Network for molecular biologists & oncologists LogoMedical Genetics Institute Logo
QR Code

ASCO Breakthrough

Abstract ID: 426802

Correspondence:
Lan N Tu at [email protected]

Personalized K-TrackTM Assay to Detect Actionable Mutations and Minimal Residual Disease in Solid Tumors

BACKGROUND

  • Minimal residual disease (MRD) refers to a small number of cancer cells that remain in the body after curative-intent treatment, causing relapse and metastasis. Current tumor biomarkers and imaging methods have limited sensitivity and specificity to monitor MRD for solid tumors.
  • Circulating tumor DNA (ctDNA) in liquid biopsy has emerged as a promising biomarker to monitor MRD.
  • Current MRD assays remain mostly inaccessible and unaffordable for patients in developing countries.
Image Results 022
Figure 1. MRD in solid tumors. MRD, or the remaining cancer cells after curative-intent treatment, is the leading cause for relapse and metastasis.

METHOD

  • Tumor-informed personalized ctDNA tracking assay
  • Streamlined and cost-effective
Image Results 022
Figure 2. Study design and workflow of K-TrackTM assay. (A) Cancer patients indicated for curative-intent surgery were enrolled. Serial plasma samples were collected before surgery and at scheduled visits. FFPE samples were also collected. (B) gDNA of paired FFPE and WBC samples were sequenced to identify all tumor-specific somatic mutations in 95 cancer-associated genes. Top 5-10 mutations were selected to monitor ctDNA presence in plasma samples by a multiplex PCR assay and ultra-deep sequencing at an average depth of 100,000X.

PRE-OPERATIVE ctDNA DETECTION

Table 1. Detection of ctDNA in plasma samples before radical surgery

Cancer typeCohort (N)Detection rate
Hepatocellular carcinoma (HCC)6096.6%
Colorectal Cancer (CRC)11585.2%
Breast Cancer (BC)115
HR(+), HER2(+/-), high risk*7040.0%
HR(-), HER2(+)3083.3%
HR(-), HER2(-)1580.0%
Non-small cell lung cancer (NSCLC)5062.0%
Gastric Cancer (GC)9445.7%
Ovarian Cancer (OC)1764.7%
(*) High risk: ≥15% predicted risk of death within 10 years using ePREDICT V2.1, or tumor size T>5 cm, or N≥4 nodes, or N=1-3 nodes and at least one of the following: T>3 cm, grade 3, high genomic risk defined as Oncotype Dx Recurrence Score >26

PROGNOSTIC VALUE OF POST-OPERATIVE ctDNA

A - Hepatocellular carcinoma (HCC)

Image ANALYTICAL VALIDATION 022
Image ANALYTICAL VALIDATION 022
Image ANALYTICAL VALIDATION 022

B - Colorectal Cancer (CRC)

Image ANALYTICAL VALIDATION 022
Image ANALYTICAL VALIDATION 022
Image ANALYTICAL VALIDATION 022

C - Breast Cancer (BC)

Image ANALYTICAL VALIDATION 022
Image ANALYTICAL VALIDATION 022
Image ANALYTICAL VALIDATION 022

D - Gastric Cancer (GC)

Image ANALYTICAL VALIDATION 022
Image ANALYTICAL VALIDATION 022
Image ANALYTICAL VALIDATION 022
Figure 3. Prognostic value of post-operative ctDNA. (A-D) Kaplan-Meier plots showed that patients with ctDNA(+) after surgery were more likely to relapse than those with ctDNA(-). The sensitivity and specificity of ctDNA to detect relapse were shown in individual graph. This is an interim analysis as the study is ongoing.

ANALYTICAL VALIDATION

  • Limit of detection at VAF ≥ 0.05%
  • A sample is defined as ctDNA(+) if one of the mutations has VAF ≥ 0.05%
Image ANALYTICAL VALIDATION 022
Figure 4. Analytical validation of K-TrackTM assay. Sensitivity and specificity at variant-level and sample-level were determined by using Seraseq® ctDNA MRD Panel Mix (SeraCare, USA).

Ethical approval The study was approved by the institutional ethics committees of the University of Medicine and Pharmacy (#300/HDDD, #81/GCN-HDDD, #14/GCN-HDDD, and 164/HDDD), Thu Duc city Hospital (#17/HDDD), and Cho Ray hospital (# 1183/GCN-HDDD).

Acknowledgement We especially thank the doctors and nurses from UMP, TD, CR hospitals for collaborating with us and all of our patients for participating in the study.

Funding This study was funded by Gene Solutions JSC, Vietnam.

CONCLUSION

  • K-TrackTM assay is streamlined and affordable with dual clinical utilities in residual cancer surveillance and actionable mutation profiling.
  • The assay could lay foundation to empower precision cancer medicine in Vietnam and developing countries

Gene Solutions divider
Clinical validation of a ctDNA-based assay for multi-cancer detection: A Vietnamese longitudinal prospective cohort study of 2795 participants
Personalized K-TrackTM Assay to Detect Actionable Mutations and Minimal Residual Disease in Solid Tumors
Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization
Gene Solutions divider