Dynamic anthropomorphic thorax phantom for quality assurance of motion management in radiotherapy.

Background and purpose: Motion management techniques are important to spare the healthy tissue adequately. However, they are complex and need dedicated quality assurance. The aim of this study was to create a dynamic phantom designed for quality assurance and to replicate a patient's size, anatomy, and tissue density. Materials and methods: A computed tomography (CT) scan of a cancer patient was used to create molds for the lungs, heart, ribs, and vertebral column via additive manufacturing. A pump system and software were developed to simulate respiratory dynamics. The extent of respiratory motion was quantified using a 4DCT scan. End-to-end tests were conducted to evaluate two motion management techniques for lung stereotactic body radiotherapy (SBRT). Results: The chest wall moved between 4 mm and 13 mm anteriorly and 2 mm to 7 mm laterally during the breathing. The diaphragm exhibited superior-inferior movement ranging from 5 mm to 16 mm in the left lung and 10 mm to 36 mm in the right lung. The left lung tumor displaced ± 7 mm superior-inferiorly and anterior-posteriorly. The CT numbers were for lung: -716 ± 108 HU (phantom) and -713 ± 70 HU (patient); bone: 460 ± 20 HU (phantom) and 458 ± 206 HU (patient); soft tissue: 92 ± 9 HU (phantom) and 60 ± 25 HU (patient). The end-to-end testing showed an excellent agreement between the measured and the calculated dose for ion chamber and film dosimetry. Conclusions: The phantom is recommended for quality assurance, evaluating the institution's specific planning and motion management strategies either through end-to-end testing or as an external audit phantom.

Erratum to: Surface guided 3DCRT in deep-inspiration breath-hold for left sided breast cancer radiotherapy: implementation and first clinical experience in Iran.

[This corrects the article DOI: 10.5603/RPOR.a2022.0103.].

A dose planning study for cardiac and lung dose sparing techniques in left breast cancer radiotherapy: Can free breathing helical tomotherapy be considered as an alternative for deep inspiration breath hold?

Purpose: To investigate the possibility to be able to offer left sided breast cancer patients, not suitable for DIBH, an organ at risk saving treatment. Materials and Methods: Twenty patients receiving radiotherapy for left breast cancer in DIBH were enrolled in the study. Planning CT scans were acquired in the same supine treatment position in FB and DIBH. 3DCRT_DIBH plans were designed and optimized using two parallel opposed tangent beams (with some additional segments) for the breast and chest wall and anterior-posterior fields for regional lymph nodes irradiation. Additionally, FB helical tomotherapy plans were optimized to minimize heart and lung dose. All forty plans were optimized with at least 95% of the total CTV covered by the 95% of prescribed dose of 50 Gy in 25 fractions. Results: HT_FB plans showed significantly better dose homogeneity and conformity compared to the 3DCRT_DIBH specially for regional nodal irradiation. The heart mean dose was almost comparable in 3DCRT_DIBH and HT_FB while the volume (%) of the heart receiving 25 Gy had a statistically significant reduction from 7.90 ± 3.33 in 3DCRT_DIBH to 0.88 ± 0.66 in HT_FB. HT_FB was also more effective in left descending artery (LAD) mean dose reduction about 100% from 30.83 ± 9.2 Gy to 9.7 ± 3.1. The ipsilateral lung volume receiving 20 Gy has a further reduction of 43 % in HT_FB compared with 3DCRT_DIBH. For low dose comparison, 3DCRT_DIBH was superior for contralateral organ sparing compared to the HT_FB due to the limited angle for dose delivery. Conclusion: For patients who cannot be a candidate for DIBH for any reason, HT in free breathing may be a good alternative and provides heart and ipsilateral lung dose sparing, however with the cost of increased dose to contralateral breast and lung.

Surface guided 3DCRT in deep-inspiration breath-hold for left sided breast cancer radiotherapy: implementation and first clinical experience in Iran.

