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Serveur d'exploration sur les relations entre la France et l'Australie

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Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters

Identifieur interne : 000706 ( Pmc/Curation ); précédent : 000705; suivant : 000707

Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters

Auteurs : M A Versluis [Pays-Bas] ; R A De Jong [Pays-Bas] ; A. Plat [Pays-Bas] ; T. Bosse [Pays-Bas] ; V T Smit [Pays-Bas] ; H. Mackay [Canada] ; M. Powell [Royaume-Uni] ; A. Leary [France] ; L. Mileshkin [Australie] ; H C Kitchener [Royaume-Uni] ; E J Crosbie [Royaume-Uni] ; R J Edmondson [Royaume-Uni] ; C L Creutzberg [Pays-Bas] ; H. Hollema [Pays-Bas] ; T. Daemen [Pays-Bas] ; G H De Bock [Pays-Bas] ; H W Nijman [Pays-Bas]

Source :

RBID : PMC:4559831

Abstract

Background:

Adjuvant therapy increases disease-free survival in endometrial cancer (EC), but has no impact on overall survival and negatively influences the quality of life. We investigated the discriminatory power of classical and immunological predictors of recurrence in a cohort of EC patients and confirmed the findings in an independent validation cohort.

Methods:

We reanalysed the data from 355 EC patients and tested our findings in an independent validation cohort of 72 patients with EC. Predictors were selected and Harrell's C-index for concordance was used to determine discriminatory power for disease-free survival in the total group and stratified for histological subtype.

Results:

Predictors for recurrence were FIGO stage, lymphovascular space invasion and numbers of cytotoxic and memory T-cells. For high risk cancer, cytotoxic or memory T-cells predicted recurrence as well as a combination of FIGO stage and lymphovascular space invasion (C-index 0.67 and 0.71 vs 0.70). Recurrence was best predicted when FIGO stage, lymphovascular space invasion and numbers of cytotoxic cells were used in combination (C-index 0.82). Findings were confirmed in the validation cohort.

Conclusions:

In high-risk EC, clinicopathological or immunological variables can predict regional or distant recurrence with equal accuracy, but the use of these variables in combination is more powerful.


