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\begin{document}

\title{Evidence-Based Surgical Guidelines for Treating Children with Wilms
Tumor in Low-Resource Settings}



\author[1]{Abdelhafeez Abdelhafeez}%
\author[2]{Tea  Reljic}%
\author[2]{Ambuj  Kumar}%
\author[3]{Tahmina  Banu}%
\author[4]{Sharon Cox}%
\author[1]{Andrew Davidoff}%
\author[5]{Ahmed Elgendy}%
\author[6]{Khalil Ghandour}%
\author[7]{Justin Gerstle}%
\author[8]{Jonathan   Karpelowsky}%
\author[1]{Sue Kaste}%
\author[9]{Nahla   Kechiche}%
\author[10]{Natia Esiashvili}%
\author[11]{Abdulrasheed Nasir}%
\author[12]{Amon  Ngongola}%
\author[13]{Jin  Marollano}%
\author[14]{Amabelle   Moreno}%
\author[15]{Arlene  Muzira }%
\author[16]{Jeannette Parkes}%
\author[17]{Lily  Saldaña}%
\author[18]{Jaime  Shalkow-Klincovstein }%
\author[19]{Gordan Vujanic}%
\author[20]{Thelma  Velasquez }%
\author[21]{Kokila  Lakoo}%
\author[1]{Sheena Mukkada}%
\author[22]{Simone Abib}%
\affil[1]{St. Jude Children's Research Hospital}%
\affil[2]{University of South Florida College of Medicine}%
\affil[3]{Chittagong Research Institute for Children Surgery (CRICS)}%
\affil[4]{Division of Paediatric Surgery, Red Cross War Memorial Children's Hospital, Department of Surgery, Faculty of Health Sciences, University of Cape Town, South Africa}%
\affil[5]{Tanta University}%
\affil[6]{King Hussein Cancer Center}%
\affil[7]{Memorial Sloan Kettering Cancer Center}%
\affil[8]{12The Children’s Hospital at Westmead, Division of Child \& Adolescent Health, The University of Sydney, Children’s Cancer Research Unit –Kids Research Institute}%
\affil[9]{University Hospital Monastir, LR12SP13, University of Monastir}%
\affil[10]{Emory University Winship Cancer Institute}%
\affil[11]{University of Ilorin Teaching Hospital}%
\affil[12]{University of Zambia University Teaching Hospital}%
\affil[13]{Childhood Cancer International }%
\affil[14]{University of the Philippines-Philippine General Hospital Department of Surgery}%
\affil[15]{Uganda Cancer Institute}%
\affil[16]{Groote Schuur Hospital}%
\affil[17]{Instituto Nacional de Salud del Niño San Borja}%
\affil[18]{National Institute of Paediatrics and ABC Cancer Centre}%
\affil[19]{Sidra Medicine, Weill Cornell Medicine – Qatar}%
\affil[20]{Unidad Nacional de Oncologia Pediatrica}%
\affil[21]{Oxford University}%
\affil[22]{Pediatric Oncology Institute – GRAACC – Federal University of São Paulo}%


