Clinical effectiveness of combined whole body hyperthermia and external beam radiation therapy (EBRT) versus EBRT alone in patients with painful bony metastases: A phase III clinical trial study.

PURPOSE: To evaluate the response rate, pain relief duration, and time it took for pain to decline or resolve after radiation therapy (RT) with or without fever-range Whole Body Hyperthermia (WBH) in bony metastatic patients with mainly primary tumor of prostate and breast cancer leading to bone pain. MATERIALS & METHODS: Bony metastatic patients with pain score ≥4 on the Brief Pain Inventory (BPI) underwent RT of 30 Gy in 10 fractions in combination with WBH with nursing care under medical supervision versus RT-alone. WBH application time was 3-4 h in three fractions with at least 48-h intervals. All patients were stratified primary site, breast or prostate cancer vs others, BPI score, and exclusion criteria. The primary endpoint was complete response (CR) (BPI equal to zero with no increase of analgesics) within two months of follow-up. RESULTS: Based on this study, the RT-alone group showed the worst pain. The study was terminated after the enrollment of a total of 61 patients, 5 years after the first enrollment (April 2016 to February 2021). Finally, the CR rate in RT + WBH revealed the most significant difference with RT-alone, 47.4% versus 5.3% respectively within 2 months post-treatment (P-value <0.05). The time of complete pain relief was 10 days for RT + WBH, while the endpoint was not reached during the RT-alone arm. Pain progression or stable disease was observed in half of the patients in RT-alone group within 4 weeks after treatment. However, this score was near zero in RT + WBHT patients in two months post-treatment. CONCLUSIONS: WBH plus RT showed significant increases in pain relief and shorter response time in comparison with RT-alone for patients with bone metastatic lesions.

Effect of a cross-linking antioxidant agent on the bond strength of adhesive resin to irradiated dentin.

It has been shown that irradiation can cause structural changes in dentin that may reduce the bond strength of adhesives to dentin. Applying cross-linking or antioxidant agents may help reverse this detrimental effect and improve adhesion to dentin. This in vitro study aimed to evaluate the effects of epigallocatechin-3-gallate (EGCG) pretreatment and the time of adhesive bonding (24 hours vs 1 month) on the shear bond strength (SBS) of All-Bond Universal (ABU) to irradiated dentin using etch-and-rinse (ER) and self-etching (SE) modes. Flat dentin surfaces prepared from 96 extracted intact human molars were divided into 8 groups (n = 12) and bonded with ABU. In the control (CO) groups (CO/ER and CO/SE), bonding was performed on nonirradiated dentin; in the irradiated (IR) groups (IR/ER and IR/SE), bonding was performed on irradiated dentin; in the irradiated pretreated groups (IR/EGCG/ER and IR/EGCG/SE), irradiated dentin received a 0.1% EGCG pretreatment before bonding; and in the irradiated delayed bonding (DL) groups (IR/DL/ER and IR/DL/SE), bonding on irradiated dentin was performed 1 month after completion of radiotherapy. The irradiation protocol consisted of a total dose of 60 Gy with 2-Gy exposure applied 5 days per week for a period of 6 weeks. After bonding procedures were completed, the specimens were stored in 100% humidity at 37°C for 24 hours and then the SBS was tested in a universal testing machine. Data were analyzed using 1-way analysis of variance and Tukey tests. There was a statistically significant difference among the 8 groups (P < 0.001). Irradiation diminished the SBS in the IR/ER and IR/SE groups compared with their controls (P < 0.001). Pretreatment with EGCG significantly increased the SBS in the IR/EGCG/ER group only (P < 0.001). The difference between the IR/ER and IR/DL/ER groups was not statistically significant, and the difference between the IR/SE and IR/DL/SE groups was marginally significant (P = 0.056). Pretreatment with EGCG after acid etching restored the SBS of ABU to irradiated dentin, resulting in an adhesive performance equivalent to that observed with nonirradiated dentin. A 1-month delay between irradiation and bonding did not improve the SBS.

