Clinical trial and real-world evidence of circulating tumor DNA monitoring to predict recurrence in patients with resected colorectal cancer
Background: Circulating tumor DNA (ctDNA) is a novel biomarker to predict recurrence in colorectal cancer (CRC). However, clinical validation data in underrepresented patient populations like Southeast Asians are lacking. Materials and methods: In our prospective clinical trial, 92 patients with sta...
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2024-12-01
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| author | H.T. Nguyen V.-A. Nguyen Hoang T.V. Nguyen N.A.L. Trinh T.H. Pham D.N. Le H.H. Ho T.D. Nguyen H.D. Nguyen T.S.L. Thi N. Nguyen D.H. Tran M.T. Le T.C. Dinh T.S. Nguyen K.C.N. The H. Mai M.T. Chu D.H. Pham N.H.T. Phuc D.N. Vinh D.-N. Nguyen X.-V. Nguyen D.S. Nguyen T.T.D. Thi H. Giang H.-N. Nguyen L.N. Tu |
| author_facet | H.T. Nguyen V.-A. Nguyen Hoang T.V. Nguyen N.A.L. Trinh T.H. Pham D.N. Le H.H. Ho T.D. Nguyen H.D. Nguyen T.S.L. Thi N. Nguyen D.H. Tran M.T. Le T.C. Dinh T.S. Nguyen K.C.N. The H. Mai M.T. Chu D.H. Pham N.H.T. Phuc D.N. Vinh D.-N. Nguyen X.-V. Nguyen D.S. Nguyen T.T.D. Thi H. Giang H.-N. Nguyen L.N. Tu |
| author_sort | H.T. Nguyen |
| collection | DOAJ |
| description | Background: Circulating tumor DNA (ctDNA) is a novel biomarker to predict recurrence in colorectal cancer (CRC). However, clinical validation data in underrepresented patient populations like Southeast Asians are lacking. Materials and methods: In our prospective clinical trial, 92 patients with stage I-IVA CRC and eligible for curative-intent surgery were recruited. Blood samples were collected before surgery, after surgery and during surveillance. ctDNA analysis was carried out using a personalized tumor-informed approach. Performance of ctDNA monitoring was further evaluated in a retrospective analysis of 32 patients who had commercial ctDNA testing. Results: Before surgery, the ctDNA detection rate was 91.2%, significantly higher than the carcinoembryonic antigen (CEA) elevation rate at 42.9%. At 2-4 weeks after surgery, ctDNA detection, not CEA, was significantly associated with shorter disease-free survival (DFS) [hazard ratio (HR) = 30.3, 95% confidence interval (CI) 3.3-278.9, P = 0.002]. Longitudinally, ctDNA positivity showed the strongest prognostic value with 100% sensitivity and specificity to detect recurrence (HR = 173.6, 95% CI 19.7 to >1000, P = 0.001); the median lead time was 8.0 months. In the real-world data analysis, post-operative ctDNA remained the only significant prognostic biomarker for DFS (HR = 44.2, 95% CI 9.2-212.0, P < 0.0001). Among relapsed patients, the most common mutations found in ctDNA were in TP53 (58.8%), APC (52.9%) and KRAS (41.2%), with high frequency of co-mutations. Conclusion: Our analysis from both clinical trial and real-world data indicated that ctDNA was an independent and strong prognostic biomarker to predict recurrence in CRC. ctDNA testing could be helpful for clinical decision making by enabling personalized intervention and surveillance strategies. |
| format | Article |
| id | doaj-art-cee9144ded564258b2eaf4bf970e2fbe |
| institution | DOAJ |
| issn | 2949-8201 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
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| series | ESMO Real World Data and Digital Oncology |
| spelling | doaj-art-cee9144ded564258b2eaf4bf970e2fbe2025-08-20T03:14:28ZengElsevierESMO Real World Data and Digital Oncology2949-82012024-12-01610007610.1016/j.esmorw.2024.100076Clinical trial and real-world evidence of circulating tumor DNA monitoring to predict recurrence in patients with resected colorectal cancerH.T. Nguyen0V.-A. Nguyen Hoang1T.V. Nguyen2N.A.L. Trinh3T.H. Pham4D.N. Le5H.H. Ho6T.D. Nguyen7H.D. Nguyen8T.S.L. Thi9N. Nguyen10D.H. Tran11M.T. Le12T.C. Dinh13T.S. Nguyen14K.C.N. The15H. Mai16M.T. Chu17D.H. Pham18N.H.T. Phuc19D.N. Vinh20D.-N. Nguyen21X.-V. Nguyen22D.S. Nguyen23T.T.D. Thi24H. Giang25H.-N. Nguyen26L.N. Tu27University Medical Center Ho Chi Minh City, Ho Chi Minh CityMedical Genetics Institute, Ho Chi Minh City; Gene Solutions, Ho Chi Minh CityThu Duc City Hospital, Ho Chi Minh CityUniversity Medical Center Ho Chi Minh City, Ho Chi Minh CityThu Duc City Hospital, Ho Chi Minh CityDong Nai General Hospital, Dong NaiMilitary Hospital 175, Ho Chi Minh CityMilitary Hospital 175, Ho Chi Minh CityThanh Nhan Hospital, HanoiNam Sai Gon International General Hospital, Ho Chi Minh City, VietnamMedical Genetics Institute, Ho Chi Minh City; Gene Solutions, Ho Chi Minh CityUniversity Medical Center Ho Chi Minh City, Ho Chi Minh CityUniversity Medical Center Ho Chi Minh City, Ho Chi Minh CityThu Duc City Hospital, Ho Chi Minh CityThu Duc City Hospital, Ho Chi Minh CityThu Duc City Hospital, Ho Chi Minh