- Email: [email protected]
[P287] Investigation of radiation induced mitotic arrest in irradiated cells
182
Abstracts / Physica Medica 52 (2018) 99–187
ability and uncertainty therefrom also for different types of treatment: conventionally fractionated and SBRT. Under the experimental conditions described above, the use of EBT3 film dosimetry analyzed with FilmQA software shows to be an accurate method for VMAT conventionally fractionated and SBRT treatment plans verifications. https://doi.org/10.1016/j.ejmp.2018.06.558
[P284] Dosimetry audits in radiotherapy: 15 years of experience and lessons learnt Kyveli Zourari a,*, Zoi Thrapsanioti a, Argiro Boziari b, Costas J. Hourdakis a a
Greek Atomic Energy Commission, Licensing and Inspections Department, Athens, Greece b Greek Atomic Energy Commission, Dosimetry and Calibration Department, Athens, Greece ⇑ Corresponding author. Purpose. Dosimetry audits (DA) are useful for the evaluation of the dosimetric quality, planned dose accuracy, treatment complexity and deliverability of radiotherapy (RT) procedures, aiming to consult on detected discrepancies and improve standards and reliability of the RT centers. Since 2002, Greek Atomic Energy Commission (EEAE) provides dosimetry auditing services of level I and II and recently III, IV in MV photon and electron beams in all RT centers of the country. Methods. DAs were conducted by means of on-site visits. The audit levels applied in sequence were: Mechanical and functional tests of the RT machine, absolute and relative dosimetry, beam and treatment planning system (TPS) output measurements under reference and non-reference conditions, end-to-end tests for the assessment of the TPS dose calculations, in basic and advanced radiotherapy techniques through 1D, 2D and 3D dosimetry. Measurements were compared to the stated by the RT center values according to acceptance and tolerance criteria. Uncertainties were estimated according to GUM. Results. 98% for photons and 95% for electrons beams fulfilled dosimetry accuracy acceptance criteria (±3%) under reference conditions, improving gradually for the latter. The assessment of TPS output for 1134 beams (790 open, 344 wedged) was satisfactory in 95% and 84% of open and wedged beams, respectively. Non-acceptable results decreased progressively through time. End-to-end dosimetry tests, applied in 727 beams, exhibited acceptable, tolerated and nonacceptable results in 94%, 3% and 3% cases, respectively. Results for IMRT, VMAT and SRS were acceptable in all cases, stressing the need for systematic review of procedures for the whole chain of the clinical practice. Conclusions. Dosimetry audit was proved to be a valuable tool for the improvement of quality in radiotherapy. Dosimetry accuracy is verified in the gross majority of RT centers. Discrepancies and bad practices were detected, presenting a decreasing incidence over the years. Guidance and recommendations provided, improved dosimetry practices and verified that the quality assurance of procedures in an institution is essential for achieving the required accuracy and safe operation. Results of this study imply challenges in TPS commissioning, especially for small fields, and challenges in multicenter comparison for complex dose distributions. https://doi.org/10.1016/j.ejmp.2018.06.559
[P286] Study on semi-automatically evaluated micronucleus frequency changes in patients with prostate adenocarcinoma undergoing low and high dose rate brachytherapy
} Kis b, S. Zsuzsa Kocsis c, Géza Sáfrány d, Csilla Timea Hulber a, Eniko Pesznyák e,* a Budapest University of Technology and Economics, Institute of Nuclear Techniques, Budapest, Hungary b National Public Health Centre – National Research Directorate for Radiobiology and Radiohygiene, Radiobiology, Budapest, Hungary c National Institute of Oncology, Centre of Radiotherapy, Department of Radiobiology and Diagnostic Onco-Cytogenetics, Budapest, Hungary d National Research Directorate for Radiobiology and Radiohygiene, National Public Health Centre, Budapest, Hungary e National Institute of Oncology, Budapest University of Technology and Economics, Centre of Radiotherapy, Budapest, Hungary ⇑ Corresponding author.
