Multitarget stool DNA testing for colorectal-cancer screening

Thomas Imperiale, David F. Ransohoff, Steven H. Itzkowitz, Theodore R. Levin, Philip Lavin, Graham P. Lidgard, David A. Ahlquist, Barry M. Berger

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. METHODS: We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. RESULTS: Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P = 0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P = 0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. CONCLUSIONS: In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results.

Original languageEnglish
Pages (from-to)1287-1297
Number of pages11
JournalNew England Journal of Medicine
Volume370
Issue number14
DOIs
StatePublished - 2014

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Early Detection of Cancer
Colorectal Neoplasms
DNA
Colonoscopy
Polyps
Hemoglobins
Immunoassay
Adenoma
Methylation
Actins
Neoplasms
Buffers
Logistic Models
Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Imperiale, T., Ransohoff, D. F., Itzkowitz, S. H., Levin, T. R., Lavin, P., Lidgard, G. P., ... Berger, B. M. (2014). Multitarget stool DNA testing for colorectal-cancer screening. New England Journal of Medicine, 370(14), 1287-1297. https://doi.org/10.1056/NEJMoa1311194

Multitarget stool DNA testing for colorectal-cancer screening. / Imperiale, Thomas; Ransohoff, David F.; Itzkowitz, Steven H.; Levin, Theodore R.; Lavin, Philip; Lidgard, Graham P.; Ahlquist, David A.; Berger, Barry M.

In: New England Journal of Medicine, Vol. 370, No. 14, 2014, p. 1287-1297.

Research output: Contribution to journalArticle

Imperiale, T, Ransohoff, DF, Itzkowitz, SH, Levin, TR, Lavin, P, Lidgard, GP, Ahlquist, DA & Berger, BM 2014, 'Multitarget stool DNA testing for colorectal-cancer screening', New England Journal of Medicine, vol. 370, no. 14, pp. 1287-1297. https://doi.org/10.1056/NEJMoa1311194
Imperiale T, Ransohoff DF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP et al. Multitarget stool DNA testing for colorectal-cancer screening. New England Journal of Medicine. 2014;370(14):1287-1297. https://doi.org/10.1056/NEJMoa1311194
Imperiale, Thomas ; Ransohoff, David F. ; Itzkowitz, Steven H. ; Levin, Theodore R. ; Lavin, Philip ; Lidgard, Graham P. ; Ahlquist, David A. ; Berger, Barry M. / Multitarget stool DNA testing for colorectal-cancer screening. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 14. pp. 1287-1297.
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abstract = "BACKGROUND: An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. METHODS: We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. RESULTS: Of the 9989 participants who could be evaluated, 65 (0.7{\%}) had colorectal cancer and 757 (7.6{\%}) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3{\%} with DNA testing and 73.8{\%} with FIT (P = 0.002). The sensitivity for detecting advanced precancerous lesions was 42.4{\%} with DNA testing and 23.8{\%} with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2{\%} with DNA testing and 46.2{\%} with FIT (P = 0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4{\%} and 5.1{\%}, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6{\%} and 94.9{\%}, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8{\%} and 96.4{\%}, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. CONCLUSIONS: In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results.",
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AU - Lidgard, Graham P.

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N2 - BACKGROUND: An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. METHODS: We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. RESULTS: Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P = 0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P = 0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. CONCLUSIONS: In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results.

AB - BACKGROUND: An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. METHODS: We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. RESULTS: Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P = 0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P = 0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. CONCLUSIONS: In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results.

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