Fully automated clinical target volume segmentation for glioblastoma radiotherapy using a deep convolutional neural network.

Purpose: Target volume delineation is a crucial step prior to radiotherapy planning in radiotherapy for glioblastoma. This step is performed manually, which is time-consuming and prone to intra- and inter-rater variabilities. Therefore, the purpose of this study is to evaluate a deep convolutional neural network (CNN) model for automatic segmentation of clinical target volume (CTV) in glioblastoma patients. Material and methods: In this study, the modified Segmentation-Net (SegNet) model with deep supervision and residual-based skip connection mechanism was trained on 259 glioblastoma patients from the Multimodal Brain Tumour Image Segmentation Benchmark (BraTS) 2019 Challenge dataset for segmentation of gross tumour volume (GTV). Then, the pre-trained CNN model was fine-tuned with an independent clinical dataset (n = 37) to perform the CTV segmentation. In the process of fine-tuning, to generate a CT segmentation mask, both CT and MRI scans were simultaneously used as input data. The performance of the CNN model in terms of segmentation accuracy was evaluated on an independent clinical test dataset (n = 15) using the Dice Similarity Coefficient (DSC) and Hausdorff distance. The impact of auto-segmented CTV definition on dosimetry was also analysed. Results: The proposed model achieved the segmentation results with a DSC of 89.60 ± 3.56% and Hausdorff distance of 1.49 ± 0.65 mm. A statistically significant difference was found for the Dmin and Dmax of the CTV between manually and automatically planned doses. Conclusions: The results of our study suggest that our CNN-based auto-contouring system can be used for segmentation of CTVs to facilitate the brain tumour radiotherapy workflow.

Gold-nanoparticle-enriched breast tissue in breast cancer treatment using the INTRABEAM® system: a Monte Carlo study.

Using a 50-kV INTRABEAM® system after breast-conserving surgery, breast skin injury and long treatment time remain the challenging problems when large-size spherical applicators are used. This study has aimed to address these problems using gold (Au) nanoparticles (NPs). For this, surface and isotropic doses were measured using a Gafchromic EBT3 film and a water phantom. The particle propagation code EGSnrc/Epp was used to score the corresponding doses using a geometry similar to that used in the measurements. The simulation was validated using a gamma index of 2%/2 mm acceptance criterion in the gamma analysis. After validation Au-NP-enriched breast tissue was simulated to quantify any breast skin dose reduction and shortening of treatment time. It turned out that the gamma value deduced for validation of the simulation was in an acceptable range (i.e., less than one). For 20 mg-Au/g-breast tissue, the calculated Dose Enhancement Ratio (DER) of the breast skin was 0.412 and 0.414 using applicators with diameters of 1.5 cm and 5 cm, respectively. The corresponding treatment times were shortened by 72.22% and 72.30% at 20 mg-Au/g-breast tissue concentration, respectively. It is concluded that Au-NP-enriched breast tissue shows significant advantages, such as reducing the radiation dose received by the breast skin as well as shortening the treatment time. Additionally, the DERs were not significantly dependent on the size of the applicators.

The effect of omega-3 fatty acid supplementation on clinical and biochemical parameters of critically ill patients with COVID-19: a randomized clinical trial.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n3-PUFAs) may exert beneficial effects on the immune system of patients with viral infections. This paper aimed to examine the effect of n3-PUFA supplementation on inflammatory and biochemical markers in critically ill patients with COVID-19. METHODS: A double-blind, randomized clinical trial study was conducted on 128 critically ill patients infected with COVID-19 who were randomly assigned to the intervention (fortified formula with n3-PUFA) (n = 42) and control (n = 86) groups. Data on 1 month survival rate, blood glucose, sodium (Na), potassium (K), blood urea nitrogen (BUN), creatinine (Cr), albumin, hematocrit (HCT), calcium (Ca), phosphorus (P), mean arterial pressure (MAP), O2 saturation (O2sat), arterial pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3), base excess (Be), white blood cells (WBCs), Glasgow Coma Scale (GCS), hemoglobin (Hb), platelet (Plt), and the partial thromboplastin time (PTT) were collected at baseline and after 14 days of the intervention. RESULTS: The intervention group had significantly higher 1-month survival rate and higher levels of arterial pH, HCO3, and Be and lower levels of BUN, Cr, and K compared with the control group after intervention (all P < 0.05). There were no significant differences between blood glucose, Na, HCT, Ca, P, MAP, O2sat, PO2, PCO2, WBCs, GCS, Hb, Plt, PTT, and albumin between two groups. CONCLUSION: Omega-3 supplementation improved the levels of several parameters of respiratory and renal function in critically ill patients with COVID-19. Further clinical studies are warranted. Trial registry Name of the registry: This study was registered in the Iranian Registry of Clinical Trials (IRCT); Trial registration number: IRCT20151226025699N3; Date of registration: 2020.5.20; URL of trial registry record: https://en.irct.ir/trial/48213.

