结肠癌英文文献抄读课件.pptx

1、BackgroundBackgroundCRC:major cause of death and disease BackgroundBackgroundProcesses of colorectal carcinogenesis lend themselves to screeningBackgroundBackgroundA substantial proportion never tested!Screening for CRC is cost-effectiveA simple,noninvasive test might improve clinical out-comes28%Ba

2、ckgroundBackgroundColorectal cancer arises from accumulated genetic and epigenetic alterationsAimAim Evaluate the multitarget stool DNA test as a tool for screeningAimAim Primary aim:DNA test in the detection of CRC Secondary aims:DNA test in the detection of advanced precancerous lesions and to com

3、pare it with a commercially available fecal immunochemical test(FIT)DNA testVSMethodsMethodsStudy Population:l 2011.6-2012.11 90 sites Asymptomatic persons Ages of 50 to 84 at average risk for CRC Scheduled to undergo screeningcolonoscopySecondary aims:DNA test in the detection of advanced precancer

4、ous lesions and to compare it with a commercially available fecal immunochemical test(FIT)A simple,noninvasive test might improve clinical out-comesA substantial proportion never tested!digestive cancer,or inflammatory bowel diseaseprevious colonoscopy,barium enema,CT,sigmoidoscopyundergone colorect

5、al resectionAdvanced precancerous lesions:Advanced adenomas high-grade dysplasiafamily historySessile serrated polyps measuring 1 cm or more in diameterundergone colorectal resectionStudy Population:Ages of 50 to 84 at average risk for CRCprevious colonoscopy,barium enema,CT,sigmoidoscopyConclusions

6、Sessile serrated polyps measuring 1 cm or more in diameterCRC,stage determined with the use of the AJCC staging systempositive results on fecal blood testing,rectal bleedingSecondary aims:DNA test in the detection of advanced precancerous lesions and to compare it with a commercially available fecal

7、 immunochemical test(FIT)CRC,stage determined with the use of the AJCC staging systemMethodsMethodsExcludedl personal history:colorectal neoplasia,digestive cancer,or inflammatory bowel diseasel previous colonoscopy,barium enema,CT,sigmoidoscopyl positive results on fecal blood testing,rectal bleedi

8、ngl undergone colorectal resectionl family historyMethodsMethodsPrimary and Secondary OutcomeslCRC,stage determined with the use of the AJCC staging systeml Advanced precancerous lesions:Advanced adenomas high-grade dysplasia with 25%villous histologic features measure 1cm in the greatest dimension

9、Sessile serrated polyps measuring 1 cm or more in diameteraberrantly methylated BMP3 and NDRG4promoter regionsmutant KRASimmunochemical assay for human hemoglobinFITMultitarget stool DNA testResultsResults127760.7%7.6%ResultsResultsResultsResultsResultsResultsFigure 3.Receiver Operating Characterist

10、ic(ROC)Curves Comparing DNA Testing and FIT for the Detection of Colorectal Cancer and Advanced Colorectal Neoplasia.ResultsResultsMultitarget DNA testing detected clinically significant lesions more efficiently than FIT.ConclusionsConclusionsA stool test combining altered human DNA and fecal hemogl

11、obin showed higher sensitivity than a commercial FIT for both CRC and advanced precancerous lesions,although with lower specificity.Translational ResearchTranslational ResearchAug.12,2014FDA Approves CologuardFirst and Only Stool DNA Noninvasive Colorectal Cancer Screening TestReceived a proposed co

12、ve-rage memorandum from the Centers for Medicare and Medicaid Services(CMS)Processes of colorectal carcinogenesis lend themselves to screeningAdvanced precancerous lesions:CRC,stage determined with the use of the AJCC staging system11 90 sitesundergone colorectal resectionAdvanced precancerous lesio

13、ns:family historyA stool test combining altered human DNA and fecal hemoglobin showed higher sensitivity than a commercial FIT for both CRC and advanced precancerous lesions,although with lower specificity.positive results on fecal blood testing,rectal bleedingpositive results on fecal blood testing

14、,rectal bleedingMultitarget stool DNA testMultitarget DNA testing detected clinically significant lesions more efficiently than FIT.An easy-to-use screen-ing testEvaluate the multitarget stool DNA test as a tool for screeningColorectal cancer arises from accumulated genetic and epigenetic alteration

15、sCRC,stage determined with the use of the AJCC staging systempositive results on fecal blood testing,rectal bleedingAsymptomatic personsAdvanced adenomas high-grade dysplasiaColorectal cancer arises from accumulated genetic and epigenetic alterationsStudy Population:People at average risk for colore

16、ctal cancer An easy-to-use screen-ing test 599$BackgroundBackgroundA substantial proportion never tested!Screening for CRC is cost-effectiveA simple,noninvasive test might improve clinical out-comes28%MethodsMethodsStudy Population:l 2011.6-2012.11 90 sites Asymptomatic persons Ages of 50 to 84 at a

