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Tu1183 Fecal Immunochemical Test Accuracy for Colorectal Cancer and Significant Neoplasia Detection in Average-Risk Population
AGA Abstracts
to lead underusers to participate in an organized FOBT CRC screening program is 2.5 times greater than that of a recall letter with direct mailing of FOBT kits. It is not significantly different between MI and CATI so that MI training of counselors is useless. However, telephone counseling cannot be recommended to date in France as it is neither effective nor cost-effective because people are difficult to reach (one in four) and to counsel (two out of three people reached) by phone. Funding: Grant from the French Institut National du Cancer.
Ld from Pirc Rat Rectal Brushings at Preneoplastic Time Point Tu1182
Tu1183
Development of a Novel Biophotonic Assay for Colonic Field Carcinogenesis Detection: Implications for Colorectal Cancer Risk Stratification Hemant K. Roy, Dhwanil Damania, Dhananjay Kunte, Hariharan Subramanian, Mart DeLaCruz, Michael J. Goldberg, Jeremy D. Rogers, Ramesh K. Wali, Vadim Backman
Fecal Immunochemical Test Accuracy for Colorectal Cancer and Significant Neoplasia Detection in Average-Risk Population Vicent Hernandez, Joaquin Cubiella, Carmen Gonzalez-Mao, Begoña Iglesias Rodriguez, Lucia Cid, Ines Castro, Luisa De-Castro, Pablo Vega, Jose Antonio Hermo, Ramiro Macenlle, Alfonso Martinez, David Martinez-Ares, Pamela Estévez Boullosa, Felipe Iglesias, Estela Cid, Carmen Vidal, Concepcion Rivera, Miriam Vazquez Campo, Elizabeth Hijona, Marta Herreros, Luis Bujanda
Introduction: Fecal tests continue to be first-line components of colorectal cancer (CRC)screening strategies advocated by groups such as USPSTF. However the current approach involves identifying minute amounts of tumor products (occult blood, DNA etc) in the "fecal sea". Thus, it is insensitive for early lesions such as advanced adenomas, the major target of CRC prevention efforts. This “needle in the haystack" problem of fecal tests could be circumvented by detection of field carcinogenesis. Our group has developed a novel optical technology, partial wave spectroscopic microscopy (PWS), which can detect that nanoscale consequences of the genetic/epigenetic manifestations of field carcinogenesis (reviewed in Gastro 2011). We have demonstrated that PWS analysis of endoscopically-normal rectal mucosa could identify patients harboring advanced adenomas elsewhere in the colon with excellent accuracy (Cancer Res 2009). However, this still is somewhat intrusive (brushing of the rectal mucosa). Recently, it has become practical to purify normal (non-apoptotic) colonocytes by isolating cells abraded by passage of a stool bolus (termed mucus layer fecal colonocytes (MLFC)). We, therefore, wanted to examine the ability of PWS to detect field carcinogenesis from these MLFC versus standard rectal brushings. Methods: Animals: We used the PIRC rat (polyposis in rat colon) which contains a germline mutation in the APC tumor suppressor gene, the initiating mutation for most sporadic CRCs (Land-Graf et al, PNAS 2007). These animals spontaneously develop colonic tumors at 12-16 weeks of age. Rectal brushings from visually normal mucosa were taken at 10 weeks of age and MLFC were also isolated from stool via a modification of a protocol from White et al. (CEBP 2009) PWS Analysis: PWS analysis was performed as previously described (PNAS 2008). The parameter disorder strength (Ld) was quantified in these cells by investigators blinded to animal genotype. Results: Morphologically normal fecal colonocytes and visually normal rectal mucosal brushings were isolated from premalignant PIRC rat and age-matched APC wildtype rats. Colonocytes were confirmed with cytokeratin staining. Colonoscopy was performed to confirm that animals were adenoma free. The Ld differential in rectal brushings(Δ PIRC versus saline)was 74% (figure 1) which was highly statistically significant (effect size 0.47, p=0.0005). This was comparable to that of MLFC (Δ PIRC versus saline 62.4%, effect size 0.389, p=0.03) (figure 2) Conclusions: We demonstrate, that a PWS (optical) fecal assay performed almost equivalently to direct colonic mucosal interrogation. This demonstrates, for first time, that an optical based fecal assay could predict long term neoplastic risk from genetic as well as sporadic CRC and thus may have utility in population based risk-stratification.