Background: The aim of the study is to evaluate the overall accuracy of the surface-guided radiotherapy (SGRT) workflow through a comprehensive commissioning and quality assurance procedures and assess the potential benefits of deep-inspiration breath-hold (DIBH) radiotherapy as a cardiac and lung dose reduction approach for left-sided breast cancer irradiation. Materials and methods: Accuracy and reproducibility of the optical surface scanner used for DIBH treatment were evaluated using different phantoms. Patient positioning accuracy and reproducibility of DIBH treatment were evaluated. Twenty patients were studied for treatment plan quality in target dose coverage and healthy organ sparing for the two different treatment techniques. Results: Reproducibility tests for the surface scanner showed good stability within 1 mm in all directions. The maximum position variation between applied shifts on the couch and the scanner measured offsets is 1 mm in all directions. The clinical study of 200 fractions showed good agreement between the surface scanner and portal imaging with the isocenter position deviation of less than 3 mm in each lateral, longitudinal, and vertical direction. The standard deviation of the DIBH level showed a value of < 2 mm during all evaluated DIBHs. Compared to the free breathing (FB) technique, DIBH showed significant reduction of 48% for heart mean dose, 43% for heart V25, and 20% for ipsilateral lung V20. Conclusion: Surface-guided radiotherapy can be regarded as an accurate tool for patient positioning and monitoring in breast radiotherapy. DIBH treatment are considered to be effective techniques in heart and ipsilateral lung dose reductions for left breast radiotherapy.

Evaluating Five Escherichia coli Derivative Strains as a Platform for Arginine Deiminase Overproduction.

AIMS: This study attempted to evaluate the five host strains, including BL21 (DE3), Rosetta (DE3), DH5α, XL1-BLUE, and SHuffle, in terms of arginine deiminase (ADI) production and enzyme activity. BACKGROUND: Escherichia coli is one of the most preferred host microorganisms for the production of recombinant proteins due to its well-characterized genome, availability of various expression vectors, and host strains. Choosing a proper host strain for the overproduction of a desired recombinant protein is very important because of the diversity of genetically modified expression strains. Various E. coli cells have been examined in different patent applications. METHODS: ADI was chosen as a bacterial enzyme that degrades L-arginine. It is effective in the treatment of some types of human cancers like melanoma and hepatocellular carcinoma (HCC), which are arginine-auxotrophic. Five mentioned E. coli strains were cultivated. The pET-3a was used as the expression vector. The competent E. coli cells were obtained through the CaCl2 method. It was then transformed with the construct of pET3a-ADI using the heat shock strategy. The ADI production levels were examined by 10% SDS-PAGE analysis. The ability of host strains for the expression of the requested recombinant protein was compared. The enzymatic activity of the obtained recombinant ADI from each studied strain was assessed by a colorimetric 96-well microtiter plate assay. RESULTS: All the five strains exhibited a significant band at 46 kDa. BL21 (DE3) produced the highest amount of ADI protein, followed by Rosetta (DE3). The following activity assay showed that ADI from BL21 (DE3) and Rosetta (DE3) had the most activity. CONCLUSION: There are some genetic and metabolic differences among the various E. coli strains, leading to differences in the amount of recombinant protein production. The results of this study can be used for the efficacy evaluation of the five studied strains for the production of similar pharmaceutical enzymes. The strains also could be analyzed in terms of proteomics.

Comparison of fast-neutron contamination of different models of Siemens medical linacs with CR-39 film.

BACKGROUND: Nowadays, radiotherapy has an important role in the treatment of cancer. The use of medical linacs in radiotherapy can have risks for patients. When radiotherapy is performed with photons with energies higher than 8 MeV, due to the photonuclear reaction of photons with various components in the head of the accelerator, the neutron is produced. This imposes an unwanted neutron dose to the patient. The purpose of this study is evaluation and comparison of fast-neutron contamination with increasing of field size and depth for Siemens Primus (15 MV), Siemens Primus Plus (18 MV), and Siemens Artiste (15 MV) linacs. MATERIALS AND METHODS: Neutron dosimetry was carried out with CR-39 films, as a fast-neutron dosimeter, using chemical etching technique. Measurements were performed in depths of 0.5, 2, 3, and 4 cm and source-to-surface distance of 100 cm. Field sizes were 10 cm × 10 cm and 30 cm × 30 cm. RESULTS: The results of measurements showed that, with increasing depth, equivalent dose is reduced. In addition, fast-neutron equivalent dose decreases with increasing the field size. CONCLUSION: Siemens Primus Plus had the highest neutron contamination in comparison with the two other linacs. Deeper tissues receive less fast-neutron doses. In radiation therapy with high-energy photon beams, neutron dose delivered to the patients should be taking into account.

Radiobiological comparison between Cobalt-60 and Iridium-192 high-dose-rate brachytherapy sources: Part I-cervical cancer.