Tumor Microenvironment, Radiology, and Artificial Intelligence: Should We Consider Tumor Periphery?

OBJECTIVES: The tumor microenvironment (TME) consists of cellular and noncellular components which enable the tumor to interact with its surroundings and plays an important role in the tumor progression and how the immune system reacts to the malignancy. In the present study, we investigate the diagnostic potential of the TME in differentiating benign and malignant lesions using image quantification and machine learning. METHODS: A total of 229 breast lesions and 220 cervical lymph nodes were included in the study. A group of expert radiologists first performed medical imaging and segmented the lesions, after which a rectangular mask was drawn, encompassing all of the contouring. The mask was extended in each axis up to 50%, and 29 radiomics features were extracted from each mask. Radiomics features that showed a significant difference in each contour were used to develop a support vector machine (SVM) classifier for benign and malignant lesions in breast and lymph node images separately. RESULTS: Single radiomics features extracted from extended contours outperformed radiologists' contours in both breast and lymph node lesions. Furthermore, when fed into the SVM model, the extended models also outperformed the radiologist's contour, achieving an area under the receiver operating characteristic curve of 0.887 and 0.970 in differentiating breast and lymph node lesions, respectively. CONCLUSIONS: Our results provide convincing evidence regarding the importance of the tumor periphery and TME in medical imaging diagnosis. We propose that the immediate tumor periphery should be considered for differentiating benign and malignant lesions in image quantification studies.

Comparison of PRIMO Monte Carlo code and Eclipse treatment planning system in calculation of dosimetric parameters in brain cancer radiotherapy.

Background: It is important to evaluate the dose calculated by treatment planning systems (TPSs) and dose distribution in tumor and organs at risk (OARs). The aim of this study is to compare dose calculated by the PRIMO Monte Carlo code and Eclipse TPS in radiotherapy of brain cancer patients. Materials and methods: PRIMO simulation code was used to simulate a Varian Clinac 600C linac. The simulations were validated for the linac by comparison of the simulation and measured results. In the case of brain cancer patients, the dosimetric parameters obtained by the PRIMO code were compared with those calculated by Eclipse TPS. Gamma function analysis with 3%, 3 mm criteria was utilized to compare the dose distributions. The evaluations were based on the dosimetric parameters for the planning target volume (PTV) and OAR including D min, D mean, and D max, homogeneity index (HI), and conformity index (CI). Results: The gamma function analysis showed a 98% agreement between the results obtained by the PRIMO code and measurement for the percent depth dose (PDD) and dose profiles. The corresponding value in comparing the dosimetric parameters from PRIMO code and Eclipse TPS for the brain patients was 94%, on average. The results of the PRIMO simulation were in good agreement with the measured data and Eclipse TPS calculations. Conclusions: Based on the results of this study, the PRIMO code can be utilized to simulate a medical linac with good accuracy and to evaluate the accuracy of treatment plans for patients with brain cancer.

The effect of dual-frequency ultrasound waves on B16F10 melanoma cells: Sonodynamic therapy using nanoliposomes containing methylene blue.

BACKGROUND: We investigated the effect of dual-frequency sonication on the viability of B16F10 melanoma cells in the presence of methylene blue (MB) encapsulated in nanoliposomes. METHODS: Treatment protocols were studied: sonication groups (40 kHz, 1 MHz and dual-frequency), the same sonication groups with nanoliposomes containing MB, MB free and nanoliposomes containing MB groups, and so sham and control groups. The nanoliposomes were prepared by the lipid film hydration method. The cell viability of the different treatment groups was evaluated by the MTT assay. RESULTS: The dual-frequency protocols caused higher viability losses compared to the kHz and MHz sonications (P < .05). In presence of the nanoliposomes containing MB, dual frequency led to 6% and 3% viability for 600 and 1200 seconds, respectively, while the corresponding values were 10% and 4% for the 40 kHz protocols and 22% and 9% for the 1 MHz, as compared to the control group (100%). The result of KI dosimetry showed that the cavitation activity of the dual-frequency protocol was about 1.23, as compared to sonication at 40 kHz and 1 MHz. CONCLUSION: Enhancement of inertial cavitation induction by dual-frequency sonication may be the primary effective mechanism, which causes increased sonochemical processes and drug release from nanocarriers.

