Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Commentary
Identifieur interne : 00AB28 ( Main/Exploration ); précédent : 00AB27; suivant : 00AB29Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Commentary
Auteurs : Jaap Verweij [Pays-Bas] ; Paolo G. Casali [Italie] ; John Zalcberg [Australie] ; Axel Lecesne [France] ; Peter Reichardt [Allemagne] ; Jean-Yves Blay [France] ; Rolf Issels [Allemagne] ; Allan Van Oosterom [Belgique] ; Pancras C. W. Hogendoorn [Pays-Bas] ; Martine Van Glabbeke [Belgique] ; Rossella Bertulli [Italie] ; Ian Judson [Royaume-Uni] ; Yoichi Kitamura [Japon] ; Kazuhiko Hayashi [Japon]Source :
- Lancet : (British edition) [ 0140-6736 ] ; 2004.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Médecine.
English descriptors
- KwdEn :
Abstract
Background Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST. Methods 946 patients were randomly allocated imatinib 400 mg either once or twice a day. Those assigned the once a day regimen who had progression were offered the option of crossover. The primary endpoint was progression-free survival. Analysis was by intention to treat. Findings At median follow-up of 760 days (IQR 644-859), 263 (56%) of 473 patients allocated imatinib once a day had progressed compared with 235 (50%) of 473 who were assigned treatment twice a day (estimated hazard ratio 0.82 [95% CI 0.69-0.98]; p=0.026). Side-effects arose in 465/470 (99%) patients allocated the once daily regimen compared with 468/472 (99%) assigned treatment twice a day. By comparison with the group treated once a day, more dose reductions (77 [16%] vs 282 [60%]) and treatment interruptions (189 [40%] vs 302 [64%]) were recorded in patients allocated the twice daily regimen, but treatment in both arms was fairly well tolerated. 52 (5%) patients achieved a complete response, 442 (47%) a partial response, and 300 (32%) stable disease, with no difference between groups. Median time to best response was 107 days (IQR 58-172). Interpretation If response induction is the only aim of treatment, a daily dose of 400 mg of imatinib is sufficient; however, a dose of 400 mg twice a day achieves significantly longer progression-free survival.
Affiliations:
- Allemagne, Australie, Belgique, France, Italie, Japon, Pays-Bas, Royaume-Uni
- Angleterre, Auvergne-Rhône-Alpes, Bavière, Berlin, District de Haute-Bavière, Grand Londres, Hollande-Méridionale, Lombardie, Rhône-Alpes, Région de Bruxelles-Capitale, Région de Kantō, Victoria (État)
- Berlin, Bruxelles, Leyde, Londres, Lyon, Melbourne, Milan, Munich, Tokyo
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Commentary</title><author><name sortKey="Verweij, Jaap" sort="Verweij, Jaap" uniqKey="Verweij J" first="Jaap" last="Verweij">Jaap Verweij</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medical Oncology, Erasmus University Medical Centre, Groene Hilledijk 301</s1><s2>3075 EA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3075 EA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Casali, Paolo G" sort="Casali, Paolo G" uniqKey="Casali P" first="Paolo G." last="Casali">Paolo G. Casali</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Medical Oncology, Instituto Tumori</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Zalcberg, John" sort="Zalcberg, John" uniqKey="Zalcberg J" first="John" last="Zalcberg">John Zalcberg</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Medical Oncology, Peter MacCallum Cancer Centre</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>3 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Lecesne, Axel" sort="Lecesne, Axel" uniqKey="Lecesne A" first="Axel" last="Lecesne">Axel Lecesne</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medical Oncology, Institute Gustave Roussy</s1><s2>Villejuif</s2><s3>FRA</s3><sZ>4 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Institute Gustave Roussy</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Reichardt, Peter" sort="Reichardt, Peter" uniqKey="Reichardt P" first="Peter" last="Reichardt">Peter Reichardt</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Haematology, Oncology, and Tumorimmunology, HELIOS-Klinikum, Charite Campus Buch</s1><s2>Berlin</s2><s3>DEU</s3><sZ>5 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Blay, Jean Yves" sort="Blay, Jean Yves" uniqKey="Blay J" first="Jean-Yves" last="Blay">Jean-Yves Blay</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Medical Oncology, Centre L Berard INSERM U590 and Hospices Civils de Lyon</s1><s2>Lyon</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Issels, Rolf" sort="Issels, Rolf" uniqKey="Issels R" first="Rolf" last="Issels">Rolf