Erin L Symonds1,2, Susanne K Pedersen3, David Murray3, Susan E Byrne1, Amitesh Roy1,4, Christos Karapetis1,4, Paul Hollington2, Philippa Rabbitt2, Frederick S Jones5, Lawrence LaPointe5, Eva Segelov6,7, Graeme P Young1. 1. Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, South Australia, Australia. 2. Bowel Health Service, Flinders Medical Centre, Bedford Park, South Australia, Australia. 3. Clinical Genomics Pty, Ltd, North Ryde, New South Wales, Australia. 4. Department of Oncology, Flinders Medical Centre, Bedford Park, South Australia, Australia. 5. Clinical Genomics, Inc, Bridgewater, New Jersey. 6. Department of Medicine, School of Clinical Sciences, Monash Health, Melbourne, Victoria, Australia. 7. Translational Oncology Research Laboratory, Monash University, Melbourne, Victoria, Australia.
Abstract
BACKGROUND: The sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence. METHODS: Blood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylated branched-chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc-finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold). RESULTS: The study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%-69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%-36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%-99.6%; CEA, 96.4%; 95% CI, 91.4%-99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9-1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3-20.6; P = .407). CONCLUSIONS: The quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylated BCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.
BACKGROUND: The sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence. METHODS: Blood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylatedbranched-chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc-finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold). RESULTS: The study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%-69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%-36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%-99.6%; CEA, 96.4%; 95% CI, 91.4%-99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9-1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3-20.6; P = .407). CONCLUSIONS: The quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylatedBCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.
Authors: Erin L Symonds; Susanne K Pedersen; Bernita Yeo; Hiba Al Naji; Susan E Byrne; Amitesh Roy; Graeme P Young Journal: Mol Oncol Date: 2022-01-24 Impact factor: 7.449
Authors: Robert S Bresalier; William M Grady; Sanford D Markowitz; Hans Jørgen Nielsen; Surinder K Batra; Paul D Lampe Journal: Cancer Epidemiol Biomarkers Prev Date: 2020-04-16 Impact factor: 4.254
Authors: Arvind Dasari; Van K Morris; Carmen J Allegra; Chloe Atreya; Al B Benson; Patrick Boland; Ki Chung; Mehmet S Copur; Ryan B Corcoran; Dustin A Deming; Andrea Dwyer; Maximilian Diehn; Cathy Eng; Thomas J George; Marc J Gollub; Rachel A Goodwin; Stanley R Hamilton; Jaclyn F Hechtman; Howard Hochster; Theodore S Hong; Federico Innocenti; Atif Iqbal; Samuel A Jacobs; Hagen F Kennecke; James J Lee; Christopher H Lieu; Heinz-Josef Lenz; O Wolf Lindwasser; Clara Montagut; Bruno Odisio; Fang-Shu Ou; Laura Porter; Kanwal Raghav; Deborah Schrag; Aaron J Scott; Qian Shi; John H Strickler; Alan Venook; Rona Yaeger; Greg Yothers; Y Nancy You; Jason A Zell; Scott Kopetz Journal: Nat Rev Clin Oncol Date: 2020-07-06 Impact factor: 65.011
Authors: Jun Gong; Andrew Hendifar; Alexandra Gangi; Karen Zaghiyan; Katelyn Atkins; Yosef Nasseri; Zuri Murrell; Jane C Figueiredo; Sarah Salvy; Robert Haile; Megan Hitchins Journal: Cancers (Basel) Date: 2021-09-10 Impact factor: 6.639