An Update on the Role of mpMRI and 68Ga-PSMA PET Imaging in Primary and Recurrent Prostate Cancer.

The objective of this work was to review comparisons of the efficacy of 68Ga-PSMA-11 (prostate-specific membrane antigen) PET/CT and multiparametric magnetic resonance imaging (mpMRI) in the detection of prostate cancer among patients undergoing initial staging prior to radical prostatectomy or experiencing recurrent prostate cancer, based on histopathological data. A comprehensive search was conducted in PubMed and Web of Science, and relevant articles were analyzed with various parameters, including year of publication, study design, patient count, age, PSA (prostate-specific antigen) value, Gleason score, standardized uptake value (SUVmax), detection rate, treatment history, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and PI-RADS (prostate imaging reporting and data system) scores. Only studies directly comparing PSMA-PET and mpMRI were considered, while those examining combined accuracy or focusing on either modality alone were excluded. In total, 24 studies comprising 1717 patients were analyzed, with the most common indication for screening being staging, followed by relapse. The findings indicated that 68Ga-PSMA-PET/CT effectively diagnosed prostate cancer in patients with suspected or confirmed disease, and both methods exhibited comparable efficacy in identifying lesion-specific information. However, notable heterogeneity was observed, highlighting the necessity for standardization of imaging and histopathology systems to mitigate inter-study variability. Future research should prioritize evaluating the combined diagnostic performance of both modalities to enhance sensitivity and reduce unnecessary biopsies. Overall, the utilization of PSMA-PET and mpMRI in combination holds substantial potential for significantly advancing the diagnosis and management of prostate cancer.

Development and Application of Prototype System Based on Light-Emitting Diode Arrays (660 nm) with a Top Hat Beam Profile in Order to Optimize Photobiomodulation Protocols for Treatment of Radiation-Induced Oral Mucositis in Rats.

Background: Oral mucositis (OM) is a common adverse effect of radiation to the head and neck. Recent research has shown that extra oral photobiomodulation (EO-PBM) reduces the severity of OM. However, appropriate EO-PBM therapy parameters for OM severity reduction have not been documented. Objective: This work aims to optimize EO-PBM radiation parameters for lowering the severity of radiation-induced OM in rats by establishing a photobiomodulation (PBM) treatment system based on light-emitting diode arrays with top-hat beam profile. Methods: The 36 rats are separated into 2 control groups and 4 groups receiving PBM treatment. The PBM groups are exposed to irradiance between 4 and 24 J/cm2 at 660 nm. The cheek pouch mucosa is removed after scarification for biochemical and histological examination. Student's t-test, and one-way analysis of variance (ANOVA) followed by Tukey's Multiple were applied to compare the statistical significance of differences between control groups and PBM treatment groups. Results: Statistical analysis reveals that PBM irradiation at 12 J/cm2 (200 sec) with a flatness of 0.8 and a diameter of 3 cm substantially decreased the level of inflammatory cytokines compared with the positive control group. Conclusions: Our results indicate that the designed treatment PBM system is capable of delivering the optical parameters necessary for therapeutic treatment.

Estimating the skin dose near to the applicator and acute toxicity in breast cancer patients: An intraoperative electron radiotherapy technique.

Introduction: Intraoperative electron radiation therapy (IOERT) is one of the most recently popular therapeutic methods for breast cancer. This study aimed to measure the skin dose near the applicator during IOERT of breast cancer patients, as well as, the incidence of acute toxicity after surgery. Materials and Methods: Thirty-six female patients participated in the current study with the prescribed dose of 21 and 12 Gy for IOERT as full and boost, respectively. The skin dose was investigated based on different applicator sizes, tumor bed thicknesses, and monitor units (MUs). The energy was chosen 8 MeV, and EBT3 film was used for the dosimetric process. In addition, the acute toxicity included healing time for the surgical wound, scaling of the skin, itching, necrosis, redness as well as seroma formation for 1 week and 1 month were recorded. The results were compared to those of 22 patients who underwent the surgery without IOERT. Results: The highest skin dose for the patients was obtained 2.09 Gy, which is lower than the threshold dose (6 Gy). Furthermore, the findings showed that the average skin dose was higher in bigger applicator sizes and MU and lower tumor bed thicknesses. The average of wound healing for the patient underwent IOERT and without the use of IOERT (as the control group) was 19.32 and 11.67 days, respectively. One month after surgery, the volume of aspirated seroma was higher in the patients who performed IOERT compared to the control group (250 ml vs. 200 ml). It is notable that there were not observed any redness, itching, scaling, and necrosis in both investigated groups. Conclusion: Owing to the results, the skin dose during IOERT was lower than the recommended level. The dose of IOERT as a full was higher than boost which can be related to the lower number of the patients in full method; however, there was a well-tolerated without severe acute complication, especially seroma formation and wound healing time in both full and boost methods.

