Abstract 5907
Background
The most recent consensus statement on the use of liquid biopsies (circulating tumor DNA – ctDNA testing) has been that it is not yet ready for prime time. However, in patients with metastatic colorectal cancer (mCRC), there is significantly more ‘shedding’ of DNA detectable in blood allowing this test to be of value. We aimed at reporting the concordance of liquid biopsies based on clonality and timing of testing in patients with mCRC.
Methods
A total of 92 mCRC patients were identified who had both a commercially available liquid and tissue next generation sequencing assay done from December 2016 to February 2019. Arbitrarily, mutations were classified as clonal or subclonal based on the 50% cutoff of the highest variant allele frequency (VAF) reported. Concordance rates, including clonal (BRAF-V600E/ RAS), subclonal and amplification concordance were calculated separately for patients for whom the liquid biopsy testing was done before initiation of treatment (n = 27) and after initiation of treatment (n = 65).
Results
Clonal concordance rates were 96.3% for patients when the liquid biopsy was done before initiation of treatment versus 64.6% for patients when the test was obtained after they were already on some systemic therapy (p value: 0.001). Similarly, subclonal and amplification concordance rates for patients in the test before treatment and test after treatment groups are summarized in the table. Moreover, the median of highest VAF% was noted to be 3.1% and 1.1% in test before treatment and test after treatment groups respectively (p value: 0.092).Table:
622P Summary of concordance rates by timing of liquid biopsy test
Test before treatment (N = 27) | Test after treatment (N = 65) | Total (N = 92) | P value | |
---|---|---|---|---|
*Clonal Concordance | 26: 96.3 (81.0, 99.9) | 42: 64.6 (51.8, 76.1) | 68: 73.9 (63.7, 82.5) | 0.001 |
BRAF | 27: 100.0 (87.2, 100.0) | 64: 98.5 (91.7, 100.0) | 91: 98.9 (94.1, 100.0) | 1.000 |
RAS | 26: 96.3 (81.0, 99.9) | 52: 80.0 (68.2, 88.9) | 78: 84.8 (75.8, 91.4) | 0.058 |
Subclonal Concordance | 21: 77.8 (57.7, 91.4) | 44: 67.7 (54.9, 78.8) | 65: 70.7 (60.2, 79.7) | 0.452 |
BRAF | 27: 100.0 (87.2, 100.0) | 65: 100.0 (94.5, 100.0) | 92: 100.0 (96.1, 100.0) | 1.000 |
RAS | 27: 100.0 (87.2, 100.0) | 62: 95.4 (87.1, 99.0) | 89: 96.7 (90.8, 99.3) | 0.553 |
Amplification Concordance | 22: 81.5 (61.9, 93.7) | 41: 63.1 (50.2, 74.7) | 63: 68.5 (58.0, 77.8) | 0.092 |
Highest Variant Allele Frequency (VAF)% | 3.1 (0.0, 84.6) | 1.1 (0.0, 90.1) | 1.5 (0.0, 90.1) | 0.092 |
Concordance rates are summarized by count: percent (95% binomial confidence interval). P values arise from Fisher’s exact tests; *Arbitrarily, 50% of the highest variant allele frequency (VAF)% value in the liquid biopsy results has been used to differentiate clonal from subclonal mutations. Highest VAF% is summarized by median (range). P values arise from Wilcoxon rank sum test
Conclusions
Liquid biopsies show a very high concordance rate in patients with metastatic colorectal cancer. It is important to take the timing of the assay into consideration alongside relevant clonal mutations while assessing the concordance of liquid biopsies, not just for mCRC but for other malignancies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4546 - Efficacy and toxicity of weekly carboplatin and paclitaxel as induction or palliative treatment in advanced esophageal cancer patients
Presenter: Femke de Man
Session: Poster Display session 2
Resources:
Abstract
5908 - Perioperative chemotherapy with Docetaxel, Oxaliplatin, Fluorouracil and Leucovorin (FLOT) versus Epirubicin, Platinum and Capecitabine or Flourouracil (EOX/ECF) in Resectable Gastric or Gastroesophageal Junction Adenocarcinoma- Safety and response data from India.
Presenter: Tanuj Chawla
Session: Poster Display session 2
Resources:
Abstract
937 - Phase II Study of Preoperative Radiotherapy Combined with S-1 plus Cisplatin in Clinically Resectable Type 4 or Large Type 3 Gastric Cancer: OGSG1205
Presenter: Shunji Endo
Session: Poster Display session 2
Resources:
Abstract
1119 - Observational Study of the Peritoneal Washing Cytology Positive Gastric Cancer without Gross Peritoneal Metastasis Underwent Radical D2 Gastrectomy.
Presenter: Jun Eul Hwang
Session: Poster Display session 2
Resources:
Abstract
3744 - Primary results of multicenter phase II study of neoadjuvant chemotherapy with S-1 and oxaliplatin for locally advanced gastric cancer (Neo G-SOX PII)
Presenter: Akira Miki
Session: Poster Display session 2
Resources:
Abstract
5091 - Multicenter Phase I/II Feasibility Study of Adjuvant Treatment with S-1 in Patients after R0-Resection of Adenocarcinoma of the Stomach and Esophagogastric Junction (GMBH-STO-0114)
Presenter: Kathrin Heinrich
Session: Poster Display session 2
Resources:
Abstract
2891 - A phase I study of Docetaxel/Oxaliplatin/S-1 (DOS) combination neoadjuvant chemotherapy for patients with locally advanced adenocarcinoma of the esophagogastric junction
Presenter: Kei Hosoda
Session: Poster Display session 2
Resources:
Abstract
2994 - Apatinib combined with docetaxel in second-line treatment of advanced gastric cancer: a prospective clinical study (Data updated)
Presenter: Mudan Yang
Session: Poster Display session 2
Resources:
Abstract
3000 - A multicenter phase II study of TAS-114 in combination with S-1 in patients with pre-treated advanced gastric cancer (EPOC1604)
Presenter: Daisuke Takahari
Session: Poster Display session 2
Resources:
Abstract
4653 - Impact of Pembrolizumab (pembro) Versus Paclitaxel on Health-Related Quality of Life (HRQoL) in Patients With Advanced Gastric or Gastroesophageal Junction (GEJ) Cancer That Has Progressed After First-Line Chemotherapy (KEYNOTE-061)
Presenter: Eric Van Cutsem
Session: Poster Display session 2
Resources:
Abstract