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\begin{document}

\title{Survival effect of complete surgical resection of the primary tumour in
patients with metastatic, high-risk neuroblastoma in a large Canadian
cohort}



\author[1]{Natashia M. Seemann}%
\author[1]{Craig Erker}%
\author[2]{Meredith Irwin}%
\author[3]{Steven R. Lopushinsky}%
\author[1]{Ketan Kulkarni}%
\author[1]{Conrad Fernandez}%
\author[1]{Rodrigo Romao}%
\affil[1]{IWK Health Centre}%
\affil[2]{The Hospital for Sick Children}%
\affil[3]{Alberta Children's Hospital}%


\vspace{-1em}



  
  \date{May 21, 2024}


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\selectlanguage{english}
\begin{abstract}
Purpose \textbf{:} To determine whether extent of surgical resection of
the primary tumour correlates with survival in patients with
International Neuroblastoma Staging System (INSS) stage 4, high-risk
neuroblastoma. Methods \textbf{:} Data were extracted for patients with
newly diagnosed INSS stage 4, high-risk neuroblastoma between 2001-2019
from the national Cancer in Young People in Canada (CYPC) database.
Complete resection was defined as gross total resection of primary
tumour based on operative reports. Primary endpoints were 3 and 5-year
event-free (EFS) and overall survival (OS). Survival analyses were
completed using log-rank test and Cox proportional hazards regression
including covariates of age, sex, decade of treatment (2001-2009 vs.
2010-2019), immunotherapy, and tandem stem-cell transplant (SCT).
Results \textbf{:} One-hundred and forty patients with complete surgical
data were included. On univariate analysis, 3-year EFS and OS for
patients that had complete vs. incomplete resection was 71\% (95\% CI
57-80\%) vs. 48\% (36-60\%) and 86\% (75-93\%) vs. 64\% (51-74\%),
p=0.008 and p=0.002, respectively. 5-year EFS and OS for patients with
complete resection also demonstrated significantly improved survival. On
Cox Proportional Hazards models adjusted for age, immunotherapy, tandem
SCT and surgical resection, only complete resection was associated with
statistically significant improved 3 yr EFS and OS, HR=0.48 (0.29-0.81;
p=0.006) and HR=0.42 (0.24-0.73; p=0.002). Conclusions \textbf{:} In a
large Canadian INSS stage 4 high-risk neuroblastoma cohort, complete
surgical resection was associated with increased EFS and OS. Within the
constraints of a retrospective study, these results suggest that the
ability to achieve primary tumor complete resection in patients with
metastatic high-risk disease is associated with improved survival.%
\end{abstract}%



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\textbf{Hosted file}

\verb`Neuroblastoma CYPC Manuscript PBC Resubmission Tracked Changes.docx`  available at \url{https://authorea.com/users/490461/articles/590378-survival-effect-of-complete-surgical-resection-of-the-primary-tumour-in-patients-with-metastatic-high-risk-neuroblastoma-in-a-large-canadian-cohort}\selectlanguage{english}
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\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1-Neuroblastoma-Paper/Figure-1-Neuroblastoma-Paper}

\end{center}
\end{figure}\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/Figure-2-Univariable-analysis-EFS/Figure-2-Univariable-analysis-EFS}

\end{center}
\end{figure}\selectlanguage{english}
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\end{figure}

\textbf{Hosted file}

\verb`Table 1 Patient Characteristics.docx`  available at \url{https://authorea.com/users/490461/articles/590378-survival-effect-of-complete-surgical-resection-of-the-primary-tumour-in-patients-with-metastatic-high-risk-neuroblastoma-in-a-large-canadian-cohort}

\textbf{Hosted file}

\verb`Table 2.docx`  available at \url{https://authorea.com/users/490461/articles/590378-survival-effect-of-complete-surgical-resection-of-the-primary-tumour-in-patients-with-metastatic-high-risk-neuroblastoma-in-a-large-canadian-cohort}

\textbf{Hosted file}

\verb`Table 3.docx`  available at \url{https://authorea.com/users/490461/articles/590378-survival-effect-of-complete-surgical-resection-of-the-primary-tumour-in-patients-with-metastatic-high-risk-neuroblastoma-in-a-large-canadian-cohort}

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