Trial reportInternational journal of radiation oncology, biology, physics2019
MRE11 as a Predictive Biomarker of Outcome After Radiation Therapy in Bladder Cancer.
Trial report in International journal of radiation oncology, biology, physics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- Clinical Biomarkers of Tumour Radiosensitivity and Predicting Benefit from Radiotherapy: A Systematic Review.Cancers · 2024Review
- Analysis of MRE11 and Mortality Among Adults With Muscle-Invasive Bladder Cancer Managed With Trimodality Therapy.JAMA network open · 2022Article
- Impact of Programmed Death-ligand 1 Expression on Oncological Outcomes in Patients with Muscle-invasive Bladder Cancer Treated with Radiation-based Therapy.European urology open science · 2022Article
- A practical approach to bladder preservation with hypofractionated radiotherapy for localised muscle-invasive bladder cancer.Clinical and translational radiation oncology · 2021Review
- Bladder preservation: Translating discovery for clinical impact in urothelial cancer.Urologic oncology · 2021Review
- Review of Experimental Studies to Improve Radiotherapy Response in Bladder Cancer: Comments and Perspectives.Cancers · 2020Review
- Bladder-sparing protocols in the treatment of muscle-invasive bladder cancer.Translational andrology and urology · 2020Review
- Genomics models in radiotherapy: From mechanistic to machine learning.Medical physics · 2020Review
- The challenge of matching assays to biology in DNA damage response biomarkers for response to radiotherapy in bladder cancer.Translational andrology and urology · 2019Article
- MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment.Molecular cancer · 2019Review
- Organ preservation in bladder cancer: an opportunity for truly personalized treatment.Nature reviews. Urology · 2019Review
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Authors and funding
25 authors at 14 institutions in 2 countries.
Funding
Abstract
purposeOrgan-confined muscle-invasive bladder cancer is treated with cystectomy or bladder preservation techniques, including radiation therapy. There are currently no biomarkers to inform management decisions and aid patient choice. Previously we showed high levels of MRE11 protein, assessed by immunohistochemistry (IHC), predicted outcome after radiation therapy, but not cystectomy. Therefore, we sought to develop the MRE11 IHC assay for clinical use and define its relationship to clinical outcome in samples from 2 major clinical trials. METHODS AND MATERIALS: Samples from the BCON and BC2001 randomized controlled trials and a cystectomy cohort were stained using automated IHC methods and scored for MRE11 in 3 centers in the United Kingdom.
resultsDespite step-wise creation of scoring cards and standard operating procedures for staining and interpretation, there was poor intercenter scoring agreement (kappa, 0.32; 95% confidence interval, 0.17-0.47). No significant associations between MRE11 scores and cause-specific survival were identified in BCON (n = 132) and BC2001 (n = 221) samples. Reoptimized staining improved agreement between scores from BCON tissue microarrays (n = 116), but MRE11 expression was not prognostic for cause-specific survival.
conclusionsManual IHC scoring of MRE11 was not validated as a reproducible biomarker of radiation-based bladder preservation success. There is a need for automated quantitative methods or a reassessment of how DNA-damage response relates to clinical outcomes.
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