Randomized, double-blind, placebo-controlled phase II trial of nanocurcumin in prostate cancer patients undergoing radiotherapy.

Clinical potential of curcumin in radiotherapy (RT) setting is outstanding and of high interest. The main purpose of this randomized controlled trial (RCT) was to assess the beneficial role of nanocurcumin to prevent and/or mitigate radiation-induced proctitis in prostate cancer patients undergoing RT. In this parallel-group study, 64 eligible patients with prostate cancer were randomized to receive either oral nanocurcumin (120 mg/day) or placebo 3 days before and during the RT course. Acute toxicities including proctitis and cystitis were assessed weekly during the treatment and once thereafter using CTCAE v.4.03 grading criteria. Baseline-adjusted hematologic nadirs were also analyzed and compared between the two groups. The patients undergoing definitive RT were followed to evaluate the tumor response. Nanocurcumin was well tolerated. Radiation-induced proctitis was noted in 18/31 (58.1%) of the placebo-treated patients versus 15/33 (45.5%) of nanocurcumin-treated patients (p = 0.313). No significant difference was also found between the two groups with regard to radiation-induced cystitis, duration of radiation toxicities, hematologic nadirs, and tumor response. In conclusion, this RCT was underpowered to indicate the efficacy of nanocurcumin in this clinical setting but could provide a considerable new translational insight to bridge the gap between the laboratory and clinical practice.

Accuracy evaluation of distance inverse square law in determining virtual electron source location in Siemens Primus linac.

AIM: The aim of this study is to evaluate the accuracy of the inverse square law (ISL) method for determining location of virtual electron source (SVir) in Siemens Primus linac. BACKGROUND: So far, different experimental methods have presented for determining virtual and effective electron source location such as Full Width at Half Maximum (FWHM), Multiple Coulomb Scattering (MCS), and Multi Pinhole Camera (MPC) and Inverse Square Law (ISL) methods. Among these methods, Inverse Square Law is the most common used method. MATERIALS AND METHODS: Firstly, Siemens Primus linac was simulated using MCNPX Monte Carlo code. Then, by using dose profiles obtained from the Monte Carlo simulations, the location of SVir was calculated for 5, 7, 8, 10, 12 and 14 MeV electron energies and 10 cm × 10 cm, 15 cm × 15 cm, 20 cm × 20 cm and 25 cm × 25 cm field sizes. Additionally, the location of SVir was obtained by the ISL method for the mentioned electron energies and field sizes. Finally, the values obtained by the ISL method were compared to the values resulted from Monte Carlo simulation. RESULTS: The findings indicate that the calculated SVir values depend on beam energy and field size. For a specific energy, with increase of field size, the distance of SVir increases for most cases. Furthermore, for a special applicator, with increase of electron energy, the distance of SVir increases for most cases. The variation of SVir values versus change of field size in a certain energy is more than the variation of SVir values versus change of electron energy in a certain field size. CONCLUSION: According to the results, it is concluded that the ISL method can be considered as a good method for calculation of SVir location in higher electron energies (14 MeV).

In Vitro Radiosensitizing Effects of Temozolomide on U87MG Cell Lines of Human Glioblastoma Multiforme.

