Mo1184 Changes in FIT result Are More Predictive Than Absolute FIT Values in Colorectal Cancer...
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screening were found to be high among these participants. Subsidy on CRC screening as a routine service, the establishment of more accessible screening infrastructure to screening participants, and educational initiatives on the details and safety of the screening tests are therefore needed. Since the screening participants who have the associated factors identified in this study were more likely to encounter psychological obstacles of CRC screening, they should receive more thorough explanation of the nature of screening tests. Mo1184 Changes in FIT result Are More Predictive Than Absolute FIT Values in Colorectal Cancer Screening Inge Stegeman, An K. Stroobants, Marco W. Mundt, Sascha C. van Doorn, Rosalie C. Mallant-Hent, Patrick M. Bossuyt, Evelien Dekker Background Fecal immunochemical testing (FIT) has a less than perfect accuracy in colorectal cancer screening. Sensitivity of FIT-based screening is low, however sensitivity could be increased by repeating FIT screening regularly. It might be possible to improve the sensitivity of FIT-based screening by considering the differences in exact values of fecal haemoglobin concentrations (delta FIT) over consecutive screening rounds. We evaluated whether these changes in FIT-results over repeated screening round are more predictive than absolute values of FIT. Methods Data were collected in the second and third round of biannual FIT- based screening pilot in the Amsterdam region of the Netherlands, for which average risk individuals aged 50-75 years were invited to perform one FIT (OC-Sensor). All persons with a test-result above the cut-off of 50 ngHb/ml buffer were recommended to undergo colonoscopy. We compared the accuracy for detecting advanced neoplasia of a single FIT with that of absolute and relative changes in FIT-results in third-round FIT positives who had tested negative in the second round. Advanced neoplasia was defined as CRC or advanced adenoma (adenoma ≥ 10 mm, adenoma with ≥ 25% villous histology, or adenoma with high grade dysplasia). Results 4928 invitees that had tested negative in the second round, participated again in the third round. Their average age was 63 years; 57% was female. In those 4928 individuals, FIT had increased by on average 18 ngHb/ml buffer between the two rounds (SD: 148). The area under the ROC curve for absolute FIT values in FIT positives was 0.64 (95%CI: 0.58 to 0.70). The corresponding area for absolute changes in FIT was 0.59 (95%CI: 0.50 to 0.67); the corresponding area for relative changes in FIT was 0.51 (95%CI: 0.38 to 0.64). Conclusion In screening participants with a FIT result over 50 ngHb/ ml buffer who had tested negative in the previous screening round, changes in FIT were less predictive of the presence of advanced neoplasia than absolute FIT values. This suggests that FIT sensitivity in population based screening programs cannot be improved by consider- ing - alternatively or additionally - changes in fecal haemoglobin level. Mo1185 A Stable and Quantitative Fecal Immunochemical Test (FIT) for Colorectal Cancer (CRC) Screening Daniel Clampett, Josie Quindere Background A current limitation of FITs designed for human eye interpretation is the inability to vary the assay positive threshold to control test positivity rate in the context of population screening. Varying the positivity threshold enables a user defined sensitivity and test positivity rate appropriate to the resources available to a screening program. Aim To evaluate the ability to control assay positivity rate of the InSure FIT (Enterix, NJ USA) approved for human eye interpretation using an automated test strip reader. We measure analytical reliability of this instrument and the impact of quantified test interpretation on clinical reporting and test positivity rate. Method The DxPress (PBM, NJ USA) is an FDA approved reader for quantifying immuno-chromatographic assays such as InSure FIT. To measure the precision of the DxPress: spiked Hb solutions (50-500ng/ml) were applied to the InSure S-601 AGA Abstracts FIT (n=30 per Hb level). Developed assays were interpreted using both human eye reading and also using the DxPress reader. The output of the test results using the DxPress was reported as the ratio between the intensity of the test line and the control line. To evaluate the hypothetical clinical impact of using this instrument, 491 patient specimens were also analysed using both interpretation methods. Results Quantitative analysis of the spiked samples (Table 1) revealed a linear relationship between the Hb concentration and the intensity ratio in the range of 50-500ng/ml (R2 = 0.9918) (IR = 0.0006[Hb]-0.0301). The reliability improved as [Hb] increased (CV ≤16% @ [Hb].100ng/ml). Visual assessment of the test results showed that 8/30 (27%) of tests were assessed as positive at 50 ng/ml by human eye reader whereas 29/30 (97%) of paired DxPress-interpreted specimens were significantly above noise background. None of the negative controls were called positive by human eye or automated reader. 