Url:
DOI: 10.1038/bjc.2015.268
PubMed: 26217922
PubMed Central: 4559831

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Links to Exploration step

PMC:4559831

Le document en format XML

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<institution>Department of Gynecology, University of Groningen, University Medical Center Groningen</institution>
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<name sortKey="Leary, A" sort="Leary, A" uniqKey="Leary A" first="A" last="Leary">A. Leary</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Mileshkin, L" sort="Mileshkin, L" uniqKey="Mileshkin L" first="L" last="Mileshkin">L. Mileshkin</name>
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<institution>Division of Medical Oncology, Peter MacCallum Cancer Center</institution>
, Victoria,
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<title xml:lang="en" level="a" type="main">Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters</title>
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<name sortKey="Versluis, M A" sort="Versluis, M A" uniqKey="Versluis M" first="M A" last="Versluis">M A Versluis</name>
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, Groningen,
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</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="De Jong, R A" sort="De Jong, R A" uniqKey="De Jong R" first="R A" last="De Jong">R A De Jong</name>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Plat, A" sort="Plat, A" uniqKey="Plat A" first="A" last="Plat">A. Plat</name>
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<institution>Department of Gynecology, University of Groningen, University Medical Center Groningen</institution>
, Groningen,
<country>The Netherlands</country>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Bosse, T" sort="Bosse, T" uniqKey="Bosse T" first="T" last="Bosse">T. Bosse</name>
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, Leiden,
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</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Smit, V T" sort="Smit, V T" uniqKey="Smit V" first="V T" last="Smit">V T Smit</name>
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<nlm:aff id="aff3">
<institution>Department of Pathology, Leiden University Medical Center</institution>
, Leiden,
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</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="Mackay, H" sort="Mackay, H" uniqKey="Mackay H" first="H" last="Mackay">H. Mackay</name>
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<nlm:aff id="aff4">
<institution>Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto</institution>
, Toronto,
<country>Canada</country>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Powell, M" sort="Powell, M" uniqKey="Powell M" first="M" last="Powell">M. Powell</name>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Department of Clinical Oncology, Barts Health NHS trust</institution>
, London,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Leary, A" sort="Leary, A" uniqKey="Leary A" first="A" last="Leary">A. Leary</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<institution>Department of Medicine, Gynecology Unit, Gustave Roussy</institution>
, Villejuif,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mileshkin, L" sort="Mileshkin, L" uniqKey="Mileshkin L" first="L" last="Mileshkin">L. Mileshkin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>Division of Medical Oncology, Peter MacCallum Cancer Center</institution>
, Victoria,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kitchener, H C" sort="Kitchener, H C" uniqKey="Kitchener H" first="H C" last="Kitchener">H C Kitchener</name>
<affiliation wicri:level="1">
<nlm:aff id="aff8">
<institution>Department of Gynecology, St Marys Hospital</institution>
, Manchester,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Crosbie, E J" sort="Crosbie, E J" uniqKey="Crosbie E" first="E J" last="Crosbie">E J Crosbie</name>
<affiliation wicri:level="1">
<nlm:aff id="aff8">
<institution>Department of Gynecology, St Marys Hospital</institution>
, Manchester,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Edmondson, R J" sort="Edmondson, R J" uniqKey="Edmondson R" first="R J" last="Edmondson">R J Edmondson</name>
<affiliation wicri:level="1">
<nlm:aff id="aff8">
<institution>Department of Gynecology, St Marys Hospital</institution>
, Manchester,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Creutzberg, C L" sort="Creutzberg, C L" uniqKey="Creutzberg C" first="C L" last="Creutzberg">C L Creutzberg</name>
<affiliation wicri:level="1">
<nlm:aff id="aff9">
<institution>Department of Clinical Oncology, Leiden University Medical Center</institution>
, Leiden,
<country>The Netherlands</country>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hollema, H" sort="Hollema, H" uniqKey="Hollema H" first="H" last="Hollema">H. Hollema</name>
<affiliation wicri:level="1">
<nlm:aff id="aff10">
<institution>Department of Pathology, University of Groningen, University Medical Center Groningen</institution>
, Groningen,
<country>The Netherlands</country>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Daemen, T" sort="Daemen, T" uniqKey="Daemen T" first="T" last="Daemen">T. Daemen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<institution>Department of Medical Microbiology, Molecular Virology Section, University of Groningen, University Medical Center Groningen</institution>
, Groningen,
<country>The Netherlands</country>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="De Bock, G H" sort="De Bock, G H" uniqKey="De Bock G" first="G H" last="De Bock">G H De Bock</name>
<affiliation wicri:level="1">
<nlm:aff id="aff12">
<institution>Department of Epidemiology, University of Groningen, University Medical Center Groningen</institution>
, Groningen,
<country>The Netherlands</country>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Nijman, H W" sort="Nijman, H W" uniqKey="Nijman H" first="H W" last="Nijman">H W Nijman</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Department of Gynecology, University of Groningen, University Medical Center Groningen</institution>
, Groningen,
<country>The Netherlands</country>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">British Journal of Cancer</title>
<idno type="ISSN">0007-0920</idno>
<idno type="eISSN">1532-1827</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
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<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Background:</title>
