\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{Comment on: Standardizing the surgical management of benign ovarian
tumors in children and adolescents: A best practice Delphi consensus
statement.~~~~}



\author[1]{Matthew Murray}%
\author[2]{Nigel Hall}%
\author[3]{Sara Stoneham}%
\author[4]{Anthony Penn}%
\author[5]{Mark Brougham }%
\author[6]{James Nicholson}%
\affil[1]{Addenbrooke's Hospital}%
\affil[2]{Southampton Children's Hospital}%
\affil[3]{University College London Hospitals NHS Foundation Trust}%
\affil[4]{Royal Manchester Children's Hospital}%
\affil[5]{Royal Hospital for Sick Children}%
\affil[6]{Adeenbrookes Hospital}%


\vspace{-1em}



  
  \date{June 13, 2024}


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








\sloppy


\textbf{Comment on: Standardizing the surgical management of benign
ovarian tumors in children and adolescents: A best practice Delphi
consensus statement.}

Matthew J. Murray\textsuperscript{1,2}, Nigel J.
Hall\textsuperscript{3}, Sara Stoneham\textsuperscript{4}, Anthony
Penn\textsuperscript{5}, Mark Brougham\textsuperscript{6}, James C.
Nicholson\textsuperscript{1,7}; on behalf of the Children's Cancer and
Leukaemia Group (CCLG) Germ Cell Tumour (GCT) Special Interest Group
(SIG).

\textsuperscript{1} Department of Paediatric Haematology and Oncology,
Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ,
UK

\textsuperscript{2} Department of Pathology, University of Cambridge,
Tennis Court Road, Cambridge, CB2 1QP, UK

\textsuperscript{3} University Surgery Unit, Faculty of Medicine,
University of Southampton, Southampton SO16 6YD, UK

\textsuperscript{4} Department of Paediatrics and Child Health,
University College Hospital London NHS Foundation Trust, London, UK

\textsuperscript{5} Department of Paediatric Oncology, Royal Manchester
Children's Hospital, Oxford Road, Manchester, M13 9WL, UK

\textsuperscript{6} Department of Paediatric Oncology, Royal Hospital
for Children \& Young People, 50 Little France Crescent, Edinburgh bio
Quarter, Edinburgh, EH16 4TJ, UK

\textsuperscript{7} Department of Paediatrics, University of Cambridge,
Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ,
UK

\textbf{Conflict of interest statement} : the authors declare no
conflicts of interest.

We read with interest the article from Braungart and colleagues,
discussing management of young females with benign ovarian tumors
{[}1{]}. This is important and timely, and we agree with the need for
clarity in management of this under-investigated group. As the authors
note, published evidence to support decisions is limited, so in certain
areas, guidance may have to rely on expert opinion. The authors
emphasize the importance of multidisciplinary team (MDT) discussion to
optimise management and risk-stratification {[}1{]}. They highlight the
importance and safety of ovarian-sparing-surgery in benign tumors, to
preserve fertility and avoid long-term effects including premature
ovarian failure {[}1{]}.

However, important aspects of their methodology are unclear. The
denominator (number of experts approached to be involved) and response
rate is not stated. The standard thresholds for accepting Delphi
statements is \textgreater{}70\% votes in support from
\textgreater{}60\% of experts in each voting round {[}2{]}, as used in
Delphi studies undertaken by the authors here {[}3,4{]}. Furthermore,
there is no indication of level of support for statement(s) not reaching
the 70\% threshold. Moreover, they list specialties involved without
defining numbers in each group, preventing assessment of the work's
objectivity and relative representation. Frequent criticisms of Delphi
method work are poor questionnaire/statement design, compounded by
inadequate definition/ selection of experts {[}5{]}. For example, `the
inclusion of other clinicians\ldots{} may be appropriate to provide an
alternative clinical view, particularly when the study is expected to
have an impact beyond a particular specialist field' {[}5{]}. Of
particular note, the study states that a `\ldots{}. Delphi panel was
instigated that included\ldots{} pediatric oncologists representing CCLG
Germ Cell Tumour Group' {[}1{]}. Unfortunately, there was no pediatric
oncologist involvement from the group in formulating the statements for
discussion. Subsequently, only one was invited to participate in the
Delphi itself, once the statements had been finalized. Furthermore,
there was no patient/parent representation in the Delphi process,
crucial to involve for a benign disease, with issues regarding surgical
approach, fertility, and the burden of proposed ultrasound follow-up.

