AustralieFrV1, PascalFrancis, Corpus, bibRecord, 001061

Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone

Identifieur interne : 001061 ( PascalFrancis/Corpus ); précédent : 001060; suivant : 001062

Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone

Auteurs : Daniel G. Branstetter ; Scott D. Nelson ; J. Carlos Manivel ; Jean-Yves Blay ; Sant Chawla ; David M. Thomas ; Susie Jun ; Ira Jacobs

Source :

Clinical cancer research [ 1078-0432 ] ; 2012.

RBID : Pascal:12-0354416

Descripteurs français

Pascal (Inist)
- Dénosumab, Tumeur maligne, Ostéogenèse, Homme, Malade, Tumeur osseuse à cellules géantes.

English descriptors

KwdEn :
- Bone giant cell tumor, Denosumab, Human, Malignant tumor, Osteogenesis, Patient.

Abstract

Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

A01	`01`	`1`		`@0 1078-0432`
A02	`01`			`@0 CCREF4`
A03		`1`		`@0 Clin. cancer res.`
A05				`@2 18`
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A08	`01`	`1`	`ENG`	`@1 Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone`
A11	`01`	`1`		`@1 BRANSTETTER (Daniel G.)`
A11	`02`	`1`		`@1 NELSON (Scott D.)`
A11	`03`	`1`		`@1 MANIVEL (J. Carlos)`
A11	`04`	`1`		`@1 BLAY (Jean-Yves)`
A11	`05`	`1`		`@1 CHAWLA (Sant)`
A11	`06`	`1`		`@1 THOMAS (David M.)`
A11	`07`	`1`		`@1 JUN (Susie)`
A11	`08`	`1`		`@1 JACOBS (Ira)`
A14	`01`			`@1 Amgen Inc @2 Seattle, Washington @3 USA @Z 1 aut.`
A14	`02`			`@1 University of California @2 Los Angeles, California @3 USA @Z 2 aut.`
A14	`03`			`@1 University of Minnesota @2 Minneapolis, Minnesota @3 USA @Z 3 aut.`
A14	`04`			`@1 University Claude Bernard Lyon I and Hôpital Edouard Heriot @2 Lyon @3 FRA @Z 4 aut.`
A14	`05`			`@1 Sarcoma Oncology Center, Santa Monica @2 California @3 USA @Z 5 aut.`
A14	`06`			`@1 Peter MacCallum Cancer Centre, East Melbourne @2 Victoria @3 AUS @Z 6 aut.`
A14	`07`			`@1 Amgen Inc., Thousand Oaks @2 California @3 USA @Z 7 aut. @Z 8 aut.`
A20				`@1 4415-4424`
A21				`@1 2012`
A23	`01`			`@0 ENG`
A43	`01`			`@1 INIST @2 26073 @5 354000504079990240`
A44				`@0 0000 @1 © 2012 INIST-CNRS. All rights reserved.`
A45				`@0 50 ref.`
A47	`01`	`1`		`@0 12-0354416`
A60				`@1 P`
A61				`@0 A`
A64	`01`	`1`		`@0 Clinical cancer research`
A66	`01`			`@0 USA`
C01	`01`		`ENG`	@0 Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.
C02	`01`	`X`		`@0 002B02R`
C02	`02`	`X`		`@0 002B15C`
C03	`01`	`X`	`FRE`	`@0 Dénosumab @2 FR @5 01`
C03	`01`	`X`	`ENG`	`@0 Denosumab @2 FR @5 01`
C03	`01`	`X`	`SPA`	`@0 Denosumab @2 FR @5 01`
C03	`02`	`X`	`FRE`	`@0 Tumeur maligne @2 NM @5 02`
C03	`02`	`X`	`ENG`	`@0 Malignant tumor @2 NM @5 02`
C03	`02`	`X`	`SPA`	`@0 Tumor maligno @2 NM @5 02`
C03	`03`	`X`	`FRE`	`@0 Ostéogenèse @5 03`
C03	`03`	`X`	`ENG`	`@0 Osteogenesis @5 03`
C03	`03`	`X`	`SPA`	`@0 Osteogénesis @5 03`
C03	`04`	`X`	`FRE`	`@0 Homme @5 04`
C03	`04`	`X`	`ENG`	`@0 Human @5 04`
C03	`04`	`X`	`SPA`	`@0 Hombre @5 04`
C03	`05`	`X`	`FRE`	`@0 Malade @5 05`
C03	`05`	`X`	`ENG`	`@0 Patient @5 05`
C03	`05`	`X`	`SPA`	`@0 Enfermo @5 05`
C03	`06`	`X`	`FRE`	`@0 Tumeur osseuse à cellules géantes @4 CD @5 96`
C03	`06`	`X`	`ENG`	`@0 Bone giant cell tumor @4 CD @5 96`
C07	`01`	`X`	`FRE`	`@0 Cancer @2 NM`
C07	`01`	`X`	`ENG`	`@0 Cancer @2 NM`
C07	`01`	`X`	`SPA`	`@0 Cáncer @2 NM`
C07	`02`	`X`	`FRE`	`@0 Anticorps monoclonal @5 37`
C07	`02`	`X`	`ENG`	`@0 Monoclonal antibody @5 37`
C07	`02`	`X`	`SPA`	`@0 Anticuerpo monoclonal @5 37`
C07	`03`	`X`	`FRE`	`@0 Pathologie du système ostéoarticulaire @5 38`
C07	`03`	`X`	`ENG`	`@0 Diseases of the osteoarticular system @5 38`
C07	`03`	`X`	`SPA`	`@0 Sistema osteoarticular patología @5 38`
C07	`04`	`X`	`FRE`	`@0 Tumeur bénigne @5 39`
C07	`04`	`X`	`ENG`	`@0 Benign neoplasm @5 39`
C07	`04`	`X`	`SPA`	`@0 Tumor benigno @5 39`
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Format Inist (serveur)