AIMS: To assess the accuracy of fecal immunochemical test (FIT) for colorectal cancer (CRC) and significant neoplasia (SN) detection in average-risk population. METHODS: Multicentric, prospective, blind, cohort study of diagnostic tests, performed on patients included in the COLOPREV study (ClinicalTrials.gov NCT00906997, designed to assess the efficacy of onetime colonoscopy and biennial FIT for reducing CRC-related mortality at 10 years). The study was approved by the Galician Ethics Committee. Patients were included if they were offered a colonoscopy as screening method or if they underwent a colonoscopy after a positive FIT. Patients were excluded if they did not sign informed consent or refused the colonoscopy. Patients collected 2 stool samples from 2 consecutive days the week before the colonoscopy was programmed. FIT was assessed using the automated OC-sensor™ (Eiken Chemical Co, Tokyo, Japan), without diet or medication restrictions. In each patient fecal Hb (ng/ml) in the first sample (FIT1) and the higher level of the two samples (FITmax) were determined. Colonoscopy was blind for the FIT result; location and number of polyps or CRC were collected. SN was defined as the presence of CRC, advanced adenomas (≥10mm, villous component or high grade dysplasia) or ≥3 adenomas. Student's t test was used to compare FIT1 and FITmax in patients with/without CRC and with/without SN. ROC curves were drawed and the area under the curve (AUC) was calculated; the best cut-off value for CRC or SN detection was determined for FIT1 and FITmax. For each cut-off and strategy, sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV; NPV) and the number of patients needed to scope (NNS) to detect a CRC or SN were calculated. RESULTS: 769 patients were included (387 female, mean age 57.56±4.53y, range 50-71). adenomas or CRC were found in 293 (38.1%) patients, of whom 123 (16%) had SN and 5 (0.7%) CRC. FIT1 and FITmax were higher in patients with SN than in those without SN (243.8±585.0 vs 23.8±145.0, p<0.001; 350.6±784.3 vs 43.3±212.9, p<0.001, respectively); patients with CRC had higher FIT1 and FITmax than patients without CRC, but the difference was not statistically significant (998.0±1075.4 vs 52.8±259.1, p=0.121; 1257.4±1531.8 vs 84.8±358.1, p=0.162, respectively). The AUC of FIT1 for CRC and SN diagnosis was 0.967 and 0.698, respectively (p<0.001); the best cut-off value for CRC was 115. The AUC of FITmax for CRC and SN was 0.952 and 0.723, respectively (p<0.001). The best cut-off value for CRC was 117. The table shows the Se, Sp, PPV, NPV and NNS of each strategy. CONCLUSIONS: FIT shows a high accuracy to detect CRC. Performing two tests does not enhance the accuracy, but could increase the sensitivity to detect SN, at the expense of increasing the number of colonoscopies needed to detect a lesion.
Tu1184 Colonoscopy, Family History of Colorectal Cancer and Colorectal Tumor Risk: Results From a French Prospective Cohort Sophie Morois, Vanessa Cottet, Antoine Racine, Françoise Clavel-Chapelon, Franck Carbonnel, Marie-Christine Boutron-Ruault
Ld from PIRC Rat Fecal Colonocytes (MLFC) at a Preneoplastic Time Point
Introduction: Colorectal cancer prevention relies in part on the efficiency of colonoscopy at detecting adenomas. However, the efficiency of colonoscopy at preventing right colon cancer has recently been questioned. Aims and methods: We used data from the French E3N cohort study to explore associations between family history of colorectal cancer (FHCC), colonoscopy screening and colorectal tumor risk in a large prospective cohort of French women. Colorectal cancer risk was investigated among 92,078 women (n=692 cases). Colorectal adenoma risk was studied among the 17,730 women who underwent a colonoscopy and among whom histology of removed polyps was retrieved (n=1,438 histologically confirmed adenomas). The Hazard Ratios (HRs) and 95% Confidence Interval (CI) were estimated
AGA Abstracts
S-768
to lead underusers to participate in an organized FOBT CRC screening program is 2.5 times greater than that of a recall letter with direct mailing of FOBT kits. It is not significantly different between MI and CATI so that MI training of counselors is useless. However, telephone counseling cannot be recommended to date in France as it is neither effective nor cost-effective because people are difficult to reach (one in four) and to counsel (two out of three people reached) by phone. Funding: Grant from the French Institut National du Cancer.
