Báo cáo khoa học

We developed an assay to accurately determine the homologous recombination deficiency status of ovarian tissue samples, including those with low DNA quality. This study was the first to analyze the prevalence and spectrum of homologous recombination deficiency in Vietnamese patients with ovarian cancer. Comprehensive assessment of homologous recombination deficiency should be performed instead of BRCA1/2 testing alone so that no patients miss their opportunity for PARPi treatment.

The clinical utilization of circulating tumor DNA (ctDNA) in breast cancer (BC) management is not well-defined. In this prospective study, 168 patients with early-stage BC were recruited, serial blood samples were collected before and after surgery. Tumor-informed ctDNA testing was performed, which sequenced tumors for 95 genes followed by bespoke mPCR to track 1–9 mutations in the plasma. ctDNA was detected before surgery in 14.6%, 40.0%, 83.8%, and 80.0% of HR+ low-risk, HR+ high-risk, HR-HER2+ and HR-HER2- patients, respectively. Pre-operative ctDNA positivity was significantly associated with decreased disease-free survival (DFS) (adjusted HR = 3.09, 95% CI 2.65–80.0, p = 0.001). After a median 26.6-month follow-up, 11 patients relapsed, and ctDNA at landmark time point 2–4 weeks after surgery was detected in 50.0% (5/10) of cases. Landmark ctDNA clearance was associated with significantly longer DFS (p = 0.0009) and positive ctDNA persistence after adjuvant therapy occurred in 36.4% (4/11) of stage-III patients. During surveillance, ctDNA detection had 90.9% sensitivity and 98.8% specificity to predict recurrence, and median lead time of 9.7 months. Patients with detected ctDNA had shorter DFS than those with undetectable ctDNA (adjusted HR = 207.05, 95% CI 41.38- > 1000, p = 0.001). Therefore, ctDNA status both before and after surgery could help stratify recurrence risk for BC patients.

In the early-stage I-III, preoperative ctDNA detection rates were 66.7%, 84.6%, 54.3%, 52.6%, 93.3%, and 75.0% for lung, colorectal, breast, gastric, liver, and ovarian cancers, respectively. After surgery, 84.4% (38/45) of patients with recurrence had ctDNA detected in the plasma, while 96.3% (210/218) of patients with no recurrence had negative results. Postoperative ctDNA positivity significantly increased the risk of recurrence (P 100 [95% CI, 26.9 to >100.0) cancers. In the metastatic stage IV, pretreatment ctDNA detection rates were 80.0%, 87.7%, 73.3%, 70.6%, 91.7%, and 81.8% for lung, colorectal, breast, gastric, liver, and ovarian cancers, respectively. Case studies were presented to demonstrate utilization of ctDNA at all cancer stages.

This study provides the first large datasets for HBOC gene analysis, BC susceptibility SNP association testing, and PRS modeling for Vietnamese women. Together, these data could aid the development of personalized BC screening recommendations for women in Vietnam.

Circulating tumor DNA (ctDNA) is a novel biomarker for predicting recurrence in colorectal cancer (CRC). Analysis from both clinical trials and real-world data indicates that ctDNA serves as an independent and strong prognostic biomarker for CRC recurrence. ctDNA testing may aid clinical decision-making by supporting personalized intervention and surveillance strategies.

The emergence of multicancer early detection (MCED) tests holds promise for improving early cancer detection and public health outcomes. However, positive MCED test results require confirmation through recommended cancer diagnostic imaging modalities. To address these challenges, we have developed a consultation and work-up protocol for definitive diagnostic results post MCED testing, named SPOT-MAS. Developed through circulating tumor DNA (ctDNA) analysis and in line with professional guidelines and advisory board consensus, this protocol standardizes information to aid general practitioners in accessing, interpreting and managing SPOT-MAS results. Clinical effectiveness is demonstrated through a series of identified cancer cases. Our research indicates that the protocol could empower healthcare professionals to confidently interpret circulating tumor DNA test results for 5 common types of cancer, thereby facilitating the clinical integration of MCED tests.