BACKGROUND: Glioma is the most common primary brain tumor with poor prognosis. Temozolomide (TMZ) has been used with irradiation (IR) to treat gliomas. The aim of the present study was to evaluate the cytotoxic and radiosensitizing effect of TMZ when combined with high-dose and high-dose rate of gamma irradiation in vitro. METHODS: Two 'U87MG' cell lines and skin fibroblast were cultured and assigned to five groups for 24, 48, and 72 hours. The groups were namely, TMZ group (2000 µM/L), IR group (5 Gy), TMZ plus IR group, control group, and control solvent group. MTT assay was applied to evaluate cell viability. Data were analyzed with SPSS 21.0 software using one-way ANOVA and Kruskal-Wallis test. P<0.05 were considered statistically significant. RESULTS: The slope of growth curve U87MG cells in semi-logarithmic scale was equal to 27.36±0.89 hours. The viability of cells was determined for different TMZ and IR treatment groups. In terms of cell viability, there were no significant differences between the control and control solvent groups (P=0.35) and between treated group by IR (5 Gy) alone and TMZ (2000 µM/ml) alone (P=0.15). Data obtained for the cell viability of combined TMZ plus IR in both cell lines compared to TMZ or IR treated group alone showed a significant difference (P=0.002). CONCLUSION: The evaluation of cells viability showed that TMZ in combination with IR on glioma cells led to a significant radiosensitivity compared to IR alone.

Comparing the monoisocentric and dual isocentric techniques in chest wall radiotherapy of mastectomy patients.

The monoisocentric (MIT) and dual isocentric (DIT) techniques are compared for the mastectomy patients undergoing chest wall radiotherapy, and a new practical method is suggested for determining the dose calculation reference point to be used in the MIT. Data of 18 mastectomy patients having chest wall radiotherapy were used. To find the appropriate dose calculation reference point for the MIT, the target tissue was divided into nine regions with 17 points as the appropriate candidates. After finding the best reference point for the MIT, dose calculations were made for each patient based on the MIT and DIT to determine the dose distributions of the target volume and organs at risk. The lateral component of the dose calculation reference point was found to be located at one-third of the distance between the geometrical center and the lateral border of the chest wall in the lateral direction toward the outer border. The longitudinal component of this point was found to be located at the geometrical center of the chest wall with a depth located around 2-3 cm under the patients' skin. There was no significant difference between the two radiotherapy planning techniques (MIT and DIT) regarding the dose distributions in the organs at risk and the 95% of the prescribed dose coverage of the target tissue. However, a significant difference for the 105% of the prescribed dose coverage, maximum dose delivered to the target tissue, and the level 2 lymph nodes dose was found, with the DIT showing higher values. Because of the good matching and no superposition observed between the treatment fields in the MIT, it was expected and confirmed that the hot and cold regions (with higher and lower doses than the prescribed dose) with the MIT are significantly fewer than that of the DIT. Therefore, to perform a better conformal radiotherapy for the patients having mastectomy, it could be recommended to use the MIT instead of the DIT and other conventional techniques.

Evaluation of Perkin Elmer Amorphous Silicon Electronic Portal Imaging Device for Small Photon Field Dosimetry.

Background: Electronic portal imaging devices (EPIDs) are applied to measure the dose and verify patients' position. Objective: The present study aims to evaluate the performance of EPID for measuring dosimetric parameters in small photon fields. Material and Methods: In this experimental study, the output factors and beam profiles were obtained using the amorphous silicon (a-Si) EPID for square field sizes ranging from 1×1 to 10×10 cm2 at energies 6 and 18 mega-voltage (MV). For comparison, the dosimetric parameters were measured with the pinpoint, diode, and Semiflex dosimeters. Additionally, the Monaco treatment planning system was selected to calculate the output factors and beam profiles. Results: There was a significant difference between the output factors measured using the EPID and that measured with the other dosimeters for field sizes lower than 8×8 cm2. In the energy of 6 MV, the gamma passing rates (3%/3 mm) between EPID and diode profile were 98%, 98%, 95%, 94%, 93%, and 94% for 1×1, 2×2, 3×3, 4×4, 5×5, and 10×10 cm2, respectively. The measured penumbra width with EPID was higher compared to that measured by the diode dosimeter for both energies. Conclusion: The EPID can measure the dosimetric parameters in small photon fields, especially for beam profiles and penumbra measurements.