Monte Carlo simulation and analytical calculation methods to investigate the potential of nanoparticles for INTRABEAM® IORT machine.

In the present study, Monte Carlo (MC) simulation and analytical calculation methods were used to investigate the potential of cancer treatment for the combination of IORT with nanoparticles (NPs). The Geant4 MC toolkit was used to simulate ZEISS INTRABEAM® IORT machine and its smallest applicator with 1.5 cm diameter. The dose enhancement effects (DEFs) were obtained for silver (Ag), gold (Au), bismuth (Bi), copper (Cu) and iron (Fe) spherical NPs considering different concentrations. In addition, analytical calculations were performed based on attenuation coefficient formula for sample NPs. Our MC results showed that the use of different NPs led to an increase in DEF up to 40%. Among different NPs, Au had the maximum DEF. In addition, analytical calculations revealed a significant increase, using NPs as well. Our study has suggested that the use of NPs in combination with IORT has the potential to enhance treatment outcomes.

Dosimetric characteristics of the INTRABEAM ® system with spherical applicators in the presence of air gaps and tissue heterogeneities.

The main aim of this study was to investigate the dosimetric characteristics of the INTRABEAM ® system in the presence of air gaps between the surface of applicators (APs) and tumor bed. Additionally, the effect of tissue heterogeneities was another focus. Investigating the dosimetric characteristics of the INTRABEAM® system is essential to deliver the required dose to the tumor bed correctly and reduce the delivered dose to the ribs and lung. Choosing the correct AP size and fitting it to the lumpectomy cavity is essential to remove the effect of air gaps and avoid inaccurate dose delivery. Consequently, the Geant4 toolkit was used to simulate the INTRABEAM ® system with spherical APs of various sizes. The wall effect of the ion chamber (IC) PTW 34013 used in the present study was checked. The simulations were validated in comparison with measurements, and then used to calculate any inaccuracies in dose delivery in the presence of 4- and 10-mm air gaps between the surface of the APs and the tumor bed. Also, the doses received due to tissue heterogeneities were characterized. It turned out that measurements and simulations were approximately in agreement (± 2%) for all sizes of APs. The perturbation factor introduced by the IC due to differences in graphite-coated polyethylene and air as compared to the phantom material was approximately equal to one for all AP. The greatest relative dose delivery difference was observed for an AP with a diameter of 1.5 cm, i.e., 44% and 70% in the presence of 4- and 10-mm air gaps, respectively. In contrast, the lowest relative dose delivery difference was observed for an AP with a diameter of 5 cm, i.e., 24% and 42% in the presence of 4- and 10-mm air gaps, respectively. Increasing APs size showed a decrease in relative dose delivery difference due to the presence of air gaps. In addition, the undesired dose received by the ribs turned out to be higher when a treatment site closer to the ribs was assumed. The undesired dose received by the ribs increased as the AP size increased. The lung dose turned out to be decreased due to the shielding effect of the ribs, small lung density, and long separation distance from the AP surface.

Normal lung tissue complication probability in MR-Linac and conventional radiotherapy.