100% of tests were assessed as positive at 100ng/ml and above by human eye and DxPress. Clinical reporting 491 clinical samples were evaluated by human eye and using DxPress and plotted against total positivity rate (Figure 1). Visual inspection of quantified results shown below demonstrates a dynamic range of test positivity rate from 0 to more than 20% TPR with an ideal dynamic range between 0 and 10% TPR. Human eye interpretation was positive in 15% of specimens, well within the dynamic range of the DxPress quantification. Conclusions The DxPress Reader provides effective quantitative analysis of the InSure FIT immuno-chromatographic assay. The DxPress was more reliable at reading weak positive specimens against background noise than skilled human operators (97% vs 27%). We have shown that quantification of the InSure FIT can be used to establish a target test positivity rate intended for rationale screening services to match downstream colonoscopic resources. Table 1 Figure 1 Mo1186 Fecal DNA Methylation Assay for the Identification of a Multiple Gastrointestinal Cancers Including Pancreatic Caner Tatsuya Morikawa, Takeshi Nagasaka, Kazuhiro Yoshida, Yoshiko Mori, Nobuhito Kubota, Yuko Takehara, Naosuke Yokomichi, Naoshi Nishida, Kiyoto Takehara, Kunitoshi Shigeyasu, Akihiro Nyuya, Rikiya Shiwaku, Manabu Suno, Toshiyoshi Fujiwara, Ajay Goel Background: The development of noninvasive screening tools for the earlier detection of neoplastic lesions is essential in reducing the mortality associated with malignant diseases, such as colorectal cancer (CRC). Recently we published that fecal DNA methylation analysis offers a robust screening tool for patients with gastric and CRC. However, currently there are no non-invasive screening tests available for patients with other gastrointestinal cancers, including pancreatic cancer. Given our extensive experience on this topic, we sought to develop a novel, non-invasive, fecal DNA methylation-based screening test, which can also identify a variety of other gastrointestinal cancers including pancreatic cancer. Methods: We have previously published a unique and highly sensitive assay that uses a single-step bisulfite modification of DNA, followed by fluorescence-based PCR to measure fecal DNA methylation. Herein, we enhanced the accuracy and robustness of our assay further by increasing the biomarker panel to 8 methylated genes, instead of 4 genes published previously. This prospective study has currently enrolled over 380 fecal samples from patients with various gastrointestinal cancers, as well as healthy volunteers. Thus far we could successfully analyzed 170 cases, with complete clinical annotation, including 56 CRCs, 28 colorectal adenomas (CAs), 24 liver, pancreatic, gall bladder, duodenal and/or gastric tumors (LPGDs). Fecal specimens from all patients were collected on 2 separate days and results validated indepen- dently. Results: Our assay successfully identified one or more methylated marker in fecal DNA collected on two separate days from 91.0% of CRC patients, 92.8% of CA patients, 70.8% of patients with LPGD, and 27.4% of subjects without neoplastic or active diseases (SNADs). The mean fecal DNA recovery scores calculated by sum total of the inspection on two days (max value was 16), was 10.4 for CRCs (95%CI= 9.2 to 11.5, p ,.0001 vs. SNADs), 9.2 for CAs (95%CI= 7.6 to 10.8, p=.0084 vs. SNADs), 6.4 for LPGDs (95%CI= 4.7 to 8.1, p=0.99 vs. SNADs), and 6.3 for SNADs (95%CI= 5.2 to 7.4), respectively. The mean methylation scores calculated by sum total of the inspection on two days (max value was AGA Abstracts
Transcript of Mo1184 Changes in FIT result Are More Predictive Than Absolute FIT Values in Colorectal Cancer...
screening were found to be high among these participants. Subsidy on CRC screening as aroutine service, the establishment of more accessible screening infrastructure to screeningparticipants, and educational initiatives on the details and safety of the screening tests aretherefore needed. Since the screening participants who have the associated factors identifiedin this study were more likely to encounter psychological obstacles of CRC screening, theyshould receive more thorough explanation of the nature of screening tests.