Issels</name><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Department of Medical oncology, Klinikum Grosshadern</s1><s2>Munich</s2><s3>DEU</s3><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>GSF-National Research Centre for Environment and Health</s1><s2>Neuherberg</s2><s3>DEU</s3><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>GSF-National Research Centre for Environment and Health</wicri:noRegion><wicri:noRegion>GSF-National Research Centre for Environment and Health</wicri:noRegion></affiliation></author><author><name sortKey="Van Oosterom, Allan" sort="Van Oosterom, Allan" uniqKey="Van Oosterom A" first="Allan" last="Van Oosterom">Allan Van Oosterom</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Oncology, University Hospital Gasthuisberg</s1><s2>Leuven</s2><s3>BEL</s3><sZ>8 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Hogendoorn, Pancras C W" sort="Hogendoorn, Pancras C W" uniqKey="Hogendoorn P" first="Pancras C. W." last="Hogendoorn">Pancras C. W. Hogendoorn</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Department of Pathology, Leiden University Medical Centre</s1><s2>Leiden</s2><s3>NLD</s3><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Van Glabbeke, Martine" sort="Van Glabbeke, Martine" uniqKey="Van Glabbeke M" first="Martine" last="Van Glabbeke">Martine Van Glabbeke</name><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>EORTC Data Centre</s1><s2>Brussels</s2><s3>BEL</s3><sZ>10 aut.</sZ></inist:fA14><country>Belgique</country><placeName><settlement type="city">Bruxelles</settlement><region nuts="2">Région de Bruxelles-Capitale</region></placeName></affiliation></author><author><name sortKey="Bertulli, Rossella" sort="Bertulli, Rossella" uniqKey="Bertulli R" first="Rossella" last="Bertulli">Rossella Bertulli</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Medical Oncology, Instituto Tumori</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Judson, Ian" sort="Judson, Ian" uniqKey="Judson I" first="Ian" last="Judson">Ian Judson</name><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Department of Medical Oncology, Royal Marsden Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Kitamura, Yoichi" sort="Kitamura, Yoichi" uniqKey="Kitamura Y" first="Yoichi" last="Kitamura">Yoichi Kitamura</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University</s1><s2>Shinjuku, Tokyo 162-8666</s2><s3>JPN</s3><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Hayashi, Kazuhiko" sort="Hayashi, Kazuhiko" uniqKey="Hayashi K" first="Kazuhiko" last="Hayashi">Kazuhiko Hayashi</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University</s1><s2>Shinjuku, Tokyo 162-8666</s2><s3>JPN</s3><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">04-0534774</idno><date when="2004">2004</date><idno type="stanalyst">PASCAL 04-0534774 INIST</idno><idno type="RBID">Pascal:04-0534774</idno><idno type="wicri:Area/PascalFrancis/Corpus">004C70</idno><idno type="wicri:Area/PascalFrancis/Curation">001444</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">004983</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">004983</idno><idno type="wicri:doubleKey">0140-6736:2004:Verweij J:progression:free:survival</idno><idno type="wicri:Area/Main/Merge">00B810</idno><idno type="wicri:Area/Main/Curation">00AB28</idno><idno type="wicri:Area/Main/Exploration">00AB28</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Commentary</title><author><name sortKey="Verweij, Jaap" sort="Verweij, Jaap" uniqKey="Verweij J" first="Jaap" last="Verweij">Jaap Verweij</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Medical Oncology, Erasmus University Medical Centre, Groene Hilledijk 301</s1><s2>3075 EA Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>3075 EA Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Casali, Paolo G" sort="Casali, Paolo G" uniqKey="Casali P" first="Paolo G." last="Casali">Paolo G. Casali</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Medical Oncology, Instituto Tumori</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Zalcberg, John" sort="Zalcberg, John" uniqKey="Zalcberg J" first="John" last="Zalcberg">John Zalcberg</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Medical Oncology, Peter MacCallum Cancer Centre</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>3 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Lecesne, Axel" sort="Lecesne, Axel" uniqKey="Lecesne A" first="Axel" last="Lecesne">Axel Lecesne</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Medical Oncology, Institute Gustave Roussy</s1><s2>Villejuif</s2><s3>FRA</s3><sZ>4 