PURPOSE: To study normal lung tissue (NLT) complications in magnetic resonance (MR) image based linac and conventional radiotherapy (RT) techniques. MATERIALS AND METHODS: The Geant4 toolkit was used to simulate a 6 MV photon beam. A homogenous magnetic field of 1.5 Tesla (T) was applied in both perpendicular and parallel directions relative to the radiation beam.Analysis of the NLT complications was assessed according to the normal lung tissue complication probability (NTCP), the mean lung dose (MLD), and percentage of the lung volume receiving doses greater than 20 Gy (V20), using a sample set of CT images generated from a commercially available 4D-XCAT digital phantom. RESULTS: The results show that the MLD and V20 were lower for MR-linac RT. The largest reduction of MLD and V20 for MR-linac RT configurations were 5 Gy and 29.3%, respectively. CONCLUSION: MR-linac RT may result in lower NLT complications when compared to conventional RT.

Is grid therapy useful for all tumors and every grid block design?

Grid therapy is a treatment technique that has been introduced for patients with advanced bulky tumors. The purpose of this study is to investigate the effect of the radiation sensitivity of the tumors and the design of the grid blocks on the clinical response of grid therapy. The Monte Carlo simulation technique is used to determine the dose distribution through a grid block that was used for a Varian 2100C linear accelerator. From the simulated dose profiles, the therapeutic ratio (TR) and the equivalent uniform dose (EUD) for different types of tumors with respect to their radiation sensitivities were calculated. These calculations were performed using the linear quadratic (LQ) and the Hug-Kellerer (H-K) models. The results of these calculations have been validated by comparison with the clinical responses of 232 patients from different publications, who were treated with grid therapy. These published results for different tumor types were used to examine the correlation between tumor radiosensitivity and the clinical response of grid therapy. Moreover, the influence of grid design on their clinical responses was investigated by using Monte Carlo simulations of grid blocks with different hole diameters and different center-to-center spacing. The results of the theoretical models and clinical data indicated higher clinical responses for the grid therapy on the patients with more radioresistant tumors. The differences between TR values for radioresistant cells and radiosensitive cells at 20 Gy and 10 Gy doses were up to 50% and 30%, respectively. Interestingly, the differences between the TR values with LQ model and H-K model were less than 4%. Moreover, the results from the Monte Carlo studies showed that grid blocks with a hole diameters of 1.0 cm and 1.25 cm may lead to about 19% higher TR relative to the grids with hole diameters smaller than 1.0 cm or larger than 1.25 cm (with 95% confidence interval). In sum-mary, the results of this study indicate that grid therapy is more effective for tumors with radioresistant characteristics than radiosensitive tumors.

Dose distribution verification for GYN brachytherapy using EBT Gafchromic film and TG-43 calculation.

AIM: Verification of dose distributions for gynecological (GYN) brachytherapy implants using EBT Gafchromic film. BACKGROUND: One major challenge in brachytherapy is to verify the accuracy of dose distributions calculated by a treatment planning system. MATERIALS AND METHODS: A new phantom was designed and fabricated using 90 slabs of 18 cm × 16 cm × 0.2 cm Perspex to accommodate a tandem and Ovoid assembly, which is normally used for GYN brachytherapy treatment. This phantom design allows the use of EBT Gafchromic films for dosimetric verification of GYN implants with a cobalt-60 HDR system or a LDR Cs-137 system. Gafchromic films were exposed using a plan that was designed to deliver 1.5 Gy of dose to 0.5 cm distance from the lateral surface of ovoids from a pair of ovoid assembly that was used for treatment vaginal cuff. For a quantitative analysis of the results for both LDR and HDR systems, the measured dose values at several points of interests were compared with the calculated data from a commercially available treatment planning system. This planning system was utilizing the TG-43 formalism and parameters for calculation of dose distributions around a brachytherapy implant. RESULTS: The results of these investigations indicated that the differences between the calculated and measured data at different points were ranging from 2.4% to 3.8% for the LDR Cs-137 and HDR Co-60 systems, respectively. CONCLUSION: The EBT Gafchromic films combined with the newly designed phantom could be utilized for verification of the dose distributions around different GYN implants treated with either LDR or HDR brachytherapy procedures.

Evaluating dose distributions of high dose rate 60Co brachytherapy in an asymmetric tumor: A comparison of different designs of vaginal cylindrical applicators.