<p>Adjuvant therapy increases disease-free survival in endometrial cancer (EC), but has no impact on overall survival and negatively influences the quality of life. We investigated the discriminatory power of classical and immunological predictors of recurrence in a cohort of EC patients and confirmed the findings in an independent validation cohort.</p>
</sec>
<sec>
<title>Methods:</title>
<p>We reanalysed the data from 355 EC patients and tested our findings in an independent validation cohort of 72 patients with EC. Predictors were selected and Harrell's C-index for concordance was used to determine discriminatory power for disease-free survival in the total group and stratified for histological subtype.</p>
</sec>
<sec>
<title>Results:</title>
<p>Predictors for recurrence were FIGO stage, lymphovascular space invasion and numbers of cytotoxic and memory T-cells. For high risk cancer, cytotoxic or memory T-cells predicted recurrence as well as a combination of FIGO stage and lymphovascular space invasion (C-index 0.67 and 0.71
<italic>vs</italic>
0.70). Recurrence was best predicted when FIGO stage, lymphovascular space invasion and numbers of cytotoxic cells were used in combination (C-index 0.82). Findings were confirmed in the validation cohort.</p>
</sec>
<sec>
<title>Conclusions:</title>
<p>In high-risk EC, clinicopathological or immunological variables can predict regional or distant recurrence with equal accuracy, but the use of these variables in combination is more powerful.</p>
</sec>
</div>
</front>
<back>
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<author>
<name sortKey="Amant, F" uniqKey="Amant F">F Amant</name>
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<name sortKey="Vergote, I" uniqKey="Vergote I">I Vergote</name>
</author>
</analytic>
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<author>
<name sortKey="Blake, P" uniqKey="Blake P">P Blake</name>
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<name sortKey="Leary, A" uniqKey="Leary A">A Leary</name>
</author>
<author>
<name sortKey="Edmondson, Rj" uniqKey="Edmondson R">RJ Edmondson</name>
</author>
<author>
<name sortKey="Powell, Me" uniqKey="Powell M">ME Powell</name>
</author>
<author>
<name sortKey="Crosbie, Ej" uniqKey="Crosbie E">EJ Crosbie</name>
</author>
<author>
<name sortKey="Kitchener, Hc" uniqKey="Kitchener H">HC Kitchener</name>
</author>
<author>
<name sortKey="Mileshkin, L" uniqKey="Mileshkin L">L Mileshkin</name>
</author>
<author>
<name sortKey="Pollock, Pm" uniqKey="Pollock P">PM Pollock</name>
</author>
<author>
<name sortKey="Smit, Vt" uniqKey="Smit V">VT Smit</name>
</author>
<author>
<name sortKey="Creutzberg, Cl" uniqKey="Creutzberg C">CL Creutzberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Vesely, Md" uniqKey="Vesely M">MD Vesely</name>
</author>
<author>
<name sortKey="Kershaw, Mh" uniqKey="Kershaw M">MH Kershaw</name>
</author>
<author>
<name sortKey="Schreiber, Rd" uniqKey="Schreiber R">RD Schreiber</name>
</author>
<author>
<name sortKey="Smyth, Mj" uniqKey="Smyth M">MJ Smyth</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Wright, Jd" uniqKey="Wright J">JD Wright</name>
</author>
<author>
<name sortKey="Barrena Medel, Ni" uniqKey="Barrena Medel N">NI Barrena Medel</name>
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<author>
<name sortKey="Fujiwara, K" uniqKey="Fujiwara K">K Fujiwara</name>
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<name sortKey="Herzog, Tj" uniqKey="Herzog T">TJ Herzog</name>
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</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Br J Cancer</journal-id>
<journal-id journal-id-type="iso-abbrev">Br. J. Cancer</journal-id>
<journal-title-group>
<journal-title>British Journal of Cancer</journal-title>
</journal-title-group>
<issn pub-type="ppub">0007-0920</issn>
<issn pub-type="epub">1532-1827</issn>
<publisher>
<publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26217922</article-id>
<article-id pub-id-type="pmc">4559831</article-id>
<article-id pub-id-type="pii">bjc2015268</article-id>
<article-id pub-id-type="doi">10.1038/bjc.2015.268</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Molecular Diagnostics</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters</article-title>
<alt-title alt-title-type="running">Recurrence prediction in endometrial cancer</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Versluis</surname>
<given-names>M A</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>de Jong</surname>
<given-names>R A</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Plat</surname>
<given-names>A</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bosse</surname>
<given-names>T</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Smit</surname>
<given-names>V T</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mackay</surname>
<given-names>H</given-names>
</name>
<xref ref-type="aff" rid="aff4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Powell</surname>
<given-names>M</given-names>
</name>
<xref ref-type="aff" rid="aff5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Leary</surname>
<given-names>A</given-names>
</name>
<xref ref-type="aff" rid="aff6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mileshkin</surname>
<given-names>L</given-names>
</name>
<xref ref-type="aff" rid="aff7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kitchener</surname>
<given-names>H C</given-names>
</name>
<xref ref-type="aff" rid="aff8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Crosbie</surname>
<given-names>E J</given-names>
</name>
<xref ref-type="aff" rid="aff8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Edmondson</surname>
<given-names>R J</given-names>
</name>
<xref ref-type="aff" rid="aff8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Creutzberg</surname>
<given-names>C L</given-names>
</name>
<xref ref-type="aff" rid="aff9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hollema</surname>
<given-names>H</given-names>
</name>
<xref ref-type="aff" rid="aff10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Daemen</surname>
<given-names>T</given-names>
</name>
<xref ref-type="aff" rid="aff11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>de Bock</surname>
<given-names>G H</given-names>
</name>
<xref ref-type="aff" rid="aff12">12</xref>
<xref ref-type="author-notes" rid="note1">
<sup>13</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nijman</surname>
<given-names>H W</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="author-notes" rid="note1">
<sup>13</sup>
</xref>
<xref ref-type="corresp" rid="caf1">*</xref>
</contrib>
