Sex Differences in Neoplastic Progression in Barrett’s Esophagus: A Multicenter Prospective Cohort Study

Carlijn A.M. Roumans; Pauline A. Zellenrath; Ewout W. Steyerberg; Iris Lansdorp-Vogelaar; Michael Doukas; Katharina Biermann; Joyce Alderliesten; Gert van Ingen; Wouter B. Nagengast; Arend Karrenbeld; Frank Ter Borg; Mariska Hage; Pieter C.J. Ter Borg; Michael A. Den Bakker; Alaa Alkhalaf; Frank C.P. Moll; Lieke Brouwer-Hol; Joop van Baarlen; Rutger Quispel; Arjan van Tilburg; Jordy P.W. Burger; Antonie J.P. van Tilburg; Ariadne H.A.G. Ooms; Thjon J. Tang; Mariëlle J.L. Romberg-Camps; Danny Goudkade; Marco J. Bruno; Dimitris Rizopoulos; Manon C.W. Spaander

doi:10.3390/cancers14133240

Sex Differences in Neoplastic Progression in Barrett’s Esophagus: A Multicenter Prospective Cohort Study

Carlijn A.M. Roumans, Pauline A. Zellenrath, Ewout W. Steyerberg, Iris Lansdorp-Vogelaar, Michael Doukas, Katharina Biermann, Joyce Alderliesten, Gert van Ingen, Wouter B. Nagengast, Arend Karrenbeld, Frank Ter Borg, Mariska Hage, Pieter C.J. Ter Borg, Michael A. Den Bakker, Alaa Alkhalaf, Frank C.P. Moll, Lieke Brouwer-Hol, Joop van Baarlen, Rutger Quispel, Arjan van TilburgJordy P.W. Burger, Antonie J.P. van Tilburg, Ariadne H.A.G. Ooms, Thjon J. Tang, Mariëlle J.L. Romberg-Camps, Danny Goudkade, Marco J. Bruno, Dimitris Rizopoulos, Manon C.W. Spaander^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 highgrade 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.

Original language	English
Article number	3240
Journal	Cancers
Volume	14
Issue number	13
DOIs	https://doi.org/10.3390/cancers14133240
Publication status	Published - 1 Jul 2022

Bibliographical note

Funding Information:
Funding: This study was funded by ZonMw within the grant of Gender and Health, number 79684.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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Roumans, C. A. M., Zellenrath, P. A., Steyerberg, E. W., Lansdorp-Vogelaar, I., Doukas, M., Biermann, K., Alderliesten, J., van Ingen, G., Nagengast, W. B., Karrenbeld, A., Borg, F. T., Hage, M., Ter Borg, P. C. J., Den Bakker, M. A., Alkhalaf, A., Moll, F. C. P., Brouwer-Hol, L., van Baarlen, J., Quispel, R., ... Spaander, M. C. W. (2022). Sex Differences in Neoplastic Progression in Barrett’s Esophagus: A Multicenter Prospective Cohort Study. Cancers, 14(13), Article 3240. https://doi.org/10.3390/cancers14133240

@article{b0b9a562367143c294cf574cfda392a4,

title = "Sex Differences in Neoplastic Progression in Barrett{\textquoteright}s Esophagus: A Multicenter Prospective Cohort Study",

abstract = "Recommendations in Barrett{\textquoteright}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 highgrade 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.",

author = "Roumans, {Carlijn A.M.} and Zellenrath, {Pauline A.} and Steyerberg, {Ewout W.} and Iris Lansdorp-Vogelaar and Michael Doukas and Katharina Biermann and Joyce Alderliesten and {van Ingen}, Gert and Nagengast, {Wouter B.} and Arend Karrenbeld and Borg, {Frank Ter} and Mariska Hage and {Ter Borg}, {Pieter C.J.} and {Den Bakker}, {Michael A.} and Alaa Alkhalaf and Moll, {Frank C.P.} and Lieke Brouwer-Hol and {van Baarlen}, Joop and Rutger Quispel and {van Tilburg}, Arjan and Burger, {Jordy P.W.} and {van Tilburg}, {Antonie J.P.} and Ooms, {Ariadne H.A.G.} and Tang, {Thjon J.} and Romberg-Camps, {Mari{\"e}lle J.L.} and Danny Goudkade and Bruno, {Marco J.} and Dimitris Rizopoulos and Spaander, {Manon C.W.}",

note = "Funding Information: Funding: This study was funded by ZonMw within the grant of Gender and Health, number 79684. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = jul,

day = "1",

doi = "10.3390/cancers14133240",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "13",

}

Roumans, CAM, Zellenrath, PA, Steyerberg, EW, Lansdorp-Vogelaar, I , Doukas, M, Biermann, K, Alderliesten, J, van Ingen, G, Nagengast, WB, Karrenbeld, A, Borg, FT, Hage, M, Ter Borg, PCJ, Den Bakker, MA, Alkhalaf, A, Moll, FCP, Brouwer-Hol, L, van Baarlen, J, Quispel, R, van Tilburg, A, Burger, JPW, van Tilburg, AJP, Ooms, AHAG, Tang, TJ, Romberg-Camps, MJL, Goudkade, D, Bruno, MJ , Rizopoulos, D & Spaander, MCW 2022, 'Sex Differences in Neoplastic Progression in Barrett’s Esophagus: A Multicenter Prospective Cohort Study', Cancers, vol. 14, no. 13, 3240. https://doi.org/10.3390/cancers14133240

TY - JOUR

T1 - Sex Differences in Neoplastic Progression in Barrett’s Esophagus

T2 - A Multicenter Prospective Cohort Study

AU - Roumans, Carlijn A.M.

AU - Zellenrath, Pauline A.

AU - Steyerberg, Ewout W.

AU - Lansdorp-Vogelaar, Iris

AU - Doukas, Michael

AU - Biermann, Katharina

AU - Alderliesten, Joyce

AU - van Ingen, Gert

AU - Nagengast, Wouter B.

AU - Karrenbeld, Arend

AU - Borg, Frank Ter

AU - Hage, Mariska

AU - Ter Borg, Pieter C.J.

AU - Den Bakker, Michael A.

AU - Alkhalaf, Alaa

AU - Moll, Frank C.P.

AU - Brouwer-Hol, Lieke

AU - van Baarlen, Joop

AU - Quispel, Rutger

AU - van Tilburg, Arjan

AU - Burger, Jordy P.W.

AU - van Tilburg, Antonie J.P.

AU - Ooms, Ariadne H.A.G.

AU - Tang, Thjon J.

AU - Romberg-Camps, Mariëlle J.L.

AU - Goudkade, Danny

AU - Bruno, Marco J.

AU - Rizopoulos, Dimitris

AU - Spaander, Manon C.W.

PY - 2022/7/1

Y1 - 2022/7/1

N2 - 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 highgrade 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.

AB - 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 highgrade 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.

UR - http://www.scopus.com/inward/record.url?scp=85133120167&partnerID=8YFLogxK

U2 - 10.3390/cancers14133240

DO - 10.3390/cancers14133240

M3 - Article

C2 - 35805012

AN - SCOPUS:85133120167

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 13

M1 - 3240

ER -

Sex Differences in Neoplastic Progression in Barrett’s Esophagus: A Multicenter Prospective Cohort Study

Abstract

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