Purpose. We compared the biological damaging effect of low and high dose rate brachytherapy (LDR and HDR) in healthy tissues of patients with prostate adenocarcinoma by following up the changes of DNA damage with cytokinesis-blocked micronucleus assay (CBMN) during and after the treatment. Methods. The CBMN assay was proven by literature to be good indicator of received dose during partial-body radiotherapy. The first blood samples were collected preceding the radiation therapy and the next ones in regular intervals after the seed insertion (LDR) or the end of treatment (HDR) (once every 3 month during the first year). The automatic analysis (scanning and image processing) was conducted by a dedicated totally automatized microscopic system. Results. We determined the MN frequency of 5 patients from each treatment group automatically and manually as well. We found that in order to ensure the reliability of the comparison of automatic scoring results an extra step has to be introduced for sample quality improvement. This way the tendency of MN frequency versus elapsed time became possible to be accurately identified and analysed for both brachytherapy techniques. Due to the relatively low whole-body equivalent dose, the best results were achieved with the user-supervised semi-automatic combined method which merges the advantages of the accuracy of manual revision and the rapidity of the automation. Conclusions. Although the signal is comparable with the order of changes, the automation-aided evaluation decreased the achieved uncertainty and made it possible to identify a definite and significant tendency in the change of MN frequency for LDR and HDR as well. Acknowledgment. This work has been carried out in the frame of VKSZ 14-1-2015-0021 Hungarian project supported by the National Research, Development and Innovation Fund. https://doi.org/10.1016/j.ejmp.2018.06.561
[P287] Investigation of radiation induced mitotic arrest in irradiated cells Diana Adliene a,*, Paulius Ruzgys b, Tadas Didvalis c, Saulius Mickevicius b, Jurgita Laurikaitiene˙ a a Kaunas University of Technology, Faculty of Mathematics and Natural Sciences, Kaunas, Lithuania b Vytautas Magnus University, Faculty of Natural Sciences, Kaunas, Lithuania c Vytautas Magnus University, The Hospital of Lithuanian University of Health Sciences Kauno Klinikos, Faculty of Natural Sciences, Kaunas, Lithuania ⇑ Corresponding author.
Purpose. Investigation of mitotic arrest in cells irradiated to radiotherapeutic doses. Methods. Chinese hamster ovary (CHO) cell line was used as an irradiation object. CHO cells were irradiated to the doses from the
Abstracts / Physica Medica 52 (2018) 99–187
range (0–10 Gy) in linear accelerator Varian ClinacDMX using 6 MeV photons. Clonogenic cell assay was used to assess radiation induced effects in irradiated cells. Cell colonies were manually counted using ImageJ software plug-in Colony Counter. Colony residence area was assessed using ImageJ software plug-in Analyze Particles, which enabled analysis of the scanned image of Petri dish with cells detecting separate cell colonies and calculating the average area of colonies within the dish. In parallel COMET assay was used for the assessment of radiation induced DNA damages in cells. Results. It was found, that the statistically significant decrease of formed cell colony’s area with the increasing irradiation dose (known as mitotic arrest process in affected cells) was stopped when the dose of 6 Gy was applied, indicating almost the same low level of mitotic activity at higher doses. It was suggested that the irradiated cells may have maximal mitotic arrest time which is irradiation dose independent at the doses P6 Gy, thus indicating the existence of the cell specific dose threshold at which maximal delayed mitosis effect with initiation of 30% of DNA damage on surviving cell fraction is present. There was no dose threshold effect observed evaluating cell viability and radiation induced DNA damages. Conclusions. Investigation results based hypothesis regarding possible existence of time dependent threshold dose for maximal delayed mitosis effect in irradiated cells was raised and discussed indicating that the application of dose threshold based irradiation model can contribute to the improvement of fractionated radiotherapy treatment efficiency. A need for more detailed investigations for verification of these findings was also indicated. https://doi.org/10.1016/j.ejmp.2018.06.562
