Half of Barrett's esophagus (BE) surveillance endoscopies do not adhere to guideline recommendations. In this multicenter prospective cohort study, we assessed the clinical consequences of... Show moreHalf of Barrett's esophagus (BE) surveillance endoscopies do not adhere to guideline recommendations. In this multicenter prospective cohort study, we assessed the clinical consequences of nonadherence to recommended surveillance intervals and biopsy protocol. Data from BE surveillance patients were collected from endoscopy and pathology reports; questionnaires were distributed among endoscopists. We estimated the association between (non)adherence and (i) endoscopic curability of esophageal adenocarcinoma (EAC), (ii) mortality, and (iii) misclassification of histological diagnosis according to a multistate hidden Markov model. Potential explanatory parameters (patient, facility, endoscopist variables) for nonadherence, related to clinical impact, were analyzed. In 726 BE patients, 3802 endoscopies were performed by 167 endoscopists. Adherence to surveillance interval was 16% for non-dysplastic (ND)BE, 55% for low-grade dysplasia (LGD), and 54% of endoscopies followed the Seattle protocol. There was no evidence to support the following statements: longer surveillance intervals or fewer biopsies than recommended affect endoscopic curability of EAC or cause-specific mortality (P > 0.20); insufficient biopsies affect the probability of NDBE (OR 1.0) or LGD (OR 2.3) being misclassified as high-grade dysplasia/EAC (P > 0.05). Better adherence was associated with older patients (OR 1.1), BE segments <= 2 cm (OR 8.3), visible abnormalities (OR 1.8, all P <= 0.05), endoscopists with a subspecialty (OR 3.2), and endoscopists who deemed histological diagnosis an adequate marker (OR 2.0). Clinical consequences of nonadherence to guidelines appeared to be limited with respect to endoscopic curability of EAC and mortality. This indicates that BE surveillance recommendations should be optimized to minimize the burden of endoscopies. Show less
Roumans, C.A.M.; Bogt, R.D. van der; Nieboer, D.; Steyerberg, E.W.; Rizopoulos, D.; Lansdorp-Vogelaar, I.; ... ; ProBar Study Grp 2022
Half of Barrett's esophagus (BE) surveillance endoscopies do not adhere to guideline recommendations. In this multicenter prospective cohort study, we assessed the clinical consequences of... Show moreHalf of Barrett's esophagus (BE) surveillance endoscopies do not adhere to guideline recommendations. In this multicenter prospective cohort study, we assessed the clinical consequences of nonadherence to recommended surveillance intervals and biopsy protocol. Data from BE surveillance patients were collected from endoscopy and pathology reports; questionnaires were distributed among endoscopists. We estimated the association between (non)adherence and (i) endoscopic curability of esophageal adenocarcinoma (EAC), (ii) mortality, and (iii) misclassification of histological diagnosis according to a multistate hidden Markov model. Potential explanatory parameters (patient, facility, endoscopist variables) for nonadherence, related to clinical impact, were analyzed. In 726 BE patients, 3802 endoscopies were performed by 167 endoscopists. Adherence to surveillance interval was 16% for non-dysplastic (ND)BE, 55% for low-grade dysplasia (LGD), and 54% of endoscopies followed the Seattle protocol. There was no evidence to support the following statements: longer surveillance intervals or fewer biopsies than recommended affect endoscopic curability of EAC or cause-specific mortality (P > 0.20); insufficient biopsies affect the probability of NDBE (OR 1.0) or LGD (OR 2.3) being misclassified as high-grade dysplasia/EAC (P > 0.05). Better adherence was associated with older patients (OR 1.1), BE segments <= 2 cm (OR 8.3), visible abnormalities (OR 1.8, all P <= 0.05), endoscopists with a subspecialty (OR 3.2), and endoscopists who deemed histological diagnosis an adequate marker (OR 2.0). Clinical consequences of nonadherence to guidelines appeared to be limited with respect to endoscopic curability of EAC and mortality. This indicates that BE surveillance recommendations should be optimized to minimize the burden of endoscopies. Show less