The surgical guidance is useful; however, a size cut-off for minimally
invasive surgery is specified, without supportive evidence {[}1{]}.
Another incongruity is for tumor marker follow-up (section 2.3, bullet
7) if they were elevated preoperatively; by definition this group should
have had normal markers at diagnosis (section 2.1, first paragraph)
{[}1{]}. In the follow-up section (2.3), bullet-points 3-5 are most
contentious as no evidence is presented for dictating time-interval to
scan, and a recent systematic review looking at this indication, which
concluded, based on available evidence, that `routine
surveillance\ldots{} should certainly be considered' and suggested
annual ultrasound {[}6{]}, was overlooked. In addition, no reference is
provided here to existing guidelines {[}7{]}. The recommended two-year
interval between ultrasounds {[}1{]} is therefore neither evidence-based
nor considers the patient/parent opinion. Furthermore, there is no
justification for gynecologic fertility referral following
ovarian-sparing-surgery where subsequent ultrasound shows normal ovarian
reserve bilaterally. Consequently, terms relating to specific aspects
that `should' include/be undertaken/performed are inappropriate.
Suggesting that `a reasonable strategy that could be considered might be
as follows\ldots{}' would be a better approach.

In summary, attempts to improve the management of young females with
benign ovarian tumors are laudable. Some of the surgical recommendations
made should help to streamline care. However, a representative group of
key stakeholders were not included in the Delphi method and most of the
follow-up recommendations cannot be justified based on use of a limited
group of experts with limited supporting evidence. What is required is a
wider collaborative approach, including GCT, surgical, gynecologic,
radiology, and importantly patient groups, to answer these questions
more robustly, preferably with international collaboration. This will
also ensure appropriate clinician engagement, minimise inconsistencies
in management and optimise outcomes for this patient group.



\textbf{References}

1. Braungart, S., et al., \emph{Standardizing the surgical management of
benign ovarian tumors in children and adolescents: A best practice
Delphi consensus statement.} Pediatr Blood Cancer, 2022: p. e29589.

2. Walker, D.A., et al., \emph{A multi-disciplinary consensus statement
concerning surgical approaches to low-grade, high-grade astrocytomas and
diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using
the Delphi method.} Neuro Oncol, 2013. \textbf{15} (4): p. 462-8.

3. Murray, M.J., et al., \emph{Consensus on the management of
intracranial germ-cell tumours.} Lancet Oncol, 2015. \textbf{16} (9): p.
e470-e477.

4. Murray, M.J., et al., \emph{Delphi method to identify expert opinion
to support children's cancer referral guidelines.} Arch Dis Child,
2020.\textbf{105} (3): p. 241-246.

5. Jones, J. and D. Hunter, \emph{Consensus methods for medical and
health services research.} BMJ, 1995. \textbf{311} (7001): p. 376-80.

6. Kiely, D., et al., \emph{Prevalence of metachronous contralateral
mature ovarian teratoma: A systematic review.} Pediatr Blood Cancer,
2021. \textbf{68} (11): p. e29237.

7. Brougham M, Nicholson J, Stoneham S, et al. Children's Cancer and
Leukaemia Group; June 2018., \emph{Interim Guidelines for the Treatment
of Extra CranialGerm Cell Tumours in Children and Adolescents.} 2018.
Accessed 15\textsuperscript{th} February 2022.

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