\vspace{-1em}



  
  \date{May 17, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Survival of Wilms tumor (WT) is \textgreater{}90\% in high-resource
settings but \textless{}30\% in low-resource settings. Adapting a
standardized surgical approach to WT is challenging in low-resource
settings, but a local control strategy is crucial to improving outcomes.
Objective: Provide resource-sensitive recommendations for the surgical
management of WT. Methods: We performed a systematic review of PubMed
and EMBASE through July 7, 2020, and used the GRADE approach to assess
evidence and recommendations. Recommendations: Initiation of treatment
should be expedited, and surgery should be done in a high-volume
setting. Cross-sectional imaging should be done to optimize preoperative
planning. For patients with typical clinical features of WT, biopsy
should not be done before chemotherapy, and neoadjuvant chemotherapy
should precede surgical resection. Also, resection should include a
large transperitoneal laparotomy, adequate lymph node sampling, and
documentation of staging findings. For WT with tumor thrombus in the
inferior vena cava, neoadjuvant chemotherapy should be given before en
bloc resection of the tumor and thrombus and evaluation for viable tumor
thrombus. For those with bilateral WT, neoadjuvant chemotherapy should
be given for 6--12 weeks. Neither routine use of complex hilar control
techniques during nephron-sparing surgery, nor nephron-sparing resection
for unilateral WT with a normal contralateral kidney is recommended.
When indicated, postoperative radiotherapy should be administered within
14 days of surgery. Post-chemotherapy pulmonary oligometastasis should
be resected when feasible, if local protocols allow omission of
whole-lung irradiation in patients with non-anaplastic histology stage
IV WT with pulmonary metastasis without evidence of extrapulmonary
metastasis. Conclusion: We provide evidence-based recommendations for
the surgical management of WT, considering the benefits/risks associated
with limited-resource settings.%
\end{abstract}%



\sloppy


\textbf{INTRODUCTION}

Wilms tumor (WT), one of the most common solid tumors, is highly curable
with affordable interventions.\textsuperscript{1} The majority (90\%) of
patients with WT in high-income countries survive with chemotherapy,
adequate surgical local control, and radiation therapy when indicated.
However, survival in low-resource settings remains poor (50\% to
\textless{}30\%), reflecting limitations in resources (physical and
human) and a lack of process standardization.\textsuperscript{2,3} The
World Health Organization's Global Initiative for Childhood Cancer
targets WT as one of six index cancers included in attempts to reduce
disparities in childhood cancer outcomes.\textsuperscript{4} Efforts to
address resource limitations include workforce training and shared
advocacy to establish sustainable resources required for multimodality
therapy and family support. Although guidance from high-income countries
is available, it may be difficult to implement in low- and middle-income
countries (LMICs) due to differences in resources and health systems.
For WT, a limited capacity to manage intraoperative bleeding and limited
access to diagnostics and radiation therapy are key factors
necessitating the adaptation of guidelines to address specific
challenges in LMICs. The aim of this work is to provide
resource-sensitive recommendations for the surgical management of
pediatric WT in limited-resource settings.

\textbf{METHODS}

\textbf{Clinical practice guidelines}

The guidelines were developed following the GRADE (Grading of
Recommendations, Assessment, Development, and Evaluation) method
(Supplemental Table S1).\textsuperscript{5} The primary target audience
for these guidelines is surgeons providing care to children with WT,
particularly in settings with limited resources. The recommendations are
also intended to be used by policymakers and senior managers as the
basis for developing national and local WT protocols and policies and
for supporting staff education and training.

\textbf{Composition of the guideline steering and development groups}

A Guideline Steering Group (GSD) was formed, consisting of two
methodologists, two clinicians, and a research associate. The Guideline
Development Group (GDG) members were identified through St. Jude Global,
the International Society of Pediatric Surgical Oncology, and the Global
Initiative for Children's Surgery. This group included content experts
and a patient advocate and was constructed to maintain geographic and
gender representation.

\textbf{Disclosure and management of potential conflicts of interest}

All members of the GSD and GDG provided conflict-of-interest disclosures
prior to the voting process.

\textbf{Clinical questions}

The key questions addressed were formulated based on the assembled list
of priority topics, questions, and critical outcomes from the scoping
exercise identified by the GSG and GDG.

\textbf{Outcomes}

The GSD and GDG discussed and identified important outcomes for patients
undergoing treatment for WT. The following outcomes were considered
during the development of the recommendations: overall survival,
mortality, tumor spillage, local recurrence, bleeding, complications,
intensity of therapy, and wrong therapy.

\textbf{Summary of the evidence}

For questions with available data, evidence profiles were produced
denoting the quality of evidence and summary of findings for each
outcome. The GDG members were invited to review and comment on all
evidence prior to the panel's meeting.

