First Clinical Experience with α-Emitting Radium-223 in the Treatment of Skeletal Metastases
Purpose: The main goals were to study the safety and tolerability of the α-emitter radium-223 ( 223 Ra) in breast and prostate cancer patients with skeletal metastases. In addition, pain palliation was evaluated. Experimental Design: Fifteen prostate and 10 breast cancer patients enrolled in a phase...
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| Veröffentlicht in: | Clinical cancer research 2005-06, Vol.11 (12), p.4451-4459 |
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| creator | NILSSON, Sten LARSEN, Roy H FOSSA, Sophie D BALTESKARD, Lise BORCH, Kari W WESTLIN, Jan-Erik SALBERG, Gro BRULAND, Oyvind S |
| description | Purpose: The main goals were to study the safety and tolerability of the α-emitter radium-223 ( 223 Ra) in breast and prostate cancer patients with skeletal metastases. In addition, pain palliation was evaluated.
Experimental Design: Fifteen prostate and 10 breast cancer patients enrolled in a phase I trial received a single i.v. injection of 223 Ra. Five patients were included at each of the dosages: 46, 93, 163, 213, or 250 kBq/kg and followed for 8 weeks. Palliative
response was evaluated according to the pain scale of the European Organization for Research and Treatment of Cancer QLQ C30
questionnaire at baseline and at 1, 4, and 8 weeks after injection.
Results: Weekly blood sampling during follow-up revealed mild and reversible myelosuppression with nadir 2 to 4 weeks after the injection.
Importantly, for thrombocytes only grade 1 toxicity was reported. Grade 3 neutropenia and leucopenia occurred in two and three
patients, respectively. Mild, transient diarrhea was observed in 10 of the 25 patients. Nausea and vomiting was more frequently
observed in the highest dosage group. Serum alkaline phosphatase decreased with nadir averages of 29.5% in females and 52.1%
in males. Pain relief was reported by 52%, 60%, and 56% of the patients after 7 days, 4, and 8 weeks, respectively. 223 Ra cleared rapidly from blood and was below 1% of initial level at 24 hours. Gamma camera images indicated, in accordance
with pretreatment 99m Tc-MDP scans, accumulation of 223 Ra in skeletal lesions. Elimination was mainly intestinal. Median survival exceeded 20 months.
Conclusions: 223 Ra was well tolerated at therapeutically relevant dosages. Phase II studies have therefore been initiated. |
| doi_str_mv | 10.1158/1078-0432.CCR-04-2244 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_580334</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>15958630</sourcerecordid><originalsourceid>FETCH-LOGICAL-c409t-5c4ecd467b3951c60646df85c9cb14b3dd4097e85cb23fbadd534d8a0855293c3</originalsourceid><addsrcrecordid>eNpFkMtKxDAUhoMo3h9BycaFi2rSJJ12KWW8gCJ4WUpIk1MbnXaGJMPoY_kiPpNnmFEhJD_h-0_CR8gRZ2ecq_Kcs1GZMSnys7p-wJDluZQbZJcrNcpEXqhNzL_MDtmL8Y0xLjmT22SHq0qVhWC75OXSh5hoPfGDt2ZCxx8zCB4GC3ThU0e_v7Jx71Pywyt9MM7Pe3xIUD_Q1AF9CmBSD0Oi05Y-vsMEEs64wz3ignhAtloziXC4PvfJ8-X4qb7Obu-vbuqL28xKVqVMWQnWyWLUiEpxW7BCFq4tla1sw2UjnENsBHjR5KJtjHNKSFcaViqVV8KKfZKt5sYFzOaNngXfm_Cpp8br9dU7JtCqZEJI5NWKt2EaY4D2r8GZXurVS3V6qU6jXgx6qRd7x6seTuzB_bfWPhE4WQMmos42mMH6-M8VpSokF8idrrjOv3YLH0BbJCEEiGCC7fATmudaSsXFDwXuki0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>First Clinical Experience with α-Emitting Radium-223 in the Treatment of Skeletal Metastases</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>NILSSON, Sten ; LARSEN, Roy H ; FOSSA, Sophie D ; BALTESKARD, Lise ; BORCH, Kari W ; WESTLIN, Jan-Erik ; SALBERG, Gro ; BRULAND, Oyvind S</creator><creatorcontrib>NILSSON, Sten ; LARSEN, Roy H ; FOSSA, Sophie D ; BALTESKARD, Lise ; BORCH, Kari W ; WESTLIN, Jan-Erik ; SALBERG, Gro ; BRULAND, Oyvind S</creatorcontrib><description>Purpose: The main goals were to study the safety and tolerability of the α-emitter radium-223 ( 223 Ra) in breast and prostate cancer patients with skeletal metastases. In addition, pain palliation was evaluated.