[P288] Use of organic plastic scintillators for determination of the beam quality correction factor for flattening filter free photon beams Grichar V. Santurio *, Claus E. Andersen Technical University of Denmark, Center for Nuclear Technologies, Roskilde, Denmark ⇑ Corresponding author. Purpose. The purpose was to use organic plastic scintillators for determination of the beam quality correction factor ðk Q;Q0 Þ for flattening filters free (FFF) photon beams increasingly used in modern radiotherapy. The values were compared with those recommended in the recent TRS-483 code of practice from the International Agency of Atomic Energy. Methods. The formalism in TRS-483 covers not only small conventional photon beams with flattening filter (WFF), but also flattening filter free (FFF) beams. TRS-483 splits the k Q;Q0 into two correction f
f
ref factors for FFF beams: k Qref WFF ;Q0 and k QFFF ;QWFF . An IBA FC-65G ionization
chamber, calibrated for conventional MV photon beams, was used to experimentally determine the k QFFF ;Q0 . The fiber-coupled scintillator (1 mm diameter; 2 mm length) was used as a water-point surrogate detector for determination of the k Q;Q0 from quality QFFF with respect QWEF . Given the high degree of water-equivalence of this detector, and in line with the studies presented in TRS-483, it was assumed that the detector was perturbation free. Corrections were, however, made for ionization quenching based on published parameters for the used scintillator and Birks formalism implemented in the Monte Carlo toolkit EGSnrc. Results. The spectral difference between WFF and FFF resulted in changes in the ionization quenching which in turn affected the FFF/WFF-ratio in the TRS-483 formalism by about 0.6% for 6 MV and by 0.35% for 10 MV, respectively. After correcting for this, the beam quality correction factor for the FFF 6 MV and 10 MV beam
183
was found to differ insignificantly, 0.3%, compared with those recommended in TRS-483 when given that uncertainty of the ionization quenching correction factor alone was about 0.15% and that additional uncertainty components (>0.5%) are associated with the measurements. Conclusions. An experimental method for determining the beam quality correction factor for FFF to WFF was carried out. The study supports that organic plastic scintillators can be used as a perturbation-free detector in MV photon beams. However, considerations should be given to the change in quenching when spectrally different beams are involved such as when computing the dose ratio for WFF and FFF beams in the TRS-483 formula for beam quality correction factor. https://doi.org/10.1016/j.ejmp.2018.06.563
[P290] Radiotherapy risk analysis from incidence reports at a national level Harald Spejborg a,*, Kirsten L. Jakobsen b, Annette R. Jakobsen c, Lene Holberg d, Knud A. Werenberg e, Bettina J. Godborg f, Eva Samsøe b a
Aarhus University Hospital, Department of Medical Physics, Aarhus, Denmark b University Hospital Herlev, Department of Oncology, Herlev, Denmark c Aalborg University Hospital, Department of Oncology, Aalborg, Denmark d Vejle Sygehus, Department of Oncology, Vejle, Denmark e Odense University Hospital, Department of Radiophysics, Odense, Denmark f Naestved Sygehus, Department of Oncology, Naestved, Denmark ⇑ Corresponding author. Purpose. In order to share data on patient risk during radiotherapy (RT) on a national level and to stimulate a learning potential between the RT-centers, a national special group of interest in RT (RT-SIG) under the national society for medical physics was formed in 2016. Since then RT-SIG has collected and analyzed patient risk data from six centers. RT-SIG is stimulating the centers to analyze and categorize data in an inter-center consistent way facilitating sharing of data and making common reports and recommendations on patient RT safety improvements. Methods. Adverse and near miss incidence reports in RT are collected and analyzed locally at each center. Events are categorized by two different systems, 1 Patient Consequence Coding (PCC) according to the kind of consequence experienced by the patient and 2 RT Pathway Coding (RPC) according to the RT process at which the incident originated. Consensus surveys are performed twice a year in order to standardize local data analysis by the local center Risk Analysis Team. During 2017 local data were collected, and incidence patterns on a national level as well as on local RT-centers were analyzed. Results. Data of the consensus surveys are presented. Preliminary results on patient data analysis from 2016 have shown a big difference in the reporting activity between the participating centers whereas the risk patterns are quite similar. The majority of the incidents are found to occur in the planning steps of the RT course, giving risk of systematic errors through the entire course of RT. New national data for 2017 including anonymized inter-center comparison results will be presented. Data indicates consistent data analysis and similar risk profiles between the six participating RT-Centers. Conclusion. Due to training of the risk analysis teams at different RT centers, it is possible to use a common data categorizing system making inter-center analysis and comparisons feasible. Data from six centers show a different reporting frequency. However, a similar risk profile indicates that pooled national data have the potential of
