MARC details
| 000 -LEADER |
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| fixed length control field |
04346nam a22004337a 4500 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION |
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| fixed length control field |
190724s20192019 xxu||||| |||| 00| 0 eng d |
| 022 ## - INTERNATIONAL STANDARD SERIAL NUMBER |
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| International Standard Serial Number |
0302-2838 |
| 024 ## - OTHER STANDARD IDENTIFIER |
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| Standard number or code |
10.1016/j.eururo.2018.09.040 [doi] |
| 024 ## - OTHER STANDARD IDENTIFIER |
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| Standard number or code |
NIHMS1508079 [mid] |
| 024 ## - OTHER STANDARD IDENTIFIER |
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| Standard number or code |
PMC6447475 [pmc] |
| 024 ## - OTHER STANDARD IDENTIFIER |
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| Standard number or code |
S0302-2838(18)30729-2 [pii] |
| 040 ## - CATALOGING SOURCE |
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| Original cataloging agency |
Ovid MEDLINE(R) |
| 099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC) |
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| PMID |
30293905 |
| 245 ## - TITLE STATEMENT |
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| Title |
Efficacy of Radium-223 in Bone-metastatic Castration-resistant Prostate Cancer with and Without Homologous Repair Gene Defects. |
| 251 ## - Source |
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| Source |
European Urology. 76(2):170-176, 2019 Aug. |
| 252 ## - Abbreviated Source |
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| Abbreviated source |
Eur Urol. 76(2):170-176, 2019 Aug. |
| 253 ## - Journal Name |
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| Journal name |
European urology |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. |
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| Year |
2019 |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. |
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| Manufacturer |
FY2020 |
| 265 ## - SOURCE FOR ACQUISITION/SUBSCRIPTION ADDRESS [OBSOLETE] |
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| Publication status |
ppublish |
| 266 ## - Date added to catalog |
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| Date added to catalog |
2018-10-10 |
| 520 ## - SUMMARY, ETC. |
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| Abstract |
BACKGROUND: Pathogenic mutations in genes mediating homologous recombination (HR) DNA repair are present in 20-30% of men with metastatic castrate-resistant prostate cancer (mCRPC). Radium-223 is a bone-seeking alpha-emitter that induces double-strand DNA breaks, thereby killing cancer cells in the bone microenvironment. |
| 520 ## - SUMMARY, ETC. |
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| Abstract |
CONCLUSIONS: In this exploratory study, bone-metastatic CRPC patients with inactivating HRD mutations demonstrated significantly improved ALP responses and time to ALP progression. These results should motivate prospective validation of the "synthetic lethality" hypothesis between HRD mutations and radium-223 activity. |
| 520 ## - SUMMARY, ETC. |
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| Abstract |
Copyright (c) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved. |
| 520 ## - SUMMARY, ETC. |
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| Abstract |
DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective single-institution study. Medical records of 190 mCRPC patients for whom germline and/or somatic DNA sequencing data were available were reviewed. Of these patients, 28 had received standard-of-care radium-223 at Johns Hopkins between February 2013 and February 2018. |
| 520 ## - SUMMARY, ETC. |
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| Abstract |
OBJECTIVE: To evaluate the potential impact of germline or somatic HR-deficiency (HRD) mutations on radium-223 efficacy in mCRPC with bone metastasis. |
| 520 ## - SUMMARY, ETC. |
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| Abstract |
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Alkaline phosphatase (ALP) responses and time-to-ALP-progression were the coprimary endpoints. Prostate-specific antigen (PSA) responses, overall survival (OS), and time to next systemic therapy were also evaluated. |
| 520 ## - SUMMARY, ETC. |
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| Abstract |
PATIENT SUMMARY: In this report, we retrospectively examined outcomes to metastatic prostate cancer in patients with and without DNA repair mutations who received radium-223, a therapy that kills cancer cells by causing direct DNA damage. Our study suggested that patients who have inherited or acquired DNA repair gene mutations derived greater benefit from radium-223 when compared with patients without these mutations. We concluded that radium-223 might have an important role in this setting; however, prospective studies are needed to confirm whether DNA repair mutations truly make radium-223 work better or not. |
| 520 ## - SUMMARY, ETC. |
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| Abstract |
RESULTS AND LIMITATIONS: Of the 28 patients included, 10 men (35.7%) had a germline/somatic HRD mutation (three in BRCA2, and one each in ATM, ATR, CHEK2, FANCG, FANCI, FANCL, and PALB2) and 18 (64.3%) did not. Men with HRD mutations (HRD+) had numerically lower ages (66 vs 73yr, p=0.25), more soft-tissue metastases (50% vs 38%, p=0.43), and higher baseline ALP levels (130 vs 108 U/l, p=0.84). Compared with HRD(-) men, HRD(+) patients showed greater ALP responses (80% vs 39%, p=0.04), longer time to ALP progression (median10.4 vs 5.8mo, hazard ratio [HR] 6.4, p=0.005), and a trend toward longer OS (median 36.9 vs 19.0mo, HR 3.3, p=0.11). PSA responses (0% vs 0%, p>0.99) and time to next systemic therapy (HR 1.5, p=0.39) were similar between the two groups. Results are limited by the retrospective nature of the analysis and the small sample size. |
| 546 ## - LANGUAGE NOTE |
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| Language note |
English |
| 650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
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| Topical term or geographic name entry element |
IN PROCESS -- NOT YET INDEXED |
| 651 ## - SUBJECT ADDED ENTRY--GEOGRAPHIC NAME |
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| Institution |
MedStar Union Memorial Hospital |
| 656 ## - INDEX TERM--OCCUPATION |
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| Department |
Internal Medicine |
| 657 ## - INDEX TERM--FUNCTION |
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| Medline publication type |
Journal Article |
| 700 ## - ADDED ENTRY--PERSONAL NAME |
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| Local Authors |
Qazi, Fahad |
| 790 ## - Authors |
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| All authors |
Antonarakis ES, Carducci MA, Denmeade SR, DeWeese TL, Eisenberger MA, Hassan S, Isaacsson Velho P, Markowski MC, Qazi F, Song DY, Thorek DL, Tran PT |
| 856 ## - ELECTRONIC LOCATION AND ACCESS |
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| DOI |
<a href="https://dx.doi.org/10.1016/j.eururo.2018.09.040">https://dx.doi.org/10.1016/j.eururo.2018.09.040</a> |
| Public note |
https://dx.doi.org/10.1016/j.eururo.2018.09.040 |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) |
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| Koha item type |
Journal Article |
| Item type description |
Article |
