scholarly journals ASCO 2021—an update on metastastic colorectal cancer

2021 ◽  
Author(s):  
Lukas Weiss
Keyword(s):  
Colorectal Cancer ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Circulating Tumor Dna ◽  
Novel Therapies ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Integrate Analysis ◽  
Tumor Dna ◽  
Antibody Drug

SummaryThe 2021 ASCO Annual Meeting provided updates on novel therapies in rare subgroups of metastatic colorectal cancer, such as immunotherapy in microsatellite instable colorectal cancer and antibody–drug conjugate therapy in HER2-positive disease. Furthermore, the concept of anti-EGFR rechallenge therapy has received additional momentum with data from the CHRONOS trial in regard to treating patients in later lines as well as how to integrate analysis of circulating tumor DNA in clinical decision-making.

A basket trial of trastuzumab deruxtecan, a HER2-targeted antibody-drug conjugate, for HER2-amplified solid tumors identified by circulating tumor DNA analysis (HERALD trial).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS3650-TPS3650 ◽  
Author(s):  
Masataka Yagisawa ◽  
Yoshiaki Nakamura ◽  
Takayuki Yoshino ◽  
Yoshito Komatsu ◽  
Shigenori Kadowaki ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Circulating Tumor Dna ◽  
Advanced Solid Tumor ◽  
Her2 Amplification ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Cancer Types ◽  
Basket Trial ◽  
Tumor Dna ◽  
Antibody Drug

TPS3650 Background: Trastuzumab deruxtecan, a new HER2-targeting antibody-drug conjugate, has been approved for unresectable or metastatic HER2-positive breast cancer by the Food and Drug Administration. In a phase I/II trial, trastuzumab deruxtecan showed a manageable safety profile and antitumor activity in HER2-positive various cancer types. In addition, a tissue-based HER2 test occasionally cannot identify accurate HER2 status due to spatial and temporal intratumoral heterogeneity, leading to potentially missing an opportunity for responders to receive benefit from anti-HER2-targeted therapy. Circulating tumor DNA (ctDNA) analysis can detect comprehensive somatic genome alterations by assessment of spatial and temporal intratumoral heterogeneity with minimal invasiveness. Methods: We designed an investigator-initiated multicenter phase II basket trial to evaluate efficacy and safety of trastuzumab deruxtecan in advanced solid tumor malignancies with HER2 amplification identified by Guardant360, a 74-gene sequencing ctDNA panel, as a part of the Nationwide Cancer Genome Screening Project (GOZILA study, UMIN000029315). The key eligibility criteria are as follows: 1) Histopathologically confirmed advanced solid tumor malignancy; 2) Identified HER2 amplification by Guardant360; 3) Failed prior standard therapy. The participants will receive intravenously 5.4 mg/kg of trastuzumab deruxtecan every 3 weeks. The primary endpoint is objective response rate (ORR). The planned sample size is 55-65. A Bayesian model considering the potential heterogeneity across cancer types will be applied to detect ORR of 5% versus 25% to a certain level while maintaining the false-positive error rate in each cancer type at 10%. Furthermore, tumor tissue, ctDNA and circulating tumor cells are serially collected and analyzed to investigate the predictive biomarkers and resistance mechanisms. The trial was activated in late 2019. At the time of the abstract submission, 2 patients have been enrolled. This trial is granted by AMED under Grant Number JP18lk0201084. Clinical trial information: JapicCTI-194707 .

scholarly journals Development and Validation of a Targeted ‘Liquid’ NGS Panel for Treatment Customization in Patients with Metastatic Colorectal Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2375
Author(s):  
Myrto Kastrisiou ◽  
George Zarkavelis ◽  
Anastasia Kougioumtzi ◽  
Prodromos Sakaloglou ◽  
Charilaos Kostoulas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Decision Making ◽  
High Sensitivity ◽  
Clinical Decision ◽  
Circulating Tumor Dna ◽  
Attractive Alternative ◽  
Analytical Sensitivity ◽  
Ras Gene ◽  
Percent Agreement

