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Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.

Identifieur interne : 003F67 ( Ncbi/Merge ); précédent : 003F66; suivant : 003F68

Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.

Auteurs : Elizabeth M. Swisher [États-Unis] ; Kevin K. Lin [États-Unis] ; Amit M. Oza [Canada] ; Clare L. Scott [Australie] ; Heidi Giordano [États-Unis] ; James Sun [États-Unis] ; Gottfried E. Konecny [États-Unis] ; Robert L. Coleman [États-Unis] ; Anna V. Tinker [Canada] ; David M. O'Malley [États-Unis] ; Rebecca S. Kristeleit [Royaume-Uni] ; Ling Ma [États-Unis] ; Katherine M. Bell-Mcguinn [États-Unis] ; James D. Brenton [Royaume-Uni] ; Janiel M. Cragun [États-Unis] ; Ana Oaknin [Espagne] ; Isabelle Ray-Coquard [France] ; Maria I. Harrell [États-Unis] ; Elaina Mann [États-Unis] ; Scott H. Kaufmann [États-Unis] ; Anne Floquet [France] ; Alexandra Leary [France] ; Thomas C. Harding [États-Unis] ; Sandra Goble [États-Unis] ; Lara Maloney [États-Unis] ; Jeff Isaacson [États-Unis] ; Andrew R. Allen [États-Unis] ; Lindsey Rolfe [États-Unis] ; Roman Yelensky [États-Unis] ; Mitch Raponi [États-Unis] ; Iain A. Mcneish [Royaume-Uni]

Source :

RBID : pubmed:27908594

Descripteurs français

English descriptors

Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor.

DOI: 10.1016/S1470-2045(16)30559-9
PubMed: 27908594

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pubmed:27908594

Le document en format XML

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<name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
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<region type="state">Massachusetts</region>
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<name sortKey="Konecny, Gottfried E" sort="Konecny, Gottfried E" uniqKey="Konecny G" first="Gottfried E" last="Konecny">Gottfried E. Konecny</name>
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<nlm:affiliation>University of California Los Angeles, Santa Monica, CA, USA.</nlm:affiliation>
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<name sortKey="Coleman, Robert L" sort="Coleman, Robert L" uniqKey="Coleman R" first="Robert L" last="Coleman">Robert L. Coleman</name>
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<name sortKey="Tinker, Anna V" sort="Tinker, Anna V" uniqKey="Tinker A" first="Anna V" last="Tinker">Anna V. Tinker</name>
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<name sortKey="O Malley, David M" sort="O Malley, David M" uniqKey="O Malley D" first="David M" last="O'Malley">David M. O'Malley</name>
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<name sortKey="Kristeleit, Rebecca S" sort="Kristeleit, Rebecca S" uniqKey="Kristeleit R" first="Rebecca S" last="Kristeleit">Rebecca S. Kristeleit</name>
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<name sortKey="Ma, Ling" sort="Ma, Ling" uniqKey="Ma L" first="Ling" last="Ma">Ling Ma</name>
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<name sortKey="Bell Mcguinn, Katherine M" sort="Bell Mcguinn, Katherine M" uniqKey="Bell Mcguinn K" first="Katherine M" last="Bell-Mcguinn">Katherine M. Bell-Mcguinn</name>
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<nlm:affiliation>The University of Arizona Cancer Center, Tucson, AZ, USA.</nlm:affiliation>
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<wicri:regionArea>The University of Arizona Cancer Center, Tucson, AZ</wicri:regionArea>
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<name sortKey="Oaknin, Ana" sort="Oaknin, Ana" uniqKey="Oaknin A" first="Ana" last="Oaknin">Ana Oaknin</name>
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<nlm:affiliation>Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.</nlm:affiliation>
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<settlement type="city">Barcelone</settlement>
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<name sortKey="Ray Coquard, Isabelle" sort="Ray Coquard, Isabelle" uniqKey="Ray Coquard I" first="Isabelle" last="Ray-Coquard">Isabelle Ray-Coquard</name>
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<nlm:affiliation>GINECO, Centre Léon Bérard and University Claude Bernard, Lyon, France.</nlm:affiliation>
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<name sortKey="Harrell, Maria I" sort="Harrell, Maria I" uniqKey="Harrell M" first="Maria I" last="Harrell">Maria I. Harrell</name>
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<nlm:affiliation>University of Washington, Seattle, WA, USA.</nlm:affiliation>
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<wicri:regionArea>University of Washington, Seattle, WA</wicri:regionArea>
