Serial circulating tumor DNA (ctDNA) and recurrence risk in patients (pts) with resectable colorectal liver metastasis (CLM).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e15131-e15131 ◽  
Author(s):  
Jeanne Tie ◽  
Yuxuan Wang ◽  
Simeon Springer ◽  
Isaac Kinde ◽  
Hui-Li Wong ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Colorectal Liver Metastasis ◽  
Recurrence Risk ◽  
Circulating Tumor Dna ◽  
Tumor Dna

scholarly journals Clearance of circulating tumor DNA in a high-risk stage-IV rectal carcinoma patient with synchronous liver metastases after conversion surgery is correlated with pathologic complete response

2021 ◽  
Vol 14 ◽  
pp. 263177452110202
Author(s):  
Yingying Huang ◽  
Wenzhuo Jia ◽  
Lijun Wang ◽  
Qiuxiang Ou ◽  
Xue Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Liver Metastasis ◽  
Colorectal Liver Metastasis ◽  
Pathologic Complete Response ◽  
Stage Iv ◽  
Complete Response ◽  
Circulating Tumor Dna ◽  
Conversion Surgery ◽  
Tumor Dna

Colorectal cancer is the third most common cancer worldwide, and its incidence continues to grow. Approximately one-third of patients with colorectal cancer develop liver metastases during the natural course of disease. Complete surgical resection is associated with very low mortality in colorectal liver metastasis patients, but only a small fraction of colorectal liver metastasis patients fulfill the selection criteria for surgical treatment. We herein describe a high-risk stage-IV rectal carcinoma patient who was initially unresectable according to the National Comprehensive Cancer Network guidelines with a clinical risk score of 4 but received conversion surgery combined with systemic chemotherapy and achieved a favorable long-term clinical outcome (pathologic complete response) of approximately 28 months. Furthermore, serial circulating tumor DNA monitoring using next-generation sequencing provided a comprehensive view of the patient’s clinical and pathologic status for better clinical decision support over the course of the disease. The absence of circulating tumor DNA/cells after conversion surgery was correlated with pathologic complete response. This case study not only demonstrated that a curative oncosurgical approach could be considered for high-risk colorectal liver metastasis patients under specific circumstances but also highlighted the role of circulating tumor DNA monitoring to gain further insight into the evolution of a patient’s response over time.

scholarly journals Evaluation of circulating tumor DNA as a biomarker in pancreatic cancer with liver metastasis

PLoS ONE ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. e0235623
Author(s):  
Yasunori Uesato ◽  
Naoki Sasahira ◽  
Masato Ozaka ◽  
Takashi Sasaki ◽  
Mitsuhisa Takatsuki ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Circulating Tumor Dna ◽  
Tumor Dna

scholarly journals Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Gong Chen ◽  
Junjie Peng ◽  
Qian Xiao ◽  
Hao-Xiang Wu ◽  
Xiaojun Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Standard Of Care ◽  
Recurrence Risk ◽  
Disease Recurrence ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Sampling Point ◽  
Radiological Imaging ◽  
Definitive Therapy ◽  
Tumor Dna

Abstract Background Precise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk. Methods From September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care. Results Preoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3–7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio [HR], 10.98; 95%CI, 5.31–22.72; P < 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39–30.19; P < 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79–95.08; P < 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months. Conclusions Postoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.

scholarly journals Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mark Jesus M. Magbanua ◽  
Wen Li ◽  
Denise M. Wolf ◽  
Christina Yau ◽  
Gillian L. Hirst ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Neoadjuvant Chemotherapy ◽  
Recurrence Risk ◽  
Circulating Tumor Dna ◽  
Resonance Imaging ◽  
Metastatic Recurrence ◽  
Increased Risk ◽  
The Impact ◽  
Tumor Dna

AbstractWe investigated whether serial measurements of circulating tumor DNA (ctDNA) and functional tumor volume (FTV) by magnetic resonance imaging (MRI) can be combined to improve prediction of pathologic complete response (pCR) and estimation of recurrence risk in early breast cancer patients treated with neoadjuvant chemotherapy (NAC). We examined correlations between ctDNA and FTV, evaluated the additive value of ctDNA to FTV-based predictors of pCR using area under the curve (AUC) analysis, and analyzed the impact of FTV and ctDNA on distant recurrence-free survival (DRFS) using Cox regressions. The levels of ctDNA (mean tumor molecules/mL plasma) were significantly correlated with FTV at all time points (p < 0.05). Median FTV in ctDNA-positive patients was significantly higher compared to those who were ctDNA-negative (p < 0.05). FTV and ctDNA trajectories in individual patients showed a general decrease during NAC. Exploratory analysis showed that adding ctDNA information early during treatment to FTV-based predictors resulted in numerical but not statistically significant improvements in performance for pCR prediction (e.g., AUC 0.59 vs. 0.69, p = 0.25). In contrast, ctDNA-positivity after NAC provided significant additive value to FTV in identifying patients with increased risk of metastatic recurrence and death (p = 0.004). In this pilot study, we demonstrate that ctDNA and FTV were correlated measures of tumor burden. Our preliminary findings based on a limited cohort suggest that ctDNA at surgery improves FTV as a predictor of metastatic recurrence and death. Validation in larger studies is warranted.