An inter-comparison between accuracy of EGSnrc and MCNPX Monte Carlo codes in dosimetric characterization of intraoperative electron beam.

BACKGROUND: Ionometric dosimetry in IOERT is a complicated process, due to the sophisticated beam setup and the necessity for dedicated protocols for ion chamber response correction. On the other hand, the Monte Carlo (MC) technique can easily overcome such limitations and be considered as an alternative dosimetry approach. This paper presents a comparative analysis of two widely used MC codes, EGSnrc and MCNPX, for intraoperative electron beam dosimetry. METHOD: The head of LIAC12, a dedicated IOERT accelerator, was modeled by both mentioned MC codes. Then, the percentage depth dose (PDD) curves, transverse dose profiles (TDPs), and output factor (OF) values were accordingly calculated within the water phantom. To realize the accuracy of MC codes in dosimetric characterization of intraoperative electron beam, their results were finally compared with those measured by corresponding ionometric dosimetry for all forms of electron energy/applicator size. RESULTS: A good agreement was observed between the simulated and measured PDDs/TDPs for both considered MC codes, such that the calculated gamma index values were always lower than unity for both considered MC codes. Nevertheless, the lower gamma index values were found in the case of the EGSnrc code. The maximum difference between the measured and calculated OF was obtained as 2.3% and 3.1% for EGSnrc and MCNPX code, respectively. CONCLUSIONS: Although both studied MC codes showed compatible results with the measured ones, EGSnrc code has superior accuracy in this regard and can be considered as a more reliable toolkit in Monte Carlo-based commissioning of dedicated IOERT accelerators.

Sumatriptan alleviates radiation-induced oral mucositis in rats by inhibition of NF-kB and ERK activation, prevention of TNF-α and ROS release.

OBJECTIVES: Oral mucositis caused by radiation therapy is a common problem in cancer patients, especially those with head and neck cancer. Numerous experimental and clinical studies have attempted to find a drug to alleviate oral mucositis. Sumatriptan, is conventionally used to treat migraine attack and cluster headache. Recently, low doses have been shown to have anti-inflammatory properties. In this study we aimed to measure the effect of sumatriptan on experimental radiotherapy-induced oral mucositis. MATERIAL AND METHODS: This study evaluates the use of sumatriptan 0.3 and 1 mg/kg in radiation-induced oral mucositis. In order to induce oral mucositis, six rats from each group received 8-Gy of X-ray in a single session. Likewise, three rats from each group received 26-Gy of X-ray. The latter dose of X-ray was used for inducing severe mucositis and apoptosis evaluation by TUNEL assay, while the first dose was used for histopathological and molecular assessments. On 8th day after irradiation, specimens were collected from their tongues for histology, TUNEL and molecular assessments. RESULTS: Radiation caused mucosal atrophy, derangement of the tissue and vasodilation. Sumatriptan significantly decreased histopathological score and alleviated mucosal atrophy. As well, there was no evidence of vasodilation in the sumatriptan group. Likewise, sumatriptan decreased the increased level of NF-kB and prevented its activation as well as ERK phosphorylation. In addition, Sumatriptan-treated rats had lower tissue level of TNF-α, reactive oxygen species and fewer apoptotic cells in TUNEL assay. CONCLUSION: Based on study results, sumatriptan mitigate radiation-induced oral mucositis by inhibiting NF-kB, ERK and limiting the release of TNF-α, oxidative stress factor and apoptosis.

Comparing the performance of some dedicated radioprotection disks in breast intraoperative electron radiotherapy: a Monte Carlo study.