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<settlement type="city">Seattle</settlement>
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<name sortKey="Mann, Elaina" sort="Mann, Elaina" uniqKey="Mann E" first="Elaina" last="Mann">Elaina Mann</name>
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<name sortKey="Kaufmann, Scott H" sort="Kaufmann, Scott H" uniqKey="Kaufmann S" first="Scott H" last="Kaufmann">Scott H. Kaufmann</name>
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<nlm:affiliation>Mayo Clinic, Rochester, MN, USA.</nlm:affiliation>
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<region type="state">Minnesota</region>
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<name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name>
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<nlm:affiliation>Institut Bergonié, Bordeaux, France.</nlm:affiliation>
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<wicri:regionArea>Institut Bergonié, Bordeaux</wicri:regionArea>
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<region type="region">Nouvelle-Aquitaine</region>
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<name sortKey="Leary, Alexandra" sort="Leary, Alexandra" uniqKey="Leary A" first="Alexandra" last="Leary">Alexandra Leary</name>
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<nlm:affiliation>Gustave Roussy Cancer Center and INSERM U981, Villejuif, France.</nlm:affiliation>
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<name sortKey="Harding, Thomas C" sort="Harding, Thomas C" uniqKey="Harding T" first="Thomas C" last="Harding">Thomas C. Harding</name>
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<region type="state">Colorado</region>
</placeName>
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<name sortKey="Goble, Sandra" sort="Goble, Sandra" uniqKey="Goble S" first="Sandra" last="Goble">Sandra Goble</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Clovis Oncology, Boulder, CO</wicri:regionArea>
<placeName>
<region type="state">Colorado</region>
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<author>
<name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Clovis Oncology, Boulder, CO</wicri:regionArea>
<placeName>
<region type="state">Colorado</region>
</placeName>
</affiliation>
</author>
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<name sortKey="Isaacson, Jeff" sort="Isaacson, Jeff" uniqKey="Isaacson J" first="Jeff" last="Isaacson">Jeff Isaacson</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Clovis Oncology, Boulder, CO</wicri:regionArea>
<placeName>
<region type="state">Colorado</region>
</placeName>
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<author>
<name sortKey="Allen, Andrew R" sort="Allen, Andrew R" uniqKey="Allen A" first="Andrew R" last="Allen">Andrew R. Allen</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Clovis Oncology, Boulder, CO</wicri:regionArea>
<placeName>
<region type="state">Colorado</region>
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<author>
<name sortKey="Rolfe, Lindsey" sort="Rolfe, Lindsey" uniqKey="Rolfe L" first="Lindsey" last="Rolfe">Lindsey Rolfe</name>
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<wicri:regionArea>Clovis Oncology, Boulder, CO</wicri:regionArea>
<placeName>
<region type="state">Colorado</region>
</placeName>
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<name sortKey="Yelensky, Roman" sort="Yelensky, Roman" uniqKey="Yelensky R" first="Roman" last="Yelensky">Roman Yelensky</name>
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<nlm:affiliation>Foundation Medicine, Cambridge, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Foundation Medicine, Cambridge, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
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<name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Clovis Oncology, Boulder, CO</wicri:regionArea>
<placeName>
<region type="state">Colorado</region>
</placeName>
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<name sortKey="Mcneish, Iain A" sort="Mcneish, Iain A" uniqKey="Mcneish I" first="Iain A" last="Mcneish">Iain A. Mcneish</name>
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<nlm:affiliation>Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.</nlm:affiliation>
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<wicri:regionArea>Institute of Cancer Sciences, University of Glasgow, Glasgow</wicri:regionArea>
<orgName type="university">Université de Glasgow</orgName>
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<settlement type="city">Glasgow</settlement>
<region type="country">Écosse</region>
