Ignite Creation Date:
2024-05-06 @ 6:24 PM
Last Modification Date:
2024-10-26 @ 2:47 PM
Study NCT ID:
NCT05642338
Status:
RECRUITING
Last Update Posted:
2022-12-08
First Post:
2022-11-28
Brief Title:
A Multicenter Prospective Cohort Study Comparing Random Biopsies Versus Wide-Area Transepithelial Brush-Sampling WATS for Surveillance of Barretts Esophagus the WATS-EURO2 Study
Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Organization:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Study Overview
Official Title:
A Multicenter Prospective Cohort Study Comparing Random Biopsies Versus Wide-Area Transepithelial Brush-Sampling WATS for Surveillance of Barretts Esophagus the WATS-EURO2 Study
Status:
RECRUITING
Status Verified Date:
2022-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
WATSEURO2
Brief Summary:
The investigators aim to study the rate of developing a biopsy-based diagnosis of high-grade dysplasia HGD and EAC in BE patients in a prospective cohort of 208 BE patients at high risk of progression ie after endoscopic removal of visible lesions containing HGDEAC andor a diagnosis of low-grade dysplasia LGD as well as in 208 BE patients with a nondysplastic BE NDBE undergoing standard BE surveillance In these patients the investigators will combine biopsy sampling with WATS at baseline and all follow-up endoscopies during a 3- year follow-up period This will allow us to study the natural history of WATS-positive-biopsynegative- cases and of WATS-specific outcomes such as basal-crypt dysplasia The study also allows us to collect specimens for future biomarker studies that may help to predict progression to HGDEAC in the absence of morphological features of dysplasia
Detailed Description:
Esophageal adenocarcinoma EAC is a disease with a poor prognosis at advanced stages
Identifying esophageal adenocarcinoma at an early stage allows for endoscopic treatment to reduce mortality and morbidity for these treated patients Adequate surveillance strategies with appropriate risk stratification are therefore essential The current endoscopic surveillance protocol relies on systemic four-quadrant biopsy at 2-cm intervals of the BE segment with additional targeted biopsies from visible abnormalities
Obtaining random biopsies is time consuming and it results at best in sampling less than 5 of the BE surface area Thus significant sampling error is inevitable Sampling the BE segment with a brush has the theoretical advantage of larger field sampling and might therefore increase the detection of dysplasia Conventional brush cytology samples however suffer from superficial sampling and difficult analysis of the thick tissue smear by a twodimensional cytology microscope The WATS system developed by CDx Diagnostics consists of a trans-epithelial cytology brush designed to sample cells from all three layers of the epithelium and the diagnosis of the brush specimen by advanced computer image analysis system at CDx Diagnostics
These advantages over conventional cytology may make this system an important diagnostic tool in BE surveillance In the European WATS study Euro-WATS1 the WATS-system was compared with random biopsies in a cohort of patients referred with low-grade dysplasia LGD high-grade dysplasia HGD or early cancer after removal of all visible abnormalities Eligible cases underwent random biopsies and WATS brushings after randomizing the order of sampling
The study showed no significant differences in the detection rate for HGD or EAC between random biopsies and WATS brushings The brush detected 3948 HGDEAC cases versus 3048 for random biopsies p012 The value of the WATS-3D brush as an adjunct to random forceps biopsies however was 48147 vs 30147 difference 12 with a number needed to treat of 8 Moreover the brush had a significantly shorter procedure time than random biopsies with a larger difference in longer BE segments Another strength of the WATS brush compared to random biopsies is that it paves the way towards a preferred future trans-oral sampling instead of endoscopic sampling Key element in the adjunctive value of WATS is the clinical relevance of WATS-positive-biopsy-negative One may argue that the morphological changes of dysplasia-positive WATS samples clearly correspond to those defining dysplasia in biopsy samples and therefore are merely different representations of the same disease which is now diagnosed at an earlier stage Others argue that the WATS-system by being more sensitive to detect dysplasia simply dilutes the disease reservoir with clinically less severe cases which do not warrant the same therapeutic approach as in cases with a biopsy based diagnosis of dysplasia The natural history of WATS-positive-biopsy-negative cases can however not be investigated in the EUROWATS1 study because this was a transversal study with no subsequent follow-up and with the vast majority of cases having undergone ablation therapy based on their referral diagnosis andor outcome of the endoscopic resection of visible lesions Another limitation of the EURO-WATS1 study was the relatively high rate of WATS brushings that were deemed ineligible for assessment of the smears In the study 23172 13 of cases had suboptimal WATS samples despite the fact that the corresponding cellblocks showed adequate cellularity It appears that the logistics in the endoscopy suite andor storage of samples prior to transportation and evaluation at CDx may have had flaws Therefore a second European WATS study WATS EURO 