<aff id="aff1">
<label>1</label>
<institution>Department of Gynecology, University of Groningen, University Medical Center Groningen</institution>
, Groningen,
<country>The Netherlands</country>
</aff>
<aff id="aff2">
<label>2</label>
<institution>Department of Radiation Oncology, University of Groningen, University Medical Center Groningen</institution>
, Groningen,
<country>The Netherlands</country>
</aff>
<aff id="aff3">
<label>3</label>
<institution>Department of Pathology, Leiden University Medical Center</institution>
, Leiden,
<country>The Netherlands</country>
</aff>
<aff id="aff4">
<label>4</label>
<institution>Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto</institution>
, Toronto,
<country>Canada</country>
</aff>
<aff id="aff5">
<label>5</label>
<institution>Department of Clinical Oncology, Barts Health NHS trust</institution>
, London,
<country>UK</country>
</aff>
<aff id="aff6">
<label>6</label>
<institution>Department of Medicine, Gynecology Unit, Gustave Roussy</institution>
, Villejuif,
<country>France</country>
</aff>
<aff id="aff7">
<label>7</label>
<institution>Division of Medical Oncology, Peter MacCallum Cancer Center</institution>
, Victoria,
<country>Australia</country>
</aff>
<aff id="aff8">
<label>8</label>
<institution>Department of Gynecology, St Marys Hospital</institution>
, Manchester,
<country>UK</country>
</aff>
<aff id="aff9">
<label>9</label>
<institution>Department of Clinical Oncology, Leiden University Medical Center</institution>
, Leiden,
<country>The Netherlands</country>
</aff>
<aff id="aff10">
<label>10</label>
<institution>Department of Pathology, University of Groningen, University Medical Center Groningen</institution>
, Groningen,
<country>The Netherlands</country>
</aff>
<aff id="aff11">
<label>11</label>
<institution>Department of Medical Microbiology, Molecular Virology Section, University of Groningen, University Medical Center Groningen</institution>
, Groningen,
<country>The Netherlands</country>
</aff>
<aff id="aff12">
<label>12</label>
<institution>Department of Epidemiology, University of Groningen, University Medical Center Groningen</institution>
, Groningen,
<country>The Netherlands</country>
</aff>
</contrib-group>
<author-notes>
<corresp id="caf1">
<label>*</label>
E-mail:
<email>h.w.nijman@umcg.nl</email>
</corresp>
<fn fn-type="present-address" id="note1">
<label>13</label>
<p>These authors contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<day>01</day>
<month>09</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub">
<day>28</day>
<month>07</month>
<year>2015</year>
</pub-date>
<volume>113</volume>
<issue>5</issue>
<fpage>786</fpage>
<lpage>793</lpage>
<history>
<date date-type="received">
<day>02</day>
<month>02</month>
<year>2015</year>
</date>
<date date-type="rev-recd">
<day>04</day>
<month>06</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>29</day>
<month>06</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2015 Cancer Research UK</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>Cancer Research UK</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/4.0/">
<license-p>From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-sa/4.0/">http://creativecommons.org/licenses/by-nc-sa/4.0/</ext-link>
</license-p>
</license>
</permissions>
<abstract>
<sec>
<title>Background:</title>
<p>Adjuvant therapy increases disease-free survival in endometrial cancer (EC), but has no impact on overall survival and negatively influences the quality of life. We investigated the discriminatory power of classical and immunological predictors of recurrence in a cohort of EC patients and confirmed the findings in an independent validation cohort.</p>
</sec>
<sec>
<title>Methods:</title>
<p>We reanalysed the data from 355 EC patients and tested our findings in an independent validation cohort of 72 patients with EC. Predictors were selected and Harrell's C-index for concordance was used to determine discriminatory power for disease-free survival in the total group and stratified for histological subtype.</p>
</sec>
<sec>
<title>Results:</title>
<p>Predictors for recurrence were FIGO stage, lymphovascular space invasion and numbers of cytotoxic and memory T-cells. For high risk cancer, cytotoxic or memory T-cells predicted recurrence as well as a combination of FIGO stage and lymphovascular space invasion (C-index 0.67 and 0.71
<italic>vs</italic>
0.70). Recurrence was best predicted when FIGO stage, lymphovascular space invasion and numbers of cytotoxic cells were used in combination (C-index 0.82). Findings were confirmed in the validation cohort.</p>
</sec>
<sec>
<title>Conclusions:</title>
<p>In high-risk EC, clinicopathological or immunological variables can predict regional or distant recurrence with equal accuracy, but the use of these variables in combination is more powerful.</p>
</sec>
</abstract>
<kwd-group>
<kwd>endometrial cancer</kwd>
<kwd>prediction model</kwd>
<kwd>tumour-infiltrating lymphocytes</kwd>
<kwd>immune system</kwd>
<kwd>patient selection</kwd>
<kwd>adjuvant treatment</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group>
<fig id="fig1">
<label>Figure 1</label>
<caption>
<p>
<bold>Examples of immunohistochemical staining for CD8 in high-risk EC (A) tumour with low number of CTLs.</bold>
(
<bold>B</bold>
) Tumour with high numbers of CTLs.</p>
</caption>
<graphic xlink:href="bjc2015268f1"></graphic>
</fig>
<fig id="fig2">
<label>Figure 2</label>
<caption>
<p>
<bold>Kaplan–Meier curve showing DFS for tumour-infiltrating CTLs below and above the median for 72 patients in the validation cohort.</bold>
</p>
</caption>
<graphic xlink:href="bjc2015268f2"></graphic>
</fig>
<fig id="fig3">
<label>Figure 3</label>
<caption>
<p>
<bold>Number of tumour-infiltrating CTLs for patients with and without recurrence for 72 patients in the validation cohort.</bold>
</p>
</caption>
<graphic xlink:href="bjc2015268f3"></graphic>
</fig>
<table-wrap id="tbl1">
<label>Table 1</label>
<caption>
<title>Baseline characteristics of the initial study cohort stratified by low- and high-risk EC, and the high-risk validation cohort</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th colspan="2" align="center" valign="top" charoff="50">
<bold>Low risk (</bold>
<italic>
<bold>n</bold>
</italic>
<bold>=250)</bold>
<hr></hr>
</th>
<th colspan="2" align="center" valign="top" charoff="50">
<bold>High risk (</bold>
<italic>
<bold>n</bold>
</italic>
<bold>=105)</bold>
<hr></hr>
</th>
<th align="center" valign="top" charoff="50"> </th>
<th colspan="2" align="center" valign="top" charoff="50">
<bold>Validation cohort (</bold>
<italic>