NO :	PASCAL 12-0354416 INIST
ET :	Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone
AU :	BRANSTETTER (Daniel G.); NELSON (Scott D.); MANIVEL (J. Carlos); BLAY (Jean-Yves); CHAWLA (Sant); THOMAS (David M.); JUN (Susie); JACOBS (Ira)
AF :	Amgen Inc/Seattle, Washington/Etats-Unis (1 aut.); University of California/Los Angeles, California/Etats-Unis (2 aut.); University of Minnesota/Minneapolis, Minnesota/Etats-Unis (3 aut.); University Claude Bernard Lyon I and Hôpital Edouard Heriot/Lyon/France (4 aut.); Sarcoma Oncology Center, Santa Monica/California/Etats-Unis (5 aut.); Peter MacCallum Cancer Centre, East Melbourne/Victoria/Australie (6 aut.); Amgen Inc., Thousand Oaks/California/Etats-Unis (7 aut., 8 aut.)
DT :	Publication en série; Niveau analytique
SO :	Clinical cancer research; ISSN 1078-0432; Coden CCREF4; Etats-Unis; Da. 2012; Vol. 18; No. 16; Pp. 4415-4424; Bibl. 50 ref.
LA :	Anglais
EA :	Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.
CC :	002B02R; 002B15C
FD :	Dénosumab; Tumeur maligne; Ostéogenèse; Homme; Malade; Tumeur osseuse à cellules géantes
FG :	Cancer; Anticorps monoclonal; Pathologie du système ostéoarticulaire; Tumeur bénigne
ED :	Denosumab; Malignant tumor; Osteogenesis; Human; Patient; Bone giant cell tumor
EG :	Cancer; Monoclonal antibody; Diseases of the osteoarticular system; Benign neoplasm
SD :	Denosumab; Tumor maligno; Osteogénesis; Hombre; Enfermo
LO :	INIST-26073.354000504079990240
ID :	12-0354416