\textbf{Review of the evidence}

Selection criteria for each question were determined \emph{a priori} .
Only comparative studies (systematic reviews, randomized controlled
trials, cohort studies, case-control studies, and cross-sectional
studies) were considered for inclusion. If randomized data were
available, data from nonrandomized studies were excluded. Electronic and
manual searches were conducted for each question. We searched PubMed and
EMBASE through July 7, 2020. Additionally, we manually reviewed the
reference lists of all relevant systematic reviews and included studies
to find additional eligible studies. The titles and abstracts of all
identified references were reviewed by a clinician and a methodologist
from the GSG. Studies identified for full-text review were then reviewed
by all members of the GSG, and any reasons for exclusion were noted.

Data from included studies were extracted by two members of the GSG. The
quality of evidence from each included study was assessed using the
appropriate risk-of-bias tool for each study design. The Cochrane RCT
tool was used for randomized controlled trials.\textsuperscript{6} The
Newcastle-Ottawa tool was used for cohort and case-control
studies.\textsuperscript{7} QUADAS was used for diagnostic accuracy
studies.\textsuperscript{8} Data on outcomes from similar studies were
pooled when appropriate by using the random-effects model. All analyses
were performed using RevMan,\textsuperscript{9} and all information was
summarized as evidence profile tables.\textsuperscript{10}

\textbf{Development of recommendations}

All training, deliberations, and voting were conducted virtually. Prior
to the panel's discussion, the GSG members presented the background and
evidence profile for each key question. The GDG members discussed the
benefits and disadvantages for patients, patients' preferences, clinical
impact, and the feasibility of each proposed intervention.

\textbf{Grading recommendations}

All questions were converted into recommendations prior to anonymous
voting. Panelists initially voted for or against each recommendation,
followed by a vote on the strength of the recommendation (strong or
weak). A simple majority of \textgreater{}50\% was considered in favor
or against a recommendation. In the case of a tie, the text of the
recommendation was modified to achieve a majority vote for or against
the recommendation.

\textbf{External review}

The recommendations were peer-reviewed by an external review group,
which provided overall feedback on the manuscript but did not change the
voting outcomes.

\textbf{Update plan}

Guidelines are to be updated every 4 years.

\textbf{Source of funding}

This guideline development effort was supported by funds from the
American Lebanese Syrian Associated Charities (ALSAC).

\textbf{RESULTS}

The priority questions guiding the evidence review and synthesis for
these guidelines are listed in (Supplemental Table S2). The glossary of
terms and phrases and their meanings for the purposes of this guideline
are summarized in Supplemental Table S3.

\textbf{RECOMMENDATIONS}

\textbf{Preoperative phase}

The panel recommends expedited initiation of treatment for the
management of WT\emph{(Strong recommendation, Quality of evidence: Very
Low).}

\emph{Panel deliberation.} WT is a rapidly growing malignancy with a
doubling time of less than 2 weeks. Therefore, any delay in diagnosis or
initiation of therapy (Supplemental Table S3) should be avoided. To
facilitate early identification of patients with WT, community awareness
should be raised regarding the signs and symptoms of WT, favorable
outcomes with timely treatment, and the urgency to seek health care.
Strengthening referral networks and prioritizing chemotherapy and
surgery for childhood cancer are essential to facilitate access to
timely care.

