Fragment length profiles of cancer mutations enhance detection of circulating tumor DNA in patients with early-stage hepatocellular carcinoma.

BACKGROUND: Late detection of hepatocellular carcinoma (HCC) results in an overall 5-year survival rate of less than 16%. Liquid biopsy (LB) assays based on detecting circulating tumor DNA (ctDNA) might provide an opportunity to detect HCC early noninvasively. Increasing evidence indicates that ctDNA detection using mutation-based assays is significantly challenged by the abundance of white blood cell-derived mutations, non-tumor tissue-derived somatic mutations in plasma, and the mutational tumor heterogeneity. METHODS: Here, we employed concurrent analysis of cancer-related mutations, and their fragment length profiles to differentiate mutations from different sources. To distinguish persons with HCC (PwHCC) from healthy participants, we built a classification model using three fragmentomic features of ctDNA through deep sequencing of thirteen genes associated with HCC. RESULTS: 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%. CONCLUSIONS: Our study provides a rationale for subsequent clinical evaluation of our assay performance in a large-scale prospective study.

Circulating DNA methylation profile improves the accuracy of serum biomarkers for the detection of nonmetastatic hepatocellular carcinoma.

Aim: 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. Methods: Differentially methylated regions in cell-free DNA between 58 nonmetastatic HCC and 121 high-risk patients with liver cirrhosis or chronic hepatitis were identified and used to train machine learning classifiers. Results: The model could distinguish HCC from high-risk non-HCC patients in a validation cohort, with an area under the curve of 0.84. Combining these markers with the three serum biomarkers (AFP, lectin-reactive AFP, des-γ-carboxy prothrombin) in a commercial test, µTASWako®, achieved an area under the curve of 0.87 and sensitivity of 68.8% at 95.8% specificity. Conclusion: HCC-specific circulating DNA methylation markers may be added to the available assay to improve the early detection of HCC.

The early detection of liver cancer in high-risk populations can help people with the disease have a higher chance of survival and better quality of life. However, this is still a healthcare challenge. Current commercial blood tests measuring protein signatures in the blood have low accuracy due to increased levels of these proteins being detected in both liver cancer patients and patients with chronic liver diseases. In this study, we identified a set of signatures in DNA released by cancer cells into the bloodstream and used them as biomarkers to distinguish liver cancer patients from high-risk patients. We also demonstrated that adding those signatures to a commercial blood test currently used in clinics could improve the accuracy in detecting liver cancer patients.

Health-Related Quality of Life Among Vietnamese Breast Cancer Women.

The aim of the study was to investigate health-related quality of life among Vietnamese breast cancer women who were treated at National Cancer Hospital, Hanoi, Vietnam, in 2018. Information about physical functioning, Role Physical, Bodily Pain, General Health, vitality, Social Functioning, Role Emotional, and Mental Health of 200 patients with breast cancer was collected through face-to-face interview, using short form-36 questionnaire. We found that the older patients (older than 50 years) had higher score of Mental Health than patients at age 50 and lower (P < .05). The patients who had better economic status had significantly higher score of Vitality (P < .05). Patients who were married and living with their partners/husband had better quality of life in General Health (P<0.05). The patients who had less than 6 months of treatment had better physical functioning score (P < .05) than the patients who had treatment longer than 6 months. Patients with caring supports from family members had higher scores of Bodily Pain, Social Functioning, Role Emotional, and Mental Health. Patients who have stressed feelings had significantly lower scores of all domains, except for Physical Functioning. The participants who usually stay up late reported lower scores of all components except for Physical Functioning and Role Physical. In conclusion, it is needed to develop psychosocial services, enhance early screening, and diagnose for the women in Vietnam.

Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization.

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening.

Estimating cost-effectiveness of screening for colorectal cancer in Vietnam.

Background:Presently, there are no national screening programs for cancer in Vietnam. This study aimed to analyze the cost-effectiveness of an annual colorectal cancer (CRC) screening program from the healthcare service provider's perspective for the Vietnamese population.Methods:The economic model consisted of adecision tree and aMarkov model. Adecision tree was constructed for comparing two strategies, including ascreening group with aguaiac-based fecal occult blood test (gFOBT) and ano-screening group in general populations, aged 50 years and above. The Markov model projected outcomes over a25-year horizon. The cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER) represented by costs per quality-adjusted life-years (QALYs).Results:When compared with no screening, ICER was $1,388per QALY with an increased cost of $ 43.98 and again of 0.032 QALY (Willingness to pay $2,590). The uptake rate of gFOBT, cost of colonoscopy, and the total cost of screening contributed to the largest impact on the ICER. PSA showed that results were robust to variation in parameter estimates, with annual screening remaining cost-effective compared with no screening.Conclusion:Our screening strategy could be considered cost-effective compared to ano screening strategy. Our findings could be potentially used to develop aCRC national screening program.