Evidence map›Paper›PMID 38224917›Full record

ArticleRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2024

The radiopharmaceutical radium-223 has immunomodulatory effects in patients and facilitates anti-programmed death receptor-1 therapy in murine models of bone metastatic prostate cancer.

Philip J Saylor, Sergey V Kozin, Aya Matsui, Saveli I Goldberg, Shuichi Aoki, Kohei Shigeta, Emilie Mamessier, Matthew R Smith, M Dror Michaelson, Richard J Lee and 1 more

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

Article in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 12% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
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

11 authors at 2 institutions in 1 country.

Philip J SaylorMGH Cancer Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: psaylor@mgh.harvard.edu.
Sergey V KozinSteele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Aya MatsuiSteele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Saveli I GoldbergSteele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Shuichi AokiSteele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Kohei ShigetaSteele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Emilie MamessierSteele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Matthew R SmithMGH Cancer Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
M Dror MichaelsonMGH Cancer Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Richard J LeeMGH Cancer Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Dan G DudaSteele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: duda@steele.mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · US

Funding

Project 3: Enhanced Sensitivity of Tumors to Proton Beam Therapy: Mechanisms and Biomarkers.P01CA261669 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI HONG, THEODORE S · 2021 to 2025
$14.0M
Multiplexed time domain fluorescence tomography of tumor biomarkers during immunotherapyR01CA260857 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Dan Gabriel Duda, Anand T.N. Kumar · 2021 to 2026
$2.7M
Vascularized tumor explants for drug testingR01CA247441 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MUNN, LANCE L. · 2021 to 2025
$1.9M
Radiation and CSPG4-specifc CAR T cell based combinatorial therapy for the in vivo treatment of TNBCR03CA256764 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DUDA, DAN GABRIEL, WANG, XINHUI · 2021 to 2022
$167k
NCI NIH HHS P01 CA261669NCI NIH HHS R01 CA247441NCI NIH HHS R01 CA260857NCI NIH HHS R03 CA256764
6 · The paper itself

Abstract

BACKGROUND & PURPOSE: Radium-223 (Ra223) improves survival in metastatic prostate cancer (mPC), but its impact on systemic immunity is unclear, and biomarkers of response are lacking. We examined markers of immunomodulatory activity during standard clinical Ra223 and studied the impact of Ra223 on response to immune checkpoint inhibition (ICI) in preclinical models. MATERIALS &

methodsWe conducted a single-arm biomarker study of Ra223 in 22 bone mPC patients. We measured circulating immune cell subsets and a panel of cytokines before and during Ra223 therapy and correlated them with overall survival (OS). Using two murine mPC models-orthotopic PtenSmad4-null and TRAMP-C1 grafts in syngeneic immunocompetent mice-we tested the efficacy of combining Ra223 with ICI.

resultsAbove-median level of IL-6 at baseline was associated with a median OS of 358 versus 947 days for below levels; p = 0.044, from the log-rank test. Baseline PlGF and PSA inversely correlated with OS (p = 0.018 and p = 0.037, respectively, from the Cox model). Ra223 treatment was associated with a mild decrease in some peripheral immune cell populations and a shift in the proportion of MDSCs from granulocytic to myeloid. In mice, Ra223 increased the proliferation of CD8

conclusionThe inflammatory cytokine IL-6 and the angiogenic biomarker PlGF at baseline were promising outcome biomarkers after standard Ra223 treatment. In mouse models, Ra223 increased intratumoral CD8

Indexed as

Bone NeoplasmsProstatic NeoplasmsRadiumAnimalsBiomarkersCytokinesDisease Models, AnimalHumansInterleukin-6MaleMiceRadiopharmaceuticalsReceptors, Death DomainTumor MicroenvironmentBiomarkersCytokinesInterleukin-6RadiopharmaceuticalsRadiumRadium-223Receptors, Death DomainImmune checkpoint blockadeImmunomodulationImmunotherapyProstate cancerTranslational research

Identifiers

PMID38224917
PMCPMC10905770
OpenAlexW4390919903

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.