The aim of this study is to evaluate organ-at-risk (OAR) doses obtained from different designs of intracavitary cylinder applicators during high-dose-rate (HDR) brachytherapy of an asymmetric vaginal tumor. Dose distributions around five cylinder applicators were obtained using the Geant4 toolkit. Three of these applicators are commercially available: single-channel, multi-channel, and shielded. Additionally, two proposed sub-configurations were evaluated: (I) a combination of the multichannel applicator with a central shield and (II) a dynamically modulated cylinder (DMC). The dose distributions of the proposed applicators were compared to those of the single-channel cylinder applicator. The results showed that using a cylindrical applicator with a higher degree of freedom in plan optimization can improve OAR, sparing up to 60% for the rectum and 20% for the bladder. In conclusion, this work suggests using a new design of a cylindrical applicator to enhance the therapeutic ratio of brachytherapy for asymmetric and irregularly shaped vaginal tumors.

Attention 3D U-NET for dose distribution prediction of high-dose-rate brachytherapy of cervical cancer: Direction modulated brachytherapy tandem applicator.

BACKGROUND: Direction Modulated Brachytherapy (DMBT) enables conformal dose distributions. However, clinicians may face challenges in creating viable treatment plans within a fast-paced clinical setting, especially for a novel technology like DMBT, where cumulative clinical experience is limited. Deep learning-based dose prediction methods have emerged as effective tools for enhancing efficiency. PURPOSE: To develop a voxel-wise dose prediction model using an attention-gating mechanism and a 3D UNET for cervical cancer high-dose-rate (HDR) brachytherapy treatment planning with DMBT six-groove tandems with ovoids or ring applicators. METHODS: A multi-institutional cohort of 122 retrospective clinical HDR brachytherapy plans treated to a prescription dose in the range of 4.8-7.0 Gy/fraction was used. A DMBT tandem model was constructed and incorporated onto a research version of BrachyVision Treatment Planning System (BV-TPS) as a 3D solid model applicator and retrospectively re-planned all cases by seasoned experts. Those plans were randomly divided into 64:16:20 as training, validating, and testing cohorts, respectively. Data augmentation was applied to the training and validation sets to increase the size by a factor of 4. An attention-gated 3D UNET architecture model was developed to predict full 3D dose distributions based on high-risk clinical target volume (CTVHR) and organs at risk (OARs) contour information. The model was trained using the mean absolute error loss function, Adam optimization algorithm, a learning rate of 0.001, 250 epochs, and a batch size of eight. In addition, a baseline UNET model was trained similarly for comparison. The model performance was evaluated on the testing dataset by analyzing the outcomes in terms of mean dose values and derived dose-volume-histogram indices from 3D dose distributions and comparing the generated dose distributions against the ground-truth dose distributions using dose statistics and clinically meaningful dosimetric indices. RESULTS: The proposed attention-gated 3D UNET model showed competitive accuracy in predicting 3D dose distributions that closely resemble the ground-truth dose distributions. The average values of the mean absolute errors were 1.82 ± 29.09 Gy (vs. 6.41 ± 20.16 Gy for a baseline UNET) in CTVHR, 0.89 ± 1.25 Gy (vs. 0.94 ± 3.96 Gy for a baseline UNET) in the bladder, 0.33 ± 0.67 Gy (vs. 0.53 ± 1.66 Gy for a baseline UNET) in the rectum, and 0.55 ± 1.57 Gy (vs. 0.76 ± 2.89 Gy for a baseline UNET) in the sigmoid. The results showed that the mean absolute error (MAE) for the bladder, rectum, and sigmoid were 0.22 ± 1.22 Gy (3.62%) (p = 0.015), 0.21 ± 1.06 Gy (2.20%) (p = 0.172), and -0.03 ± 0.54 Gy (1.13%) (p = 0.774), respectively. The MAE for D90, V100%, and V150% of the CTVHR were 0.46 ± 2.44 Gy (8.14%) (p = 0.018), 0.57 ± 11.25% (5.23%) (p = 0.283), and -0.43 ± 19.36% (4.62%) (p = 0.190), respectively. The proposed model needs less than 5 s to predict a full 3D dose distribution of 64 × 64 × 64 voxels for any new patient plan, thus making it sufficient for near real-time applications and aiding with decision-making in the clinic. CONCLUSIONS: Attention gated 3D-UNET model demonstrated a capability in predicting voxel-wise dose prediction, in comparison to 3D UNET, for DMBT intracavitary brachytherapy planning. The proposed model could be used to obtain dose distributions for near real-time decision-making before DMBT planning and quality assurance. This will guide future automated planning, making the workflow more efficient and clinically viable.