Simple Summary Barrett's esophagus (BE) is the only known precursor lesion of esophageal adenocarcinoma (EAC). Endoscopic surveillance plays an important role in the timely detection of neoplastic... Show moreSimple Summary Barrett's esophagus (BE) is the only known precursor lesion of esophageal adenocarcinoma (EAC). Endoscopic surveillance plays an important role in the timely detection of neoplastic progression. However, the cost-effectiveness of current surveillance strategies is debatable. Previous studies have shown that male Barrett's patients have lower neoplastic progression risk than females. However, these studies do not provide a more practical translation of these sex disparities into different surveillance intervals. The current multicenter prospective cohort study aimed to evaluate sex differences in 868 BE patients; not only with respect to neoplastic progression risk, but also concerning the difference in time to detection of high-grade dysplasia (HGD)/EAC: time to neoplastic progression was estimated to be almost twice as low in males than in females. In contrast, the stage of neoplasia appeared to be higher in females. Our results can guide future discussions for sex-specific guidelines, supporting the implementation of neoplastic risk stratification per individual patient in BE surveillance. Recommendations in Barrett's esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11-4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33-10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29-0.95) and HGD (AR 0.40, 95% CI 0.19-0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models. Show less
Objectives: The current surveillance strategy in Barrett's esophagus (BE) uses only histological findings of the last endoscopy to assess neoplastic progression risk. As predictor values vary... Show moreObjectives: The current surveillance strategy in Barrett's esophagus (BE) uses only histological findings of the last endoscopy to assess neoplastic progression risk. As predictor values vary across endoscopies, single measurements may not be an accurate reflection. Our aim was to explore the value of using longitudinal evolutions (i.e. successive measurements) of histological findings (low-grade dysplasia (LGD)) and immunohistochemical biomarkers (p53 and SOX2) by investigating the association with Barrett's progression. Methods: In this proof-of-principle study of a longitudinal dynamic risk estimation model with a multicenter cohort design, 631 BE patients from 15 Dutch hospitals who were under surveillance were included. Longitudinal dynamic values of LGD, p53, and SOX2 were included in a multivariate joint model to estimate the risk of high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC). Results: Longitudinal evolutions of aberrant expression of p53 (HR 1.26, p < 0.01) and SOX2 (HR 1.43, p < 0.01) were associated with an increased HGD/EAC risk. We also found weak evidence of an association with the longitudinal evolution of the presence of LGD (HR 1.02, p = 0.12). The performance of the model was good (AUC 0.80-0.88). Using this model, for each future BE patient the probability of aberrant expression of biomarkers based on multiple longitudinal observations can be estimated. This probability is translated in progression risk, expressed as HR. Conclusions: This study provides solid ground to further explore a paradigm shift from currently recommended fixed intervals towards personalized surveillance, in which tailored risk estimations and corresponding surveillance intervals can be updated at every FU endoscopy for individual BE patients. Show less
Pouw, R.E.; Bisschops, R.; Gecse, K.B.; Hertogh, G. de; Iacucci, M.; Rutter, M.; ... ; Hooft, J.E. van 2021
PurposeTo compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or... Show morePurposeTo compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL.Patients and MethodsPatients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.4-Gy radiotherapy) followed by surgery or surgery alone. HRQOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and –Oesophageal Cancer Module (QLQ-OES24) questionnaires pretreatment and at 3, 6, 9, and 12 months postoperatively. The nCRT group also received preoperative questionnaires. Physical functioning (PF; QLQ-C30) and eating problems (EA; QLQ-OES24) were chosen as predefined primary end points. Predefined secondary end points were global QOL (GQOL; QLQ-C30), fatigue (FA; QLQ-C30), and emotional problems (EM; QLQ-OES24).ResultsA total of 363 patients were analyzed. No statistically significant differences in postoperative HRQOL were found between treatment groups. In the nCRT group, PF, EA, GQOL, FA, and EM scores deteriorated 1 week after nCRT (Cohen’s d: −0.93, P < .001; 0.47, P < .001; −0.84, P < .001; 1.45, P < .001; and 0.32, P = .001, respectively). In both treatment groups, all end points declined 3 months postoperatively compared with baseline (Cohen’s d: −1.00, 0.33, −0.47, −0.34, and 0.33, respectively; all P < .001), followed by a continuous gradual improvement. EA, GQOL, and EM were restored to baseline levels during follow-up, whereas PF and FA remained impaired 1 year postoperatively (Cohen’s d: 0.52 and −0.53, respectively; both P < .001).ConclusionAlthough HRQOL declined during nCRT, no effect of nCRT was apparent on postoperative HRQOL compared with surgery alone. In addition to the improvement in survival, these findings support the view that nCRT according to the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study–regimen can be regarded as a standard of care. Show less
Shapiro, J.; Biermann, K.; Klaveren, D. van; Offerhaus, G.J.A.; Kate, F.J.W. ten; Meijer, S.L.; ... ; Lanschot, J.J.B. van 2017
