In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 3559-3559
Abstract:
3559 Background: Recently, conflicting evidence has emerged showing the association of ctDNA level and cancer progression. The aim of our study was the development of a method for detecting ctDNA in plasma and the investigation of the prognostic value of ctDNA retention after surgery in the prospective way. Methods: This prospective, single-center, sample collection study; pts with early-stage malignancies of the different origin were included. Tumor somatic mutations were determined by target sequencing of DNA from FFPE tumor blocks. Sequencing was performed using the custom NGS panel covering regions of frequent somatic mutations in 50 genes. Tumor-specific mutations were monitored in plasma samples taken before and after surgery. The median time between surgery and plasma collection was 7 days (5-15). Mutations of plasma ctDNA were determined by ddPCR. The plasma sample was considered "positive" if the content of ctDNA was more than 0.5 copies of mutant DNA in ml plasma. We needed 265 pts for improving 1-year disease free survival (DFS) from 60% to 80% with α=0.01, β=0.1, 10% loss of f.-up and duration of the study for 2 years. Results: The study comprised 271 pts with various cancers including colorectal – 91 (33,6%), pancreatic – 37 (13,7%), breast – 66 (24,4%), lung – 35 (12,9%) and gastric cancer – 42 (15,5%). Pts with stage I was 50 (18,5%), stage II – 118 (43,5%) and stage III – 103 (38%). The median time of the f.-up was 9 mos. (1-37). No significant association was found between the level of ctDNA before surgery and DFS either in the general group or in groups stratified by tumor sites (HR 2.4, 95%CI 0.8-7.1, р=0.12 and HR 1.5, 95%CI 0.4-6.3, р=0.5, correspondingly). ctDNA was detected in the plasma after surgery in 57 (10%) pts: 9 (9.9%) cases of colorectal, 10 (27%) - pancreatic, 9 (13.6%) - breast, 19 (54.3%) - lung, and 10 (23.8%) - gastric cancer. Progression of the disease was detected in 28/57 (49%) pts with ctDNA(+) and 17/214 (8%) - in ctDNA(-) pts (p 〈 0.001). One-year DFS in ctDNA(+) and ctDNA(-) pts were 57% and 87%, respectively (HR 6.1, 95%CI 3.3-11.2, p 〈 0,001). ctDNA positivity after surgery was an independent negative prognostic factor according to Cox regression model fitted to T, N, and adjuvant chemotherapy (HR 5.7, 95%CI 3.1-10.8, p 〈 0.001). Conclusions: These results demonstrate the prognostic significance of ctDNA persisting after surgery in pts with the early stage of the different malignancies. Further clinical validation of this approach is required in trails with modifications of the adjuvant treatment, according to the content of ctDNA.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.3559
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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