2 study will be performed in which after the baseline endoscopy with WATS brushing and random biopsies endoscopic follow-up is continued until a biopsy-based diagnosis of HGD or cancer is made The WATS EURO 2 study will therefore allow us to study the natural history of WATS-positive-biopsynegative cases will enable us to re-evaluate the role of the WATS-3D brush as a potential substitute for random sampling after optimizing sample collection and preparation in the study Finally the samples collected in this study will also allow us to perform future biomarker studies on both the brush and biopsy material to find the best sampling method for biomarker risk stratification in the future It is undisputed that patients referred with LGD HGD or early cancer should have all visible lesions removed by ER techniques In general the endoscopic resection specimen will then show a diagnosis of HGD or early cancer Follow-up studies have shown that the chance of the development of metachronous HGDEAC in the remaining BE segment is about 10 per year Therefore ablation therapy is advised for the remaining BE segment
The same 10 annual progression rate to HGDEAC applies for patients with a confirmed diagnosis of LGD For these patients guidelines suggest that ablation therapy may be a valid alternative to subsequent surveillance The actual decision to ablate the remaining Barretts segment after endoscopic resection of HGDEAC or to prophylactically ablate for LGD is made on a per patient basis in which age and comorbidity are important additional factors to be taken into account Follow-up studies after ER of visible lesions containing HGDEAC have found that metachronous lesions are all found at an endoscopically treatable stage with the majority of patients not developing recurrent disease The same holds for prophylactic ablation in cases with LGD a significant proportion of patients will not progress or not even manifest their baseline diagnosis of LGD upon follow-up In the SURF-study 30 of the LGD-patients randomized to endoscopic surveillance did not have their LGD diagnosis reproduced during 4 subsequent endoscopies in 3-years follow-up and all cases that progressed to HGDEAC were diagnosed at an endoscopically curable stage Furthermore RFA still is accompanied by complications such as esophageal stenosis and requires multiple hospital visits Even upon complete endoscopic eradication of all Barretts mucosa guidelines still dictate endoscopic surveillance after ablation virtually at the same frequency as for Barretts cases not prophylactically treated Therefore keeping Barretts patients under strict endoscopic surveillance after ER of visible lesions or for flat LGD is an acceptable strategy that does not divert from current guidelines
In the current study the investigators aim to study the rate of developing a biopsy-based diagnosis of HGDEAC in Barretts patients at high risk of progression ie after endoscopic removal of visible lesions containing HGDEAC andor a diagnosis of LGD as well as in patients in a standard Barretts surveillance program In these patients the investigators will combine biopsy sampling with WATS brushing at baseline and all follow-up endoscopies This will allow us to study the natural history of WATS-positive-biopsy negative case and of WATS-specific outcomes such as basal-crypt dysplasia and to further evaluate the role of the WATS brush as a potential substitute to random biopsies
The study also allows us to collect specimens for future biomarker studies that may help to predict progression to HGDEAC in the absence of morphological features of dysplasia
Identifying esophageal adenocarcinoma at an early stage allows for endoscopic treatment to reduce mortality and morbidity for these treated patients Adequate surveillance strategies with appropriate risk stratification are therefore essential The current endoscopic surveillance protocol relies on systemic four-quadrant biopsy at 2-cm intervals of the BE segment with additional targeted biopsies from visible abnormalities
Obtaining random biopsies is time consuming and it results at best in sampling less than 5 of the BE surface area Thus significant sampling error is inevitable Sampling the BE segment with a brush has the theoretical advantage of larger field sampling and might therefore increase the detection of dysplasia Conventional brush cytology samples however suffer from superficial sampling and difficult analysis of the thick tissue smear by a twodimensional cytology microscope The WATS system developed by CDx Diagnostics consists of a trans-epithelial cytology brush designed to sample cells from all three layers of the epithelium and the diagnosis of the brush specimen by advanced computer image analysis system at CDx Diagnostics
These advantages over conventional cytology may make this system an important diagnostic tool in BE surveillance In the European WATS study Euro-WATS1 the WATS-system was compared with random biopsies in a cohort of patients referred with low-grade dysplasia LGD high-grade dysplasia HGD or early cancer after removal of all visible abnormalities Eligible cases underwent random biopsies and WATS brushings after randomizing the order of sampling
