458P Circulating tumor DNA analysis predicting recurrence risk in patients with stage I-III colorectal cancer

Gu, Jin; Lei, Fang; Wang, X.; Huang, Wei; He, X.; Hong, Yuan; Zeng, Qingmin; Wang, Y.; Gao, Qingkun; Niu, Pei; Huang, Dandan; Gao, Zhaoya; Ding, Changming; Zhai, Zhiwei; An, Kyungeh; Chen, H.; Zhao, Xupeng; Chen, S.; Bai, Yansen

doi:10.1016/j.annonc.2021.08.979

Cited by 3 publications

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“…The current prospective studies with ctDNA have a small number of patients and do not reflect the true value of ctDNA in MRD monitoring [ 40 ]. Our meta-analyses included 23 studies with 3568 patients [ 9 , 18 , 20 , 21 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 44 , 45 ]. This speaks to the rapidly expanding number of studies on the topic.…”

Section: Discussionmentioning

confidence: 99%

“… Forest plots showing the pooled hazard ratio based on ctDNA method: ( A ) post-surgical ctDNA positive versus ctDNA negative status via tumor-informed method; ( B ) post-surgical ctDNA positive versus ctDNA negative status via tumor-agnostic method. The hazard ratio for each adverse event is represented by a square, and the horizontal lines crossing the squares represent the 95% confidence interval (CI) [ 9 , 18 , 20 , 21 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. …”

Section: Figurementioning

confidence: 99%

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Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis

Chidharla

Rapoport

Agarwal

et al. 2023

IJMS

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Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess the recurrence risk and patient selection for adjuvant chemotherapy. We performed a meta-analysis of post-operative ctDNA in stage I–IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3568 patients with evaluable ctDNA in CRC patient post-curative-intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I–III and oligometastatic stage IV CRC patients. Results showed that the pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA-positive versus -negative patients in all stages was 7.27 (95% CI 5.49–9.62), p < 0.00001. Subgroup analysis revealed pooled HRs of 8.14 (95% CI 5.60–11.82) and 4.83 (95% CI 3.64–6.39) for stages I–III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA-positive versus -negative patients in all stages was 10.59 (95% CI 5.59–20.06), p < 0.00001. Circulating tumor DNA (ctDNA) analysis has revolutionized non-invasive cancer diagnostics and monitoring, with two primary forms of analysis emerging: tumor-informed techniques and tumor-agnostic or tumor-naive techniques. Tumor-informed methods involve the initial identification of somatic mutations in tumor tissue, followed by the targeted sequencing of plasma DNA using a personalized assay. In contrast, the tumor-agnostic approach performs ctDNA analysis without prior knowledge of the patient’s tumor tissue molecular profile. This review highlights the distinctive features and implications of each approach. Tumor-informed techniques enable the precise monitoring of known tumor-specific mutations, leveraging the sensitivity and specificity of ctDNA detection. Conversely, the tumor-agnostic approach allows for a broader genetic and epigenetic analysis, potentially revealing novel alterations and enhancing our understanding of tumor heterogeneity. Both approaches have significant implications for personalized medicine and improved patient outcomes in the field of oncology. The subgroup analysis based on the ctDNA method showed pooled HRs of 8.66 (95% CI 6.38–11.75) and 3.76 (95% CI 2.58–5.48) for tumor-informed and tumor-agnostic, respectively. Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.