PURPOSE: This study aimed to compare the biological effective doses (BEDs) to clinical target volume (CTV) and organs at risk (OARs) for cervical cancer patients treated with high-dose-rate (HDR) Iridium-192 (192 Ir) or Cobalt-60 (60 Co) brachytherapy (BT) boost and to determine if the radiobiological differences between the two isotopes are clinically relevant. METHODS: Considering all radiosensitivity parameters and their reported variations, the BEDs to CTV and OARs during HDR 60 Co/192 Ir BT boost were evaluated at the voxel level. The anatomical differences between individuals were also taken into account by retrospectively considering 25 cervical cancer patients. The intrafraction repair, proliferation, hypoxia-induced radiosensitivity heterogeneity, relative biological effectiveness (RBE), and source aging dose-rate variation were also taken into account. The comparisons in CTV were performed based on equivalent uniform BED (EUBED). RESULTS: Considering nominal parameters with no RBE correction, the CTV EUBEDs were almost similar with a median ratio of ∼1.00 (p < 0.00001), whereas RBE correction resulted in 3.9%-5.5% (p = 0.005, median = 4.8%) decrease for 60 Co with respect to 192 Ir. For OARs, the median values of D2cc (in EQD23 ) for 60 Co were lower than that of 192 Ir up to 9.2% and 11.3% (p < 0.00001) for nominal parameters and fast repair conditions, respectively. In addition, for a nominal value (reported range) of radiosensitive parameters, the CTV EUBED differences of up to 6% (5%-10%) were assessed for HDR-BT component. CONCLUSION: The RBE values are the most important cause of discrepancies between the two sources. By comparing BED/EUBEDs to CTV and OARs between 60 Co and 192 Ir sources, this numerical study suggests that a dose escalation to ∼4% is feasible and safe while sparing well the surrounding normal tissues. This 4% dose escalation should be benchmarked with clinical evidences (such as the results of clinical trials) before it can be used in clinical practice.

Amino Acids Sequence-based Analysis of Arginine Deiminase from Different Prokaryotic Organisms: An In Silico Approach.

BACKGROUND: Arginine deiminase is a bacterial enzyme, which degrades L-arginine. Some human cancers such as hepatocellular carcinoma (HCC) and melanoma are auxotrophic for arginine. Therefore, PEGylated arginine deiminase (ADI-PEG20) is a good anticancer candidate with antitumor effects. It causes local depletion of L-arginine and growth inhibition in arginineauxotrophic tumor cells. The FDA and EMA have granted orphan status to this drug. Some recently published patents have dealt with this enzyme or its PEGylated form. OBJECTIVE: Due to increasing attention to it, we aimed to evaluate and compare 30 arginine deiminase proteins from different bacterial species through in silico analysis. METHODS: The exploited analyses included the investigation of physicochemical properties, multiple sequence alignment (MSA), motif, superfamily, phylogenetic and 3D comparative analyses of arginine deiminase proteins thorough various bioinformatics tools. RESULTS: The most abundant amino acid in the arginine deiminase proteins is leucine (10.13%) while the least amino acid ratio is cysteine (0.98%). Multiple sequence alignment showed 47 conserved patterns between 30 arginine deiminase amino acid sequences. The results of sequence homology among 30 different groups of arginine deiminase enzymes revealed that all the studied sequences located in amidinotransferase superfamily. Based on the phylogenetic analysis, two major clusters were identified. Considering the results of various in silico studies; we selected the five best candidates for further investigations. The 3D structures of the best five arginine deiminase proteins were generated by the I-TASSER server and PyMOL. The RAMPAGE analysis revealed that 81.4%-91.4%, of the selected sequences, were located in the favored region of arginine deiminase proteins. CONCLUSION: The results of this study shed light on the basic physicochemical properties of thirty major arginine deiminase sequences. The obtained data could be employed for further in vivo and clinical studies and also for developing the related therapeutic enzymes.

Cardiac regeneration using human-induced pluripotent stem cell-derived biomaterial-free 3D-bioprinted cardiac patch in vivo.

