|Table of Contents|

Predictive value of circulating tumor DNA detection on prognosis of patients with stage Ⅱ colorectal cancer after operation

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 21
Page:
3968-3972
Research Field:
Publishing date:

Info

Title:
Predictive value of circulating tumor DNA detection on prognosis of patients with stage Ⅱ colorectal cancer after operation
Author(s):
ZHAI Xiaolu1; WANG Yan2; WANG Fei3; YIN Dian1
1.Department of Oncology;2.Department of Geriatrics;3.Department of Gastrointestinal Surgery,Nantong First People's Hospital（the Second Affiliated Hospital of Nantong University),Jiangsu Nantong 226001,China.
Keywords:
circulating tumor DNA; liquid biopsy; colorectal cancer; prognosis
PACS:
R735.3
DOI:
10.3969/j.issn.1672-4992.2023.21.012
Abstract:
Objective:To comprehensively analyze the correlation between circulating tumor DNA and clinicopathological features of patients with stage Ⅱ colorectal cancer and its influence on prognosis.Methods:Useing chi square test or Fisher's exact test to compare the differences in clinical pathological characteristics between two groups of ctDNA positive and negative patients.The Kaplan-Meier method Log-Rank test was used to compare disease-free survival（DFS) between the two groups of patients with positive and negative ctDNA.To calculate the risk ratio（HR) of DFS using single factor and multi factor Cox regression analysis.Results:Among 135 patients with stage Ⅱ CRC，28（21%) were ctDNA positive and 107（79%) were ctDNA negative.Among the 28 ctDNA positive patients，23（82%) recurred or died during the follow-up period，and of the 107 ctDNA negative patients，14（13%) recurred or died during the follow-up period.Compared with patients with ctDNA negative stage Ⅱ CRC，the proportion of T4 stage tumors，vascular lymphatic or neural invasion，and tumor recurrence in ctDNA positive patients was significantly higher（all P<0.05).The DFS of patients with ctDNA positive phase Ⅱ CRC was significantly shorter than that of patients with ctDNA negative（Log-Rank test，P=0.011)，indicating a worse prognosis.Further multivariate Cox analysis showed that ctDNA positive（HR=2.94，95%CI=1.98~5.12，P<0.001)，stage T4 tumors（HR=2.14，95%CI=1.44~4.28，P=0.015)，and vascular lymphatic nerve invasion（HR=1.34，95%CI=1.04~1.64，P=0.042) were independent prognostic risk factors for DFS in stage Ⅱ CRC patients.Conclusion:ctDNA is a sensitive prognostic biomarker that can accurately identify the risk of postoperative recurrence in CRC patients，and then targeted relapse detection and postoperative adjuvant chemotherapy can improve patient survival.

References:

［1］SUNG H，FERLAY J，SIEGEL RL，et al.Global cancer statistics 2020:Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin，2021，71(3):209-249.
［2］MENG R，VENUGOPAL K，THOMAS H，et al.Cancer staging at diagnosis data comparisons in South Australia［J］.Sci Rep，2020，10(1):1008.
［3］LACY AM，DELGADO S，CASTELLS A，et al.The long-term results of a randomized clinical trial of laparoscopy-assisted versus open surgery for colon cancer［J］.Ann Surg，2008，248(1):1-7.
［4］GRAY R，BARNWELL J，MCCONKEY C，et al.Adjuvant chemotherapy versus observation in patients with colorectal cancer:A randomised study［J］.Lancet，2007，370(9604):2020-2029.
［5］CUNNINGHAM D，ATKIN W，LENZ HJ，et al.Colorectal cancer［J］.Lancet，2010，375(9719):1030-1047.
［6］MORRIS M，PLATELL C，IACOPETTA B.Tumor-infiltrating lymphocytes and perforation in colon cancer predict positive response to 5-fluorouracil chemotherapy［J］.Clin Cancer Res，2008，14(5):1413-1417.
［7］NIEDZWIECKI D，BERTAGNOLLI MM，WARREN RS，et al.Documenting the natural history of patients with resected stage Ⅱ adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation:Results from CALGB 9581［J］.J Clin Oncol，2011，29(23):3146-3152.
［8］WELLS KO，HAWKINS AT，KRISHNAMURTHY DM，et al.Omission of adjuvant chemotherapy is associated with increased mortality in patients with T3N0 colon cancer with inadequate lymph node harvest［J］.Dis Colon Rectum，2017，60(1):15-21.
［9］BENSON AR，SCHRAG D，SOMERFIELD MR，et al.American society of clinical oncology recommendations on adjuvant chemotherapy for stage Ⅱ colon cancer［J］.J Clin Oncol，2004，22(16):3408-3419.
［10］ANDRE T，BONI C，NAVARRO M，et al.Improved overall survival with oxaliplatin，fluorouracil，and leucovorin as adjuvant treatment in stage Ⅱ or Ⅲ colon cancer in the mosaic trial［J］.J Clin Oncol，2009，27(19):3109-3116.
［11］TOURNIGAND C，ANDRE T，BONNETAIN F，et al.Adjuvant therapy with fluorouracil and oxaliplatin in stage Ⅱ and elderly patients（between ages 70 and 75 years) with colon cancer:Subgroup analyses of the multicenter international study of oxaliplatin，fluorouracil，and leucovorin in the adjuvant treatment of colon cancer trial［J］.J Clin Oncol，2012，30(27):3353-3360.
［12］O'CONNOR ES，GREENBLATT DY，LOCONTE NK，et al.Adjuvant chemotherapy for stage Ⅱ colon cancer with poor prognostic features［J］.J Clin Oncol，2011，29(25):3381-3388.
［13］DIEHL F，SCHMIDT K，CHOTI MA，et al.Circulating mutant DNA to assess tumor dynamics［J］.Nat Med，2008，14(9):985-990.
［14］TAKEMASA I，HAMABE A，ISHII M.Perspectives for circulating tumor DNA in clinical management of colorectal cancer［J］.Int J Clin Oncol，2021，26(8):1420-1430.
［15］DASARI A，GROTHEY A，KOPETZ S.Circulating tumor DNA-defined minimal residual disease in solid tumors:Opportunities to accelerate the development of adjuvant therapies［J］.J Clin Oncol，2018，36(35):O2018789032.
［16］TIE J，KINDE I，WANG Y，et al.Circulating tumor dna as an early marker of therapeutic response in patients with metastatic colorectal cancer［J］.Ann Oncol，2015，26(8):1715-1722.
［17］GARLAN F，LAURENT-PUIG P，SEFRIOUI D，et al.Early evaluation of circulating tumor DNA as marker of therapeutic efficacy in metastatic colorectal cancer patients（placol study)［J］.Clin Cancer Res，2017，23(18):5416-5425.
［18］PARIKH AR，MOJTAHED A，SCHNEIDER JL，et al.Serial ctDNA monitoring to predict response to systemic therapy in metastatic gastrointestinal cancers［J］.Clin Cancer Res，2020，26(8):1877-1885.
［19］BETTEGOWDA C，SAUSEN M，LEARY RJ，et al.Detection of circulating tumor DNA in early-and late-stage human malignancies［J］.Sci Transl Med，2014，6(224):224r.
［20］LIN JK，LIN PC，LIN CH，et al.Clinical relevance of alterations in quantity and quality of plasma dna in colorectal cancer patients:Based on the mutation spectra detected in primary tumors［J］.Ann Surg Oncol，2014，21(Suppl 4):S680-S686.
［21］WANG Y，LI L，COHEN JD，et al.Prognostic potential of circulating tumor DNA measurement in postoperative surveillance of nonmetastatic colorectal cancer［J］.JAMA Oncol，2019，5(8):1118-1123.
［22］MUSHER BL，MELSON JE，AMATO G，et al.Evaluation of circulating tumor dna for methylated bcat1 and IKZF1 to detect recurrence of stage Ⅱ/stage Ⅲ colorectal cancer（CRC)［J］.Cancer Epidemiol Biomarkers Prev，2020，29(12):2702-2709.
［23］CHEN G，PENG J，XIAO Q，et al.Postoperative circulating tumor DNA as markers of recurrence risk in stages Ⅱ to Ⅲ colorectal cancer［J］.J Hematol Oncol，2021，14(1):80.
［24］TIE J，WANG Y，TOMASETTI C，et al.Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage Ⅱ colon cancer［J］.Sci Transl Med，2016，8(346):346r-392r.
［25］GRANCHER A，BEAUSSIRE L，MANFREDI S，et al.Postoperative circulating tumor DNA detection is associated with the risk of recurrence in patients resected for a stage Ⅱ colorectal cancer［J］.Front Oncol，2022，12:973167.
［26］CHAN HT，NAGAYAMA S，CHIN YM，et al.Clinical significance of clonal hematopoiesis in the interpretation of blood liquid biopsy［J］.Mol Oncol，2020，14(8):1719-1730.
［27］REINERT T，HENRIKSEN TV，CHRISTENSEN E，et al.Analysis of plasma cell-free dna by ultra deep sequencing in patients with stages Ⅰ to Ⅲ colorectal cancer［J］.JAMA Oncol，2019，5(8):1124-1131.
［28］TIE J，COHEN JD，LO SN，et al.Prognostic significance of postsurgery circulating tumor DNA in nonmetastatic colorectal cancer:Individual patient pooled analysis of three cohort studies［J］.Int J Cancer，2021，148(4):1014-1026.
［29］HENRIKSEN TV，TARAZONA N，FRYDENDAHL A，et al.Circulating tumor DNA in stage Ⅲ colorectal cancer，beyond minimal residual disease detection，toward assessment of adjuvant therapy efficacy and clinical behavior of recurrences［J］.Clin Cancer Res，2022，28(3):507-517.
［30］肖泽文,陶冀.CTC、ctDNA在结直肠癌诊断中的研究进展［J］. 现代肿瘤医学，2019,27（10)：1840-1844. XIAO ZW,TAO J.Research progress of circulating tumor cells and circulating tumor DNA in the diagnosis of colorectal cancer［J］. Modern Oncology，2019,27（10)：1840-1844.
［31］MARCUELLO M，VYMETALKOVA V，NEVES R，et al.Circulating biomarkers for early detection and clinical management of colorectal cancer［J］.Mol Aspects Med，2019，69:107-122.

Memo

Memo:
江苏省南通市卫生和计划生育科研课题（编号：QA2020011）
Last Update: 2023-09-28