<bold>n</bold>
</italic>
<bold>=72)</bold>
<hr></hr>
</th>
</tr>
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">
<bold>Number</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>% or Inter-quartile range (IQ)</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>Number</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>% or Inter-quartile range (IQ)</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>Difference between low and high risk</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>Number</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>% or Inter-quartile range (IQ)</bold>
</th>
</tr>
<tr>
<th align="left" valign="top" charoff="50">
<bold>Median age</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>64</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>IQ: 56–73</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>65</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>IQ: 56–73</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>chi</bold>
<sup>
<bold>2</bold>
</sup>
<bold>; df;</bold>
<italic>
<bold>P-value</bold>
</italic>
</th>
<th align="center" valign="top" charoff="50">
<bold>69</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>IQ: 61–76</bold>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td colspan="8" align="left" valign="top" charoff="50">
<bold>Treatment</bold>
<hr></hr>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Surgery</td>
<td align="center" valign="top" charoff="50">250</td>
<td align="center" valign="top" charoff="50">100.0</td>
<td align="center" valign="top" charoff="50">105</td>
<td align="center" valign="top" charoff="50">100.0</td>
<td align="center" valign="top" charoff="50">—</td>
<td align="center" valign="top" charoff="50">72</td>
<td align="center" valign="top" charoff="50">100.0</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Adjuvant radiotherapy</td>
<td align="center" valign="top" charoff="50">127</td>
<td align="center" valign="top" charoff="50">50.8</td>
<td align="center" valign="top" charoff="50">80</td>
<td align="center" valign="top" charoff="50">76.2</td>
<td align="center" valign="top" charoff="50">19.6; 1; <0.001</td>
<td align="center" valign="top" charoff="50">42</td>
<td align="center" valign="top" charoff="50">56.8</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Chemotherapy</td>
<td align="center" valign="top" charoff="50">5</td>
<td align="center" valign="top" charoff="50">2.0</td>
<td align="center" valign="top" charoff="50">4</td>
<td align="center" valign="top" charoff="50">3.8</td>
<td align="center" valign="top" charoff="50">1.0; 1; =0.332</td>
<td align="center" valign="top" charoff="50">13</td>
<td align="center" valign="top" charoff="50">17.6</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>FIGO</bold>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">53.0; 3; <0.001</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Stage 1</td>
<td align="center" valign="top" charoff="50">164</td>
<td align="center" valign="top" charoff="50">65.6</td>
<td align="center" valign="top" charoff="50">32</td>
<td align="center" valign="top" charoff="50">30.5</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">35</td>
<td align="center" valign="top" charoff="50">49.3</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Stage 2</td>
<td align="center" valign="top" charoff="50">40</td>
<td align="center" valign="top" charoff="50">16.0</td>
<td align="center" valign="top" charoff="50">18</td>
<td align="center" valign="top" charoff="50">17.1</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">9</td>
<td align="center" valign="top" charoff="50">12.6</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Stage 3</td>
<td align="center" valign="top" charoff="50">40</td>
<td align="center" valign="top" charoff="50">16.0</td>
<td align="center" valign="top" charoff="50">37</td>
<td align="center" valign="top" charoff="50">35.2</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">23</td>
<td align="center" valign="top" charoff="50">0.32</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Stage 4</td>
<td align="center" valign="top" charoff="50">6</td>
<td align="center" valign="top" charoff="50">2.4</td>
<td align="center" valign="top" charoff="50">18</td>
<td align="center" valign="top" charoff="50">17.1</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">4</td>
<td align="center" valign="top" charoff="50">0.1</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Missing</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">
<italic>1</italic>
</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>Invasion myometrium</bold>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">22.2; 1; <0.001</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">163</td>
<td align="center" valign="top" charoff="50">65.2</td>
<td align="center" valign="top" charoff="50">40</td>
<td align="center" valign="top" charoff="50">38.1</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">13</td>
<td align="center" valign="top" charoff="50">19.7</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> >half</td>
<td align="center" valign="top" charoff="50">87</td>
<td align="center" valign="top" charoff="50">34.8</td>
<td align="center" valign="top" charoff="50">65</td>
<td align="center" valign="top" charoff="50">61.9</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">53</td>
<td align="center" valign="top" charoff="50">80.3</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Missing</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">
<italic>6</italic>
</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>Lymph nodes (any)</bold>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">4.9; 1;
<bold>=0.027</bold>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Negative</td>
<td align="center" valign="top" charoff="50">67</td>
<td align="center" valign="top" charoff="50">79.8</td>
<td align="center" valign="top" charoff="50">46</td>
<td align="center" valign="top" charoff="50">63.9</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t1-fn2">a</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t1-fn2">a</xref>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Positive</td>
<td align="center" valign="top" charoff="50">17</td>
<td align="center" valign="top" charoff="50">20.2</td>
<td align="center" valign="top" charoff="50">26</td>
<td align="center" valign="top" charoff="50">36.1</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">9</td>
<td align="center" valign="top" charoff="50">12.7</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Not assessed</td>