One of the leading causes of death worldwide is heart failure. Despite advances in the treatment and prevention of heart failure, the number of affected patients continues to increase. We have recently developed 3D-bioprinted biomaterial-free cardiac tissue that has the potential to improve cardiac function. This study aims to evaluate the in vivo regenerative potential of these 3D-bioprinted cardiac patches. The cardiac patches were generated using 3D-bioprinting technology in conjunction with cellular spheroids created from a coculture of human-induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and endothelial cells. Once printed and cultured, the cardiac patches were implanted into a rat myocardial infarction model (n = 6). A control group (n = 6) without the implantation of cardiac tissue patches was used for comparison. The potential for regeneration was measured 4 weeks after the surgery with histology and echocardiography. 4 weeks after surgery, the survival rates were 100% and 83% in the experimental and the control group, respectively. In the cardiac patch group, the average vessel counts within the infarcted area were higher than those within the control group. The scar area in the cardiac patch group was significantly smaller than that in the control group. (Figure S1) Echocardiography showed a trend of improvement of cardiac function for the experimental group, and this trend correlated with increased patch production of extracellular vesicles. 3D-bioprinted cardiac patches have the potential to improve the regeneration of cardiac tissue and promote angiogenesis in the infarcted tissues and reduce the scar tissue formation.

Assessment of radiation leakage from treatment applicator of Siemens Primus Plus and Siemens Artiste linear accelerators.

AIM: The purpose of this study is to measure radiation leakage of Siemens Primus Plus and Siemens Artiste linear accelerators in electron mode and to compare the leakage level with that recommended by the International Electrotechnical Commission (IEC) standard. MATERIALS AND METHODS: In this assessment, Siemens Primus Plus linear accelerator with 10 cm × 10 cm, 15 cm × 15 cm, and 25 cm × 25 cm applicators was used. The radiation leakage in lateral and vertical directions was measured for Siemens Primus Plus and Siemens Artiste linear accelerators. RESULTS: Data derived from radiation leakage measurement for Siemens Primus Plus and Siemens Artiste linear accelerators in lateral direction from the field edge and in vertical direction from the applicator were reported. The radiation leakage data were then compared with the IEC standard to evaluate in-air field leakage. CONCLUSION: Comparing the radiation leakage level from fields with the IEC standard for two applicators, the maximum that was occurred for 12 MeV electron beam and applicator size of 10 cm × 10 cm in Siemens Artiste linear accelerator was 2.3%, which is less than the IEC's recommended limit of 10%. It is concluded that the leakage amount is much less than the specified limit and that both of the linear accelerators have high level of safety. Considering the measurement stage, it also needs to be noted that the beam angle affected the radiation leakage level from field edge, and in 25° angle, it is higher than in 0° angle. Comparing radiation leakage from the right side of the field for the two linear accelerators, the amount of leakage for Siemens Primus Plus linear accelerator is more than Siemens Artiste linear accelerator.

A revised dosimetric characterization of 60Co BEBIG source: From single-source data to clinical dose distribution.

PURPOSE: Although the dosimetric characterization of 60Co BEBIG source can be found in several literature studies, the data sets show major discrepancies and the lack of uncertainty analyses. This study tried to determine an accurate dosimetric data set for this source using Monte Carlo (MC) simulations along with detailed uncertainty analysis. To explore how different dosimetric data sets can make changes in practical situations, clinical dose distributions based on our results were compared with the dose distributions derived from Granero et al. and consensus data sets. METHODS AND MATERIALS: The MC simulations were performed with Monte Carlo N-Particle eXtended code (MCNPX) version 2.6.0 and the TG-43 parameters were estimated adhering to the American Association of Physicists in Medicine (AAPM) and European SocieTy for Radiotherapy and Oncology (ESTRO) 229 report. The dose rate distributions for single-source and two typical clinical cases, including one intracavitary and one interstitial, were calculated using an in-house code on the basis of the TG-43 formalism. RESULTS: The total uncertainties for water dose rate on source transverse axis at 1 cm and 5 cm, air kerma strength, and dose rate constant were evaluated to be 0.10%, 0.09%, 0.04%, and 0.11%, respectively. Meaningful differences were found for the interstitial case in which 22% of clinical target volume (CTV) showed differences from ±1% to ±10% or even larger. CONCLUSIONS: The MC uncertainty was derived about 16 times smaller than the typical MC component stated in TG-138, partly because of large number of histories and partly because the spectra of 60Co and also its photons' attenuation coefficients are adequately accurate. The results showed that in the clinical situations, the applicator geometry and the superposition of single-source dose distributions can reduce the differences observed between several data sets.