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Institute Gustave Roussy</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Reichardt, Peter" sort="Reichardt, Peter" uniqKey="Reichardt P" first="Peter" last="Reichardt">Peter Reichardt</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Haematology, Oncology, and Tumorimmunology, HELIOS-Klinikum, Charite Campus Buch</s1><s2>Berlin</s2><s3>DEU</s3><sZ>5 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Blay, Jean Yves" sort="Blay, Jean Yves" uniqKey="Blay J" first="Jean-Yves" last="Blay">Jean-Yves Blay</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Medical Oncology, Centre L Berard INSERM U590 and Hospices Civils de Lyon</s1><s2>Lyon</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Issels, Rolf" sort="Issels, Rolf" uniqKey="Issels R" first="Rolf" last="Issels">Rolf Issels</name><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Department of Medical oncology, Klinikum Grosshadern</s1><s2>Munich</s2><s3>DEU</s3><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>GSF-National Research Centre for Environment and Health</s1><s2>Neuherberg</s2><s3>DEU</s3><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>GSF-National Research Centre for Environment and Health</wicri:noRegion><wicri:noRegion>GSF-National Research Centre for Environment and Health</wicri:noRegion></affiliation></author><author><name sortKey="Van Oosterom, Allan" sort="Van Oosterom, Allan" uniqKey="Van Oosterom A" first="Allan" last="Van Oosterom">Allan Van Oosterom</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Oncology, University Hospital Gasthuisberg</s1><s2>Leuven</s2><s3>BEL</s3><sZ>8 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Hogendoorn, Pancras C W" sort="Hogendoorn, Pancras C W" uniqKey="Hogendoorn P" first="Pancras C. W." last="Hogendoorn">Pancras C. W. Hogendoorn</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>Department of Pathology, Leiden University Medical Centre</s1><s2>Leiden</s2><s3>NLD</s3><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Van Glabbeke, Martine" sort="Van Glabbeke, Martine" uniqKey="Van Glabbeke M" first="Martine" last="Van Glabbeke">Martine Van Glabbeke</name><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>EORTC Data Centre</s1><s2>Brussels</s2><s3>BEL</s3><sZ>10 aut.</sZ></inist:fA14><country>Belgique</country><placeName><settlement type="city">Bruxelles</settlement><region nuts="2">Région de Bruxelles-Capitale</region></placeName></affiliation></author><author><name sortKey="Bertulli, Rossella" sort="Bertulli, Rossella" uniqKey="Bertulli R" first="Rossella" last="Bertulli">Rossella Bertulli</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Medical Oncology, Instituto Tumori</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Judson, Ian" sort="Judson, Ian" uniqKey="Judson I" first="Ian" last="Judson">Ian Judson</name><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Department of Medical Oncology, Royal Marsden Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Kitamura, Yoichi" sort="Kitamura, Yoichi" uniqKey="Kitamura Y" first="Yoichi" last="Kitamura">Yoichi Kitamura</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University</s1><s2>Shinjuku, Tokyo 162-8666</s2><s3>JPN</s3><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Hayashi, Kazuhiko" sort="Hayashi, Kazuhiko" uniqKey="Hayashi K" first="Kazuhiko" last="Hayashi">Kazuhiko Hayashi</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University</s1><s2>Shinjuku, Tokyo 162-8666</s2><s3>JPN</s3><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Lancet : (British edition)</title><title level="j" type="abbreviated">Lancet : (Br. ed.)</title><idno type="ISSN">0140-6736</idno><imprint><date when="2004">2004</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Lancet : (British edition)</title><title level="j" type="abbreviated">Lancet : (Br. ed.)</title><idno type="ISSN">0140-6736</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic agent</term><term>Clinical trial</term><term>Critical study</term><term>Enzyme inhibitor</term><term>Evolution</term><term>Free form</term><term>Gastrointestinal tumor</term><term>High dose</term><term>Imatinib</term><term>Medicine</term><term>Prognosis</term><term>Protein-tyrosine kinase</term><term>Stroma</term><term>Survival</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Imatinib</term><term>Pronostic</term><term>Evolution</term><term>Forme libre</term><term>Survie</term><term>Stroma</term><term>Dose forte</term><term>Protein-tyrosine kinase</term><term>Inhibiteur enzyme</term><term>Essai clinique</term><term>Etude