Re-irradiation of recurrent head and neck cancers using pulsed reduced dose rate radiotherapy: An institutional series.

PURPOSE/OBJECTIVE(S): Pulsed reduced dose rate (PRDR) radiation (RT) is a re-irradiation (Re-RT) technique that potentially overcomes dose/volume constraints in the setting of previous RT. There is minimal data for its use for recurrent or secondary primary head and neck squamous cell carcinoma (HNSCC). In this study, we report preliminary data from our institution of a consecutive cohort of HNSCC patients who received PRDR Re-RT. MATERIALS/METHODS: Nine patients received PRDR Re-RT from August 2020 to January 2023 and had analyzable data. Intensity modulated RT was used for treatment delivery and a wait time between 20 cGy arc/helical deliveries was used to achieve the effective low dose rate. Data collected included patient demographic information, prior interventions, diagnosis, radiation therapy dose and fractionation, progression free survival, overall survival, and toxicity rates. RESULTS: The median time to PRDR-RT from completion of initial RT was 13 months (range, 6-50 months). All but one patient underwent salvage surgery prior to PRDR-RT. The median follow-up after Re-RT was 7 months. The median OS from PRDR-RT was 7 months (range, 1-32 months). Median PFS was 7 months (range, 1-32 months). One patient (11.1 %) had acute grade 3 toxicity, and two patients (22.2 %) had late grade 3 toxicities. There were no grade 4+ toxicities. CONCLUSION: PRDR Re-RT is a feasible treatment strategy for patients with recurrent or second primary HNSCC. Initial findings from this retrospective review suggest reasonable survival outcomes and potentially improved toxicity; prospective data is needed to establish the safety and efficacy of this technique.

The association between enteral nutrition with survival of critical patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) results in several complications and mortality in intensive care unit (ICU) patients. Limited studies have investigated the effect of enteral nutrition (EN) on the survival of COVID-19 patients in the ICU. The aim of this study was to investigate the association of EN with biochemical and pathological indices associated with mortality in ICU patients with COVID-19. METHODS: This case-control study was conducted on 240 patients with COVID-19 hospitalized in the ICU including 120 eventual nonsurvived as the cases and 120 survived patients as the controls. All of the patients received EN as a high protein high volume or standard formula. Data on general information, anthropometric measurements, and the results of lab tests were collected. RESULTS: The recovered patients received significantly more high protein (60.8% vs. 39.6%, p = .004) and high volume (61.6% vs. 42.3%, p = .005) formula compared to the nonsurvived group. Mortality was inversely associated with high volume (odds ratio [OR]: 0.45 confidence interval [CI]95%, p = .008) and high protein (OR: 0.42 CI95%, p = .003) formula. The results remained significant after adjusting for age and sex. Further adjustment for underlying diseases, smoking, body mass index, and the acute physiology and chronic health evaluation II (APACHE II) score did not change the results. CONCLUSION: The findings of the study showed that there was a significant inverse association between mortality and high volume and high protein formula in patients with COVID-19. Further investigation is warranted.

Targeting human c-Myc promoter duplex DNA with actinomycin D by use of multi-way analysis of quantum-dot-mediated fluorescence resonance energy transfer.