Abstracts / Physica Medica 52 (2018) 99–187
ability and uncertainty therefrom also for different types of treatment: conventionally fractionated and SBRT. Under the experimental conditions described above, the use of EBT3 film dosimetry analyzed with FilmQA software shows to be an accurate method for VMAT conventionally fractionated and SBRT treatment plans verifications. https://doi.org/10.1016/j.ejmp.2018.06.558
[P284] Dosimetry audits in radiotherapy: 15 years of experience and lessons learnt Kyveli Zourari a,*, Zoi Thrapsanioti a, Argiro Boziari b, Costas J. Hourdakis a a
Greek Atomic Energy Commission, Licensing and Inspections Department, Athens, Greece b Greek Atomic Energy Commission, Dosimetry and Calibration Department, Athens, Greece ⇑ Corresponding author. Purpose. Dosimetry audits (DA) are useful for the evaluation of the dosimetric quality, planned dose accuracy, treatment complexity and deliverability of radiotherapy (RT) procedures, aiming to consult on detected discrepancies and improve standards and reliability of the RT centers. Since 2002, Greek Atomic Energy Commission (EEAE) provides dosimetry auditing services of level I and II and recently III, IV in MV photon and electron beams in all RT centers of the country. Methods. DAs were conducted by means of on-site visits. The audit levels applied in sequence were: Mechanical and functional tests of the RT machine, absolute and relative dosimetry, beam and treatment planning system (TPS) output measurements under reference and non-reference conditions, end-to-end tests for the assessment of the TPS dose calculations, in basic and advanced radiotherapy techniques through 1D, 2D and 3D dosimetry. Measurements were compared to the stated by the RT center values according to acceptance and tolerance criteria. Uncertainties were estimated according to GUM. Results. 98% for photons and 95% for electrons beams fulfilled dosimetry accuracy acceptance criteria (±3%) under reference conditions, improving gradually for the latter. The assessment of TPS output for 1134 beams (790 open, 344 wedged) was satisfactory in 95% and 84% of open and wedged beams, respectively. Non-acceptable results decreased progressively through time. End-to-end dosimetry tests, applied in 727 beams, exhibited acceptable, tolerated and nonacceptable results in 94%, 3% and 3% cases, respectively. Results for IMRT, VMAT and SRS were acceptable in all cases, stressing the need for systematic review of procedures for the whole chain of the clinical practice. Conclusions. Dosimetry audit was proved to be a valuable tool for the improvement of quality in radiotherapy. Dosimetry accuracy is verified in the gross majority of RT centers. Discrepancies and bad practices were detected, presenting a decreasing incidence over the years. Guidance and recommendations provided, improved dosimetry practices and verified that the quality assurance of procedures in an institution is essential for achieving the required accuracy and safe operation. Results of this study imply challenges in TPS commissioning, especially for small fields, and challenges in multicenter comparison for complex dose distributions. https://doi.org/10.1016/j.ejmp.2018.06.559
[P286] Study on semi-automatically evaluated micronucleus frequency changes in patients with prostate adenocarcinoma undergoing low and high dose rate brachytherapy
} Kis b, S. Zsuzsa Kocsis c, Géza Sáfrány d, Csilla Timea Hulber a, Eniko Pesznyák e,* a Budapest University of Technology and Economics, Institute of Nuclear Techniques, Budapest, Hungary b National Public Health Centre – National Research Directorate for Radiobiology and Radiohygiene, Radiobiology, Budapest, Hungary c National Institute of Oncology, Centre of Radiotherapy, Department of Radiobiology and Diagnostic Onco-Cytogenetics, Budapest, Hungary d National Research Directorate for Radiobiology and Radiohygiene, National Public Health Centre, Budapest, Hungary e National Institute of Oncology, Budapest University of Technology and Economics, Centre of Radiotherapy, Budapest, Hungary ⇑ Corresponding author.