Mo1184
Changes in FIT result Are More Predictive Than Absolute FIT Values inColorectal Cancer ScreeningInge Stegeman, An K. Stroobants, Marco W. Mundt, Sascha C. van Doorn, Rosalie C.Mallant-Hent, Patrick M. Bossuyt, Evelien Dekker
Background Fecal immunochemical testing (FIT) has a less than perfect accuracy in colorectalcancer screening. Sensitivity of FIT-based screening is low, however sensitivity could beincreased by repeating FIT screening regularly. It might be possible to improve the sensitivityof FIT-based screening by considering the differences in exact values of fecal haemoglobinconcentrations (delta FIT) over consecutive screening rounds. We evaluated whether thesechanges in FIT-results over repeated screening round are more predictive than absolutevalues of FIT. Methods Data were collected in the second and third round of biannual FIT-based screening pilot in the Amsterdam region of the Netherlands, for which average riskindividuals aged 50-75 years were invited to perform one FIT (OC-Sensor). All personswith a test-result above the cut-off of 50 ngHb/ml buffer were recommended to undergocolonoscopy. We compared the accuracy for detecting advanced neoplasia of a single FITwith that of absolute and relative changes in FIT-results in third-round FIT positives whohad tested negative in the second round. Advanced neoplasia was defined as CRC or advancedadenoma (adenoma ≥ 10 mm, adenoma with ≥ 25% villous histology, or adenoma withhigh grade dysplasia). Results 4928 invitees that had tested negative in the second round,participated again in the third round. Their average age was 63 years; 57% was female. Inthose 4928 individuals, FIT had increased by on average 18 ngHb/ml buffer between thetwo rounds (SD: 148). The area under the ROC curve for absolute FIT values in FIT positiveswas 0.64 (95%CI: 0.58 to 0.70). The corresponding area for absolute changes in FIT was0.59 (95%CI: 0.50 to 0.67); the corresponding area for relative changes in FIT was 0.51(95%CI: 0.38 to 0.64). Conclusion In screening participants with a FIT result over 50 ngHb/ml buffer who had tested negative in the previous screening round, changes in FIT wereless predictive of the presence of advanced neoplasia than absolute FIT values. This suggeststhat FIT sensitivity in population based screening programs cannot be improved by consider-ing - alternatively or additionally - changes in fecal haemoglobin level.
Mo1185
A Stable and Quantitative Fecal Immunochemical Test (FIT) for ColorectalCancer (CRC) ScreeningDaniel Clampett, Josie Quindere
Background A current limitation of FITs designed for human eye interpretation is the inabilityto vary the assay positive threshold to control test positivity rate in the context of populationscreening. Varying the positivity threshold enables a user defined sensitivity and test positivityrate appropriate to the resources available to a screening program. Aim To evaluate theability to control assay positivity rate of the InSure FIT (Enterix, NJ USA) approved forhuman eye interpretation using an automated test strip reader. We measure analyticalreliability of this instrument and the impact of quantified test interpretation on clinicalreporting and test positivity rate. Method The DxPress (PBM, NJ USA) is an FDA approvedreader for quantifying immuno-chromatographic assays such as InSure FIT. To measure theprecision of the DxPress: spiked Hb solutions (50-500ng/ml) were applied to the InSure
S-601 AGA Abstracts