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<title xml:lang="en">Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.</title>
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<name sortKey="Swisher, Elizabeth M" sort="Swisher, Elizabeth M" uniqKey="Swisher E" first="Elizabeth M" last="Swisher">Elizabeth M. Swisher</name>
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<name sortKey="Lin, Kevin K" sort="Lin, Kevin K" uniqKey="Lin K" first="Kevin K" last="Lin">Kevin K. Lin</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<name sortKey="Oza, Amit M" sort="Oza, Amit M" uniqKey="Oza A" first="Amit M" last="Oza">Amit M. Oza</name>
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<nlm:affiliation>Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Princess Margaret Cancer Centre, University Health Network, Toronto, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L" last="Scott">Clare L. Scott</name>
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<nlm:affiliation>Royal Melbourne Hospital, Melbourne, VIC, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Royal Melbourne Hospital, Melbourne, VIC</wicri:regionArea>
<wicri:noRegion>VIC</wicri:noRegion>
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<name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Clovis Oncology, Boulder, CO</wicri:regionArea>
<placeName>
<region type="state">Colorado</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
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<nlm:affiliation>Foundation Medicine, Cambridge, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Foundation Medicine, Cambridge, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Konecny, Gottfried E" sort="Konecny, Gottfried E" uniqKey="Konecny G" first="Gottfried E" last="Konecny">Gottfried E. Konecny</name>
<affiliation wicri:level="2">
<nlm:affiliation>University of California Los Angeles, Santa Monica, CA, USA.</nlm:affiliation>
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<region type="state">Californie</region>
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<name sortKey="Coleman, Robert L" sort="Coleman, Robert L" uniqKey="Coleman R" first="Robert L" last="Coleman">Robert L. Coleman</name>
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<name sortKey="Tinker, Anna V" sort="Tinker, Anna V" uniqKey="Tinker A" first="Anna V" last="Tinker">Anna V. Tinker</name>
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<name sortKey="Ma, Ling" sort="Ma, Ling" uniqKey="Ma L" first="Ling" last="Ma">Ling Ma</name>
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<name sortKey="Bell Mcguinn, Katherine M" sort="Bell Mcguinn, Katherine M" uniqKey="Bell Mcguinn K" first="Katherine M" last="Bell-Mcguinn">Katherine M. Bell-Mcguinn</name>
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<wicri:regionArea>The University of Arizona Cancer Center, Tucson, AZ</wicri:regionArea>
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<region type="state">Arizona</region>
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<name sortKey="Ray Coquard, Isabelle" sort="Ray Coquard, Isabelle" uniqKey="Ray Coquard I" first="Isabelle" last="Ray-Coquard">Isabelle Ray-Coquard</name>
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<name sortKey="Harrell, Maria I" sort="Harrell, Maria I" uniqKey="Harrell M" first="Maria I" last="Harrell">Maria I. Harrell</name>
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<nlm:affiliation>University of Washington, Seattle, WA, USA.</nlm:affiliation>
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<name sortKey="Mann, Elaina" sort="Mann, Elaina" uniqKey="Mann E" first="Elaina" last="Mann">Elaina Mann</name>
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<region type="state">Colorado</region>
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<name sortKey="Kaufmann, Scott H" sort="Kaufmann, Scott H" uniqKey="Kaufmann S" first="Scott H" last="Kaufmann">Scott H. Kaufmann</name>
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<region type="state">Minnesota</region>
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<name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name>
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<nlm:affiliation>Institut Bergonié, Bordeaux, France.</nlm:affiliation>
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<wicri:regionArea>Institut Bergonié, Bordeaux</wicri:regionArea>
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<region type="region">Nouvelle-Aquitaine</region>
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<name sortKey="Leary, Alexandra" sort="Leary, Alexandra" uniqKey="Leary A" first="Alexandra" last="Leary">Alexandra Leary</name>