<td align="center" valign="top" charoff="50">166</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">33</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>Lymphovascular invasion</bold>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">42.3; 1;
<italic><</italic>
0.001</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> No</td>
<td align="center" valign="top" charoff="50">194</td>
<td align="center" valign="top" charoff="50">81.9</td>
<td align="center" valign="top" charoff="50">48</td>
<td align="center" valign="top" charoff="50">47.1</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">23</td>
<td align="center" valign="top" charoff="50">46.0</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Yes</td>
<td align="center" valign="top" charoff="50">43</td>
<td align="center" valign="top" charoff="50">18.1</td>
<td align="center" valign="top" charoff="50">54</td>
<td align="center" valign="top" charoff="50">52.9</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">27</td>
<td align="center" valign="top" charoff="50">54.0</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Missing</td>
<td align="center" valign="top" charoff="50">13</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">3</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">22</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>Differentiation grade</bold>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">350.2; 3;
<italic><</italic>
0.001</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Grade 1</td>
<td align="center" valign="top" charoff="50">159</td>
<td align="center" valign="top" charoff="50">63.6</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">3</td>
<td align="center" valign="top" charoff="50">6.7</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Grade 2</td>
<td align="center" valign="top" charoff="50">91</td>
<td align="center" valign="top" charoff="50">36.4</td>
<td align="center" valign="top" charoff="50">1</td>
<td align="center" valign="top" charoff="50">1.0</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">5</td>
<td align="center" valign="top" charoff="50">11.1</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Grade 3</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">98</td>
<td align="center" valign="top" charoff="50">93.3</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">37</td>
<td align="center" valign="top" charoff="50">82.2</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Undifferentiated</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">6</td>
<td align="center" valign="top" charoff="50">5.7</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Missing</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">27</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>Tumour type</bold>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">136.4; 3;
<bold>
<italic><</italic>
0.001</bold>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Endometrioid</td>
<td align="center" valign="top" charoff="50">250</td>
<td align="center" valign="top" charoff="50">100.0</td>
<td align="center" valign="top" charoff="50">56</td>
<td align="center" valign="top" charoff="50">53.4</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">45</td>
<td align="center" valign="top" charoff="50">68.1</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Serous papillary</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">18</td>
<td align="center" valign="top" charoff="50">17.1</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">9</td>
<td align="center" valign="top" charoff="50">13.6</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Clear cell</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">25</td>
<td align="center" valign="top" charoff="50">23.8</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">18</td>
<td align="center" valign="top" charoff="50">27.3</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Undifferentiated</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">6</td>
<td align="center" valign="top" charoff="50">5.7</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">6</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>HLA class 1</bold>
<xref ref-type="fn" rid="t1-fn3">b</xref>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">1.6; 1; =0.212</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Normal expression</td>
<td align="center" valign="top" charoff="50">110</td>
<td align="center" valign="top" charoff="50">57.9</td>
<td align="center" valign="top" charoff="50">44</td>
<td align="center" valign="top" charoff="50">50.0</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">—</td>
<td align="center" valign="top" charoff="50">—</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Loss of expression</td>
<td align="center" valign="top" charoff="50">85</td>
<td align="center" valign="top" charoff="50">42.1</td>
<td align="center" valign="top" charoff="50">44</td>
<td align="center" valign="top" charoff="50">50.0</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">—</td>
<td align="center" valign="top" charoff="50">—</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Missing</td>
<td align="center" valign="top" charoff="50">48</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">17</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>Memory T cells</bold>
<xref ref-type="fn" rid="t1-fn3">b</xref>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">3.7; 1; =0.056</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> None</td>
<td align="center" valign="top" charoff="50">69</td>
<td align="center" valign="top" charoff="50">37.7</td>
<td align="center" valign="top" charoff="50">41</td>
<td align="center" valign="top" charoff="50">45.9</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">38</td>
<td align="center" valign="top" charoff="50">61.3</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Present</td>
<td align="center" valign="top" charoff="50">130</td>
<td align="center" valign="top" charoff="50">62.3</td>
<td align="center" valign="top" charoff="50">47</td>
<td align="center" valign="top" charoff="50">54.1</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">24</td>
<td align="center" valign="top" charoff="50">38.7</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Missing</td>
<td align="center" valign="top" charoff="50">51</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">17</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">12</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>CTLs</bold>
