BIOE 301Bioengineering and Prostate CancerChallenge: Should we screen?Cost of screeningSlide 5Efficacy of screeningWhy are RCTs so Important? Lead Time BiasSlide 8Should we screen?Screening guidelinesDo All Countries Screen with PSA?Bioengineering and Ovarian CancerStatistics on Ovarian CancerGlobal Burden of Ovarian CancerRisk factorsPathophysiologyScreening of Ovarian CancerTransvaginal SonographyDiagnostic LaparoscopyDetection and TreatmentScreening ScenariosSlide 22Slide 23Slide 24Does Ultrasound Screening Work?Ongoing Clinical TrialsOvarian CancerChallengeCancer Screening ExamsLets play…Here’s how to play:Slide 32Slide 33Slide 34Slide 35Slide 36Slide 37Slide 38Proteomics: Mass SpectrometerData AnalysisOvaCheckSlide 42Comparative AnalysisSlide 44ResponseDr. Koop, where were you?Slide 47Slide 48Slide 49Slide 50Slide 51Slide 52Slide 53DNA MicroarrayNew screening technologiesBIOE202: Advances in bioengineeringNext TimeBIOE 301Lecture FifteenDavid J. [email protected] Hours: Mon 1-4 PMRisk factorsDetectionTreatmentNew technologiesChallengesBioengineering and Prostate CancerChallenge: Should we screen?Costs Efficacy of screeningDRE/PSA test $30-100Prostate biopsy$700-1500Cost of screeningScreening Performance:Se = 73%; Sp = 90%Number Tested:N=1,000,000; Prevalence = 2% Costs:Screening = $30; Follow up biopsy = $1500What is detection cost?What is cost/cancer found?Test PositiveTest NegativeDisease Present14,600 5,400 # with Disease = 20,000Disease Absent98,000 882,000 #without Disease = 980,000# Test Pos = 112,600# Test Neg = 887,400Total Tested = 1,000,000Cost to Detect =$30*1,000,000+$1500*112,600 =$168,900,000 Cost/Cancer = $168,900,000/14,600=$13,623Efficacy of screeningDRE Case studiesMixed resultsPSA test Mortality decreased 42% since 1993 in Tyrol, AustriaRCT’sERSPCPLCOWhy are RCTs so Important?Lead Time BiasShould we screen?Yes:Localized prostate cancer is curableAdvanced prostate cancer is fatalSome studies (not RCTs) show decreased mortality in screened patientsNo:False-positives lead to unnecessary biopsiesOver-detection of latent cancersWe will detect many cancers that may never have produced symptoms before patients died of other causes (slow growing cancer of old age)No RCTs showing decreased mortalityScreening guidelinesDo All Countries Screen with PSA?United States:Conflicting recommendationsEurope:NoNot enough evidence that screening reduces mortalityBioengineering and Ovarian CancerStatistics on Ovarian CancerUnited States:Incidence: 22,430Mortality: 15,280Worldwide:Incidence: 190,000Mortality: 114,000Global Burden of Ovarian CancerRisk factorsAgeMost ovarian cancers develop after menopause Personal or family history of breast, ovarian, endometrial, prostate or colon cancer.Reproductive history Increases with the more lifetime cycles of ovulation that awoman has undergone. Thus, women who haveundergone hormonal treatment for infertility, never usedbirth control pills, and who never became pregnant are athigher risk for ovarian cancerPathophysiologyScreening of Ovarian CancerPelvic and rectal examCA125 testTransvaginal sonographyTransvaginal SonographyDiagnostic LaparoscopyComplication Rate = 0.5 – 1%Detection and TreatmentScreeningPelvic examCA125 testTransvaginal ultrasoundDiagnosisDiagnostic laparoscopyTreatment:Surgery, radiation therapy, chemotherapy5 year survivalLocalized disease: 93% (20% diagnosed at this stage)Screening ScenariosScenario #1:Screen 1,000,000 women with CA125p = .0001 (100 cancers)Se=35%, Sp=98.5%Cost = $30Follow with laparoscopyComplication rate = 1%Cost=$2,000TP=35 FP=14,999 Complications=150 PPV =0.23% NPV =99.99%Cost per cancer found = $1,716,200Screening ScenariosScenario #2:Screen 1,000,000 women with transvaginal USP = .0001 (100 cancers)Se=100%, Sp=96%Cost = $150Follow with laparoscopyComplication rate = 1%Cost=$2,000TP=100 FP=39,996 Complications=401 PPV =0.25% NPV =100%Cost per cancer found = $300,672Screening ScenariosScenario #3:Screen 1,000,000 women >age 50 with TVUSP = .0005 (500 cancers)Se=100%, Sp=96%Cost = $150Follow with laparoscopyComplication rate = 1%Cost=$2,000TP=500 FP=39,980 Complications=405 PPV =1.24% NPV =100%Cost per cancer found = $60,670Screening ScenariosScenario #3 cont.:Screen 1,000,000 women > age 50 with TVUSP = .0005 (500 cancers)Se=100%, Sp=??%Cost = $150How high does Sp need to be for PPV to reach 25%?Sp = 99.985%Does Ultrasound Screening Work?Two studies of over 10,000 low-risk women:The positive predictive value was only 2.6%Ultrasound screening of 100,000 women over age 45 would:Detect 40 cases of ovarian cancer, Result in 5,398 false positives Result in over 160 complications from diagnostic laparoscopyJacobs I. Screening for early ovarian cancer. Lancet; 2:171-172, 1988.Ongoing Clinical TrialsUnited Kingdom200,000 postmenopausal womenCA 125Qlevel plus transvaginal ultrasound examination Transvaginal ultrasound alone No screeningUnited States:37,000Qwomen (aged 55–74)Annual CA 125Qlevel and transvaginal ultrasound examinationNo screeningEurope:120,000 postmenopausal womenNo screening, Transvaginal ultrasound at intervals of 18 monthsTransvaginal ultrasound at intervals of 3Qyearshttp://www.mja.com.au/public/issues/178_12_160603/and10666_fm.pdfRisk factorsDetectionTreatmentChallengesNew technologiesOvarian CancerChallengeBetter screening methods to detect early stages of ovarian cancerCancer Screening ExamsCellular/Morphological MarkersPap smearSerum protein markersPSACA125DNA markersHPV DNALets play…Where in the World is C. Everett Koop?How do we choose a target?Here’s how to play:Take a good look at each of the following pictures and try to spot C. Everett Koop.A. He is in a mitochondria.B. He is on a nucleus.C. He is on a chromosome.A. He is behind endoplasmic reticulum.B. He is behind a Golgi apparatus.C. He is behind a vacuole.A. He is on a protein.B. He is on a gene.C. He is on a chromosome.A. He is in helicase.B. He is in a nuclear pore.C. He is on a ribosome.A. He is on DNA.B. He is on a protein.C. He is on RNAA. He is on a sea turtle.B. He is on a
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