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<nlm:affiliation>Gustave Roussy Cancer Center and INSERM U981, Villejuif, France.</nlm:affiliation>
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<name sortKey="Harding, Thomas C" sort="Harding, Thomas C" uniqKey="Harding T" first="Thomas C" last="Harding">Thomas C. Harding</name>
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<name sortKey="Goble, Sandra" sort="Goble, Sandra" uniqKey="Goble S" first="Sandra" last="Goble">Sandra Goble</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
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<name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
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<region type="state">Colorado</region>
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<name sortKey="Isaacson, Jeff" sort="Isaacson, Jeff" uniqKey="Isaacson J" first="Jeff" last="Isaacson">Jeff Isaacson</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
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<region type="state">Colorado</region>
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<name sortKey="Allen, Andrew R" sort="Allen, Andrew R" uniqKey="Allen A" first="Andrew R" last="Allen">Andrew R. Allen</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
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<region type="state">Colorado</region>
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<name sortKey="Rolfe, Lindsey" sort="Rolfe, Lindsey" uniqKey="Rolfe L" first="Lindsey" last="Rolfe">Lindsey Rolfe</name>
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<nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation>
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<wicri:regionArea>Clovis Oncology, Boulder, CO</wicri:regionArea>
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<region type="state">Colorado</region>
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<name sortKey="Yelensky, Roman" sort="Yelensky, Roman" uniqKey="Yelensky R" first="Roman" last="Yelensky">Roman Yelensky</name>
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<nlm:affiliation>Foundation Medicine, Cambridge, MA, USA.</nlm:affiliation>
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<wicri:regionArea>Foundation Medicine, Cambridge, MA</wicri:regionArea>
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<region type="state">Massachusetts</region>
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<name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
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<name sortKey="Mcneish, Iain A" sort="Mcneish, Iain A" uniqKey="Mcneish I" first="Iain A" last="Mcneish">Iain A. Mcneish</name>
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<term>Aged</term>
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<term>BRCA2 Protein (genetics)</term>
<term>Drug Resistance, Neoplasm (drug effects)</term>
<term>Fallopian Tube Neoplasms (drug therapy)</term>
<term>Fallopian Tube Neoplasms (genetics)</term>
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<term>Follow-Up Studies</term>
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<term>Neoplasm Recurrence, Local (genetics)</term>
<term>Neoplasm Recurrence, Local (pathology)</term>
<term>Neoplasm Staging</term>
<term>Neoplasms, Glandular and Epithelial (drug therapy)</term>
<term>Neoplasms, Glandular and Epithelial (genetics)</term>
<term>Neoplasms, Glandular and Epithelial (pathology)</term>
<term>Ovarian Neoplasms (drug therapy)</term>
<term>Ovarian Neoplasms (genetics)</term>
<term>Ovarian Neoplasms (pathology)</term>
<term>Peritoneal Neoplasms (drug therapy)</term>
<term>Peritoneal Neoplasms (genetics)</term>
<term>Peritoneal Neoplasms (pathology)</term>
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<term>Poly(ADP-ribose) Polymerase Inhibitors (therapeutic use)</term>
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<term>Tumeurs de la trompe de Fallope (anatomopathologie)</term>
<term>Tumeurs de la trompe de Fallope (génétique)</term>
<term>Tumeurs de la trompe de Fallope (traitement médicamenteux)</term>
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<term>Antineoplastic Agents</term>
<term>Platinum</term>
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<term>Récidive tumorale locale</term>
<term>Tumeurs de l'ovaire</term>
<term>Tumeurs de la trompe de Fallope</term>
<term>Tumeurs du péritoine</term>
<term>Tumeurs épithéliales épidermoïdes et glandulaires</term>
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<term>Drug Resistance, Neoplasm</term>