The panel suggests surgery at a high-volume setting for patients with WT
undergoing resection. \emph{(Weak recommendation, Quality of evidence:
Very Low; Table 1).}

\emph{Panel deliberation.} Cancer units may have the capacity to offer
common diagnostic and treatment services; however, pediatric oncologic
surgery requires multidisciplinary capacity available at national cancer
referral centers.\textsuperscript{11-15} When scaling-up surgical
oncology care (Supplemental Table S2), it is fundamental to balance the
competing priorities of quality and access. National cancer centers
should be accessible and well connected with a network of primary health
and cancer units to deliver affordable, equitable, and high-quality
care. The cost effectiveness of treating cancer in centers with higher
capabilities was shown in the third edition of Disease Control
Priorities.\textsuperscript{16}

The panel recommends abdominal and pelvic cross-sectional imaging for
preoperative planning in patients with suspected WT \emph{(Strong
recommendation, Quality of evidence: Very Low).}

\emph{Panel deliberation.} Cross-sectional imaging provides more
in-depth knowledge of tumor anatomy, including focality and extent,
which is important for preoperative surgical
planning.\textsuperscript{17-22} Surgeons should develop skills to
adequately interpret cross-sectional imaging delineating tumor extent
and laterality for surgical planning. Although there is a paucity of
evidence to compare outcomes of ultrasound-guided management versus
cross-sectional imaging--guided management, the latter approach provides
more comprehensive images of the tumor and its critical anatomy for the
operating surgeon. When cross-sectional imaging is not readily
available, abdominal ultrasound imaging may be used to guide therapy and
provide valuable details about tumor origin, extent, and laterality.

The panel suggests chest computerized tomography (CT)-guided staging for
the management of WT. \emph{(Weak recommendation, Quality of evidence:
Very Low; Table 2)}

\emph{Panel deliberation.} Chest CT is significantly more sensitive than
chest x-ray; management guided by chest CT is associated with improved
event-free survival but not overall survival.\textsuperscript{23-27}
When CT is not available, chest x-ray may guide therapy without
compromising overall survival.

The panel recommends against biopsy for patients with typical clinical
features of WT. \emph{(Strong recommendation, Quality of evidence: Very
Low)}

\emph{Panel deliberation.} Children who present with typical clinical
features of WT (Supplemental Table S3), including age (\textgreater{}6
months and \textless{}7 years), symptoms, laboratory test results, and
imaging features, should receive neoadjuvant chemotherapy without tissue
diagnosis. In the context of limited diagnostic capacity, routinely
performing biopsies in patients with typical WT presentation may delay
therapy and increase complications. Open biopsy can upstage WT, thereby
compromising local control.\textsuperscript{28,29}

The panel recommends biopsy (or upfront surgical resection when safe)
for patients with renal tumor with an atypical clinical
feature.\emph{(Strong recommendation, Quality of evidence: Very Low)}

\emph{Panel deliberation.} Other tumors that are not of renal origin,
such as neuroblastoma and Burkitt lymphoma, should be excluded by
clinical examination, laboratory investigations, and imaging. Patients
who present with primary renal tumors but with clinical features that
are atypical of WT should have tissue confirmation to plan therapy
appropriately. Atypical presentations of WT include age older than 7
years or younger than 6 months, absence of imaging features that are
typical of WT, infants with pulmonary metastases,
extra-pulmonary/hepatic metastases, lactate dehydrogenase levels more
than four times the normal limits, and hypercalcemia (Supplemental Table
S3). In these scenarios, pre-therapy biopsy is
indicated.\textsuperscript{30} Image-guided core needle biopsy, if
available, is the approach of choice; open biopsy is associated with the
risk of tumor spillage and should be avoided. Alternatively, if the
tumor is deemed resectable, then upfront resection may be considered to
provide tissue diagnosis and plan appropriate further treatment.