FIT (n=30 per Hb level). Developed assays were interpreted using both human eye readingand also using the DxPress reader. The output of the test results using the DxPress wasreported as the ratio between the intensity of the test line and the control line. To evaluatethe hypothetical clinical impact of using this instrument, 491 patient specimens were alsoanalysed using both interpretation methods. Results Quantitative analysis of the spikedsamples (Table 1) revealed a linear relationship between the Hb concentration and theintensity ratio in the range of 50-500ng/ml (R2 = 0.9918) (IR = 0.0006[Hb]-0.0301). Thereliability improved as [Hb] increased (CV≤16% @ [Hb].100ng/ml). Visual assessment ofthe test results showed that 8/30 (27%) of tests were assessed as positive at 50 ng/ml byhuman eye reader whereas 29/30 (97%) of paired DxPress-interpreted specimens weresignificantly above noise background. None of the negative controls were called positive byhuman eye or automated reader. 100% of tests were assessed as positive at 100ng/ml andabove by human eye and DxPress. Clinical reporting 491 clinical samples were evaluatedby human eye and using DxPress and plotted against total positivity rate (Figure 1). Visualinspection of quantified results shown below demonstrates a dynamic range of test positivityrate from 0 to more than 20% TPR with an ideal dynamic range between 0 and 10% TPR.Human eye interpretation was positive in 15% of specimens, well within the dynamic rangeof the DxPress quantification. Conclusions The DxPress Reader provides effective quantitativeanalysis of the InSure FIT immuno-chromatographic assay. The DxPress was more reliableat reading weak positive specimens against background noise than skilled human operators(97% vs 27%). We have shown that quantification of the InSure FIT can be used to establisha target test positivity rate intended for rationale screening services to match downstreamcolonoscopic resources.
Table 1
Figure 1
Mo1186
Fecal DNA Methylation Assay for the Identification of a MultipleGastrointestinal Cancers Including Pancreatic CanerTatsuya Morikawa, Takeshi Nagasaka, Kazuhiro Yoshida, Yoshiko Mori, Nobuhito Kubota,Yuko Takehara, Naosuke Yokomichi, Naoshi Nishida, Kiyoto Takehara, KunitoshiShigeyasu, Akihiro Nyuya, Rikiya Shiwaku, Manabu Suno, Toshiyoshi Fujiwara, AjayGoel
Background: The development of noninvasive screening tools for the earlier detection ofneoplastic lesions is essential in reducing the mortality associated with malignant diseases,such as colorectal cancer (CRC). Recently we published that fecal DNA methylation analysisoffers a robust screening tool for patients with gastric and CRC. However, currently thereare no non-invasive screening tests available for patients with other gastrointestinal cancers,including pancreatic cancer. Given our extensive experience on this topic, we sought todevelop a novel, non-invasive, fecal DNA methylation-based screening test, which can alsoidentify a variety of other gastrointestinal cancers including pancreatic cancer. Methods: Wehave previously published a unique and highly sensitive assay that uses a single-step bisulfitemodification of DNA, followed by fluorescence-based PCR tomeasure fecal DNAmethylation.Herein, we enhanced the accuracy and robustness of our assay further by increasing thebiomarker panel to 8 methylated genes, instead of 4 genes published previously. Thisprospective study has currently enrolled over 380 fecal samples from patients with variousgastrointestinal cancers, as well as healthy volunteers. Thus far we could successfully analyzed170 cases, with complete clinical annotation, including 56 CRCs, 28 colorectal adenomas(CAs), 24 liver, pancreatic, gall bladder, duodenal and/or gastric tumors (LPGDs). Fecalspecimens from all patients were collected on 2 separate days and results validated indepen-dently. Results: Our assay successfully identified one or more methylated marker in fecalDNA collected on two separate days from 91.0% of CRC patients, 92.8% of CA patients,70.8% of patients with LPGD, and 27.4% of subjects without neoplastic or active diseases(SNADs). The mean fecal DNA recovery scores calculated by sum total of the inspection ontwo days (max value was 16), was 10.4 for CRCs (95%CI= 9.2 to 11.5, p ,.0001 vs. SNADs),9.2 for CAs (95%CI= 7.6 to 10.8, p=.0084 vs. SNADs), 6.4 for LPGDs (95%CI= 4.7 to 8.1,p=0.99 vs. SNADs), and 6.3 for SNADs (95%CI= 5.2 to 7.4), respectively. The meanmethylation scores calculated by sum total of the inspection on two days (max value was
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