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<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>Fallopian Tube Neoplasms</term>
<term>Neoplasm Recurrence, Local</term>
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<term>Fallopian Tube Neoplasms</term>
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<term>Mutation germinale</term>
<term>Protéine BRCA1</term>
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<term>Fallopian Tube Neoplasms</term>
<term>Neoplasm Recurrence, Local</term>
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<term>Peritoneal Neoplasms</term>
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<term>Antinéoplasiques</term>
<term>Platine</term>
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<term>Indoles</term>
<term>Poly(ADP-ribose) Polymerase Inhibitors</term>
</keywords>
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<term>Récidive tumorale locale</term>
<term>Tumeurs de l'ovaire</term>
<term>Tumeurs de la trompe de Fallope</term>
<term>Tumeurs du péritoine</term>
<term>Tumeurs épithéliales épidermoïdes et glandulaires</term>
</keywords>
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<term>Indoles</term>
<term>Inhibiteurs de poly(ADP-ribose) polymérases</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Aged</term>
<term>Female</term>
<term>Follow-Up Studies</term>
<term>Humans</term>
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<term>Salvage Therapy</term>
<term>Survival Rate</term>
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<term>Agences internationales</term>
<term>Femelle</term>
<term>Humains</term>
<term>Poly(ADP-ribose) polymerases</term>
<term>Pronostic</term>
<term>Résistance aux médicaments antinéoplasiques</term>
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<term>Sujet âgé</term>
<term>Taux de survie</term>
<term>Thérapie de rattrapage</term>
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<div type="abstract" xml:lang="en">Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor.</div>
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<Day>02</Day>
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<Month>06</Month>
<Day>13</Day>
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<Year>2017</Year>
<Month>09</Month>
<Day>22</Day>
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<Volume>18</Volume>
<Issue>1</Issue>
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<Year>2017</Year>
<Month>Jan</Month>
</PubDate>
</JournalIssue>
<Title>The Lancet. Oncology</Title>
<ISOAbbreviation>Lancet Oncol.</ISOAbbreviation>
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<ArticleTitle>Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.</ArticleTitle>
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<Abstract>
<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma were classified into one of three predefined homologous recombination deficiency subgroups on the basis of tumour mutational analysis: BRCA mutant (deleterious germline or somatic), BRCA wild-type and LOH high (LOH high group), or BRCA wild-type and LOH low (LOH low group). We prespecified a cutoff of 14% or more genomic LOH for LOH high. Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 28 day cycles until disease progression or any other reason for discontinuation. The primary endpoint was progression-free survival. All patients treated with at least one dose of rucaparib were included in the safety analyses and all treated patients who were classified were included in the primary endpoint analysis. This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing.</AbstractText>
<AbstractText Label="FINDINGS" NlmCategory="RESULTS">256 patients were screened and 206 were enrolled between Oct 30, 2013, and Dec 19, 2014. At the data cutoff date (Jan 18, 2016), 204 patients had received rucaparib, with 28 patients remaining in the study. 192 patients could be classified into one of the three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). Tumours from 12 patients were established as BRCA wild-type, but could not be classified for LOH, because of insufficient neoplastic nuclei in the sample. The median duration of treatment for the 204 patients was 5·7 months (IQR 2·8-10·1). 24 patients in the BRCA mutant subgroup, 56 patients in the LOH high subgroup, and 59 patients in the LOH low subgroup had disease progression or died. Median progression-free survival after rucaparib treatment was 12·8 months (95% CI 9·0-14·7) in the BRCA mutant subgroup, 5·7 months (5·3-7·6) in the LOH high subgroup, and 5·2 months (3·6-5·5) in the LOH low subgroup. Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16-0·44, p<0·0001) and LOH high (0·62, 0·42-0·90, p=0·011) subgroups compared with the LOH low subgroup. The most common grade 3 or worse treatment-emergent adverse events were anaemia or decreased haemoglobin (45 [22%] patients), and elevations in alanine aminotransferase or aspartate aminotransferase (25 [12%]). Common serious adverse events included small intestinal obstruction (10 [5%] of 204 patients), malignant neoplasm progression (10 [5%]), and anaemia (nine [4%]). Three patients died during the study (two because of disease progression and one because of sepsis and disease progression). No treatment-related deaths occurred.</AbstractText>