\textbf{Operative phase}

The panel suggests neoadjuvant chemotherapy for the treatment of
patients with the typical clinical features of WT. \emph{(Weak
recommendation; Quality of evidence: Moderate; Table 3)}

\emph{Panel deliberation.} Neoadjuvant chemotherapy goals are to
decrease tumor size, prevent tumor spillage, and risk-stratify
postoperative treatment based on tumor response. Neoadjuvant
chemotherapy is also associated with lowering the incidence of tumor
spillage and decreasing the stage of the
disease.\textsuperscript{31-33}This may be particularly relevant in
limited-resource settings, where tumor stage at diagnosis is mostly
advanced, and therapy intensification is challenging because of barriers
to accessing radiation therapy and supportive care. In some settings,
upfront surgical resection is considered a measure to adapt to issues
related to chemotherapy supply chain and accessibility. In these cases,
surgical resection is performed at the time of diagnosis at the
reference center, followed by chemotherapy close to the patient's
residence. Upfront resection may prevent the administration of
inappropriate therapy in a small percentage of patients and may help
select patients with very low--risk WT who can be treated with surgery
alone. However, a surgery-only approach is more appropriate in the
context of advanced diagnostic capacity supporting molecular and genomic
tumor analysis.\textsuperscript{34,35}

The panel suggests adequate trans-peritoneal laparotomy incision for
resection of WT. \emph{(Weak recommendation; Quality of evidence: Very
Low; Table 4)}

\emph{Panel deliberation.} WT surgical oncology principles include
optimal visualization of vital anatomical structures to avoid injury,
minimal tumor handling to prevent tumor spillage, and adequate surgical
staging, particularly with lymph node sampling. Minimally invasive
surgery is an attractive approach for treating small tumors; however, it
should not compromise staging, lymph node sampling, or prevention of
tumor capsule injury.\textsuperscript{36-39}

The panel recommends adequate and documented surgical staging for the
management of WT. \emph{(Strong recommendation; Quality of evidence:
Very Low)}

\emph{Panel deliberation.} Postsurgical therapy relies on pathologic
staging and surgical staging. In some scenarios, especially in the
context of limited diagnostic capacity, documented surgical findings may
be the only indicator of tumor spillage. Failure to perform lymph node
sampling results in suboptimal tumor staging. This may lead to
inadequate therapy or, conversely, to overtreatment with associated
potential toxicities. Adequately documented surgical staging should
include lymph node sampling and documentation of local invasion, seeding
or tumor spillage, and vascular extension (Supplemental Table
S3).\textsuperscript{28,40-45}

The panel recommends sampling of lymph nodes at the time of resection of
WT; pathologic assessment of lymph node histology before and after
chemotherapy is feasible and of value in staging. \emph{(Strong
recommendation; Quality of evidence: Very Low)}

\emph{Panel deliberation.} Determining lymph node involvement by
histology is feasible both before and after neoadjuvant
chemotherapy.\textsuperscript{46} Lymph node sampling is an integral
part of staging and should be completed at the time of tumor resection,
regardless of whether neoadjuvant chemotherapy was
given.\textsuperscript{28,40-45} At the time of sampling, five to seven
lymph nodes should be obtained to reduce the risk of a false-negative
finding.\textsuperscript{41,44}

The panel recommends neoadjuvant chemotherapy for the management of WT
with inferior vena cava thrombus extension. \emph{(Strong
recommendation; Quality of evidence: Very Low; Table 5)}

\emph{Panel deliberation.} Neoadjuvant chemotherapy is associated with
the mitigation of complications during the surgical resection of WT with
tumor thrombus in the inferior vena cava. Also, the need for
cardiopulmonary bypass may be reduced in patients with pretreated
supra-diaphragmatic vena cava
thrombus.\textsuperscript{19,47-50}Neoadjuvant chemotherapy should be
used in all patients with WT and tumor thrombus in the inferior vena
cava; this is particularly relevant in limited-resource settings.

The panel recommends evaluating the presence of viable tumor cells
within the thrombus for patients with WT and inferior vena cava
extension. \emph{(Strong recommendation; Quality of evidence: Very Low)}

\emph{Panel deliberation.} Up to two thirds of tumor thrombi include
viable tumor cells.\textsuperscript{51,52} Viable tumor thrombus in the
context of incomplete macroscopic resection increases the risk of WT
relapse and death.\textsuperscript{51,52} When complete gross resection
of the tumor thrombus is achieved, the viability of the thrombus may be
considered in determining the need for radiation therapy.

