AUTHOR=Nguyen Huu Thinh , Nguyen Trieu Vu , Nguyen Hoang Van-Anh , Tran Duc Huy , Le Trinh Ngoc An , Le Minh Triet , Nguyen Tran Tuan-Anh , Pham Thanh Huyen , Dinh Thi Cuc , Nguyen Tien Sy , Nguyen The Ky Cuong , Mai Hoa , Chu Minh Tuan , Pham Dinh Hoang , Nguyen Xuan Chi , Ngo Ha Thien My , Nguyen Duy Sinh , Nguyen Du Quyen , Lu Y-Thanh , Do Thi Thanh Thuy , Truong Dinh Kiet , Nguyen Quynh Tho , Nguyen Hoai-Nghia , Giang Hoa , Tu Lan N. TITLE=Tumor genomic profiling and personalized tracking of circulating tumor DNA in Vietnamese colorectal cancer patients JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1069296 DOI=10.3389/fonc.2022.1069296 ISSN=2234-943X ABSTRACT=Background

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. During post-operative surveillance, clinical tools are limited to stratify risk of recurrence and detect residual disease.

Method

In this prospective multi-center study, 103 CRC patients eligible for curative-intent surgery were recruited. Genomic DNA from tumor tissue and paired white blood cells were sequenced to profile all tumor-derived somatic mutations in 95 cancer-associated genes. Our bioinformatic algorithm identified top mutations unique for individual patient, which were then used to monitor the presence of circulating tumor DNA (ctDNA) in serial plasma samples.

Results

The top mutated genes in our cohort were APC, TP53 and KRAS. 41.7% of the patients harbored KRAS and NRAS mutations predictive of resistance to Cetuximab and Panitumumab respectively; 41.7% had mutations targeted by either approved or experimental drugs. Using a personalized subset of top ranked mutations, we detected ctDNA in 90.5% of the pre-operative plasma samples, whereas carcinoembryonic antigen (CEA) was elevated in only 41.3% of them. Interim analysis after 16-month follow-up revealed post-operative detection of ctDNA in two patients that had recurrence, with the lead time of 4-10.5 months ahead of clinical diagnosis. CEA failed to predict recurrence in both cases.

Conclusion

Our assay showed promising dual clinical utilities in residual cancer surveillance and actionable mutation profiling for targeted therapies in CRC patients. This could lay foundation to empower precision cancer medicine in Vietnam and other developing countries.