<AbstractText Label="INTERPRETATION" NlmCategory="CONCLUSIONS">In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. These results extend the potential usefulness of PARP inhibitors in the treatment setting beyond BRCA mutant tumours.</AbstractText>
<AbstractText Label="FUNDING" NlmCategory="BACKGROUND">Clovis Oncology, US Department of Defense Ovarian Cancer Research Program, Stand Up To Cancer-Ovarian Cancer Research Fund Alliance-National Ovarian Cancer Coalition Dream Team Translational Research Grant, and V Foundation Translational Award.</AbstractText>
<CopyrightInformation>Copyright © 2017 Elsevier Ltd. All rights reserved.</CopyrightInformation>
</Abstract>
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<LastName>Swisher</LastName>
<ForeName>Elizabeth M</ForeName>
<Initials>EM</Initials>
<AffiliationInfo>
<Affiliation>University of Washington, Seattle, WA, USA. Electronic address: swishere@uw.edu.</Affiliation>
</AffiliationInfo>
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<LastName>Lin</LastName>
<ForeName>Kevin K</ForeName>
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<Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation>
</AffiliationInfo>
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<LastName>Oza</LastName>
<ForeName>Amit M</ForeName>
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<Affiliation>Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.</Affiliation>
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<ForeName>Clare L</ForeName>
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<Affiliation>Royal Melbourne Hospital, Melbourne, VIC, Australia.</Affiliation>
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<LastName>Giordano</LastName>
<ForeName>Heidi</ForeName>
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<Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation>
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<Affiliation>University of California Los Angeles, Santa Monica, CA, USA.</Affiliation>
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<Affiliation>The University of Texas MD Anderson Cancer Center, Houston, TX, USA.</Affiliation>
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<ForeName>Rebecca S</ForeName>
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<Affiliation>University College London, Cancer Institute, London, UK.</Affiliation>
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<ForeName>Katherine M</ForeName>
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<Affiliation>Memorial Sloan-Kettering Cancer Center, New York, NY, USA.</Affiliation>
</AffiliationInfo>
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<LastName>Brenton</LastName>
<ForeName>James D</ForeName>
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<Affiliation>Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.</Affiliation>
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<ForeName>Janiel M</ForeName>
<Initials>JM</Initials>
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<Affiliation>The University of Arizona Cancer Center, Tucson, AZ, USA.</Affiliation>
</AffiliationInfo>
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<Initials>A</Initials>
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</AffiliationInfo>
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<LastName>Ray-Coquard</LastName>
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<Affiliation>GINECO, Centre Léon Bérard and University Claude Bernard, Lyon, France.</Affiliation>
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<ForeName>Maria I</ForeName>
<Initials>MI</Initials>
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<Affiliation>University of Washington, Seattle, WA, USA.</Affiliation>
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<LastName>Mann</LastName>
<ForeName>Elaina</ForeName>
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<Initials>A</Initials>
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<Affiliation>Gustave Roussy Cancer Center and INSERM U981, Villejuif, France.</Affiliation>
