Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters
Abstract Backround Accurate 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 o...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-10-01
|
| Series: | Radiation Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13014-022-02131-1 |
| _version_ | 1811226592663306240 |
|---|---|
| author | Ioana M. Marinescu Manuel Rogg Simon Spohn Moritz von Büren Marius Kamps Cordula A. Jilg Elena Fountzila Kyriaki Papadopoulou Lara Ceci Alisa Bettermann Juri Ruf Matthias Benndorf Sonja Adebahr Daniel Zips Anca L. Grosu Christoph Schell Constantinos Zamboglou |
| author_facet | Ioana M. Marinescu Manuel Rogg Simon Spohn Moritz von Büren Marius Kamps Cordula A. Jilg Elena Fountzila Kyriaki Papadopoulou Lara Ceci Alisa Bettermann Juri Ruf Matthias Benndorf Sonja Adebahr Daniel Zips Anca L. Grosu Christoph Schell Constantinos Zamboglou |
| author_sort | Ioana M. Marinescu |
| collection | DOAJ |
| description | Abstract Backround Accurate 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. Methods Twenty 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. Results In 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. Conclusion In 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. |
| first_indexed | 2024-04-12T09:27:47Z |
| format | Article |
| id | doaj.art-33c81c387e9a4b16b5dfaef6029b7aba |
| institution | Directory Open Access Journal |
| issn | 1748-717X |
| language | English |
| last_indexed | 2024-04-12T09:27:47Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Radiation Oncology |
| spelling | doaj.art-33c81c387e9a4b16b5dfaef6029b7aba2022-12-22T03:38:26ZengBMCRadiation Oncology1748-717X2022-10-0117111010.1186/s13014-022-02131-1Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parametersIoana M. Marinescu0Manuel Rogg1Simon Spohn2Moritz von Büren3Marius Kamps4Cordula A. Jilg5Elena Fountzila6Kyriaki Papadopoulou7Lara Ceci8Alisa Bettermann9Juri Ruf10Matthias Benndorf11Sonja Adebahr12Daniel Zips13Anca L. Grosu14Christoph Schell15Constantinos Zamboglou16Department of Radiation Oncology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgInstitute for Surgical Pathology, Medical Center – University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgDepartment of Urology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgDepartment of Urology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgDepartment of Urology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgSecond Department of Medical Oncology, Euromedica General Clinic of ThessalonikiLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of ThessalonikiDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgDepartment of Nuclear Medicine, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgDepartment of Radiology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgMedical Faculty and University Hospital, Radiation Oncology, Eberhard Karls University TübingenDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgInstitute for Surgical Pathology, Medical Center – University of FreiburgDepartment of Radiation Oncology, Faculty of Medicine, Medical Center – University of Freiburg, University of FreiburgAbstract Backround Accurate 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. Methods Twenty 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. Results In 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. Conclusion In 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.https://doi.org/10.1186/s13014-022-02131-1Prostate cancerIntrinsic radio sensitivityγH2AX fociStandardized uptake valuesRadiotherapy |
| spellingShingle | Ioana M. Marinescu Manuel Rogg Simon Spohn Moritz von Büren Marius Kamps Cordula A. Jilg Elena Fountzila Kyriaki Papadopoulou Lara Ceci Alisa Bettermann Juri Ruf Matthias Benndorf Sonja Adebahr Daniel Zips Anca L. Grosu Christoph Schell Constantinos Zamboglou Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters Radiation Oncology Prostate cancer Intrinsic radio sensitivity γH2AX foci Standardized uptake values Radiotherapy |
| title | Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters |
| title_full | Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters |
| title_fullStr | Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters |
| title_full_unstemmed | Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters |
| title_short | Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters |
| title_sort | ex vivo γh2ax assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters |
| topic | Prostate cancer Intrinsic radio sensitivity γH2AX foci Standardized uptake values Radiotherapy |
| url | https://doi.org/10.1186/s13014-022-02131-1 |
| work_keys_str_mv | AT ioanammarinescu exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT manuelrogg exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT simonspohn exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT moritzvonburen exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT mariuskamps exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT cordulaajilg exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT elenafountzila exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT kyriakipapadopoulou exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT laraceci exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT alisabettermann exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT juriruf exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT matthiasbenndorf exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT sonjaadebahr exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT danielzips exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT ancalgrosu exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT christophschell exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters AT constantinoszamboglou exvivogh2axassayfortumorradiosensitivityinprimaryprostatecancerpatientsandcorrelationwithclinicalparameters |