Prediction of auditory brain stem responses damage in patients with head-and-neck cancers receiving radiotherapy using the functional assays of normal tissue complication probability models.

AIM: The purpose of this study was to set four NTCP models on clinical data and develop a model that calculates the possibility of hearing damage due to irradiation of healthy and at-risk brainstem tissue. MATERIALS AND METHODS: ABR tests were performed on 50 head-and-neck cancer patients three years after radiotherapy for evaluation of lesions in a part of the auditory nerve or the auditory pathway in the brainstem. RESULTS: It indicated a significant difference in the latency of the waves assessed by the ABR test between the two groups. The paired sample t-test indicated the latency time of waves I, III, V, I-III, and I-V (P < 0.001) in the right ear, and in the left ear latency time of waves III, V, I-III, I-V, and III-V (P < 0.001) were significantly higher in the case group's ear than those in the control group. The confidence interval of the fitted parameters was 95% for NTCP models. ABR test's binary outcome with differential dose-volume histograms (dDVHs) was calculated and imported as input to the NTCP modeling. The values of the parameters n = 2.3-2.9 and the value s = 1 were obtained, which indicated that the brainstem organ is seriality. CONCLUSION: The best model ranked for the prediction of brainstem hearing damage was the logit model, which had the lowest Akaike value. The nervousness of the auditory organ of the brainstem (VIII nerve) can be declared as one of the reasons for being independent of the received dose.

Trends of Colorectal Cancer Incidence, Prevalence and Mortality in Worldwide From 1990 to 2017.

Background: Colorectal cancer is a major health problem both in developing and developed countries. This cancer is among the top three commonly diagnosed cancers in males and females. In this context, assessing the Incidence, Prevalence and Mortality Rate trend of this cancer is of great importance. Methods: We used the data from the GBD 2017 study to assess the global trend of 3 important indicators of colorectal cancer burden and to examine the relationship between trends of these indicators with Human Development Index (HDI). We used the multivariate mixed effects modeling framework with time and HDI as the covariates. Results: Trend analysis of colorectal cancer burden indicators showed a rather steady trend for mortality rate, while it revealed increasing slopes for both the incidence and prevalence rates. In addition, our findings showed a direct relationship between prevalence and incidence rates of this cancer and HDI level and indirect association between mortality rate and level of HDI. Conclusion: There were significant changes in indicators of colorectal cancer during the study period. The inverse relationship between mortality due to this cancer and socio-economic status of the countries indicated an urgent need for screening the patients and promoting the level of care in countries with lower levels of HDI.

Radiotherapy Combination: Insight from Tumor Immune Microenvironment (TIME).

The view of Radiotherapy (RT) as a simple inducer of DNA damage resulting in tumor cell death has dramatically changed in recent years, and it is now widely accepted that RT can trigger an immune response which provides a sound basis for combining RT with immunotherapy. Given that, radiation can be delivered with different regimens, its effect on immune responses and Tumor Immune Microenvironment (TIME) may vary with dose and fractionation schedule. This fractional dose dependency may need to be more considered because of recent developments in RT delivery techniques making it possible to deliver precisely higher dosages per fraction (hypofractionation) while reducing exposure to normal tissues. Although combining radiotherapy with immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy, the selection of the best-matched combination of immunotherapy with each radiotherapy scheme remains to be addressed. Thus, for designing better therapeutic combinations, it is necessary to understand the immunological effects of RT. Here, we review the impact of conventional and different hypofractionation radiation schedules on the TIME. Subsequently, we highlight how knowing about these interactions may have implications for choosing a rational combination with targeted therapies.

Estimating cancer risks due to whole lungs low dose radiotherapy with different techniques for treating COVID-19 pneumonia.