</AffiliationInfo>
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<LastName>Harding</LastName>
<ForeName>Thomas C</ForeName>
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<Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation>
</AffiliationInfo>
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<LastName>Goble</LastName>
<ForeName>Sandra</ForeName>
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<ForeName>Lindsey</ForeName>
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<Affiliation>Foundation Medicine, Cambridge, MA, USA.</Affiliation>
</AffiliationInfo>
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<LastName>Raponi</LastName>
<ForeName>Mitch</ForeName>
<Initials>M</Initials>
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</AffiliationInfo>
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<ForeName>Iain A</ForeName>
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<AccessionNumber>NCT01891344</AccessionNumber>
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<GrantID>G0501974</GrantID>
<Agency>Medical Research Council</Agency>
<Country>United Kingdom</Country>
</Grant>
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<Month>11</Month>
<Day>29</Day>
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<Country>England</Country>
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<ISSNLinking>1470-2045</ISSNLinking>
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<name sortKey="Swisher, Elizabeth M" sort="Swisher, Elizabeth M" uniqKey="Swisher E" first="Elizabeth M" last="Swisher">Elizabeth M. Swisher</name>
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<name sortKey="Allen, Andrew R" sort="Allen, Andrew R" uniqKey="Allen A" first="Andrew R" last="Allen">Andrew R. Allen</name>
<name sortKey="Bell Mcguinn, Katherine M" sort="Bell Mcguinn, Katherine M" uniqKey="Bell Mcguinn K" first="Katherine M" last="Bell-Mcguinn">Katherine M. Bell-Mcguinn</name>
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<name sortKey="Cragun, Janiel M" sort="Cragun, Janiel M" uniqKey="Cragun J" first="Janiel M" last="Cragun">Janiel M. Cragun</name>
<name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name>
<name sortKey="Goble, Sandra" sort="Goble, Sandra" uniqKey="Goble S" first="Sandra" last="Goble">Sandra Goble</name>
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<name sortKey="O Malley, David M" sort="O Malley, David M" uniqKey="O Malley D" first="David M" last="O'Malley">David M. O'Malley</name>
<name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name>
<name sortKey="Rolfe, Lindsey" sort="Rolfe, Lindsey" uniqKey="Rolfe L" first="Lindsey" last="Rolfe">Lindsey Rolfe</name>
<name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name>
<name sortKey="Yelensky, Roman" sort="Yelensky, Roman" uniqKey="Yelensky R" first="Roman" last="Yelensky">Roman Yelensky</name>
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<name sortKey="Oza, Amit M" sort="Oza, Amit M" uniqKey="Oza A" first="Amit M" last="Oza">Amit M. Oza</name>
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<name sortKey="Tinker, Anna V" sort="Tinker, Anna V" uniqKey="Tinker A" first="Anna V" last="Tinker">Anna V. Tinker</name>
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<name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L" last="Scott">Clare L. Scott</name>
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<name sortKey="Kristeleit, Rebecca S" sort="Kristeleit, Rebecca S" uniqKey="Kristeleit R" first="Rebecca S" last="Kristeleit">Rebecca S. Kristeleit</name>
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<name sortKey="Brenton, James D" sort="Brenton, James D" uniqKey="Brenton J" first="James D" last="Brenton">James D. Brenton</name>
<name sortKey="Mcneish, Iain A" sort="Mcneish, Iain A" uniqKey="Mcneish I" first="Iain A" last="Mcneish">Iain A. Mcneish</name>
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<country name="Espagne">
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<name sortKey="Oaknin, Ana" sort="Oaknin, Ana" uniqKey="Oaknin A" first="Ana" last="Oaknin">Ana Oaknin</name>
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<country name="France">
<region name="Auvergne-Rhône-Alpes">
<name sortKey="Ray Coquard, Isabelle" sort="Ray Coquard, Isabelle" uniqKey="Ray Coquard I" first="Isabelle" last="Ray-Coquard">Isabelle Ray-Coquard</name>
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<name sortKey="Leary, Alexandra" sort="Leary, Alexandra" uniqKey="Leary A" first="Alexandra" last="Leary">Alexandra Leary</name>
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