scholarly journals Monitoring of Early Changes of Circulating Tumor DNA in the Plasma of Rectal Cancer Patients Receiving Neoadjuvant Concomitant Chemoradiotherapy: Evaluation for Prognosis and Prediction of Therapeutic Response

2020 ◽  
Vol 10 ◽  
Author(s):  
Filip Pazdirek ◽  
Marek Minarik ◽  
Lucie Benesova ◽  
Tereza Halkova ◽  
Barbora Belsanova ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Therapeutic Response ◽  
Circulating Tumor Dna ◽  
Concomitant Chemoradiotherapy ◽  
Prognosis And Prediction ◽  
Tumor Dna

scholarly journals The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 73
Author(s):  
Christopher Boniface ◽  
Christopher Deig ◽  
Carol Halsey ◽  
Taylor Kelley ◽  
Michael B. Heskett ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Feasibility Study ◽  
Locally Advanced ◽  
Circulating Tumor Dna ◽  
Study Patient ◽  
Patient Specific ◽  
Clinical Recurrence ◽  
Tumor Dna

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n = 3) and rectal cancer (n = 2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the Dual-Index Degenerate Adaptor-Sequencing (DIDA-Seq) error-correction method, we serially interrogated plasma cell-free DNA at 28–41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient- and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

ctDNA as a prognostic factor in operable colon cancer patients: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Emre Yekedüz ◽  
Elif Berna Köksoy ◽  
Hakan Akbulut ◽  
Yüksel Ürün ◽  
Güngör Utkan
Keyword(s):  
Colon Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Circulating Tumor Dna ◽  
Random Effects Model ◽  
Inverse Variance ◽  
Increased Risk ◽  
Significant Step ◽  
Tumor Dna

Aim: Using circulating tumor DNA (ctDNA) instead of historical clinicopathological factors to select patients for adjuvant chemotherapy (ACT) may reduce inappropriate therapy. Material & methods: MEDLINE was searched on March 31, 2020. Studies, including data related to the prognostic value of ctDNA in the colon cancer patients after surgery and after ACT, were included. The generic inverse-variance method with a random-effects model was used for meta-analysis. Results: Four studies were included for this meta-analysis. ctDNA-positive colon cancer patients after surgery and ACT had a significantly increased risk of recurrence compared with ctDNA-negative patients. Conclusions: ctDNA is an independent prognostic factor, and this meta-analysis is a significant step for using ctDNA instead of historical prognostic factors in the adjuvant setting.

scholarly journals Small EVs-Associated DNA as Complementary Biomarker to Circulating Tumor DNA in Plasma of Metastatic Colorectal Cancer Patients

2021 ◽  
Vol 14 (2) ◽  
pp. 128
Author(s):  
Silvia Galbiati ◽  
Francesco Damin ◽  
Dario Brambilla ◽  
Lucia Ferraro ◽  
Nadia Soriani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Digital Pcr ◽  
Extracellular Vesicle ◽  
Circulating Tumor Dna ◽  
Mutation Status ◽  
Promising Practice ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.

scholarly journals High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT

2021 ◽  
Vol 28 (4) ◽  
pp. 2373-2384
Author(s):  
Tzu-Ju Chen ◽  
Yu-Feng Tian ◽  
Chia-Lin Chou ◽  
Ti-Chun Chan ◽  
Hong-Lin He ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Concurrent Chemoradiotherapy ◽  
Therapeutic Response ◽  
Tumor Regression ◽  
Free Survival ◽  
Cancer Transcriptome ◽  
Poor Outcomes ◽  
Univariate Analyses ◽  
Local Recurrence Free Survival

Background: Patients with rectal cancer can prospectively be favored for neoadjuvant concurrent chemoradiotherapy (CCRT) to downstage before a radical proctectomy, but the risk stratification and clinical outcomes remain disappointing. Methods: From a published rectal cancer transcriptome dataset (GSE35452), we highlighted extracellular matrix (ECM)-linked genes and identified the serine protease inhibitor Kazal-type 4 (SPINK4) gene as the most relevant among the top 10 differentially expressed genes associated with CCRT resistance. We accumulated the cases of 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery and collected tumor specimens for the evaluation of the expression of SPINK4 using immunohistochemistry. Results: The results revealed that high SPINK4 immunoexpression was significantly related to advanced pre-CCRT and post-CCRT tumor status (both p < 0.001), post-CCRT lymph node metastasis (p = 0.001), more vascular and perineurial invasion (p = 0.015 and p = 0.023), and a lower degree of tumor regression (p = 0.001). In univariate analyses, high SPINK4 immunoexpression was remarkably correlated with worse disease-specific survival (DSS) (p < 0.0001), local recurrence-free survival (LRFS) (p = 0.0017), and metastasis-free survival (MeFS) (p < 0.0001). Furthermore, in multivariate analyses, high SPINK4 immunoexpression remained independently prognostic of inferior DSS and MeFS (p = 0.004 and p = 0.002). Conclusion: These results imply that high SPINK4 expression is associated with advanced clinicopathological features and a poor therapeutic response among rectal cancer patients undergoing CCRT, thus validating the prospective prognostic value of SPINK4 for those patients.

scholarly journals Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer

2015 ◽  
Vol 26 (8) ◽  
pp. 1715-1722 ◽  
Author(s):  
J. Tie ◽  
I. Kinde ◽  
Y. Wang ◽  
H.L. Wong ◽  
J. Roebert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapeutic Response ◽  
Circulating Tumor Dna ◽  
Early Marker ◽  
Tumor Dna
Sign in / Sign up

Export Citation Format

Share Document