Actinomycin D (Act D), an oncogenic c-Myc promoter binder, interferes with the action of RNA polymerase. There is great demand for high-throughput technology able to monitor the activity of DNA-binding drugs. To this end, binding of 7-aminoactinomycin D (7AAD) to the duplex c-Myc promoter was investigated by use of 2D-photoluminescence emission (2D-PLE), and the resulting data were subjected to analysis by use of convenient and powerful multi-way approaches. Fluorescence measurements were performed by use of the quantum dot (QD)-conjugated c-Myc promoter. Intercalation of 7AAD within duplex base pairs resulted in efficient energy transfer from drug to QD via fluorescence resonance energy transfer (FRET). Multi-way analysis of the three-way data array obtained from titration experiments was performed by use of restricted Tucker3 and hard trilinear decomposition (HTD). These techniques enable analysis of high-dimensional and complex data from nanobiological systems which include several spectrally overlapped structures. It was almost impossible to obtain robust and meaningful information about the FRET process for such high overlap data by use of classical analysis. The soft approach had the important advantage over univariate classical methods of enabling us to investigate the source of variance in the fluorescence signal of the DNA-drug complex. It was established that hard trilinear decomposition analysis of FRET-measured data overcomes the problem of rank deficiency, enabling calculation of concentration profiles and pure spectra for all species, including non-fluorophores. The hard modeling approach was also used for determination of equilibrium constants for the hybridization and intercalation equilibria, using nonlinear fit data analysis. The intercalation constant 3.6 × 10(6) mol(-1) L and hybridization stability 1.0 × 10(8) mol(-1) L obtained were in good agreement with values reported in the literature. The analytical concentration of the QD-labeled DNA was determined by use of nonlinear fitting, without using external standard calibration samples. This study was a successful application of multi-way chemometric methods to investigation of nano-biotechnological systems where several overlapped species coexist in solution.

Multiway study of hybridization in nanoscale semiconductor labeled DNA based on fluorescence resonance energy transfer.

The resolution of the ternary-binary complex competition of a target sequence and of its two complementary probes in sandwich DNA hybridization is reported. To achieve this goal, Fluorescence Resonance Energy Transfer (FRET) between oligonucleotide-functionalized quantum dot (QD) nanoprobes (QD donor-QD acceptor) upon hybridization with a label free target was monitored by two-dimensional photoluminescence excitation spectroscopy (2D-PLE). Detection of a target oligonucleotide strand, using sandwiched nanoassembly in a separation-free format, was performed with the appearance of a new feature in the photoluminescence excitation (PLE) plot. From the obtained data, energy transfer efficiency and Förster radius (R0) were calculated. In particular, our results demonstrated that energy transfer by using QD donor-QD acceptor FRET pairs is more efficient in comparison with QD donor-organic dye acceptor pairs. Soft and model based analysis of 2D-PLE data was implemented by means of PARAFAC and hard trilinear decomposition (HTD), allowing to fit a proper model for FRET-based sandwich DNA hybridization systems. This study is the first successful application of a multiway chemometric technique to consider FRET based DNA hybridization in sandwiched nanoassemblies. A multi-equilibria model was properly fitted to the data and confirmed there is a competition between ternary and binary complex formation. Equilibrium constants of DNA hybridization in sandwiched nanoassemblies were estimated for the first time. Equilibrium constants illustrated that the extent of hybridization in one side on the target strand depends on hybridization conditions on the other side of the strand. Effects of guanine (G) and cytosine (C) contents of strands on the extent and rate of hybridization were investigated. In addition to equilibrium constants of binary and ternary complexes, the pure profiles of all resolved structures were estimated. Ultimately, the described method calculated the analytical concentration of probes as a measure of surface modification yield with DNA using nonlinear fit analysis, without using any calibration sample.

A systematic review of the normal tissue complication probability models and parameters: Head and neck cancers treated with conformal radiotherapy.

This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue complication probability (NTCP) based on clinical data from head and neck cancer patients treated with conformal radiotherapy. A systematic literature search was carried out according to the PRISMA guideline for the identification of relevant publications in six electronic databases of Embase, PubMed, Scopus, and Google Scholar to July 2022 using specific keywords in the paper's title and abstract. The initial search resulted in 1368 articles for all organs for the review article about the NTCP parameters. One hundred and seventy-eight articles were accepted for all organs with complete parameters for the mentioned models and finally, 20 head and neck cancer articles were accepted for review. Analysis of the studies shows that the Lyman-Kutcher-Burman (LKB) model properly links the NTCP curve parameters to the postradiotherapy endpoints. In the LKB model for esophagus, the minimum, and maximum corresponding parameters were reported as TD50 = 2.61 Gy with grade ≥3 radiation-induced esophagitis endpoints as the minimum TD50 and TD50 = 68 Gy as the maximum ones. nmin = 0.06, nmax = 1.04, mmin = 0.1, and mmax = 0.65, respectively. Unfortunately, there was not a wide range of published articles on other organs at risk like ear or cauda equina except Burman et al. (Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys Ther. 1991;21:123-135). Findings suggest that the validation of different radiobiological models and their corresponding parameters need to be investigated in vivo and in vitro for developing a more accurate NTCP model to be used for radiotherapy treatment planning optimization.