critique</term><term>Médecine</term><term>Anticancéreux</term><term>Tumeur gastrointestinal</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Médecine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST. Methods 946 patients were randomly allocated imatinib 400 mg either once or twice a day. Those assigned the once a day regimen who had progression were offered the option of crossover. The primary endpoint was progression-free survival. Analysis was by intention to treat. Findings At median follow-up of 760 days (IQR 644-859), 263 (56%) of 473 patients allocated imatinib once a day had progressed compared with 235 (50%) of 473 who were assigned treatment twice a day (estimated hazard ratio 0.82 [95% CI 0.69-0.98]; p=0.026). Side-effects arose in 465/470 (99%) patients allocated the once daily regimen compared with 468/472 (99%) assigned treatment twice a day. By comparison with the group treated once a day, more dose reductions (77 [16%] vs 282 [60%]) and treatment interruptions (189 [40%] vs 302 [64%]) were recorded in patients allocated the twice daily regimen, but treatment in both arms was fairly well tolerated. 52 (5%) patients achieved a complete response, 442 (47%) a partial response, and 300 (32%) stable disease, with no difference between groups. Median time to best response was 107 days (IQR 58-172). Interpretation If response induction is the only aim of treatment, a daily dose of 400 mg of imatinib is sufficient; however, a dose of 400 mg twice a day achieves significantly longer progression-free survival.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Belgique</li><li>France</li><li>Italie</li><li>Japon</li><li>Pays-Bas</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Auvergne-Rhône-Alpes</li><li>Bavière</li><li>Berlin</li><li>District de Haute-Bavière</li><li>Grand Londres</li><li>Hollande-Méridionale</li><li>Lombardie</li><li>Rhône-Alpes</li><li>Région de Bruxelles-Capitale</li><li>Région de Kantō</li><li>Victoria (État)</li></region><settlement><li>Berlin</li><li>Bruxelles</li><li>Leyde</li><li>Londres</li><li>Lyon</li><li>Melbourne</li><li>Milan</li><li>Munich</li><li>Tokyo</li></settlement></list><tree><country name="Pays-Bas"><noRegion><name sortKey="Verweij, Jaap" sort="Verweij, Jaap" uniqKey="Verweij J" first="Jaap" last="Verweij">Jaap Verweij</name></noRegion><name sortKey="Hogendoorn, Pancras C W" sort="Hogendoorn, Pancras C W" uniqKey="Hogendoorn P" first="Pancras C. W." last="Hogendoorn">Pancras C. W. Hogendoorn</name></country><country name="Italie"><region name="Lombardie"><name sortKey="Casali, Paolo G" sort="Casali, Paolo G" uniqKey="Casali P" first="Paolo G." last="Casali">Paolo G. Casali</name></region><name sortKey="Bertulli, Rossella" sort="Bertulli, Rossella" uniqKey="Bertulli R" first="Rossella" last="Bertulli">Rossella Bertulli</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Zalcberg, John" sort="Zalcberg, John" uniqKey="Zalcberg J" first="John" last="Zalcberg">John Zalcberg</name></region></country><country name="France"><noRegion><name sortKey="Lecesne, Axel" sort="Lecesne, Axel" uniqKey="Lecesne A" first="Axel" last="Lecesne">Axel Lecesne</name></noRegion><name sortKey="Blay, Jean Yves" sort="Blay, Jean Yves" uniqKey="Blay J" first="Jean-Yves" last="Blay">Jean-Yves Blay</name></country><country name="Allemagne"><region name="Berlin"><name sortKey="Reichardt, Peter" sort="Reichardt, Peter" uniqKey="Reichardt P" first="Peter" last="Reichardt">Peter Reichardt</name></region><name sortKey="Issels, Rolf" sort="Issels, Rolf" uniqKey="Issels R" first="Rolf" last="Issels">Rolf Issels</name><name sortKey="Issels, Rolf" sort="Issels, Rolf" uniqKey="Issels R" first="Rolf" last="Issels">Rolf Issels</name></country><country name="Belgique"><noRegion><name sortKey="Van Oosterom, Allan" sort="Van Oosterom, Allan" uniqKey="Van Oosterom A" first="Allan" last="Van Oosterom">Allan Van Oosterom</name></noRegion><name sortKey="Van Glabbeke, Martine" sort="Van Glabbeke, Martine" uniqKey="Van Glabbeke M" first="Martine" last="Van Glabbeke">Martine Van Glabbeke</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Judson, Ian" sort="Judson, Ian" uniqKey="Judson I" first="Ian" last="Judson">Ian Judson</name></region></country><country name="Japon"><region name="Région de Kantō"><name sortKey="Kitamura, Yoichi" sort="Kitamura, Yoichi" uniqKey="Kitamura Y" first="Yoichi" last="Kitamura">Yoichi Kitamura</name></region><name sortKey="Hayashi, Kazuhiko" sort="Hayashi, Kazuhiko" uniqKey="Hayashi K" first="Kazuhiko" last="Hayashi">Kazuhiko Hayashi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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