CityThu Duc City Hospital, Ho Chi Minh CityThu Duc City Hospital, Ho Chi Minh CityThu Duc City Hospital, Ho Chi Minh CityMedical Genetics Institute, Ho Chi Minh City; Gene Solutions, Ho Chi Minh CityMedical Genetics Institute, Ho Chi Minh City; Gene Solutions, Ho Chi Minh CityMedical Genetics Institute, Ho Chi Minh City; Gene Solutions, Ho Chi Minh CityMedical Genetics Institute, Ho Chi Minh City; Gene Solutions, Ho Chi Minh CityMedical Genetics Institute, Ho Chi Minh City; Gene Solutions, Ho Chi Minh CityMedical Genetics Institute, Ho Chi Minh CityMedical Genetics Institute, Ho Chi Minh City; Gene Solutions, Ho Chi Minh CityMedical Genetics Institute, Ho Chi Minh City; Gene Solutions, Ho Chi Minh CityMedical Genetics Institute, Ho Chi Minh City; Gene Solutions, Ho Chi Minh City; Correspondence to: Dr Lan N. Tu, Medical Genetics Institute and Gene Solutions, 186-188 Nguyen Duy Duong, District 10, Ho Chi Minh City, Vietnam. Tel: +84-888843489Background: Circulating tumor DNA (ctDNA) is a novel biomarker to predict recurrence in colorectal cancer (CRC). However, clinical validation data in underrepresented patient populations like Southeast Asians are lacking. Materials and methods: In our prospective clinical trial, 92 patients with stage I-IVA CRC and eligible for curative-intent surgery were recruited. Blood samples were collected before surgery, after surgery and during surveillance. ctDNA analysis was carried out using a personalized tumor-informed approach. Performance of ctDNA monitoring was further evaluated in a retrospective analysis of 32 patients who had commercial ctDNA testing. Results: Before surgery, the ctDNA detection rate was 91.2%, significantly higher than the carcinoembryonic antigen (CEA) elevation rate at 42.9%. At 2-4 weeks after surgery, ctDNA detection, not CEA, was significantly associated with shorter disease-free survival (DFS) [hazard ratio (HR) = 30.3, 95% confidence interval (CI) 3.3-278.9, P = 0.002]. Longitudinally, ctDNA positivity showed the strongest prognostic value with 100% sensitivity and specificity to detect recurrence (HR = 173.6, 95% CI 19.7 to >1000, P = 0.001); the median lead time was 8.0 months. In the real-world data analysis, post-operative ctDNA remained the only significant prognostic biomarker for DFS (HR = 44.2, 95% CI 9.2-212.0, P < 0.0001). Among relapsed patients, the most common mutations found in ctDNA were in TP53 (58.8%), APC (52.9%) and KRAS (41.2%), with high frequency of co-mutations. Conclusion: Our analysis from both clinical trial and real-world data indicated that ctDNA was an independent and strong prognostic biomarker to predict recurrence in CRC. ctDNA testing could be helpful for clinical decision making by enabling personalized intervention and surveillance strategies.http://www.sciencedirect.com/science/article/pii/S2949820124000547minimal residual disease (MRD)disease-free survival (DFS)circulating tumor DNAcolorectal cancerrecurrenceprognosis |
| spellingShingle | H.T. Nguyen V.-A. Nguyen Hoang T.V. Nguyen N.A.L. Trinh T.H. Pham D.N. Le H.H. Ho T.D. Nguyen H.D. Nguyen T.S.L. Thi N. Nguyen D.H. Tran M.T. Le T.C. Dinh T.S. Nguyen K.C.N. The H. Mai M.T. Chu D.H. Pham N.H.T. Phuc D.N. Vinh D.-N. Nguyen X.-V. Nguyen D.S. Nguyen T.T.D. Thi H. Giang H.-N. Nguyen L.N. Tu Clinical trial and real-world evidence of circulating tumor DNA monitoring to predict recurrence in patients with resected colorectal cancer ESMO Real World Data and Digital Oncology minimal residual disease (MRD) disease-free survival (DFS) circulating tumor DNA colorectal cancer recurrence prognosis |
| title | Clinical trial and real-world evidence of circulating tumor DNA monitoring to predict recurrence in patients with resected colorectal cancer |
| title_full | Clinical trial and real-world evidence of circulating tumor DNA monitoring to predict recurrence in patients with resected colorectal cancer |
| title_fullStr | Clinical trial and real-world evidence of circulating tumor DNA monitoring to predict recurrence in patients with resected colorectal cancer |
| title_full_unstemmed | Clinical trial and real-world evidence of circulating tumor DNA monitoring to predict recurrence in patients with resected colorectal cancer |
| title_short | Clinical trial and real-world evidence of circulating tumor DNA monitoring to predict recurrence in patients with resected colorectal cancer |
| title_sort | clinical trial and real world evidence of circulating tumor dna monitoring to predict recurrence in patients with resected colorectal cancer |
| topic | minimal residual disease (MRD) disease-free survival (DFS) circulating tumor DNA colorectal cancer recurrence prognosis |
| url | http://www.sciencedirect.com/science/article/pii/S2949820124000547 |
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