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Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis

Chidharla

Rapoport

Agarwal

et al. 2023

IJMS

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“…Еще одним объяснением расхождения данных о частоте выявления цоДНК может быть пороговое значение ее уровня, принятое за положительное, а также метод определения этого маркера. Как и в большинс тве исследований [8][9][10][11][12][13][14][15][16][17][18][19], в ходе которых применялись различные тест-системы для определения цоДНК, в нашей работе показано независимое прогностическое значение наличия цоДНК после операции.…”

Section: Discussionunclassified

The prognostic value of circulating in blood tumor DNA as a marker of minimal residual disease in stage I–III colorectal cancer

et al. 2022

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Introduction. Studies on non-metastatic colorectal cancer have demonstrated the prognostic role of circulating tumor (ctDNA) after surgery, and the ability to identify patients with the greatest risk of progression. This makes it possible in the future to personalize neoadjuvant and adjuvant treatment.The study objective – to evaluate the correlation of the ctDNA status before and after surgery with a clinical outcome in patients with stage I–III colorectal cancer.Materials and methods. The study included data from patients with morphologically verified colorectal cancer with stage I–III who were treated at the N. N. Blokhin National Oncology Research Center in the period from 2016 to 2021. Blood samples were collected before and after surgical treatment (on the 7–10th day after surgery). The minimum permissible concentration at which ctDNA in a plasma sample was considered positive was 0.4 copies of mutant DNA in 1 mcL of plasma. The main criterion of effectiveness was disease-free survival (DFS). The presence of cDNA before and after surgery was a negative prognostic factor for progression in stage I–III of CRC. Patients with positive cDNA after surgery had worse DFS results despite adjuvant chemotherapy. Patients with stage II CRC with negative ctDNA, regardless of adjuvant CT after surgery, did not have disease progression in 100 % of cases.Results. The study included 146 patients with stage I–III colorectal cancer. Progression was detected in 34 patients. The median follow-up time was 22 months (0–66 months). Data on progression were known in 119 patients. Positive cDNA data were detected before surgery in 55 of 120 patients (45 %), after surgery in 46 of 119 (38.6 %). In the group with positive cDNA before surgery, the median DFS was 35 months (95 % confidence interval (CI) 24,0–45.9), in the group with negative cDNA before surgery, the median DFS was not achieved (hazard ratio (HR) 4.6; 95 % CI 2.0–10.4), 1‑year DFS in the cDNA positive group was 62 % versus 100 % in the cDNA negative group (p <0.001). In the group with positive cDNA after surgery, the median DFS was 20 months (95 % CI 8,1–31,9), in the group with negative cDNA was not achieved (HR 27,7; 95 % CI 6,6–116,6; p <0,001). Patients with positive cDNA after surgery had worse DFS scores despite adjuvant chemotherapy. Patients with stage II CRC without ctDNA after surgery in 100 % did not have disease progression regardless of adjuvant CT.Conclusion. The presence of cDNA before and after surgery was a negative prognostic factor of progression after surgical treatment at stage I–III. The high negative prognostic value of cDNA makes it possible to select patients with stage II who do not need adjuvant chemotherapy.

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“…However, methods and strategies for detecting ctDNA-MRD in patients vary from study to study and from cancer to cancer, which presents a challenge for clinicians to interpret MRD results. For example, the current detection methods, including Droplet Digital PCR (ddPCR), 8 multiplex PCR next generation sequencing (mPCR-NGS), 9 whole genome sequencing (WGS), 10 Fast Aneuploidy Screening Test-sequencing System (FAST-SeqS), 11 hybridization capture-based NGS, 12 circulating single-molecule amplification and resequencing technology (cSMART), 13 Guardant Reveal, 14 ctDNA methylation assays, 15 single-cell universal poly (A)-independent RNA sequencing (SUPeR-seq), 16 which makes result diversity.…”

Section: Introductionmentioning

confidence: 99%

Circulating tumour DNA-Based molecular residual disease detection in resectable cancers: a systematic review and meta-analysis

Zheng,

Qin,

Wang

et al. 2024

eBioMedicine

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458P Circulating tumor DNA analysis predicting recurrence risk in patients with stage I-III colorectal cancer

Cited by 3 publications

References 0 publications

Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis

Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis

The prognostic value of circulating in blood tumor DNA as a marker of minimal residual disease in stage I–III colorectal cancer

Circulating tumour DNA-Based molecular residual disease detection in resectable cancers: a systematic review and meta-analysis

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