<xref ref-type="fn" rid="t1-fn3">b</xref>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">0.6; 1; =0.423</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Below median</td>
<td align="center" valign="top" charoff="50">100</td>
<td align="center" valign="top" charoff="50">48.0</td>
<td align="center" valign="top" charoff="50">48</td>
<td align="center" valign="top" charoff="50">50.7</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">38</td>
<td align="center" valign="top" charoff="50">63.3</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Above median</td>
<td align="center" valign="top" charoff="50">112</td>
<td align="center" valign="top" charoff="50">52.0</td>
<td align="center" valign="top" charoff="50">44</td>
<td align="center" valign="top" charoff="50">49.3</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">22</td>
<td align="center" valign="top" charoff="50">39.7</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Missing</td>
<td align="center" valign="top" charoff="50">38</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">13</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">12</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>Ratio cytotoxic/regulatory T cells</bold>
<xref ref-type="fn" rid="t1-fn3">b</xref>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">10,0; 1; =0.002</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">88</td>
<td align="center" valign="top" charoff="50">44.2</td>
<td align="center" valign="top" charoff="50">58</td>
<td align="center" valign="top" charoff="50">61.5</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">—</td>
<td align="center" valign="top" charoff="50">—</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> >median</td>
<td align="center" valign="top" charoff="50">113</td>
<td align="center" valign="top" charoff="50">55.8</td>
<td align="center" valign="top" charoff="50">33</td>
<td align="center" valign="top" charoff="50">38.5</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">—</td>
<td align="center" valign="top" charoff="50">—</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Missing</td>
<td align="center" valign="top" charoff="50">49</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">14</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t1-fn1">
<p>Abreviations: CTLs=cytotoxic T cells; EC=endometrial cancer; HLA=human leukocyte antigen. Percentages exclude missing values.</p>
</fn>
<fn id="t1-fn2">
<label>a</label>
<p>Data on the number of lymph node dissections performed in the validation cohort was unknown.</p>
</fn>
<fn id="t1-fn3">
<label>b</label>
<p>Values before imputation. Relative efficiency of imputation was between 0.97 and 1.00.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tbl2">
<label>Table 2</label>
<caption>
<title>Disease outcome in 355 patients with EC stratified by low- and high-risk EC, and the high-risk validation cohort</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th colspan="2" align="center" valign="top" charoff="50">
<bold>Low risk (</bold>
<italic>
<bold>n</bold>
</italic>
<bold>=250)</bold>
<hr></hr>
</th>
<th colspan="2" align="center" valign="top" charoff="50">
<bold>High risk (</bold>
<italic>
<bold>n</bold>
</italic>
<bold>=105)</bold>
<hr></hr>
</th>
<th align="center" valign="top" charoff="50">
<bold>Difference between low and high risk</bold>
</th>
<th colspan="2" align="center" valign="top" charoff="50">
<bold>Validation cohort (</bold>
<italic>
<bold>n</bold>
</italic>
<bold>=74)</bold>
<hr></hr>
</th>
</tr>
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">
<bold>Number</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>%</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>Number</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>%</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>chi</bold>
<sup>
<bold>2</bold>
</sup>
<bold>; df;</bold>
<italic>
<bold>P-value</bold>
</italic>
</th>
<th align="center" valign="top" charoff="50">
<bold>Number</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>%</bold>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">
<bold>Recurrent disease</bold>
</td>
<td align="center" valign="top" charoff="50">52</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">34</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">5.4; 1; =0.02</td>
<td align="center" valign="top" charoff="50">37</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Local</td>
<td align="center" valign="top" charoff="50">21</td>
<td align="center" valign="top" charoff="50">40.4</td>
<td align="center" valign="top" charoff="50">9</td>
<td align="center" valign="top" charoff="50">26.5</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Regional</td>
<td align="center" valign="top" charoff="50">6</td>
<td align="center" valign="top" charoff="50">11.5</td>
<td align="center" valign="top" charoff="50">5</td>
<td align="center" valign="top" charoff="50">14.7</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">9</td>
<td align="center" valign="top" charoff="50">24.3</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Distant</td>
<td align="center" valign="top" charoff="50">25</td>
<td align="center" valign="top" charoff="50">48.1</td>
<td align="center" valign="top" charoff="50">20</td>
<td align="center" valign="top" charoff="50">58.8</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">24</td>
<td align="center" valign="top" charoff="50">64.9</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Missing</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">4</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>Death</bold>
</td>
<td align="center" valign="top" charoff="50">62</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">46</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">18,0; 2;
<italic><</italic>
0.001</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Death of disease</td>
<td align="center" valign="top" charoff="50">29</td>
<td align="center" valign="top" charoff="50">46.8</td>
<td align="center" valign="top" charoff="50">31</td>
<td align="center" valign="top" charoff="50">67.4</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">22</td>
<td align="center" valign="top" charoff="50">78.9</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Death of other disease</td>
<td align="center" valign="top" charoff="50">33</td>
<td align="center" valign="top" charoff="50">53.2</td>
<td align="center" valign="top" charoff="50">15</td>
<td align="center" valign="top" charoff="50">32.6</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">6</td>