Radiation-shielding of healthy tissue is mandatory in breast intraoperative electron radiotherapy (IOERT). In this regard, dedicated radioprotection disks have been introduced. The aim of this study was to evaluate and compare the performance of three radioprotection disks widely used for breast IOERT. A Monte Carlo simulation approach was used for this purpose. The considered disks included Al + Pb, PMMA + Copper, and PTFE + Steel. They were stimulated by means of the MCNPX Monte Carlo code at depths around R100 and R90 of different electron energies in a water phantom, and their impact on the dosimetric properties of the therapeutic beam was evaluated in both correct and upside down disk placements. The electron energy spectrum immediately above and below each disk was calculated and analyzed. Furthermore, performance characteristics of the studied disks such as backscatter factors (BSFs) and transmission factors (TFs) at different electron energies were determined and compared. The results show that the Al + Pb disk most effectively attenuates the beam, while at the same time exhibits maximum BSF values. Employing the PMMA + Copper disk can minimize the BSF value but at the expense of an increased TF. The Al + Pb disk showed the best performance from the radiation protection viewpoint, while its highest BSF values could lead to perturbation of dose homogeneity within the target volume. PTFE + Steel disk showed an intermediate performance regarding the electron backscattering and transmission among the studied disks. The reverse placement of each disk can substantially increase the BSF value as compared to the correct situation but had less impact on the TF value.

Monte Carlo-based determination of radiation leakage dose around a dedicated IOERT accelerator.

Evaluating the stray radiation around medical electron accelerators is a mandatory issue. Surveying the radiation leakage dose is important for patients, technicians, and health physicists, due to radiation protection aspects. Consequently, radiation leakage dose around the head of a mobile-dedicated intraoperative radiotherapy accelerator (LIAC), at different electron energies and field sizes have been evaluated in this study. More specifically, the MCNPX Monte Carlo code was used to model the LIAC head, connected applicator, and employed water phantom. Radiation leakage dose around the LIAC head was calculated for different energy and field sizes through tuning the Monte Carlo results to the practically measured doses. These measurements were performed using an Advance Markus ionization chamber inside an automated MP3-XS water phantom. The good agreement between the calculated dose distributions within the water tank and corresponding dose measurements show that the simulation model of the LIAC head is appropriate for radiation leakage assessment. The obtained radiation leakage dose distribution highly depends on the electron energy and applicator diameter. With increasing the electron energy, the leakage dose decreased, while increasing the field size increased the leakage dose. It is concluded that the rate of stray radiation and leakage dose around the LIAC head in both vertical and horizontal planes were acceptable according to the recommended radiation protection criteria. To meet the recommended dose limit (100 µSv/week for controlled areas), the maximum number of patients should be kept to four patients per week inside a standard and unshielded operating room.

Impact of image reconstruction methods on quantitative accuracy and variability of FDG-PET volumetric and textural measures in solid tumors.

OBJECTIVE: This study aims to assess the impact of different image reconstruction methods on PET/CT quantitative volumetric and textural parameters and the inter-reconstruction variability of these measurements. METHODS: A total of 25 oncology patients with 65 lesions (between 2017 and 2018) and a phantom with signal-to-background ratios (SBR) of 2 and 4 were included. All images were retrospectively reconstructed using OSEM, PSF only, TOF only, and TOFPSF with 3-, 5-, and 6.4-mm Gaussian filters. The metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. The relative percent error (ΔMTV and ΔTLG) with respect to true values, volume recovery coefficients, and Dice similarity coefficient, as well as inter-reconstruction variabilities were quantified and assessed. In clinical scans, textural features (coefficient of variation, skewness, and kurtosis) were determined. RESULTS: Among reconstruction methods, mean ΔMTV differed by -163.5 ± 14.1% to 6.3 ± 6.2% at SBR2 and -42.7 ± 36.7% to 8.6 ± 3.1 at SBR4. Dice similarity coefficient significantly increased by increasing SBR from 2 to 4, ranging from 25.7 to 83.4% between reconstruction methods. Mean ΔTLG was -12.0 ± 1.7 for diameters > 17 mm and -17.8 ± 7.8 for diameters ≤ 17 mm at SBR4. It was -31.7 ± 4.3 for diameters > 17 mm and -14.2 ± 5.8 for diameters ≤ 17 mm at SBR2. Textural features were prone to variations by reconstruction methods (p < 0.05). CONCLUSIONS: Inter-reconstruction variability was significantly affected by the target size, SBR, and cut-off threshold value. In small tumors, inter-reconstruction variability was noteworthy, and quantitative parameters were strongly affected. TOFPSF reconstruction with small filter size produced greater improvements in performance and accuracy in quantitative PET/CT imaging. KEY POINTS: • Quantitative volumetric PET evaluation is critical for the analysis of tumors. • However, volumetric and textural evaluation is prone to important variations according to different image reconstruction settings. • TOFPSF reconstruction with small filter size improves quantitative analysis.

Evaluating the performance of TG-43 protocol in esophageal HDR brachytherapy viewpoint to trachea inhomogeneity.