Experimental Design: Fifteen prostate and 10 breast cancer patients enrolled in a phase I trial received a single i.v. injection of 223 Ra. Five patients were included at each of the dosages: 46, 93, 163, 213, or 250 kBq/kg and followed for 8 weeks. Palliative
response was evaluated according to the pain scale of the European Organization for Research and Treatment of Cancer QLQ C30
questionnaire at baseline and at 1, 4, and 8 weeks after injection.
Results: Weekly blood sampling during follow-up revealed mild and reversible myelosuppression with nadir 2 to 4 weeks after the injection.
Importantly, for thrombocytes only grade 1 toxicity was reported. Grade 3 neutropenia and leucopenia occurred in two and three
patients, respectively. Mild, transient diarrhea was observed in 10 of the 25 patients. Nausea and vomiting was more frequently
observed in the highest dosage group. Serum alkaline phosphatase decreased with nadir averages of 29.5% in females and 52.1%
in males. Pain relief was reported by 52%, 60%, and 56% of the patients after 7 days, 4, and 8 weeks, respectively. 223 Ra cleared rapidly from blood and was below 1% of initial level at 24 hours. Gamma camera images indicated, in accordance
with pretreatment 99m Tc-MDP scans, accumulation of 223 Ra in skeletal lesions. Elimination was mainly intestinal. Median survival exceeded 20 months.
Conclusions: 223 Ra was well tolerated at therapeutically relevant dosages. Phase II studies have therefore been initiated.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-04-2244</identifier><identifier>PMID: 15958630</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Alkaline Phosphatase - blood ; Alpha Particles - adverse effects ; Alpha Particles - therapeutic use ; Antineoplastic agents ; Biological and medical sciences ; Bone Neoplasms - diagnostic imaging ; Bone Neoplasms - radiotherapy ; Bone Neoplasms - secondary ; Breast Neoplasms - pathology ; Breast Neoplasms - radiotherapy ; Diarrhea - etiology ; Dose-Response Relationship, Radiation ; Fatigue - etiology ; Female ; Follow-Up Studies ; Humans ; Injections, Intravenous ; Leukopenia - etiology ; Male ; Medical sciences ; Metabolic Targeting ; Middle Aged ; Nausea - etiology ; Neutropenia - etiology ; Pain - etiology ; Pharmacology. Drug treatments ; Phase I clinical trial ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - radiotherapy ; Radionuclide Imaging ; Radium - adverse effects ; Radium - blood ; Radium - therapeutic use ; Treatment Outcome ; Vomiting - etiology ; α-Particle Therapy</subject><ispartof>Clinical cancer research, 2005-06, Vol.11 (12), p.4451-4459</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-5c4ecd467b3951c60646df85c9cb14b3dd4097e85cb23fbadd534d8a0855293c3</citedby><cites>FETCH-LOGICAL-c409t-5c4ecd467b3951c60646df85c9cb14b3dd4097e85cb23fbadd534d8a0855293c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3343,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16856413$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15958630$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1948721$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>NILSSON, Sten</creatorcontrib><creatorcontrib>LARSEN, Roy H</creatorcontrib><creatorcontrib>FOSSA, Sophie D</creatorcontrib><creatorcontrib>BALTESKARD, Lise</creatorcontrib><creatorcontrib>BORCH, Kari W</creatorcontrib><creatorcontrib>WESTLIN, Jan-Erik</creatorcontrib><creatorcontrib>SALBERG, Gro</creatorcontrib><creatorcontrib>BRULAND, Oyvind S</creatorcontrib><title>First Clinical Experience with α-Emitting Radium-223 in the Treatment of Skeletal Metastases</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: The main goals were to study the safety and tolerability of the α-emitter radium-223 ( 223 Ra) in breast and prostate cancer patients with skeletal metastases. In addition, pain palliation was evaluated.
Experimental Design: Fifteen prostate and 10 breast cancer patients enrolled in a phase I trial received a single i.v. injection of 223 Ra. Five patients were included at each of the dosages: 46, 93, 163, 213, or 250 kBq/kg and followed for 8 weeks. Palliative
response was evaluated according to the pain scale of the European Organization for Research and Treatment of Cancer QLQ C30
questionnaire at baseline and at 1, 4, and 8 weeks after injection.