<td align="center" valign="top" charoff="50">21.4</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Missing</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">3</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>Total</bold>
</td>
<td align="center" valign="top" charoff="50">62</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">46</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">31</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t2-fn1">
<p>Abbreviation: EC=endometrial cancer. Percentages exclude missing values.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tbl3">
<label>Table 3</label>
<caption>
<title>Hazard ratios and discriminatory power (C-index) for disease-free survival in the original cohort (
<italic>n</italic>
=355)</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">
<bold>HR (95% CI)</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>C-index</bold>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">FIGO, LVSI</td>
<td align="center" valign="top" charoff="50">4.5 (3.3–6.3), 4.4 (3.4–5–8)</td>
<td align="center" valign="top" charoff="50">0.81</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">CTLs</td>
<td align="center" valign="top" charoff="50">0.35 (0.27–0.46)</td>
<td align="center" valign="top" charoff="50">0.60</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Memory T-cells</td>
<td align="center" valign="top" charoff="50">0.44 (0.34–0.57)</td>
<td align="center" valign="top" charoff="50">0.61</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">FIGO, LVSI, CTLs</td>
<td align="center" valign="top" charoff="50">4.1 (3.0–5.8), 4.5 (3.4–5.9), 0.41 (0.32–0.53)</td>
<td align="center" valign="top" charoff="50">0.83</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">FIGO, LVSI, memory T cells</td>
<td align="center" valign="top" charoff="50">4.2 (3.0–5.8), 4.9 (3.7–6.4), 0.39 (0.30–0.50)</td>
<td align="center" valign="top" charoff="50">0.83</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t3-fn1">
<p>Abbreviations: CI=confidence interval; CTLs=cytotoxic T cells; HR=hazard ratio; FIGO=FIGO disease classification 1988, LVSI=lymphovascular invasion.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tbl4">
<label>Table 4</label>
<caption>
<title>Hazard ratios and discriminatory power (C-index) for disease-free survival, stratified by low- and high-risk EC</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th colspan="2" align="center" valign="top" charoff="50">
<bold>Low risk (</bold>
<italic>
<bold>n</bold>
</italic>
<bold>=250)</bold>
<hr></hr>
</th>
<th colspan="2" align="center" valign="top" charoff="50">
<bold>High risk (</bold>
<italic>
<bold>n</bold>
</italic>
<bold>=105)</bold>
<hr></hr>
</th>
</tr>
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">
<bold>HR (95% CI)</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>C-index</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>HR (95% CI)</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>C-index</bold>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">FIGO, LVSI</td>
<td align="center" valign="top" charoff="50">5.1 (3.5–7.6), 8.0 (5.6–11.3)</td>
<td align="center" valign="top" charoff="50">0.85</td>
<td align="center" valign="top" charoff="50">3.8 (2.0–7.0), 2.0 (1.3–3.0)</td>
<td align="center" valign="top" charoff="50">0.70</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">CTLs</td>
<td align="center" valign="top" charoff="50">0.61 (0.43–0.86)</td>
<td align="center" valign="top" charoff="50">0.52</td>
<td align="center" valign="top" charoff="50">0.23 (0.15–0.37)</td>
<td align="center" valign="top" charoff="50">0.67</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Memory T cells</td>
<td align="center" valign="top" charoff="50">0.90 (0.85–0.96)</td>
<td align="center" valign="top" charoff="50">0.59</td>
<td align="center" valign="top" charoff="50">0.75 (0.66–0.84)</td>
<td align="center" valign="top" charoff="50">0.71</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">FIGO, LVSI, CTLs</td>
<td align="center" valign="top" charoff="50">5.1 (3.4–7.5), 8.1 (5.7–11.5), 1.2 (0.79–1.7)</td>
<td align="center" valign="top" charoff="50">0.86</td>
<td align="center" valign="top" charoff="50">3.2 (1.7–5.9), 2.0 (1.3–3.1), 0.29 (0.19–0.45)</td>
<td align="center" valign="top" charoff="50">0.79</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">FIGO, LVSI, memory T cells</td>
<td align="center" valign="top" charoff="50">4.4 (2.9–6.7), 7.5 (5.1–11.1), 1.2 (0.86–1.7)</td>
<td align="center" valign="top" charoff="50">0.87</td>
<td align="center" valign="top" charoff="50">1.7 (0.9–3.3), 2.9 (1.8–4.6), 0.73 (0.64–0.83)</td>
<td align="center" valign="top" charoff="50">0.76</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t4-fn1">
<p>Abbreviations: CI=confidence interval; CTLs=cytotoxic T cells; HR=hazard ratio; FIGO=FIGO disease classification 1988, LVSI=lymphovascular invasion.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tbl5">
<label>Table 5</label>
<caption>
<title>Hazard ratios and predictive value (C-index) for disease-free survival in the high-risk validation cohort (
<italic>n</italic>
=72)</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">
<bold>HR (95% CI)</bold>
</th>
<th align="center" valign="top" charoff="50">
<bold>C-index</bold>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">FIGO, LVSI</td>
<td align="center" valign="top" charoff="50">3.02 (2.23–4.01); 1.00 (1.00–1.00)</td>
<td align="center" valign="top" charoff="50">0.71</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">CTLs</td>
<td align="center" valign="top" charoff="50">0.16 (0.11–0.24)</td>
<td align="center" valign="top" charoff="50">0.71</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Memory T cells</td>
<td align="center" valign="top" charoff="50">0.42 (0.30–0.59)</td>
<td align="center" valign="top" charoff="50">0.61</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">FIGO, LVSI, CTLs</td>
<td align="center" valign="top" charoff="50">2.51 (1.83–3.45); 1.00 (1.00–1.00); 0.17 (0.12–0.25)</td>
<td align="center" valign="top" charoff="50">0.79</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">FIGO, LVSI, memory T cell</td>
<td align="center" valign="top" charoff="50">2.96 (2.17–4.05); 1.00 (1.00–1.00); 0.42 (0.29–0.60)</td>
<td align="center" valign="top" charoff="50">0.74</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t5-fn1">
<p>Abbreviations: CI=confidence interval; CTLs=cytotoxic T cells; HR=hazard ratio; FIGO=FIGO disease classification 1988, LVSI=lymphovascular invasion.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
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