Ld from Pirc Rat Rectal Brushings at Preneoplastic Time Point Tu1182
Tu1183
Development of a Novel Biophotonic Assay for Colonic Field Carcinogenesis Detection: Implications for Colorectal Cancer Risk Stratification Hemant K. Roy, Dhwanil Damania, Dhananjay Kunte, Hariharan Subramanian, Mart DeLaCruz, Michael J. Goldberg, Jeremy D. Rogers, Ramesh K. Wali, Vadim Backman
Fecal Immunochemical Test Accuracy for Colorectal Cancer and Significant Neoplasia Detection in Average-Risk Population Vicent Hernandez, Joaquin Cubiella, Carmen Gonzalez-Mao, Begoña Iglesias Rodriguez, Lucia Cid, Ines Castro, Luisa De-Castro, Pablo Vega, Jose Antonio Hermo, Ramiro Macenlle, Alfonso Martinez, David Martinez-Ares, Pamela Estévez Boullosa, Felipe Iglesias, Estela Cid, Carmen Vidal, Concepcion Rivera, Miriam Vazquez Campo, Elizabeth Hijona, Marta Herreros, Luis Bujanda
Introduction: Fecal tests continue to be first-line components of colorectal cancer (CRC)screening strategies advocated by groups such as USPSTF. However the current approach involves identifying minute amounts of tumor products (occult blood, DNA etc) in the "fecal sea". Thus, it is insensitive for early lesions such as advanced adenomas, the major target of CRC prevention efforts. This “needle in the haystack" problem of fecal tests could be circumvented by detection of field carcinogenesis. Our group has developed a novel optical technology, partial wave spectroscopic microscopy (PWS), which can detect that nanoscale consequences of the genetic/epigenetic manifestations of field carcinogenesis (reviewed in Gastro 2011). We have demonstrated that PWS analysis of endoscopically-normal rectal mucosa could identify patients harboring advanced adenomas elsewhere in the colon with excellent accuracy (Cancer Res 2009). However, this still is somewhat intrusive (brushing of the rectal mucosa). Recently, it has become practical to purify normal (non-apoptotic) colonocytes by isolating cells abraded by passage of a stool bolus (termed mucus layer fecal colonocytes (MLFC)). We, therefore, wanted to examine the ability of PWS to detect field carcinogenesis from these MLFC versus standard rectal brushings. Methods: Animals: We used the PIRC rat (polyposis in rat colon) which contains a germline mutation in the APC tumor suppressor gene, the initiating mutation for most sporadic CRCs (Land-Graf et al, PNAS 2007). These animals spontaneously develop colonic tumors at 12-16 weeks of age. Rectal brushings from visually normal mucosa were taken at 10 weeks of age and MLFC were also isolated from stool via a modification of a protocol from White et al. (CEBP 2009) PWS Analysis: PWS analysis was performed as previously described (PNAS 2008). The parameter disorder strength (Ld) was quantified in these cells by investigators blinded to animal genotype. Results: Morphologically normal fecal colonocytes and visually normal rectal mucosal brushings were isolated from premalignant PIRC rat and age-matched APC wildtype rats. Colonocytes were confirmed with cytokeratin staining. Colonoscopy was performed to confirm that animals were adenoma free. The Ld differential in rectal brushings(Δ PIRC versus saline)was 74% (figure 1) which was highly statistically significant (effect size 0.47, p=0.0005). This was comparable to that of MLFC (Δ PIRC versus saline 62.4%, effect size 0.389, p=0.03) (figure 2) Conclusions: We demonstrate, that a PWS (optical) fecal assay performed almost equivalently to direct colonic mucosal interrogation. This demonstrates, for first time, that an optical based fecal assay could predict long term neoplastic risk from genetic as well as sporadic CRC and thus may have utility in population based risk-stratification.