Results: Weekly blood sampling during follow-up revealed mild and reversible myelosuppression with nadir 2 to 4 weeks after the injection.
Importantly, for thrombocytes only grade 1 toxicity was reported. Grade 3 neutropenia and leucopenia occurred in two and three
patients, respectively. Mild, transient diarrhea was observed in 10 of the 25 patients. Nausea and vomiting was more frequently
observed in the highest dosage group. Serum alkaline phosphatase decreased with nadir averages of 29.5% in females and 52.1%
in males. Pain relief was reported by 52%, 60%, and 56% of the patients after 7 days, 4, and 8 weeks, respectively. 223 Ra cleared rapidly from blood and was below 1% of initial level at 24 hours. Gamma camera images indicated, in accordance
with pretreatment 99m Tc-MDP scans, accumulation of 223 Ra in skeletal lesions. Elimination was mainly intestinal. Median survival exceeded 20 months.
Conclusions: 223 Ra was well tolerated at therapeutically relevant dosages. Phase II studies have therefore been initiated.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alkaline Phosphatase - blood</subject><subject>Alpha Particles - adverse effects</subject><subject>Alpha Particles - therapeutic use</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Bone Neoplasms - diagnostic imaging</subject><subject>Bone Neoplasms - radiotherapy</subject><subject>Bone Neoplasms - secondary</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - radiotherapy</subject><subject>Diarrhea - etiology</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Fatigue - etiology</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Leukopenia - etiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic Targeting</subject><subject>Middle Aged</subject><subject>Nausea - etiology</subject><subject>Neutropenia - etiology</subject><subject>Pain - etiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Phase I clinical trial</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - radiotherapy</subject><subject>Radionuclide Imaging</subject><subject>Radium - adverse effects</subject><subject>Radium - blood</subject><subject>Radium - therapeutic use</subject><subject>Treatment Outcome</subject><subject>Vomiting - etiology</subject><subject>α-Particle Therapy</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtKxDAUhoMo3h9BycaFi2rSJJ12KWW8gCJ4WUpIk1MbnXaGJMPoY_kiPpNnmFEhJD_h-0_CR8gRZ2ecq_Kcs1GZMSnys7p-wJDluZQbZJcrNcpEXqhNzL_MDtmL8Y0xLjmT22SHq0qVhWC75OXSh5hoPfGDt2ZCxx8zCB4GC3ThU0e_v7Jx71Pywyt9MM7Pe3xIUD_Q1AF9CmBSD0Oi05Y-vsMEEs64wz3ignhAtloziXC4PvfJ8-X4qb7Obu-vbuqL28xKVqVMWQnWyWLUiEpxW7BCFq4tla1sw2UjnENsBHjR5KJtjHNKSFcaViqVV8KKfZKt5sYFzOaNngXfm_Cpp8br9dU7JtCqZEJI5NWKt2EaY4D2r8GZXurVS3V6qU6jXgx6qRd7x6seTuzB_bfWPhE4WQMmos42mMH6-M8VpSokF8idrrjOv3YLH0BbJCEEiGCC7fATmudaSsXFDwXuki0</recordid><startdate>20050615</startdate><enddate>20050615</enddate><creator>NILSSON, Sten</creator><creator>LARSEN, Roy H</creator><creator>FOSSA, Sophie D</creator><creator>BALTESKARD, Lise</creator><creator>BORCH, Kari W</creator><creator>WESTLIN, Jan-Erik</creator><creator>SALBERG, Gro</creator><creator>BRULAND, Oyvind S</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20050615</creationdate><title>First Clinical Experience with α-Emitting Radium-223 in the Treatment of Skeletal Metastases</title><author>NILSSON, Sten ; LARSEN, Roy H ; FOSSA, Sophie D ; BALTESKARD, Lise ; BORCH, Kari W ; WESTLIN, Jan-Erik ; SALBERG, Gro ; BRULAND, Oyvind S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-5c4ecd467b3951c60646df85c9cb14b3dd4097e85cb23fbadd534d8a0855293c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alkaline Phosphatase - blood</topic><topic>Alpha Particles - adverse effects</topic><topic>Alpha Particles - therapeutic use</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Bone Neoplasms - diagnostic imaging</topic><topic>Bone Neoplasms - radiotherapy</topic><topic>Bone Neoplasms - secondary</topic><topic>Breast Neoplasms - pathology</topic><topic>Breast Neoplasms - radiotherapy</topic><topic>Diarrhea - etiology</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Fatigue - etiology</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Leukopenia - etiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic Targeting</topic><topic>Middle Aged</topic><topic>Nausea - etiology</topic><topic>Neutropenia - etiology</topic><topic>Pain - etiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Phase I clinical trial</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - radiotherapy</topic><topic>Radionuclide Imaging</topic><topic>Radium - adverse effects</topic><topic>Radium - blood</topic><topic>Radium - therapeutic use</topic><topic>Treatment Outcome</topic><topic>Vomiting - etiology</topic><topic>α-Particle Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>NILSSON, Sten</creatorcontrib><creatorcontrib>LARSEN, Roy H</creatorcontrib><creatorcontrib>FOSSA, Sophie D</creatorcontrib><creatorcontrib>BALTESKARD, Lise</creatorcontrib><creatorcontrib>BORCH, Kari W</creatorcontrib><creatorcontrib>WESTLIN, Jan-Erik</creatorcontrib><creatorcontrib>SALBERG, Gro</creatorcontrib><creatorcontrib>BRULAND, Oyvind S</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>NILSSON, Sten</au><au>LARSEN, Roy H</au><au>FOSSA, Sophie D</au><au>BALTESKARD, Lise</au><au>BORCH, Kari W</au><au>WESTLIN, Jan-Erik</au><au>SALBERG, Gro</au><au>BRULAND, Oyvind S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>First Clinical Experience with α-Emitting Radium-223 in the Treatment of Skeletal Metastases</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2005-06-15</date><risdate>2005</risdate><volume>11</volume><issue>12</issue><spage>4451</spage><epage>4459</epage><pages>4451-4459</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: The main goals were to study the safety and tolerability of the α-emitter radium-223 ( 223 Ra) in breast and prostate cancer patients with skeletal metastases. In addition, pain palliation was evaluated.
Experimental Design: Fifteen prostate and 10 breast cancer patients enrolled in a phase I trial received a single i.v. injection of 223 Ra. Five patients were included at each of the dosages: 46, 93, 163, 213, or 250 kBq/kg and followed for 8 weeks. Palliative
response was evaluated according to the pain scale of the European Organization for Research and Treatment of Cancer QLQ C30
questionnaire at baseline and at 1, 4, and 8 weeks after injection.
Results: Weekly blood sampling during follow-up revealed mild and reversible myelosuppression with nadir 2 to 4 weeks after the injection.
Importantly, for thrombocytes only grade 1 toxicity was reported. Grade 3 neutropenia and leucopenia occurred in two and three
patients, respectively. Mild, transient diarrhea was observed in 10 of the 25 patients. Nausea and vomiting was more frequently
observed in the highest dosage group. Serum alkaline phosphatase decreased with nadir averages of 29.5% in females and 52.1%
in males. Pain relief was reported by 52%, 60%, and 56% of the patients after 7 days, 4, and 8 weeks, respectively. 223 Ra cleared rapidly from blood and was below 1% of initial level at 24 hours. Gamma camera images indicated, in accordance
with pretreatment 99m Tc-MDP scans, accumulation of 223 Ra in skeletal lesions. Elimination was mainly intestinal. Median survival exceeded 20 months.
Conclusions: 223 Ra was well tolerated at therapeutically relevant dosages. Phase II studies have therefore been initiated.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>15958630</pmid><doi>10.1158/1078-0432.CCR-04-2244</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2005-06, Vol.11 (12), p.4451-4459 |
| issn | 1078-0432 1557-3265 |
| language | eng |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Alkaline Phosphatase - blood Alpha Particles - adverse effects Alpha Particles - therapeutic use Antineoplastic agents Biological and medical sciences Bone Neoplasms - diagnostic imaging Bone Neoplasms - radiotherapy Bone Neoplasms - secondary Breast Neoplasms - pathology Breast Neoplasms - radiotherapy Diarrhea - etiology Dose-Response Relationship, Radiation Fatigue - etiology Female Follow-Up Studies Humans Injections, Intravenous Leukopenia - etiology Male Medical sciences Metabolic Targeting Middle Aged Nausea - etiology Neutropenia - etiology Pain - etiology Pharmacology. Drug treatments Phase I clinical trial Prostatic Neoplasms - pathology Prostatic Neoplasms - radiotherapy Radionuclide Imaging Radium - adverse effects Radium - blood Radium - therapeutic use Treatment Outcome Vomiting - etiology α-Particle Therapy |
| title | First Clinical Experience with α-Emitting Radium-223 in the Treatment of Skeletal Metastases |
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