17、verage risk for CRC Scheduled to undergo screeningcolonoscopyMethodsMethodsPrimary and Secondary OutcomeslCRC,stage determined with the use of the AJCC staging systeml Advanced precancerous lesions:Advanced adenomas high-grade dysplasia with 25%villous histologic features measure 1cm in the greatest

18、 dimension Sessile serrated polyps measuring 1 cm or more in diameterResultsResultsFigure 3.Receiver Operating Characteristic(ROC)Curves Comparing DNA Testing and FIT for the Detection of Colorectal Cancer and Advanced Colorectal Neoplasia.ConclusionsConclusionsA stool test combining altered human D

19、NA and fecal hemoglobin showed higher sensitivity than a commercial FIT for both CRC and advanced precancerous lesions,although with lower specificity.11 90 sitesA stool test combining altered human DNA and fecal hemoglobin showed higher sensitivity than a commercial FIT for both CRC and advanced pr

20、ecancerous lesions,although with lower specificity.CRC,stage determined with the use of the AJCC staging systemAsymptomatic personspositive results on fecal blood testing,rectal bleedingdigestive cancer,or inflammatory bowel diseaseAges of 50 to 84 at average risk for CRCprevious colonoscopy,barium

21、enema,CT,sigmoidoscopyPrimary and Secondary Outcomesmeasure 1cm in the greatest dimensionAdvanced adenomas high-grade dysplasiaSessile serrated polyps measuring 1 cm or more in diameterCRC,stage determined with the use of the AJCC staging systemFDA Approves CologuardSecondary aims:DNA test in the de

22、tection of advanced precancerous lesions and to compare it with a commercially available fecal immunochemical test(FIT)A simple,noninvasive test might improve clinical out-comespositive results on fecal blood testing,rectal bleedingpositive results on fecal blood testing,rectal bleedingPrimary and S

23、econdary OutcomesScheduled to undergo screeningcolonoscopyAdvanced precancerous lesions:Receiver Operating Characteristic(ROC)Curves Comparing DNA Testing and FIT for the Detection of Colorectal Cancer and Advanced Colorectal Neoplasia.undergone colorectal resectionAdvanced adenomas high-grade dyspl

24、asiaMultitarget DNA testing detected clinically significant lesions more efficiently than FIT.undergone colorectal resectionA substantial proportion never tested!CRC,stage determined with the use of the AJCC staging systemFDA Approves CologuardCRC,stage determined with the use of the AJCC staging sy

25、stemCRC,stage determined with the use of the AJCC staging systemCRC,stage determined with the use of the AJCC staging systemwith 25%villous histologic featuresCRC,stage determined with the use of the AJCC staging systemFirst and Only Stool DNA Noninvasive Colorectal Cancer Screening TestSecondary ai

26、ms:DNA test in the detection of advanced precancerous lesions and to compare it with a commercially available fecal immunochemical test(FIT)Sessile serrated polyps measuring 1 cm or more in diameterConclusionsdigestive cancer,or inflammatory bowel diseasepersonal history:colorectal neoplasia,Advance

27、d precancerous lesions:Colorectal cancer arises from accumulated genetic and epigenetic alterationsprevious colonoscopy,barium enema,CT,sigmoidoscopyPrimary aim:DNA test in the detection of CRCEvaluate the multitarget stool DNA test as a tool for screeningCRC,stage determined with the use of the AJC

28、C staging systemprevious colonoscopy,barium enema,CT,sigmoidoscopyPrimary and Secondary OutcomesAsymptomatic personsMultitarget DNA testing detected clinically significant lesions more efficiently than FIT.positive results on fecal blood testing,rectal bleedingMultitarget stool DNA testpositive resu

29、lts on fecal blood testing,rectal bleedingAsymptomatic personsfamily historyA substantial proportion never tested!Advanced precancerous lesions:Processes of colorectal carcinogenesis lend themselves to screeningpositive results on fecal blood testing,rectal bleedingPrimary and Secondary OutcomesMult

30、itarget DNA testing detected clinically significant lesions more efficiently than FIT.Advanced precancerous lesions:Advanced precancerous lesions:measure 1cm in the greatest dimensionAdvanced adenomas high-grade dysplasiaPrimary and Secondary Outcomesdigestive cancer,or inflammatory bowel diseaseSes

31、sile serrated polyps measuring 1 cm or more in diameterpositive results on fecal blood testing,rectal bleedingCRC,stage determined with the use of the AJCC staging systemundergone colorectal resectionScreening for CRC is cost-effectivewith 25%villous histologic featuresSecondary aims:DNA test in the

32、 detection of advanced precancerous lesions and to compare it with a commercially available fecal immunochemical test(FIT)Sessile serrated polyps measuring 1 cm or more in diameterCRC,stage determined with the use of the AJCC staging systemAsymptomatic personsA simple,noninvasive test might improve clinical out-comesTranslational Researchprevious colonoscopy,barium enema,CT,sigmoidoscopywith 25%villous histologic featuresAdvanced adenomas high-grade dysplasiapositive results on fecal blood testing,rectal bleedingmeasure 1cm in the greatest dimensionPrimary and Secondary Outcomes