Growth pattern of colorectal liver metastasis as a marker of recurrence risk

2015 ◽  
Vol 32 (4) ◽  
pp. 369-381 ◽  
Author(s):  
R. L. Eefsen ◽  
P. B. Vermeulen ◽  
I. J. Christensen ◽  
O. D. Laerum ◽  
M. B. Mogensen ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Colorectal Liver Metastasis ◽  
Growth Pattern ◽  
Recurrence Risk

scholarly journals BRAF Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 998 ◽  
Author(s):  
Leo Mas ◽  
Jean-Baptiste Bachet ◽  
Valerie Taly ◽  
Olivier Bouché ◽  
Julien Taieb ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Mutation Analysis ◽  
Braf Mutation ◽  
Circulating Tumor Dna ◽  
Kappa Coefficient ◽  
Plasma Samples ◽  
Mutation Status ◽  
Tumor Dna

In patients with metastatic colorectal cancer (mCRC), RAS and BRAF mutations are currently determined by tumor sample analysis. Here, we report BRAF mutation status analysis in paired tumor tissue and plasma samples of mCRC patients included in the AGEO RASANC prospective cohort study. Four hundred and twenty-five patients were enrolled. Plasma samples were analyzed by next-generation sequencing (NGS). When no mutation was identified, we used two methylated specific biomarkers (digital droplet PCR) to determine the presence or absence of circulating tumor DNA (ctDNA). Patients with conclusive ctDNA results were defined as those with at least one mutation or one methylated biomarker. The kappa coefficient and accuracy were 0.79 (95% CI: 0.67–0.91) and 97.3% (95% CI: 95.2–98.6%) between the BRAF status in plasma and tissue for patients with available paired samples (n = 405), and 0.89 (95% CI: 0.80–0.99) and 98.5% (95% CI: 96.4–99.5%) for those with conclusive ctDNA (n = 323). The absence of liver metastasis was the main factor associated to inconclusive ctDNA results. In patients with liver metastasis, the kappa coefficient was 0.91 (95% CI, 0.81–1.00) and accuracy was 98.6% (95% CI, 96.5–99.6%). We demonstrate satisfying concordance between tissue and plasma BRAF mutation detection, especially in patients with liver metastasis, arguing for plasma ctDNA testing for routine BRAF mutation analysis in these patients.

scholarly journals Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer

JAMA Oncology ◽  
2019 ◽  
Vol 5 (12) ◽  
pp. 1710 ◽  
Author(s):  
Jeanne Tie ◽  
Joshua D. Cohen ◽  
Yuxuan Wang ◽  
Michael Christie ◽  
Koen Simons ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Recurrence Risk ◽  
Circulating Tumor Dna ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Dna Analyses ◽  
Risk And Benefit ◽  
Tumor Dna

Serial circulating tumor DNA analysis to assess recurrence risk, benefit of adjuvant therapy, growth rate and early relapse detection in stage III colorectal cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3540-3540
Author(s):  
Tenna V Vesterman Henriksen ◽  
Noelia Tarazona ◽  
Amanda Frydendahl ◽  
Thomas Reinert ◽  
Juan Antonio Carbonell-Asins ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Rate ◽  
High Risk ◽  
Growth Rates ◽  
Recurrence Risk ◽  
Circulating Tumor Dna ◽  
Stage Iii ◽  
Ct Scans ◽  
Risk Patients ◽  
Tumor Dna

3540 Background: Challenges in the postoperative management of stage III colorectal cancer include: 1) selection of high-risk patients for adjuvant chemotherapy (ACT), 2) lack of markers to assess ACT efficacy, 3) assessment of recurrence risk after ACT, and 4) lack of markers to guide treatment decisions for high-risk patients e.g. additional therapy or intensified surveillance. Circulating tumor DNA (ctDNA) is a promising marker with potential to mitigate the challenges. Here we used serial ctDNA measurements to assess the correlation between recurrence and ctDNA detection: postoperative, during and after ACT, and during surveillance; and to assess growth rates of metachronous metastases. Uniquely, we also used concurrent CT scans and ctDNA measurements to compare the sensitivity for detecting recurrence. Methods: Stage III CRC patients treated with curative intent at Danish and Spanish hospitals in 2014-2019 were recruited (n = 166). Blood samples (n = 1227) were collected prior to and immediately after surgery, and every third month for up to 36 months. Per patient 16 personal mutations were used to quantify plasma ctDNA (Signatera, bespoke mPCR NGS assay). Results: Detection of ctDNA was a strong recurrence predictor, both postoperatively (HR 7.2, 95% CI 3.8-13.8, P< 0.001), directly after ACT (HR = 18.2, 95% CI 7.1-46, P < 0.001), and when measured serially after end of treatment (HR = 41, 95% CI 16-100, P < 0.001). The recurrence rate of postoperative ctDNA positive patients treated with ACT was 80% (16/20). Patients who stayed ctDNA positive during ACT all recurred. Serial post-treatment ctDNA measurements revealed exponential growth for all recurrence patients following either a SLOW (26%-increase/month) or a FAST (126%-increase/month) pattern (P < 0.001). From ctDNA detection to radiologic recurrence, ctDNA levels of FAST patients increased by a median 117-fold, and up to 554-fold. The 3-year overall survival was 43% for FAST patients and 100% for SLOW and non-recurrence patients (HR = 41.3, 95% CI 7.5-228, P < 0.001). Coinciding CT scans and ctDNA measurements (n = 113 patients, 235 coinciding events, median 2 per patient) showed a high agreement (92%) and ctDNA either detected residual disease before the CT scan (n = 7 patients) or at the same time (n = 14 patients). The median lead-time was 7.5 months. Conclusions: The study confirmed the prognostic power of serial postoperative ctDNA analysis. Moreover, it provided novel analyses demonstrating that ctDNA is more sensitive for recurrence detection than CT scans and can be used for tumor growth rate assessments. The difference between FAST and SLOW growing tumors suggest that growth rates could guide whom to start on systemic therapy rapidly and whom to send for diagnostic imaging. Altogether, the study highlights many potential utilities of ctDNA in guiding clinical decision-making.

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