Purpose. We compared the biological damaging effect of low and high dose rate brachytherapy (LDR and HDR) in healthy tissues of patients with prostate adenocarcinoma by following up the changes of DNA damage with cytokinesis-blocked micronucleus assay (CBMN) during and after the treatment. Methods. The CBMN assay was proven by literature to be good indicator of received dose during partial-body radiotherapy. The first blood samples were collected preceding the radiation therapy and the next ones in regular intervals after the seed insertion (LDR) or the end of treatment (HDR) (once every 3 month during the first year). The automatic analysis (scanning and image processing) was conducted by a dedicated totally automatized microscopic system. Results. We determined the MN frequency of 5 patients from each treatment group automatically and manually as well. We found that in order to ensure the reliability of the comparison of automatic scoring results an extra step has to be introduced for sample quality improvement. This way the tendency of MN frequency versus elapsed time became possible to be accurately identified and analysed for both brachytherapy techniques. Due to the relatively low whole-body equivalent dose, the best results were achieved with the user-supervised semi-automatic combined method which merges the advantages of the accuracy of manual revision and the rapidity of the automation. Conclusions. Although the signal is comparable with the order of changes, the automation-aided evaluation decreased the achieved uncertainty and made it possible to identify a definite and significant tendency in the change of MN frequency for LDR and HDR as well. Acknowledgment. This work has been carried out in the frame of VKSZ 14-1-2015-0021 Hungarian project supported by the National Research, Development and Innovation Fund. https://doi.org/10.1016/j.ejmp.2018.06.561
[P287] Investigation of radiation induced mitotic arrest in irradiated cells Diana Adliene a,*, Paulius Ruzgys b, Tadas Didvalis c, Saulius Mickevicius b, Jurgita Laurikaitiene˙ a a Kaunas University of Technology, Faculty of Mathematics and Natural Sciences, Kaunas, Lithuania b Vytautas Magnus University, Faculty of Natural Sciences, Kaunas, Lithuania c Vytautas Magnus University, The Hospital of Lithuanian University of Health Sciences Kauno Klinikos, Faculty of Natural Sciences, Kaunas, Lithuania ⇑ Corresponding author.
Purpose. Investigation of mitotic arrest in cells irradiated to radiotherapeutic doses. Methods. Chinese hamster ovary (CHO) cell line was used as an irradiation object. CHO cells were irradiated to the doses from the
Abstracts / Physica Medica 52 (2018) 99–187
range (0–10 Gy) in linear accelerator Varian ClinacDMX using 6 MeV photons. Clonogenic cell assay was used to assess radiation induced effects in irradiated cells. Cell colonies were manually counted using ImageJ software plug-in Colony Counter. Colony residence area was assessed using ImageJ software plug-in Analyze Particles, which enabled analysis of the scanned image of Petri dish with cells detecting separate cell colonies and calculating the average area of colonies within the dish. In parallel COMET assay was used for the assessment of radiation induced DNA damages in cells. Results. It was found, that the statistically significant decrease of formed cell colony’s area with the increasing irradiation dose (known as mitotic arrest process in affected cells) was stopped when the dose of 6 Gy was applied, indicating almost the same low level of mitotic activity at higher doses. It was suggested that the irradiated cells may have maximal mitotic arrest time which is irradiation dose independent at the doses P6 Gy, thus indicating the existence of the cell specific dose threshold at which maximal delayed mitosis effect with initiation of 30% of DNA damage on surviving cell fraction is present. There was no dose threshold effect observed evaluating cell viability and radiation induced DNA damages. Conclusions. Investigation results based hypothesis regarding possible existence of time dependent threshold dose for maximal delayed mitosis effect in irradiated cells was raised and discussed indicating that the application of dose threshold based irradiation model can contribute to the improvement of fractionated radiotherapy treatment efficiency. A need for more detailed investigations for verification of these findings was also indicated. https://doi.org/10.1016/j.ejmp.2018.06.562
[P288] Use of organic plastic scintillators for determination of the beam quality correction factor for flattening filter free photon beams Grichar V. Santurio *, Claus E. Andersen Technical University of Denmark, Center for Nuclear Technologies, Roskilde, Denmark ⇑ Corresponding author. Purpose. The purpose was to use organic plastic scintillators for determination of the beam quality correction factor ðk Q;Q0 Þ for flattening filters free (FFF) photon beams increasingly used in modern radiotherapy. The values were compared with those recommended in the recent TRS-483 code of practice from the International Agency of Atomic Energy. Methods. The formalism in TRS-483 covers not only small conventional photon beams with flattening filter (WFF), but also flattening filter free (FFF) beams. TRS-483 splits the k Q;Q0 into two correction f