AIM: The aim of this study is to evaluate the effect of air within trachea on dose calculations of esophageal HDR brachytherapy treatment planning. BACKGROUND: Dose calculations in esophageal HDR brachytherapy treatment planning systems are greatly based on TG-43 protocol which in all materials are considered to be water equivalent. MATERIALS AND METHODS: A cylindrical PMMA phantom with a tube in the center (neck equivalent phantom) accompanied by Flexitron HDR brachytherapy system was used in this study. Brachytherapy applicators with various diameters were placed inside the esophageal tube and EDR2 film was used for dosimetry. The absorbed dose by reference point of esophageal HDR brachytherapy and anterior wall of trachea were measured and compared with those calculated by Flexiplan treatment planning system. RESULTS: Based on the performed statistical analysis (t-test) with 95% confidence level (t-value >1.96), there was a meaningful difference between the results of film dosimetry and treatment planning at all of the points understudy. CONCLUSION: The meaningful difference between the results of film dosimetry and treatment planning indicates that the trachea inhomogeneity has a considerable effect on dose calculations of Flexiplan treatment planning software featuring the TG-43 dose calculation algorithm. This mismatch can affect the accuracy of performed treatment plan and irradiation.

Education and training of medical physics in Iran: The past, the present and the future.

PURPOSE: The aim of this study was to investigate the current status of education and training programs in medical physics in Iran. METHODS: A questionnaire was designed and sent to 274 IAMP (Iranian Association of Medical Physicists) members focusing on these two topics: the educational situation (course syllabus, number of faculty members, number of PhD and MSc students and sub-fields offered in the department) and the professional situation (work experience, workplaces of medical physicists, postgraduate degrees that were granted and the amount of therapy and imaging equipment). RESULTS: Medical physics education in Iran is provided at 14 universities at master and doctorate levels. All medical physics departments offer an MSc program and 6 of them offer a PhD program. Most medical physics faculty (24%) work in the radiotherapy physics sub-specialty. Also, about 95 medical physics students graduate every year. There are six major peer-reviewed Iranian journals that publish medical physics papers in English. In addition, there are 74 radiotherapy machines including Co-60 and LINACs (LINear ACcelerators) across Iran as of 2013. CONCLUSIONS: The curriculum of medical physics programs (MSc and PhD) in Iran must be improved to include long-term clinical courses in the four major sub-specialties of radiotherapy, medical imaging, nuclear medicine and radiation protection. It is hoped that clinical medical physicists will go through nationally-accredited exams before assuming independent clinical responsibilities. Moreover, the work situation of the medical physics profession in Iran should be clear and the government authorities must recognize importance of this interdisciplinary field in medicine.

Commissioning of beam shaper applicator for conformal intraoperative electron radiotherapy.

Beam shaper is a newly designed device for beam shaping in IOERT. The aim of this study is evaluating the performance of this device for conformal IOERT and preparing it for clinical applications. Dosimetric characteristics for different combinations of energy/field size were determined by ionometric dosimetry, film dosimetry and Monte Carlo simulation. Desirable dosimetric characteristics of beam shaper make it a useful tool for conformal IOERT. Usability of Monte Carlo simulation in any clinical setup of beam shaper was demonstrated.

A novel position-sensitive mega-size dosimeter for photoneutrons in high-energy X-ray medical accelerators.

PURPOSE: A novel position-sensitive mega-size polycarbonate (MSPC) dosimeter is introduced. It provides photoneutron (PN) dose equivalent matrix of positions in and out of a beam of a high energy X-ray medical accelerator under a single exposure. METHODS: A novel position-sensitive MSPC dosimeter was developed and applied. It has an effective etched area of 50×50cm(2), as used in this study, processed in a mega-size electrochemical etching chamber to amplify PN-induced-recoil tracks to a point viewed by the unaided eyes. Using such dosimeters, PN dose equivalents, dose equivalent profiles and isodose equivalent distribution of positions in and out of beams for different X-ray doses and field sizes were determined in a Siemens ONCOR Linac. RESULTS: The PN dose equivalent at each position versus X-ray dose was linear up to 20Gy studied. As the field size increased, the PN dose equivalent in the beam was also increased but it remained constant at positions out of the beam up to 20cm away from the beam edge. The jaws and MLCs due to material differences and locations relative to the target produce different PN contributions. CONCLUSIONS: The MSPC dosimeter introduced in this study is a perfect candidate for PN dosimetry with unique characteristics such as simplicity, efficiency, dose equivalent response, large size, flexibility to be bent, resembling the patient's skin, highly position-sensitive with high spatial resolution, highly insensitive to X-rays, continuity in measurements and need to a single dosimeter to obtain PN dose equivalent matrix data under a single X-ray exposure.