BACKGROUND: Low dose radiotherapy (LDRT) of whole lungs with photon beams is a novel method for treating COVID-19 pneumonia. This study aimed to estimate cancer risks induced by lung LDRT for different radiotherapy delivery techniques. METHOD: Four different radiotherapy techniques, including 3D-conformal with anterior and posterior fields (3D-CRT AP-PA), 3D-conformal with 8 coplanar fields (3D-CRT 8 fields), eight fields intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy using 2 full arcs (VMAT) were planned on the CT images of 32 COVID-19 patients with the prescribed dose of 1 Gy to the lungs. Organ average and maximum doses, and PTV dose distribution indexes were compared between different techniques. The radiation-induced cancer incidence and cancer-specific mortality, and cardiac heart disease risks were estimated for the assessed techniques. RESULTS: In IMRT and VMAT techniques, heart (mean and max), breast (mean, and max), and stomach (mean) doses and also maximum dose in the body were significantly lower than the 3D-CRT techniques. The calculated conformity indexes were similar in all the techniques. However, the homogeneity indexes were lower (i.e., better) in intensity-modulated techniques (P < 0.03) with no significant differences between IMRT and VMAT plans. Lung cancer incident risks for all the delivery techniques were similar (P > 0.4). Cancer incidence and mortality risks for organs located closer to lungs like breast and stomach were higher in 3D-CRT techniques than IMRT or VMAT techniques (excess solid tumor cancer incidence risks for a 30 years man: 1.94 ± 0.22% Vs. 1.68 ± 0.17%; and women: 6.66 ± 0.81% Vs. 4.60 ± 0.43%: cancer mortality risks for 30 years men: 1.63 ± 0.19% Vs. 1.45 ± 0.15%; and women: 3.63 ± 0.44% Vs. 2.94 ± 0.23%). CONCLUSION: All the radiotherapy techniques had low cancer risks. However, the overall estimated risks induced by IMRT and VMAT radiotherapy techniques were lower than the 3D-CRT techniques and can be used clinically in younger patients or patients having greater concerns about radiation induced cancers.

Introducing new plan evaluation indices for prostate dose painting IMRT plans based on apparent diffusion coefficient images.

BACKGROUND: Dose painting planning would be more complicated due to different levels of prescribed doses and more complex evaluation with conventional plan quality indices considering uniform dose prescription. Therefore, we tried to introduce new indices for evaluating the dose distribution conformity and homogeneity of treatment volumes based on the tumoral cell density and relative volumes of each lesion in prostate IMRT. METHODS: CT and MRI scans of 20 male patients having local prostate cancer were used for IMRT DP planning. Apparent diffusion coefficient (ADC) images were imported to a MATLAB program to identify lesion regions based on ADC values automatically. Regions with ADC values lower than 750 mm2/s and regions with ADC values higher than 750 and less than 1500 mm2/s were considered CTV70Gy (clinical tumor volume with 70 Gy prescribed dose), and CTV60Gy, respectively. Other regions of the prostate were considered as CTV53Gy. New plan evaluation indices based on evaluating the homogeneity (IOE(H)), and conformity (IOE(C)) were introduced, considering the relative volume of each lesion and cellular density obtained from ADC images. These indices were compared with conventional homogeneity and conformity indices and IOEs without considering cellular density. Furthermore, tumor control probability (TCP) was calculated for each patient, and the relationship of the assessed indices were evaluated with TCP values. RESULTS: IOE (H) and IOE (C) with considering cellular density had significantly lower values compared to conventional indices and IOEs without considering cellular density. (P < 0.05). TCP values had a stronger relationship with IOE(H) considering cell density (R2 = -0.415), and IOE(C) without considering cell density (R2 = 0.624). CONCLUSION: IOE plan evaluation indices proposed in this study can be used for evaluating prostate IMRT dose painting plans. We suggested to consider cell densities in the IOE(H) calculation formula and it's appropriate to calculate IOE(C) without considering cell density values.

Evaluating the relationship between dosimetric parameters and esophagitis in patients who experienced radiotherapy in the cervicothoracic region.