The detection of actionable mutations in tumor tissue is a prerequisite for treatment customization in patients with metastatic colorectal cancer (mCRC). Analysis of circulating tumor DNA (ctDNA) for the identification of such mutations in patients’ plasma is an attractive alternative to invasive tissue biopsies. Despite having the high analytical sensitivity required for ctDNA analysis, digital polymerase chain reaction (dPCR) technologies can only detect a very limited number of hotspot mutations, whilst a broader mutation panel is currently needed for clinical decision making. Recent advances in next-generation sequencing (NGS) have led to high-sensitivity platforms that allow screening of multiple genes at a single assay. Our goal was to develop a small, cost- and time-effective NGS gene panel that could be easily integrated in the day-to-day clinical routine in the management of patients with mCRC. We designed a targeted panel comprising hotspots in six clinically relevant genes (KRAS, NRAS, MET, BRAF, ERBB2 and EGFR) and validated it in a total of 68 samples from 30 patients at diagnosis, first and second disease progression. Results from our NGS panel were compared against plasma testing with BEAMing dPCR regarding the RAS gene status. The overall percent of agreement was 83.6%, with a positive and negative percent agreement of 74.3% and 96.2%, respectively. Further comparison of plasma NGS with standard tissue testing used in the clinic showed an overall percent agreement of 86.7% for RAS status, with a positive and negative percent agreement of 81.2% and 92.8%, respectively. Thus, our study strongly supports the validity and efficiency of an affordable targeted NGS panel for the detection of clinically relevant mutations in patients with mCRC.

INVESTIGATION KRAS MUTATION IN CIRCULATION TUMOR DNA IN DIFFERENT STAGES OF COLORECTAL CANCER

2019 ◽  
Vol 65 (5) ◽  
pp. 701-707
Author(s):  
Vitaliy Shubin ◽  
Yuriy Shelygin ◽  
Sergey Achkasov ◽  
Yevgeniy Rybakov ◽  
Aleksey Ponomarenko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Volume ◽  
Kras Mutation ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Kras Gene ◽  
Kras Mutations ◽  
Droplet Pcr ◽  
Tumor Dna

To determine mutations in the plasma KRAS gene in patients with colorectal cancer was the aim of this study. The material was obtained from 44 patients with colorectal cancer of different stages (T1-4N0-2bM0-1c). Plasma for the presence of KRAS gene mutation in circulating tumor DNA was investigated using digital droplet polymerase chain reaction (PCR). KRAS mutations in circulating tumor DNA isolated from 1 ml of plasma were detected in 13 (30%) patients with cancer of different stages. Of these, with stage II, there were 3 patients, with III - 5 and with IV - 5. Patients who did not have mutations in 1 ml of plasma were analyzed for mutations of KRAS in circulating tumor DNA isolated from 3 ml of plasma. Five more patients with KRAS mutations were found with II and III stages. The highest concentrations of circulating tumor DNA with KRAS mutation were found in patients with stage IV. The increase in plasma volume to 3 ml did not lead to the identification of mutations in I stage. This study showed that digital droplet PCR allows identification of circulating tumor DNA with the KRAS mutations in patients with stage II-IV of colon cancer. The results can be used to determine the degree of aggressiveness of the tumor at different stages of the disease, but not the 1st, and it is recommended to use a plasma volume of at least 3 ml.

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 Genomic profiling of cell-free circulating tumor DNA in patients with colorectal cancer and its fidelity to the genomics of the tumor biopsy

2019 ◽  
Vol 10 (5) ◽  
pp. 831-840 ◽  
Author(s):  
Gerald Li ◽  
Dean Pavlick ◽  
Jon H. Chung ◽  
Todd Bauer ◽  
Bradford A. Tan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Tumor Biopsy ◽  
Tumor Dna

scholarly journals Choice of faecal immunochemical test matters: comparison of OC-Sensor and HM-JACKarc, in the assessment of patients at high risk of colorectal cancer

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Caroline J. Chapman ◽  
Ayan Banerjea ◽  
David J Humes ◽  
Jaren Allen ◽  
Simon Oliver ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Decision Making ◽  
Full Range ◽  
Clinical Decision ◽  
Detection Rates ◽  
Faecal Immunochemical Test ◽  
Specimen Collection ◽  
Increased Risk ◽  
Immunochemical Test

AbstractObjectivesCurrently, NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 μg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed.MethodsTwo specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 µg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons.ResultsA total of 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 µg Hb/g faeces for OC-S and 318.1 and 1.0 µg Hb/g faeces for HM-J respectively. Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p<0.001. Using a f-Hb of 4 µg Hb/g faeces for both tests found an agreement of 88.1%, at 10 µg Hb/g faeces 91.7% and at 150 µg Hb/g faeces 96.3%. A total of 114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p<0.001.ConclusionsWe found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb.

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