Comparing the dosimetric characteristics of the electron beam from dedicated intraoperative and conventional radiotherapy accelerators.

The specific design of the mobile dedicated intraoperative radiotherapy (IORT) accelerators and different electron beam collimation system can change the dosimetric characteristics of electron beam with respect to the conventional accelerators. The aim of this study is to measure and compare the dosimetric characteristics of electron beam produced by intraoperative and conventional radiotherapy accelerators. To this end, percentage depth dose along clinical axis (PDD), transverse dose profile (TDP), and output factor of LIAC IORT and Varian 2100C/D conventional radiotherapy accelerators were measured and compared. TDPs were recorded at depth of maximum dose. The results of this work showed that depths of maximum dose, R90, R50, and RP for LIAC beam are lower than those of Varian beam. Furthermore, for all energies, surface doses related to the LIAC beam are substantially higher than those of Varian beam. The symmetry and flatness of LIAC beam profiles are more desirable compared to the Varian ones. Contrary to Varian accelerator, output factor of LIAC beam substantially increases with a decrease in the size of the applicator. Dosimetric characteristics of beveled IORT applicators along clinical axis were different from those of the flat ones. From these results, it can be concluded that dosimetric characteristics of intraoperative electron beam are substantially different from those of conventional clinical electron beam. The dosimetric characteristics of the LIAC electron beam make it a useful tool for intraoperative radiotherapy purposes.

Commissioning and initial acceptance tests for a commercial convolution dose calculation algorithm for radiotherapy treatment planning in comparison with Monte Carlo simulation and measurement.

In this study the commissioning of a dose calculation algorithm in a currently used treatment planning system was performed and the calculation accuracy of two available methods in the treatment planning system i.e., collapsed cone convolution (CCC) and equivalent tissue air ratio (ETAR) was verified in tissue heterogeneities. For this purpose an inhomogeneous phantom (IMRT thorax phantom) was used and dose curves obtained by the TPS (treatment planning system) were compared with experimental measurements and Monte Carlo (MCNP code) simulation. Dose measurements were performed by using EDR2 radiographic films within the phantom. Dose difference (DD) between experimental results and two calculation methods was obtained. Results indicate maximum difference of 12% in the lung and 3% in the bone tissue of the phantom between two methods and the CCC algorithm shows more accurate depth dose curves in tissue heterogeneities. Simulation results show the accurate dose estimation by MCNP4C in soft tissue region of the phantom and also better results than ETAR method in bone and lung tissues.

Evaluation of the Combined Effect of 2ME2 and (60)Co on the Inducement of DNA Damage by IUdR in a Spheroid Model of the U87MG Glioblastoma Cancer Cell Line Using Alkaline Comet Assay.

OBJECTIVE: In this study, we investigated the combined effect of 2-Methoxyestradiol (2ME2) and (60)Co on the cytogenetic damage of iododeoxyuridine (IUdR) in the spheroid model of U87MG glioblastoma cancer cell lines by alkaline comet assay. MATERIALS AND METHODS: U87MG cells were cultured as spheroids with diameters of 350 µm. As control, the spheroids of one plate were not treated. Other cultures were pretreated with 2ME2 (250 µM) for one volume doubling time (1 VDT). After this time, the subsequent treatments were performed according to the following groups: Vehicle (this sample was not treated in the 2(nd) VDT) Treated with 2ME2 (250 µM) for 1 VDT Treated simultaneously with 2ME2 (250 µM) and IUdR (1 µM) for 1 VDT Treated with 2ME2 (250 µM) for 1 VDT then irradiated with (60)Co (2 Gy) Treated simultaneously with 2ME2 (250 µM) and IUdR (1 µM) for 1 VDT then irradiated with (60)Co (2 Gy) Then the DNA damage was evaluated using the alkaline comet assay method. RESULTS: The results showed that 2ME2 in combination with gamma irradiation of (60)Co significantly (p<0.001) increased the DNA damage by IUdR as compared to the control group. Thus the combination of these two agents increased the cytogenetic effects of IUdR in the spheroid culture model of U87MG glioblastoma cell lines. CONCLUSION: By inhibiting the HIF-1α protein and preventing the G0 phase arrest, 2ME2 causes an increased progression into S phase and increases the IUdR absorption. Then the DNA damage in the spheroid cells increases as the uptake of IUdR is increased. These results suggest that the combined use of 2ME2 and (60)Co can increase the radiosensitization effect of IUdR.