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\begin{document}

\title{Serum HE4 predicts progestin treatment response in endometrial cancer
and atypical hyperplasia: a prospective observational study}



\author[1]{Chloe Barr}%
\author[1]{Heather Agnew}%
\author[1]{James Bolton}%
\author[1]{rhona mcvey}%
\author[2]{Emma Crosbie}%
\affil[1]{Manchester University NHS Foundation Trust}%
\affil[2]{The University of Manchester}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\begin{abstract}
Abstract Objective: To investigate serum human epididymis-4 (HE4) as a
predictive biomarker of intrauterine progestin response in endometrial
cancer and atypical endometrial hyperplasia (AEH). Design: Prospective
observational study. Setting: Consecutive sample of women attending a
tertiary gynaecological oncology centre in the North West of England.
Population: Women with AEH or early stage, low grade endometrial cancer
who were unfit or declined primary surgical management; 48 in the
discovery cohort and 28 in the validation cohort. Methods: Women were
treated with a levonorgestrel intrauterine system (LNG-IUS) for 12
months. Endometrial biopsies and imaging were performed to assess
treatment response. Pre-treatment serum HE4 was analysed by
chemiluminescence immunoassay and diagnostic accuracy and logistic
regression analyses performed. Main outcome measure: Progestin response
at 12 months defined by histology and imaging. Results: Baseline serum
HE4 was significantly higher in non-responders than responders in both
discovery {[}134.6pmol/L (IQR:94.0-292.4) vs 76.5pmol/L (IQR:59.7-87.3),
p\textless{}0.001{]} and validation cohorts {[}108.2pmol/L
(IQR:80.3-119.2) vs 64.4pmol/L (IQR:53.0-73.0), p=0.004{]}. An
HE4[?]77pmol/L had a sensitivity and specificity for progestin treatment
response of 83.3\% and 53.3\% in the discovery cohort, and 85.7\% and
76.2\% and in the validation cohort, respectively. When expressed as a
continuous variable, the AUC was 0.81 (95\%CI:0.67-0.95) and 0.87
(95\%CI:0.73-1.00) for the discovery and validation cohorts, with every
1pmol/L of HE4 increasing the likelihood of progestin treatment failure
by 2\% and 5\%, after adjustment for age and histology, respectively
(p=0.02 and p=0.18). Conclusion: Serum HE4 shows promise as a predictive
biomarker of progestin treatment response in endometrial cancer and AEH.%
\end{abstract}%



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\textbf{Hosted file}

\verb`Mirena Response HE4_main document.docx`  available at \url{https://authorea.com/users/500772/articles/581471-serum-he4-predicts-progestin-treatment-response-in-endometrial-cancer-and-atypical-hyperplasia-a-prospective-observational-study}

\textbf{Hosted file}

\verb`Mirena reponse HE4_figures.docx`  available at \url{https://authorea.com/users/500772/articles/581471-serum-he4-predicts-progestin-treatment-response-in-endometrial-cancer-and-atypical-hyperplasia-a-prospective-observational-study}

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