\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{A switch to dactinomycin: What is the cutoff value for hCG?.
(Mini-commentary on BJOG-19-1677.R1)}



\author[1]{Yi Jou Tai}%
\affil[1]{National Taiwan University Hospital}%


\vspace{-1em}



  
  \date{March 13, 2025}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


Mini-commentary on BJOG-19-1677.R1: Risk-factors for second-line
dactinomycin failure after methotrexate treatment for low-risk
gestational trophoblastic neoplasia: a retrospective study

\textbf{A switch to dactinomycin: What is the cutoff value for hCG?}

Yi-Jou Tai

Department of Obstetrics and Gynecology, College of Medicine,

National Taiwan University

Taipei, Taiwan

Contact: 017363@ntuh.gov.tw

A third of patients with gestational trophoblastic disease (GTD) scored
as low risk (FIGO score 0-6) failed the initial methotrexate (MTX)
treatment. These patients require second-line treatment, either with
single-agent (dactinomycin) or with combination chemotherapy (EMA/CO).
The successful treatment rates for second-line dactinomycin is
approximately 85\%. Compared with dactinomycin, EMA/CO had higher rates
of hCG normalisation and lower relapse rates after treatment completion.
But treatments with combination chemotherapy are associated with an
increased risk of secondary malignancies and hasten the onset of
menopause (Rustin et al. J Clin Oncol 1996;14:2769--73).

Choices of treatment regimens after resistance to MTX have been
dependent on varied serum hCG values. Those with hCG levels greater than
100 or 300 IU/l commenced on combination chemotherapy although higher
hCG did not preclude dactinomycin use (McNeish et al. J Clin Oncol 2002;
20: 1838--1844 and Sita-Lumsden et al. Br J Cancer. 2012 Nov 20;
107(11): 1810-1814). The present study examined the question of whether
there is an hCG level beyond which second-line dactinomycin may fail in
women who still scored in the low-risk category (BJOG 2020 xxxx). The
cure rate (66.7\%) after second-line dactinomycin therapy was lower than
reported probably because patients who withdrew from MTX due to
intolerance and toxicity were excluded for this analysis.

Although not statistically significant, discrepancies exist with regard
to the histopathologic diagnosis between groups as more post-molar GTN
were treated in the dactinomycin-success group. Two patients had
choriocarcinoma in the dactinomycin-failure group which were clinical
relevant to increased resistance to chemotherapy (Strohl et al. Gynecol
Oncol. 2016 May;141(2):276-280).

Roles of second curettage or hysterectomy for resistant or relapsed
disease are still under clinical debate and the presence of lung
metastases in low-risk GTD is associated with MTX resistance (Frijstein
et al. BJOG. 2020 Feb;127(3):389-395). Despite being limited by its
retrospective design and small sample size, the authors included these
variables in their analysis. Only the hCG level pre-dactinomcycin
treatment remained predictive of treatment failure on multivariate
analysis with odds ratio 2.93 (95\% CI 1.02-8.40, p=0.045). Without
selection based on pre-treatment hCG levels, the authors demonstrated
the reducing efficacy of second-line dactinomycin with increasing hCG
levels and suggested treatment with EMA/CO directly at hCG level above
40 ng/mL. However, the cut-off concentration of hCG should not be
applied using other assays as performed in the present study.

The disease site and FIGO score for the 45 MTX-failure patients were not
analysed in this study therefore whether the dactinomycin failure group
represented a less favourable subgroup predisposing to treatment
failures is unanswered. I agree with the authors that high hCG level
pre-dactinomcycin treatment is a significant adverse factor.
Nevertheless, cure rates with the established therapies for GTD are
extremely high; therefore increased treatment duration (in this study, a
maximum of 3.5 month) led by resistance to second-line dactinomycin
should be balanced against the toxicity profiles of combination
chemotherapy.

\textbf{Disclosure of interests:} None declared. A completed disclosure
of interest form is available to view online as supporting information.

\selectlanguage{english}
\FloatBarrier
\end{document}

