ArticleRadiation oncology (London, England)2022
Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters.
Article in Radiation oncology (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 9 citations in OpenAlex.
- Can PSMA PET detect intratumour heterogeneity in histological PSMA expression of primary prostate cancer? Analysis of [European journal of nuclear medicine and molecular imaging · 2025Article
- Article
- Quantitative PSMA-PET parameters in localized prostate cancer: prognostic and potential predictive value.Radiation oncology (London, England) · 2024Article
- Emerging frontiers in androgen receptor research for prostate Cancer: insights from the 2nd international androgen receptor Symposium.Journal of experimental & clinical cancer research : CR · 2024Article
- Genetic profiling in radiotherapy: a comprehensive review.Frontiers in oncology · 2024Review
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17 authors at 7 institutions in 3 countries.
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Abstract
backroundAccurate surrogate parameters for radio resistance are warranted for individualized radiotherapy (RT) concepts in prostate cancer (PCa). The purpose of this study was to assess intertumoral heterogeneity in terms of radio resistance using an ex-vivo γH2AX assay after irradiation of prostate biopsy cores and to investigate its correlation with clinical features of respective patients as well as imaging and genomic features of tumor areas.
methodsTwenty one patients with histologically-proven PCa and pre-therapeutic multiparametric resonance imaging and prostate-specific membrane antigen positron emission tomography were included in the study. Biopsy cores were collected from 26 PCa foci. Residual γH2AX foci were counted 24 h after ex-vivo irradiation (with 0 and 4 Gy) of biopsy specimen and served as a surrogate for radio resistance. Clinical, genomic (next generation sequencing) and imaging features were collected and their association with the radio resistance was studied.
resultsIn total 18 PCa lesions from 16 patients were included in the final analysis. The median γH2AX foci value per PCa lesion was 3.12. According to this, the patients were divided into two groups (radio sensitive vs. radio resistant) with significant differences in foci number (p < 0.0001). The patients in the radio sensitive group had significantly higher prostate specific antigen serum concentration (p = 0.015), tumor areas in the radio sensitive group had higher SUV (standardized uptake values in PSMA PET)-max and -mean values (p = 0.0037, p = 0.028) and lower ADC (apparent diffusion coefficient-mean values, p = 0.049). All later parameters had significant (p < 0.05) correlations in Pearson's test. One patient in the radio sensitive group displayed a previously not reported loss of function frameshift mutation in the NBN gene (c.654_658delAAAAC) that introduces a premature termination codon and results in a truncated protein.
conclusionIn this pilot study, significant differences in intertumoral radio resistance were observed and clinical as well as imaging parameters may be applied for their prediction. After further prospective validation in larger patient cohorts these finding may lead to individual RT dose prescription for PCa patients in the future.
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