Evidence map›Paper›PMID 30293905›Full record

ArticleEuropean urology2019

Efficacy of Radium-223 in Bone-metastatic Castration-resistant Prostate Cancer with and Without Homologous Repair Gene Defects.

Pedro Isaacsson Velho, Fahad Qazi, Sayeedul Hassan, Michael A Carducci, Samuel R Denmeade, Mark C Markowski, Daniel L Thorek, Theodore L DeWeese, Daniel Y Song, Phuoc T Tran and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
9.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 95 citations in OpenAlex.

  1. Trial
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  6. Circulating Tumor DNA Genomic Profiling inJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026
    Observational
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  19. Phase I Study of Niraparib in Combination with Radium-223 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Pedro Isaacsson VelhoJohns Hopkins Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Fahad QaziMedStar Health, Baltimore, MD, USA.
Sayeedul HassanSinai Hospital of Baltimore, Baltimore, MD, USA.
Michael A CarducciJohns Hopkins Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
Samuel R DenmeadeJohns Hopkins Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
Mark C MarkowskiJohns Hopkins Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Daniel L ThorekJohns Hopkins Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.
Theodore L DeWeeseJohns Hopkins Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, USA.
Daniel Y SongJohns Hopkins Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, USA.
Phuoc T TranJohns Hopkins Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, USA.
Mario A EisenbergerJohns Hopkins Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
Emmanuel S AntonarakisJohns Hopkins Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: eantona1@jhmi.edu.
Johns Hopkins University · USMedStar Health · USSinai Hospital · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Integrating bioinformatics into multiscale models for hepatocellular carcinomaU01CA212007 · NCI · JOHNS HOPKINS UNIVERSITY · PI EWALD, ANDREW JOSEF, FERTIG, ELANA · 2018 to 2022
$3.2M
Structure-Functions Studies of Twist1-induced Radioresistance in Lung CancerR01CA166348 · NCI · JOHNS HOPKINS UNIVERSITY · PI TRAN, PHUOC T. · 2013 to 2017
$1.7M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA166348NCI NIH HHS U01 CA212007
6 · The paper itself

Abstract

backgroundPathogenic 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 α-emitter that induces double-strand DNA breaks, thereby killing cancer cells in the bone microenvironment.

objectiveTo evaluate the potential impact of germline or somatic HR-deficiency (HRD) mutations on radium-223 efficacy in mCRPC with bone metastasis. DESIGN, SETTING, AND

participantsThis 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. 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. 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.

conclusionsIn 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. 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.

Indexed as

Bone NeoplasmsProstatic Neoplasms, Castration-ResistantAgedAlkaline PhosphataseBiomarkers, TumorGerm-Line MutationHumansMaleNeoplasm StagingProstate-Specific AntigenRadioisotopesRadiumRecombinational DNA RepairSurvival AnalysisTreatment OutcomeAlkaline PhosphataseBiomarkers, TumorProstate-Specific AntigenRadioisotopesRadiumRadium-223CancerDNA repairGermlineMutationsProstate cancerRadium-223Somatic

Identifiers

PMID30293905
PMCPMC6447475
OpenAlexW2894805938

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.