Dosimetric comparison between microSelectron iridium-192 and flexi cobalt-60 sources in high-dose-rate brachytherapy using Geant4 Monte Carlo code.

Purpose: Manufacturing of miniaturized high activity iridium-192 (192Ir) sources have been made a market preference in modern brachytherapy. Smaller dimensions of the sources are flexible for smaller diameter of the applicators, and it is also suitable for interstitial implants. Presently, cobalt-60 (60Co) sources have been commercialized as an alternative to 192Ir sources for high-dose-rate (HDR) brachytherapy, since 60Co source have an advantage of longer half-life comparing with 192Ir source. One of them is the HDR 60Co Flexisource manufactured by Elekta. The purpose of this study was to compare the TG-43 dosimetric parameters of HDR flexi 60Co and HDR microSelectron 192Ir sources. Material and methods: Monte Carlo simulation code of Geant4 (v.11.0) was applied. Following the recommendations of AAPM TG-43 formalism report, Monte Carlo code of HDR flexi 60Co and HDR microSelectron 192Ir was validated by calculating radial dose function, anisotropy function, and dose-rate constants in a water phantom. Finally, results of both radionuclide sources were compared. Results: The calculated dose-rate constants per unit air-kerma strength in water medium were 1.108 cGy h-1U-1 for HDR microSelectron 192Ir, and 1.097 cGy h-1U-1 for HDR flexi 60Co source, with the percentage uncertainty of 1.1% and 0.2%, respectively. The values of radial dose function for distances above 22 cm for HDR flexi 60Co source were higher than that of the other source. The anisotropic values sharply increased to the longitudinal sides of HDR flexi 60Co source, and the rise was comparatively sharper to that of the other source. Conclusions: The primary photons from the lower-energy HDR microSelectron 192Ir source have a limited range and are partially attenuated when considering the results of radial and anisotropic dose distribution functions. This implies that a HDR flexi 60Co radionuclide could be used to treat tumors beyond the source compared with a HDR microSelectron 192Ir source, despite the fact that 192Ir has a lower exit dose than HDR flexi 60Co radionuclide source.

Efficacy of Nanoparticles in dose enhancement with high dose rate of Iridium-192 and Cobalt-60 radionuclide sources in the Treatment of Cancer: A systematic review.

ABSTRACTS: A key challenge in radiation therapy is to maximize the radiation dose to cancer cells while minimizing damage to healthy tissues. In recent years, the introduction of remote after-loading technology such as high-dose-rate (HDR) brachytherapy becomes the safest and more precise way of radiation delivery compared to classical low-dose-rate (LDR) brachytherapy. However, the axially symmetric dose distribution of HDR with single channel cylindrical applicator, the physical "dead-space" with multichannel applicators, and shielding material heterogeneities are the main challenges of HDR brachytherapy. Thus, this review aimed to quantitatively evaluate the dose enhancement factor (DEF) produced by high atomic number nanoparticles (NPs) which increases the interaction probability of photons mainly through the photoelectric effect induced in the great number of atoms contained in each nanoparticle. The NPs loaded to the target volume create a local intensification effect on the target tissue that allows imparting the prescribed therapeutic dose using lower fluxes of irradiation and spare the surrounding healthy tissues. An electronic database such as PubMed/Medline, Embase, Scopus, and Google Scholar was searched to retrieve the required articles. Unpublished articles were also reached by hand from available sources. The dose is increased using the high atomic number of nanoparticle elements under the high dose iridium radionuclide whereas the cobalt-60 radionuclide source did not. However, much work is required to determine the dose distribution outside the target organ or tumor to spare the surrounding healthy tissues for the iridium source and make compressive work to have more data for the cobalt source.