The panel recommends neoadjuvant chemotherapy followed by \emph{en bloc}
surgical resection of WT with the inferior vena cava thrombus extension.
\emph{(Strong recommendation; Quality of evidence: Very Low)}

\emph{Panel deliberation.} Intravascular tumor extension increases the
complexity of surgical resection and is associated with an increased
risk of bleeding and other complications; however, resection is an
integral part of the local control strategy of tumor thrombus. Complete
resection of the tumor thrombus should be the goal of surgery whenever
possible.\textsuperscript{51,52} WT with inferior vena cava extension
should be managed in a referral center. Extending neoadjuvant therapy
beyond 6 weeks is not associated with improved surgical resection,
further thrombus regression, or survival advantage.\textsuperscript{53}

The panel recommends neoadjuvant chemotherapy for 6 to 12 weeks for
patients with bilateral WT requiring nephron-sparing
resection.\emph{(Strong recommendation; Quality of evidence: Very Low)}

\emph{Panel deliberation.} Tumor response to chemotherapy should be
assessed at 6 weeks and 12 weeks; maximal tumor shrinkage occurs within
the first 12 weeks of neoadjuvant chemotherapy.\textsuperscript{54}
Tumors that show no response to chemotherapy after 6 weeks should be
resected to prevent the side effects of protracted chemotherapy.
Protracted chemotherapy may subject patients with stromal-type tumor to
unnecessary toxicities or delay appropriate therapy for patients with
anaplasia.

The panel suggests not to routinely use complex hilar techniques,
including continuous vascular clamping and bench surgery, for bleeding
control in patients with bilateral WT requiring nephron-sparing
resection. \emph{(Weak recommendation; Quality of evidence: Very Low)}

\emph{Panel deliberation.} Large series have demonstrated that
nephron-sparing surgery can be successfully completed using intermittent
manual compression.\textsuperscript{55,56} However, selected patients
may require more complex hilar control maneuvers. Surgeons should avoid
prolonged ischemia (more than 20 min)\textsuperscript{57,58} of the
residual renal tissue, as it is associated with adverse outcome of renal
function.

The panel suggests intraoperative histologic confirmation of uncertain
margins in patients with WT requiring nephron-sparing
resection.\emph{(Weak recommendation; Quality of evidence: Very Low)}

\emph{Panel deliberation.} Intraoperative margin biopsy should be
considered for areas of uncertain margins and potential residual
disease. Frozen sections, however, are not needed routinely, especially
when the tumor was resected with either a margin of normal renal
parenchyma or an intact capsule.

The panel suggests that nephron-sparing resection not be performed in
patients with unilateral WT. \emph{(Weak recommendation; Quality of
evidence: Very Low; Table 6)}

\emph{Panel deliberation.} Nephron-sparing surgery for unilateral WT may
be associated with increased risk of tumor spillage and is not the
standard of care.\textsuperscript{59-63} Nephron-sparing surgery may be
feasible, especially in small polar tumors; however, the primary
priority is to achieve complete tumor resection with negative margins.
Nephrectomy for unilateral WT is associated with high overall survival
and high recurrence-free survival, with an extremely low incidence of
renal failure in patients who do not have cancer-predisposition
syndrome. Nephron-sparing surgery is indicated primarily for patients
with unilateral WT in the context of cancer-predisposition syndrome or
for those who have only one kidney.