This study exploited hepatocellular carcinoma (HCC)-specific circulating DNA methylation profiles to improve the accuracy of a current screening assay for HCC patients in high-risk populations.

Population-specific profiling of mutations in cancer genes is of critical importance for the understanding of cancer biology in general as well as the establishment of optimal diagnostics and treatment guidelines for that particular population.

We have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.

K-4CARE™ assay provides comprehensive and reliable genomic information that fulfills all guideline-based biomarker testing for both targeted therapy and immunotherapy. Integration of ctDNA tracking helps clinicians to further monitor treatment response and ultimately provide well-rounded care to cancer patients.

eLife assessment: This study provides insights into the early detection of malignancies with noninvasive methods by developing a framework, which assesses methylation, CNA, and other genomic features. They established a solid model in discriminating malignancies from healthy controls, as well as the ability to distinguish tumor of origin. This important study will demonstrate its practical impacts in the clinic and other researchers of the field.

Of all genetic test results, 3% (49/1632) were identified with mutations related to HCCS. Over 77% of them belonged to Lynch syndrome. PMS2 appeared to be the gene with the highest mutation frequency, while MLH1 was the lowest. This study provided new evidence for HCCS mutation spectrum in Vietnamese population and the success in promoting cascade test in high-risk family members through financial and technical support.

The article showed that a multimodal liquid biopsy assay based on analysis of cfDNA methylation, CNA and EM could enhance the accuracy for the detection of early- stage breast cancer. By identifying distinct profiles of genome-wide methylation changes (GWM), copy number alterations (CNA), and 4-nucleotide oligomer (4-mer) end motifs (EM) in cfDNA of breast cancer patients, combination model outperformed base models built from individual features, achieving an AUC of 0.91 (95% CI: 0.87-0.95), a sensitivity of 65% at 96% specificity.

Our model achieved an area under the curve (AUC) of 0.88, a sensitivity of 89%, and a specificity of 82% in the discovery cohort consisting of 55 PwHCC and 55 healthy participants. In an independent validation cohort of 54 PwHCC and 53 healthy participants, the established model achieved comparable classification performance with an AUC of 0.86 and yielded a sensitivity and specificity of 81%.

Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location.

Hereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown.

Evaluate SPOT-MAS performance on detection of 4 common cancer types AUC 0.93; SEN: 73.9%; SPEC 95.9%

Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops after treatment.

The identification and quantification of actionable mutations are critical for guiding targeted therapy and monitoring drug response in colorectal cancer. Liquid biopsy (LB) based on plasma cell-free DNA analysis has emerged as a noninvasive approach with many clinical advantages over conventional tissue sampling.

Colorectal cancer (CRC) is the fifth most common cancer with rising prevalence in Vietnam. However, there is no data about the mutational landscape and actionable alterations in the Vietnamese patients.

Using top-ranked mutations, we detected ctDNA in pre-operative plasma in 24.6–43.5% of the hormone-receptor-positive groups and 76.9–80.8% of the hormone-receptor-negative groups. The detection rate was associated with breast cancer subtypes and clinicopathological features that increased the risk of relapse. Interim analysis after a 15-month follow-up revealed post-operative detection of ctDNA in all three patients that had recurrence, with a lead time of 7–13 months ahead of clinical diagnosis.

Early detection of colorectal cancer (CRC) provides substantially better survival rates. This study aimed to develop a blood-based screening assay named SPOT-MAS (‘screen for the presence of tumor by DNA methylation and size’) for early CRC detection with high accuracy.

Identification of tumor-derived mutation (TDM) in liquid biopsies (LB), especially in early-stage patients, faces several challenges, including low variant-allele frequencies, interference by white blood cell (WBC)-derived mutations (WDM), benign somatic mutations and tumor heterogeneity.

Population-specific profiling of mutations in cancer genes is of critical importance for the understanding of cancer biology in general as well as the establishment of optimal diagnostics and treatment guidelines for that particular population.

Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients.

The identification and quantification of actionable mutations are of critical importance for effective genotype-directed therapies, prognosis and drug response monitoring in patients with non-small-cell lung cancer (NSCLC).