Bystander Response Following High-Dose X-irradiation; Time-dependent Nature of GammaH2AX Foci and Cell Death Consequences.

Background: The paradigm shifts in target theory could be defined as the radiation-triggered bystander response in which the radiation deleterious effects occurred in the adjacent cells. Objective: This study aims to assess bystander response in terms of DNA damage and their possible cell death consequences following high-dose radiotherapy. Temporal characteristics of gH2AX foci as a manifestation of DNA damage were also evaluated. Material and Methods: In this experimental study, bystander response was investigated in human carcinoma cells of HeLa and HN5, neighboring those that received high doses. Medium transfer was performed from 10 Gy-irradiated donors to 1.5 Gy-irradiated recipients. GammaH2AX foci, clonogenic and apoptosis assays were investigated. The gH2AX foci time-point study was implemented 1, 4, and 24 h after the medium exchange. Results: DNA damage was enhanced in HeLa and HN5 bystander cells with the ratio of 1.27 and 1.72, respectively, which terminated in more than two-fold clonogenic survival decrease, along with gradual apoptosis increase. GammH2AX foci temporal characterization revealed maximum foci scoring at the 1 h time-point in HeLa, and also 4 h in HN5, which remained even 24 h after the medium sharing in higher level than the control group. Conclusion: The time-dependent nature of bystander-induced gH2AX foci as a DNA damage surrogate marker was highlighted with the persistent foci at 24 h. considering an outcome of bystander-induced DNA damage, predominant role of clonogenic cell death was also elicited compared to apoptosis. Moreover, the role of high-dose bystander response observed in the current work clarified bystander potential implications in radiotherapy.

Human osteosarcoma cells in response to ELF-MF: Morphological remodeling compared to cell proliferation.

Purpose: The present study aimed to assess the effects of extremely low-frequency electromagnetic fields (ELF-MF) on structural changes of human osteosarcoma cells by analyzing the stained cytoskeleton for assessing the relationship between the fractal dimension parameter and proliferation rate of radiation-induced cells. Materials and Methods: In this study, 2-mT magnetic fields with various waveforms, including sinusoidal, triangular, and pulsed shapes, were employed to determine the biological effects of ELF-EMF on the human osteosarcoma MG-63 cell line. All experiments were performed in two modes: continuous exposure at 3 h and fractionated irradiations at 3 consecutive days. Afterward, the proliferation assay was implemented for assessing the cell proliferation in each group. Moreover, immunofluorescence staining and confocal imaging were performed to determine the cell shape index. Furthermore, fractal dimension analysis was carried out by processing morphological images. Results: The proliferation and shape index parameters of radiation-induced osteosarcomas significantly decreased compared with non-irradiated cells. In addition, fractal dimensions significantly increased following fractionated exposure at 3 consecutive days. Conclusions: Assessing the fractal dimensions can be considered as a new morphological index for the prognosis of the structural remodeling of human osteosarcoma cells in response to fractionated irradiation of ELF-MF. In addition, various waveforms induce a similar effect on morphological remodeling and cell proliferation.

The association between obesity with treatment duration, ICU length of stay and the risk of death in critically ill patients with COVID-19.

BACKGROUND: Despite the confirmed association between higher BMI with increased risk of the acute respiratory distress syndrome (ARDS), the association between obesity with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) is not clear. The present study aimed to investigate the association between obesity with treatment duration, ICU length of stay, and the risk of death in critically ill patients with COVID-19. METHODS: This case-control study was performed on 223 patients with COVID-19 including 148 surviving patients as the control group and 75 eventually dead patients as the case group in Rasht, Iran. Data on demographic factors, comorbidities, anthropometric measurements, the length of hospitalization and the mortality were obtained from patients' medical records. RESULTS: The mortality rate was significantly associated with weight (OR = 1.04, 95% CI: 1.002-1.083, p = .04), but not with BMI after adjustments for age, gender, length of stay in ICU, chronic diseases and smoking. The results did not change after further adjustments for biochemical and pathological factors. CONCLUSIONS: Weight was positively associated with mortality after controlling for confounding variables. Further studies should consider the patient's body composition such as fat mass to establish the relationship between obesity and COVID-19 outcomes.