scholarly journals Dynamic changes in levels of gene mutations using circulating tumor DNA (ctDNA) and efficacy of 1st-line modified (m)-FOLFOXIRI plus bevacizumab (bev) for metastatic colorectal cancer (mCRC) harboring RAS mutation (mt) (JACCRO CC-11)

2017 ◽  
Vol 28 ◽  
pp. v184
Author(s):  
Y. Sunakawa ◽  
T. Sekikawa ◽  
J. Usher ◽  
H. Satake ◽  
Y. Jaimes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Gene Mutations ◽  
Circulating Tumor Dna ◽  
Dynamic Changes ◽  
Ras Mutation ◽  
Tumor Dna

RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment With Anti-EGFR Antibodies in Patients With Metastatic Colorectal Cancer

2020 ◽  
pp. 898-911
Author(s):  
Yu Sunakawa ◽  
Masato Nakamura ◽  
Masahiro Ishizaki ◽  
Masato Kataoka ◽  
Hironaga Satake ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Circulating Tumor Dna ◽  
Wild Type ◽  
Phase Ii Trials ◽  
Ras Mutation ◽  
Ras Mutations ◽  
Ras Status ◽  
Tumor Dna

PURPOSE Several trials have evaluated the efficacy of rechallenge treatment with anti–epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with metastatic colorectal cancer (mCRC). A recent trial indicated that RAS status in circulating tumor DNA (ctDNA) may potentially predict patients with RAS wild-type mCRC resistant to anti-EGFR mAb who would benefit from rechallenge treatment, and the findings should be further investigated. MATERIAL AND METHODS We enrolled patients whose plasma samples were collected in prospective phase II trials, the JACCRO CC-08 (n = 36) and CC-09 (n = 25), which evaluated rechallenge chemotherapy with anti-EGFR mAb for KRAS wild-type mCRC. RAS in ctDNA was analyzed at the time points of baseline, 8 weeks, and progression using OncoBEAM RAS CRC kit. RESULTS Sixteen patients were enrolled in this study, with a response rate of 0% and a disease control rate (DCR) of 62.5%. RAS mutations were found at baseline in six patients. The DCR was 33% in patients with RAS mutations in ctDNA, whereas it was 80% in patients without RAS mutation at baseline. Patients with RAS mutation at baseline had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without RAS mutation (median PFS, 2.3 v 4.7 months; hazard ratio [HR], 6.2; P = .013; median OS, 3.8 v 16.0 months; HR, 12.4; P = .0028). Six of 10 patients without RAS mutation at baseline acquired RAS mutations at progression. Postprogression survival after rechallenge treatment was numerically shorter in patients with RAS mutation at progression. CONCLUSION RAS status in ctDNA was significantly associated with clinical outcomes in patients with mCRC receiving rechallenge treatment with anti-EGFR mAb. These findings could support the clinical utility of OncoBEAM RAS CRC kits for anti-EGFR mAb rechallenge in RAS wild-type mCRC.

Efficacy of an anti-EGFR after ctDNA conversion from mutated RAS status of metastatic colorectal cancer: Results of a pilot study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15574-e15574
Author(s):  
Mohamed Bouchahda ◽  
Raphael Saffroy ◽  
Abdoulaye Karaboué ◽  
Jocelyne Hamelin ◽  
Pasquale Innominato ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pilot Study ◽  
Metastatic Colorectal Cancer ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Additional Treatment ◽  
Ras Mutation ◽  
Prior Chemotherapy ◽  
Ras Status ◽  
Tumor Dna

e15574 Background: This pilot study aimed at the evaluation of the efficacy of anti-EGFR therapy in patients with initially RAS-mutated metastatic colorectal cancer, whose liquid biopsy found no RAS mutation after prior chemotherapy failure. Methods: Sixteen patients with RAS-mutated metastatic colorectal cancer in the solid tumor were included, after they had received 1 to 3 prior chemotherapy lines without anti-EGFR. Before inclusion, RAS genotyping was performed in circulating tumor DNA (ctDNA) from liquid biopsy, after a median duration of ̃24 months after the initial RAS status determination. No RAS mutation was detected in the circulating tumor DNA from 9 patients (56%), who then received cetuximab-FOLFIRI. The 7 patients who had persistent RAS mutation in the liquid biopsy (44%) were treated according to standard recommendations without anti-EGFR. Results: The median progression free survival was 8.2 months [95%CL, 4.5 – 11.8] in patients without detectable ctDNA RAS mutation, as compared to 3.5 months [2.1 – 4.9] in the ctDNA mutated patients (p < 0.001). The median overall survival was 22.3 months [17.3 - 27.3] in the patients with undetectable ctDNA RAS mutation, whereas it was 4.7 months [2.6 - 6.7] in those with ctDNA RAS mutation (p = 0.013). These results suggested the efficacy of cetuximab-based chemotherapy in patients with initially RAS mutated metastatic colorectal cancer, who later displayed no detectable ctDNA RAS mutation. Conclusions: The introduction of an anti-EGFR could provide an additional treatment option for patients with metastatic colorectal cancer with apparent conversion of initial RAS mutation, based on ctDNA assessment after prior failure on anti-EGFR-free chemotherapy.

scholarly journals Monitoring circulating tumor DNA revealed dynamic changes in KRAS status in patients with metastatic colorectal cancer.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e15630-e15630 ◽  
Author(s):  
Yuji Takayama ◽  
Koichi Suzuki ◽  
Taro Fukui ◽  
Kosuke Ichida ◽  
Fumiaki Watanabe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Circulating Tumor Dna ◽  
Dynamic Changes ◽  
Kras Status ◽  
Tumor Dna

scholarly journals Monitoring circulating tumor DNA revealed dynamic changes in KRAS status in patients with metastatic colorectal cancer

Oncotarget ◽  
2018 ◽  
Vol 9 (36) ◽  
pp. 24398-24413 ◽  
Author(s):  
Yuji Takayama ◽  
Koichi Suzuki ◽  
Yuta Muto ◽  
Kosuke Ichida ◽  
Taro Fukui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Circulating Tumor Dna ◽  
Dynamic Changes ◽  
Kras Status ◽  
Tumor Dna

scholarly journals Impact of Emergent Circulating Tumor DNA RAS Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer

2018 ◽  
Vol 24 (22) ◽  
pp. 5602-5609 ◽  
Author(s):  
Tae Won Kim ◽  
Marc Peeters ◽  
Anne Thomas ◽  
Peter Gibbs ◽  
Kristina Hool ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Circulating Tumor Dna ◽  
Ras Mutation ◽  
Tumor Dna

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 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
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