\textbf{Postoperative phase}

The panel suggests postoperative abdominal radiation therapy within 14
days of surgery for patients with WT who require adjuvant radiation
therapy. \emph{(Weak recommendation; Quality of evidence: Very Low)}

\emph{Panel deliberation.} Postoperatively, patients who need radiation
therapy, especially those with high-risk WT, should be referred to a
radiation oncologist within 1 week of surgery to receive abdominal
radiation within 14 days. A radiation oncologist should be part of the
multi-disciplinary team discussion of all patients at diagnosis, so
referral and need for radiation therapy can be anticipated. Delayed
radiation therapy of the abdominal primary tumor in non-metastatic
patients is associated with suboptimal local
control.\textsuperscript{64-66} In contrast, for patients with
metastatic disease, radiation of the abdominal primary within 14 days
post nephrectomy is of no clear significance. Therefore, in these
patients, abdominal irradiation can be performed at the same time as
lung irradiation (when indicated). Suboptimal nutritional status of
patients should be considered when combining whole-lung radiation
therapy with flank versus whole-abdomen radiation therapy.

The panel suggests that resection of residual pulmonary oligometastasis
after completion of chemotherapy (when feasible) be considered in a
setting of local protocols that allow the omission of whole-lung
irradiation in patients with favorable histology, stage IV WT with
pulmonary metastasis. \emph{(Weak recommendation; Quality of evidence:
Very Low)}

\emph{Panel deliberation.} The decision to omit whole-lung irradiation
is based on tumor biology, histological risk group of the abdominal
primary, and chemosensitivity; and can be applied in the context of
local treatment protocols. Lung irradiation can be avoided for patients
with non-anaplastic histology who are complete responders (i.e., those
who have no residual pulmonary metastases on a chest CT after
chemotherapy). In patients with residual post-chemotherapy
oligometastasis that are amenable to resection, radiation therapy can be
omitted if there was no residual viable tumor in the surgically cleared
nodules.\textsuperscript{60-62,67,68} Resection of residual nodules may
be helpful when institutional protocols/guidelines allow the omission of
whole-lung radiotherapy in patients with non-anaplastic histology and no
viable tumor in respected lesions.

\textbf{DISCUSSION}

A clinician panel used the GRADE approach to produce evidence-based
recommendations for the surgical management of pediatric WT. Nineteen
recommendations were formulated to address preoperative, operative, and
postoperative concerns identified by surgeons practicing in
limited-resource settings. The guidelines address key questions
prioritized by the panel in the three phases of patient care. The panel
included multidisciplinary WT experts and maintained geographic and
gender balance. It produced recommendations based on the available
evidence and the identified priority outcomes and goals relevant in
limited-resource settings.

A few themes were identified throughout panel deliberations. In a
limited-resource setting, childhood tumor treatment is often effective
only if the patient presents early; therefore, access to timely therapy
is of paramount importance. In addition, a multidisciplinary childhood
cancer team incorporating radiologists, pathologists, oncologists,
radiation oncologists, and surgical specialists who discuss the case
prior to any surgical intervention is essential to ensure high quality
of care. Establishing a multidisciplinary team discussion or tumor
boards is a cornerstone of building capacity for pediatric oncology
care. One of the key limitations identified by the panel was a paucity
of evidence to address the selected questions. When evidence exists, it
is frequently of low quality. Well-designed, randomized controlled
trials and cost-effectiveness analyses are needed to examine the impact
of the included preoperative, operative, and postoperative interventions
on the outcome of WT.

Diagnostic capacity is limited in LMICs, and this continues to pose a
significant challenge to improving the outcomes of children with WT.
When there is no access to cross-sectional images, ultrasound and x-ray
images may guide therapy. The availability of pathologic analyses of
frozen sections may also be limited in LMICs. However, there is no
evidence to support the utility or cost-effectiveness of frozen sections
in WT surgery. The therapeutic interventions recommended by the panel
are affordable; most are considered standard of care across settings
with various resources and are not associated with increased risk to
patients. These recommendations are, therefore, practical and can serve
as a reference for practice standardization that may improve the
surgical outcomes of WT globally.

\textbf{Acknowledgement}

Thanks to Angela McArthur for editing the manuscript.

Thanks to Kathy Pritchard-Jones for providing helpful comments.

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