The study showed no significant differences in the detection rate for HGD or EAC between random biopsies and WATS brushings The brush detected 3948 HGDEAC cases versus 3048 for random biopsies p012 The value of the WATS-3D brush as an adjunct to random forceps biopsies however was 48147 vs 30147 difference 12 with a number needed to treat of 8 Moreover the brush had a significantly shorter procedure time than random biopsies with a larger difference in longer BE segments Another strength of the WATS brush compared to random biopsies is that it paves the way towards a preferred future trans-oral sampling instead of endoscopic sampling Key element in the adjunctive value of WATS is the clinical relevance of WATS-positive-biopsy-negative One may argue that the morphological changes of dysplasia-positive WATS samples clearly correspond to those defining dysplasia in biopsy samples and therefore are merely different representations of the same disease which is now diagnosed at an earlier stage Others argue that the WATS-system by being more sensitive to detect dysplasia simply dilutes the disease reservoir with clinically less severe cases which do not warrant the same therapeutic approach as in cases with a biopsy based diagnosis of dysplasia The natural history of WATS-positive-biopsy-negative cases can however not be investigated in the EUROWATS1 study because this was a transversal study with no subsequent follow-up and with the vast majority of cases having undergone ablation therapy based on their referral diagnosis andor outcome of the endoscopic resection of visible lesions Another limitation of the EURO-WATS1 study was the relatively high rate of WATS brushings that were deemed ineligible for assessment of the smears In the study 23172 13 of cases had suboptimal WATS samples despite the fact that the corresponding cellblocks showed adequate cellularity It appears that the logistics in the endoscopy suite andor storage of samples prior to transportation and evaluation at CDx may have had flaws Therefore a second European WATS study WATS EURO 2 study will be performed in which after the baseline endoscopy with WATS brushing and random biopsies endoscopic follow-up is continued until a biopsy-based diagnosis of HGD or cancer is made The WATS EURO 2 study will therefore allow us to study the natural history of WATS-positive-biopsynegative cases will enable us to re-evaluate the role of the WATS-3D brush as a potential substitute for random sampling after optimizing sample collection and preparation in the study Finally the samples collected in this study will also allow us to perform future biomarker studies on both the brush and biopsy material to find the best sampling method for biomarker risk stratification in the future It is undisputed that patients referred with LGD HGD or early cancer should have all visible lesions removed by ER techniques In general the endoscopic resection specimen will then show a diagnosis of HGD or early cancer Follow-up studies have shown that the chance of the development of metachronous HGDEAC in the remaining BE segment is about 10 per year Therefore ablation therapy is advised for the remaining BE segment
The same 10 annual progression rate to HGDEAC applies for patients with a confirmed diagnosis of LGD For these patients guidelines suggest that ablation therapy may be a valid alternative to subsequent surveillance The actual decision to ablate the remaining Barretts segment after endoscopic resection of HGDEAC or to prophylactically ablate for LGD is made on a per patient basis in which age and comorbidity are important additional factors to be taken into account Follow-up studies after ER of visible lesions containing HGDEAC have found that metachronous lesions are all found at an endoscopically treatable stage with the majority of patients not developing recurrent disease The same holds for prophylactic ablation in cases with LGD a significant proportion of patients will not progress or not even manifest their baseline diagnosis of LGD upon follow-up In the SURF-study 30 of the LGD-patients randomized to endoscopic surveillance did not have their LGD diagnosis reproduced during 4 subsequent endoscopies in 3-years follow-up and all cases that progressed to HGDEAC were diagnosed at an endoscopically curable stage Furthermore RFA still is accompanied by complications such as esophageal stenosis and requires multiple hospital visits Even upon complete endoscopic eradication of all Barretts mucosa guidelines still dictate endoscopic surveillance after ablation virtually at the same frequency as for Barretts cases not prophylactically treated Therefore keeping Barretts patients under strict endoscopic surveillance after ER of visible lesions or for flat LGD is an acceptable strategy that does not divert from current guidelines
In the current study the investigators aim to study the rate of developing a biopsy-based diagnosis of HGDEAC in Barretts patients at high risk of progression ie after endoscopic removal of visible lesions containing HGDEAC andor a diagnosis of LGD as well as in patients in a standard Barretts surveillance program In these patients the investigators will combine biopsy sampling with WATS brushing at baseline and all follow-up endoscopies This will allow us to study the natural history of WATS-positive-biopsy negative case and of WATS-specific outcomes such as basal-crypt dysplasia and to further evaluate the role of the WATS brush as a potential substitute to random biopsies
The study also allows us to collect specimens for future biomarker studies that may help to predict progression to HGDEAC in the absence of morphological features of dysplasia
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None