Links to Exploration step

Pascal:12-0354416

Le document en format XML

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<author><name sortKey="Nelson, Scott D" sort="Nelson, Scott D" uniqKey="Nelson S" first="Scott D." last="Nelson">Scott D. Nelson</name>
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<author><name sortKey="Thomas, David M" sort="Thomas, David M" uniqKey="Thomas D" first="David M." last="Thomas">David M. Thomas</name>
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<front><div type="abstract" xml:lang="en">Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.</div>
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<fA14 i1="04"><s1>University Claude Bernard Lyon I and Hôpital Edouard Heriot</s1>
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<fA14 i1="05"><s1>Sarcoma Oncology Center, Santa Monica</s1>
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<s2>Victoria</s2>
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<fA14 i1="07"><s1>Amgen Inc., Thousand Oaks</s1>
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<fA64 i1="01" i2="1"><s0>Clinical cancer research</s0>
</fA64>
<fA66 i1="01"><s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.</s0>
</fC01>
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</fC02>
<fC02 i1="02" i2="X"><s0>002B15C</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Dénosumab</s0>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Denosumab</s0>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Denosumab</s0>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Tumeur maligne</s0>
<s2>NM</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Malignant tumor</s0>
<s2>NM</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Tumor maligno</s0>
<s2>NM</s2>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Ostéogenèse</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Osteogenesis</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Osteogénesis</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Homme</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Human</s0>
<s5>04</s5>
</fC03>
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<s5>04</s5>
</fC03>
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<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Patient</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Enfermo</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Tumeur osseuse à cellules géantes</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Bone giant cell tumor</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Cancer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Cancer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Cáncer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Anticorps monoclonal</s0>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Monoclonal antibody</s0>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Anticuerpo monoclonal</s0>
<s5>37</s5>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Pathologie du système ostéoarticulaire</s0>
<s5>38</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Diseases of the osteoarticular system</s0>
<s5>38</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Sistema osteoarticular patología</s0>
<s5>38</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Tumeur bénigne</s0>
<s5>39</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Benign neoplasm</s0>
<s5>39</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Tumor benigno</s0>
<s5>39</s5>
</fC07>
<fN21><s1>275</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
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<server><NO>PASCAL 12-0354416 INIST</NO>
<ET>Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone</ET>
<AU>BRANSTETTER (Daniel G.); NELSON (Scott D.); MANIVEL (J. Carlos); BLAY (Jean-Yves); CHAWLA (Sant); THOMAS (David M.); JUN (Susie); JACOBS (Ira)</AU>
<AF>Amgen Inc/Seattle, Washington/Etats-Unis (1 aut.); University of California/Los Angeles, California/Etats-Unis (2 aut.); University of Minnesota/Minneapolis, Minnesota/Etats-Unis (3 aut.); University Claude Bernard Lyon I and Hôpital Edouard Heriot/Lyon/France (4 aut.); Sarcoma Oncology Center, Santa Monica/California/Etats-Unis (5 aut.); Peter MacCallum Cancer Centre, East Melbourne/Victoria/Australie (6 aut.); Amgen Inc., Thousand Oaks/California/Etats-Unis (7 aut., 8 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Clinical cancer research; ISSN 1078-0432; Coden CCREF4; Etats-Unis; Da. 2012; Vol. 18; No. 16; Pp. 4415-4424; Bibl. 50 ref.</SO>
<LA>Anglais</LA>
<EA>Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.</EA>
<CC>002B02R; 002B15C</CC>
<FD>Dénosumab; Tumeur maligne; Ostéogenèse; Homme; Malade; Tumeur osseuse à cellules géantes</FD>
<FG>Cancer; Anticorps monoclonal; Pathologie du système ostéoarticulaire; Tumeur bénigne</FG>
<ED>Denosumab; Malignant tumor; Osteogenesis; Human; Patient; Bone giant cell tumor</ED>
<EG>Cancer; Monoclonal antibody; Diseases of the osteoarticular system; Benign neoplasm</EG>
<SD>Denosumab; Tumor maligno; Osteogénesis; Hombre; Enfermo</SD>
<LO>INIST-26073.354000504079990240</LO>
<ID>12-0354416</ID>
</server>
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Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone

Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone

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