AIMS: To assess the accuracy of fecal immunochemical test (FIT) for colorectal cancer (CRC) and significant neoplasia (SN) detection in average-risk population. METHODS: Multicentric, prospective, blind, cohort study of diagnostic tests, performed on patients included in the COLOPREV study (ClinicalTrials.gov NCT00906997, designed to assess the efficacy of onetime colonoscopy and biennial FIT for reducing CRC-related mortality at 10 years). The study was approved by the Galician Ethics Committee. Patients were included if they were offered a colonoscopy as screening method or if they underwent a colonoscopy after a positive FIT. Patients were excluded if they did not sign informed consent or refused the colonoscopy. Patients collected 2 stool samples from 2 consecutive days the week before the colonoscopy was programmed. FIT was assessed using the automated OC-sensor™ (Eiken Chemical Co, Tokyo, Japan), without diet or medication restrictions. In each patient fecal Hb (ng/ml) in the first sample (FIT1) and the higher level of the two samples (FITmax) were determined. Colonoscopy was blind for the FIT result; location and number of polyps or CRC were collected. SN was defined as the presence of CRC, advanced adenomas (≥10mm, villous component or high grade dysplasia) or ≥3 adenomas. Student's t test was used to compare FIT1 and FITmax in patients with/without CRC and with/without SN. ROC curves were drawed and the area under the curve (AUC) was calculated; the best cut-off value for CRC or SN detection was determined for FIT1 and FITmax. For each cut-off and strategy, sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV; NPV) and the number of patients needed to scope (NNS) to detect a CRC or SN were calculated. RESULTS: 769 patients were included (387 female, mean age 57.56±4.53y, range 50-71). adenomas or CRC were found in 293 (38.1%) patients, of whom 123 (16%) had SN and 5 (0.7%) CRC. FIT1 and FITmax were higher in patients with SN than in those without SN (243.8±585.0 vs 23.8±145.0, p<0.001; 350.6±784.3 vs 43.3±212.9, p<0.001, respectively); patients with CRC had higher FIT1 and FITmax than patients without CRC, but the difference was not statistically significant (998.0±1075.4 vs 52.8±259.1, p=0.121; 1257.4±1531.8 vs 84.8±358.1, p=0.162, respectively). The AUC of FIT1 for CRC and SN diagnosis was 0.967 and 0.698, respectively (p<0.001); the best cut-off value for CRC was 115. The AUC of FITmax for CRC and SN was 0.952 and 0.723, respectively (p<0.001). The best cut-off value for CRC was 117. The table shows the Se, Sp, PPV, NPV and NNS of each strategy. CONCLUSIONS: FIT shows a high accuracy to detect CRC. Performing two tests does not enhance the accuracy, but could increase the sensitivity to detect SN, at the expense of increasing the number of colonoscopies needed to detect a lesion.
Tu1184 Colonoscopy, Family History of Colorectal Cancer and Colorectal Tumor Risk: Results From a French Prospective Cohort Sophie Morois, Vanessa Cottet, Antoine Racine, Françoise Clavel-Chapelon, Franck Carbonnel, Marie-Christine Boutron-Ruault
Ld from PIRC Rat Fecal Colonocytes (MLFC) at a Preneoplastic Time Point
Introduction: Colorectal cancer prevention relies in part on the efficiency of colonoscopy at detecting adenomas. However, the efficiency of colonoscopy at preventing right colon cancer has recently been questioned. Aims and methods: We used data from the French E3N cohort study to explore associations between family history of colorectal cancer (FHCC), colonoscopy screening and colorectal tumor risk in a large prospective cohort of French women. Colorectal cancer risk was investigated among 92,078 women (n=692 cases). Colorectal adenoma risk was studied among the 17,730 women who underwent a colonoscopy and among whom histology of removed polyps was retrieved (n=1,438 histologically confirmed adenomas). The Hazard Ratios (HRs) and 95% Confidence Interval (CI) were estimated
AGA Abstracts
S-768