f
ref factors for FFF beams: k Qref WFF ;Q0 and k QFFF ;QWFF . An IBA FC-65G ionization
chamber, calibrated for conventional MV photon beams, was used to experimentally determine the k QFFF ;Q0 . The fiber-coupled scintillator (1 mm diameter; 2 mm length) was used as a water-point surrogate detector for determination of the k Q;Q0 from quality QFFF with respect QWEF . Given the high degree of water-equivalence of this detector, and in line with the studies presented in TRS-483, it was assumed that the detector was perturbation free. Corrections were, however, made for ionization quenching based on published parameters for the used scintillator and Birks formalism implemented in the Monte Carlo toolkit EGSnrc. Results. The spectral difference between WFF and FFF resulted in changes in the ionization quenching which in turn affected the FFF/WFF-ratio in the TRS-483 formalism by about 0.6% for 6 MV and by 0.35% for 10 MV, respectively. After correcting for this, the beam quality correction factor for the FFF 6 MV and 10 MV beam
183
was found to differ insignificantly, 0.3%, compared with those recommended in TRS-483 when given that uncertainty of the ionization quenching correction factor alone was about 0.15% and that additional uncertainty components (>0.5%) are associated with the measurements. Conclusions. An experimental method for determining the beam quality correction factor for FFF to WFF was carried out. The study supports that organic plastic scintillators can be used as a perturbation-free detector in MV photon beams. However, considerations should be given to the change in quenching when spectrally different beams are involved such as when computing the dose ratio for WFF and FFF beams in the TRS-483 formula for beam quality correction factor. https://doi.org/10.1016/j.ejmp.2018.06.563
[P290] Radiotherapy risk analysis from incidence reports at a national level Harald Spejborg a,*, Kirsten L. Jakobsen b, Annette R. Jakobsen c, Lene Holberg d, Knud A. Werenberg e, Bettina J. Godborg f, Eva Samsøe b a
Aarhus University Hospital, Department of Medical Physics, Aarhus, Denmark b University Hospital Herlev, Department of Oncology, Herlev, Denmark c Aalborg University Hospital, Department of Oncology, Aalborg, Denmark d Vejle Sygehus, Department of Oncology, Vejle, Denmark e Odense University Hospital, Department of Radiophysics, Odense, Denmark f Naestved Sygehus, Department of Oncology, Naestved, Denmark ⇑ Corresponding author. Purpose. In order to share data on patient risk during radiotherapy (RT) on a national level and to stimulate a learning potential between the RT-centers, a national special group of interest in RT (RT-SIG) under the national society for medical physics was formed in 2016. Since then RT-SIG has collected and analyzed patient risk data from six centers. RT-SIG is stimulating the centers to analyze and categorize data in an inter-center consistent way facilitating sharing of data and making common reports and recommendations on patient RT safety improvements. Methods. Adverse and near miss incidence reports in RT are collected and analyzed locally at each center. Events are categorized by two different systems, 1 Patient Consequence Coding (PCC) according to the kind of consequence experienced by the patient and 2 RT Pathway Coding (RPC) according to the RT process at which the incident originated. Consensus surveys are performed twice a year in order to standardize local data analysis by the local center Risk Analysis Team. During 2017 local data were collected, and incidence patterns on a national level as well as on local RT-centers were analyzed. Results. Data of the consensus surveys are presented. Preliminary results on patient data analysis from 2016 have shown a big difference in the reporting activity between the participating centers whereas the risk patterns are quite similar. The majority of the incidents are found to occur in the planning steps of the RT course, giving risk of systematic errors through the entire course of RT. New national data for 2017 including anonymized inter-center comparison results will be presented. Data indicates consistent data analysis and similar risk profiles between the six participating RT-Centers. Conclusion. Due to training of the risk analysis teams at different RT centers, it is possible to use a common data categorizing system making inter-center analysis and comparisons feasible. Data from six centers show a different reporting frequency. However, a similar risk profile indicates that pooled national data have the potential of