Scaffolds for epithelial tissue engineering customized in elastomeric molds.

Restoration of soft tissue defects remains a challenge for surgical reconstruction. In this study, we introduce a new approach to fabricate poly(d,l-lactic acid) (PDLLA) scaffolds with anatomical shapes customized to regenerate three-dimensional soft tissue defects. Highly concentrated polymer/salt mixtures were molded in flexible polyether molds. Microcomputed tomography showed that with this approach it was possible to produce scaffolds with clinically acceptable volume ratio maintenance (>90%). Moreover, this technique allowed us to customize the average pore size and pore interconnectivity of the scaffolds by using variations of salt particle size. In addition, this study demonstrated that with the increasing porosity and/or the decreasing of the average pore size of the PDLLA scaffolds, their mechanical properties decrease and they degrade more slowly. Cell culture results showed that PDLLA scaffolds with an average pore size of 100 µm enhance the viability and proliferation rates of human gingival epithelial cells up to 21 days. The simple method proposed in this article can be extended to fabricate porous scaffolds with customizable anatomical shapes and optimal pore structure for epithelial tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 880-890, 2018.

Effects of Siemens TT-D carbon fiber table top on beam attenuation, and build up region of 6 MV photon beam.

AIM: This study deals with Monte Carlo simulations of the effects which the 550 TXT carbon fiber couch can have on the relevant parameters of a 6 MV clinical photon beam in three field sizes. BACKGROUND: According to the reports issued by the International Commission on Radiation Units and Measurements (ICRU), the calculated dose across a high gradient distribution should be within 2% of the relative dose, or within 0.2 cm of the isodose curve position in the target volume. Nowadays, the use of posterior oblique beam has become a common practice. It is clear that, in radiotherapy, the presence of the couch affects the beam intensity and, as a result, the skin dose. MATERIALS AND METHODS: Firstly, Siemens linear accelerator validation for 6 MV photon beam was performed, and satisfactory agreement between Monte Carlo and experimental data for various field sizes was observed. Secondly, the couch transmission factor for the reference field size and depth was computed, and the skin dose enhancement by the couch was assessed. RESULTS: The largest impact of the carbon fiber couch effect was observed for the 5 × 5 cm2 field size. Such evaluation has not been reported for this couch before. CONCLUSION: Despite providing minimal attenuation for the primary radiation, the assumption that carbon fiber couches are radiotranslucent is not valid, and the effects of couches of this type on the transmission factor, and on the skin dose should be carefully investigated for each field size and depth.

Evaluation of Organs at Risk's Dose in External Radiotherapy of Brain Tumors.

BACKGROUND: Radiotherapy plays an important role in the management of most malignant and many benign primary central nervous system (CNS) tumors. Radiotherapy affects both tumor cells and uninvolved normal cells; so, it is important to estimate absorbed dose to organs at risk in this kind of treatment. The aim of this study was to determine the absorbed dose to chiasma, lens, optic nerve, retina, parotid, thyroid and submandibular gland in frontal lobe brain tumors radiotherapy based on treatment planning system (TPS) calculation and direct measurement on the phantom. METHODS: A head and neck phantom was constructed using natural human bone and combination of paraffin wax and Sodium Chloride (NaCl) as tissue-equivalent material. Six cylinders were made of phantom material which had cavities to insert Thermoluminescent Dosimeters (TLDs) at several depths in order to measure absorbed dose to chiasma, lens, optic nerve, retina, parotid, thyroid and submandibular gland. Three routine conventional plans associated with tumors of this region and a new purposed technique were performed on the phantom and dose distribution and absorbed dose to critical organs were compared using treatment planning system (TPS) calculation and direct measurement on the phantom. RESULTS: Absorbed doses were measured with calibrated TLDs and are expressed in centigray (cGy). In all techniques absorbed dose to all organs except the lenses were at their tolerance dose levels and in the new purposed technique, absorbed dose to chiasma was significantly reduced. CONCLUSION: Our findings showed differences in the range of 1-5% in all techniques between TPS calculation and direct measurements for all organs except submandibular glands and thyroid. Because submandibular glands and thyroid are far from primary radiation field, TLD reading in these regions although small but differs from TPS calculation which shows very smaller doses. This might be due to scattered radiation which is not well considered in the TPS. In the new technique, because the chiasma is out of the radiation field, absorbed dose was reduced significantly.