.

This study is currently the largest clinical study published in the field of colorectal cancer MRD, and innovatively included the blood sampling points 3-7 days after surgery for the first time
.

The results proved that positive ctDNA MRD 3-7 days after surgery is an independent indicator that can predict the recurrence of bowel cancer

③.
Breaking the bottleneck of conventional imaging technology in the early and mid-stage colorectal cancer recurrence model is of great clinical significance

The use of Shihe Gene's ultra-high-sensitivity liquid biopsy technology has confirmed the important application value of ctDNA MRD in the direction of postoperative recurrence risk monitoring of colon cancer, and can provide effective guidance for early and mid-stage bowel cancer precision medicine
.

Accurate adjuvant treatment based on the guidance of ctDNA MRD can better achieve patient risk stratification and timely adjust treatment plans.

Analysis conclusion:

CtDNA MRD independently predicts a significant risk of recurrence 3-7 days after surgery

Plasma samples of 240 patients with colorectal cancer were collected 3-7 days after surgery and performed ultra-sensitive NGS liquid biopsy
.

Among the 20 patients with positive blood ctDNA MRD after surgery, the risk of recurrence was significantly higher than that of negative patients, with an HR of 10.

CtDNA MRD after adjuvant therapy predicts a significant risk of recurrence

       Collect plasma samples from 137 patients after adjuvant treatment and perform ultra-high-sensitivity NGS liquid biopsy
.

Among the 12 patients with positive ctDNA MRD after adjuvant therapy, the risk of recurrence was significantly higher than that of negative patients, with an HR of 12.

       ctDNA dynamic monitoring earlier than imaging 5.
01 month suggests tumor recurrence

       Subsequent ctDNA multi-point dynamic monitoring results showed that patients evaluated as positive for ctDNA MRD during the dynamic monitoring process had a significantly higher risk of recurrence than negative patients, with an HR as high as 32.
02 (Figure c)
.

In addition, ctDNA dynamic monitoring can prompt tumor recurrence earlier than imaging detection, with a median advance of 5.

       Shihe Gene independently developed ultra-high-sensitivity liquid biopsy technology to help manage the entire perioperative period

       In 2015, Shihe Gene took the lead in launching tumor liquid biopsy testing in China, and it has tested more than 200,000 cases
.

Based on a large amount of liquid biopsy experience, S&P has further developed ultra-high-sensitivity liquid biopsy technology, and developed the early and mid-term tumor perioperative full-process management product-Shuning

       Expert Reviews:

       ★Professor Xu Ruihua: "Early and mid-stage colorectal cancer is faced with two major problems after radical resection: how to identify patients at high risk of recurrence for accurate decision-making assistance? How to detect tumor recurrence earlier for timely intervention?

       In recent years, blood circulating tumor DNA (ctDNA) detection technology has become more and more perfect, and has great application potential in identifying patients with high recurrence risk and early warning of tumor recurrence, but there is still a lack of high-quality evidence-based medical evidence
.

       This study is a prospective and observational cohort study jointly carried out by the colorectal cancer multidisciplinary team of our center, the team of Professor Cai Sanjun from the Cancer Hospital of Fudan University, and the team of Professor Ding Kefeng from the Second Affiliated Hospital of Zhejiang University School of Medicine.
Can the ctDNA test identify colon cancer patients with a high risk of recurrence and warn of tumor recurrence in advance
? The results of the study confirmed that postoperative ctDNA-positive patients have a significantly higher risk of recurrence than ctDNA-negative patients.
Dynamic ctDNA detection can predict tumor recurrence in advance compared with conventional imaging methods such as CT examination
.
This study provides strong evidence for the application of ctDNA detection in the precise stratification of postoperative recurrence risk, which is expected to guide the precise treatment decision-making of early and mid-stage colorectal cancer patients after surgery and adjuvant therapy
.
"

       ★Professor Ding Kefeng: "This is the first domestic multi-center clinical study using ctDNA detection technology to explore the risk of recurrence after colorectal cancer surgery
.
For the current difficulties in the diagnosis and treatment of colorectal cancer after surgery, such as: what kind of patient’s risk of recurrence after surgery Is there a high need for chemotherapy? Is there a way to detect tumor recurrence early? The large sample research data provided by our three major tumor centers clearly indicates the direction of problem solving
.
Research shows that ctDNA status is closely related to the risk of recurrence and recurrence time after surgery, and ctDNA can compare Conventional methods provide early warning of tumor recurrence 5.
01 months in advance
.
This will open a new door for precise chemotherapy and precise follow-up after colorectal cancer surgery, and provide a plan for early detection and early intervention of tumor recurrence
.

       ★Professor Peng Junjie: "Colorectal cancer is the third most common malignant tumor in China in terms of morbidity and mortality.
Surgical resection is the most important treatment for stage I-III colorectal cancer, but there are still 30-50% of patients after radical resection.
Recurrence
.
At present, the most commonly used clinical recurrence and metastasis monitoring methods are mainly tumor markers and imaging detection, but the sensitivity is relatively poor
.
Liquid biopsy is an emerging monitoring technology in recent years, in which plasma ctDNA is a sensitive marker of tumor burden.
It can become a new method to predict the recurrence and metastasis of colon cancer after surgery
.

       In this study, 240 patients with stage II-III colorectal cancer were included in the three major domestic tumor centers.
It is the largest research cohort that has so far evaluated the effectiveness of plasma ctDNA monitoring for colorectal cancer in China
.
The results of the study confirm that plasma ctDNA detection can predict tumor recurrence and metastasis 3 to 7 days after surgery, and provide a reference for the formulation of clinical adjuvant chemotherapy; continuous plasma ctDNA dynamic monitoring reflects tumor burden, which can be compared with tumor markers and imaging detection Early indication of tumor recurrence and metastasis provides a time window for early clinical intervention
.

       In addition, this study also found that the recurrence rate of ctDNA-negative patients is extremely low, suggesting that patients with negative ctDNA monitoring can reduce the number of CT examinations, thereby reducing radiation exposure and unnecessary inspection costs, thereby optimizing the current recurrence monitoring strategy
.
"