Purpose: Prescribing radiotherapy or concurrent chemoradiation for cervicothoracic cancers inevitably leads to esophagitis. The purpose of the current study was to evaluate the correlation between the dose-volume parameters and the esophagitis in patients who received radiotherapy in the cervicothoracic region. Materials and Methods: Forty cancerous patients whose radiotherapy fields were in the cervicothoracic region have been rolled. The correlation between the dosimetric and clinical factors with esophagitis was analyzed through binary logistic regression model and Pearson correlation tests and was quantified with receiver operating characteristic curve. Results: The patients participating in the study were selected from breast (6 cases), lymphoma (7 cases), and head-neck (27 cases) patients with prescription doses of 36-72 Gy. Increasing esophagus mean dose resulted in an increase of acute esophagitis significantly (P = 0.05). Furthermore, by one-gray increase in the esophagus median dose, the possibility of esophagitis increased by 9.3% (P = 0.02). To prevent acute esophagitis (Grade ≥2), D50 should be kept below 7 Gy. To limit acute esophagitis, V40 should be kept below 19% (P = 0.04). Conclusions: Based on the correlation analysis of the current study, concurrent chemoradiotherapy, DMean, D50, D80, and V40 are known as reliable predictive dosimetric parameters of acute esophagitis incidence in patients who experienced radiotherapy in the cervicothoracic region.

Prediction of chronic kidney disease in abdominal cancers radiation therapy using the functional assays of normal tissue complication probability models.

Aim: The purpose of this study is to predict chronic kidney disease (CKD) in the radiotherapy of abdominal cancers by evaluating clinical and functional assays of normal tissue complication probability (NTCP) models. Materials and Methods: Radiation renal damage was analyzed in 50 patients with abdominal cancers 12 months after radiotherapy through a clinical estimated glomerular filtration rate (eGFR). According to the common terminology criteria for the scoring system of adverse events, Grade 2 CKD (eGFR ≤30-59 ml/min/1.73 m2) was considered as the radiation therapy endpoint. Modeling and parameter estimation of NTCP models were performed for the Lyman-equivalent uniform dose (EUD), the logit-EUD critical volume (CV), the relative seriality, and the mean dose model. Results: The confidence interval of the fitted parameters was 95%. The parameter value of D50 was obtained 22-38 Gy, and the n and s parameters were equivalent to 0.006 -3 and 1, respectively. According to the Akaike's information criterion, the mean dose model predicts radiation-induced CKD more accurately than the other models. Conclusion: Although the renal medulla consists of many nephrons arranged in parallel, each nephron has a seriality architecture as renal functional subunits. Therefore, based on this principle and modeling results in this study, the whole kidney organs may have a serial-parallel combination or a secret architecture.

Radiation dose and schedule influence the abscopal effect in a bilateral murine CT26 tumor model.

Radiotherapy (RT) can induce immune-mediated responses in local irradiated tumors, and non-irradiated distant metastasis is termed the abscopal effect. Here, we aimed to evaluate the impact of different RT doses and fractions on anti-tumor responses within local irradiated and distance non-irradiated tumor microenvironments. In mice bearing CT26 tumors, the primary tumor was irradiated with three different RT doses (16 Gy × 1F, 10 Gy × 2F, and 3 Gy × 10F) with the same biologically effective dose. Tumor volumes and immune cells changes were assessed in irradiated and non-irradiated tumors. Survival times were evaluated over 90 days. Only 16 Gy × 1F radiation increased CD8 + T cells number in the irradiated (p = 0.043) and non-irradiated (p = 0.047) tumors compared to the untreated group. A high frequency of tumor-associated macrophages-1 (TAM-1) and low TAM-2 was found in 16 Gy × 1F irradiated mice. Moreover, 16 Gy × 1F significantly induced interferon gamma (IFNγ)-producing CD8 + cells in the spleen compared to controls (p = 0.021). Hypofraction regimens (16 Gy × 1F, 10 Gy × 2F) caused a reduction in myeloid-derived suppressor cells in the irradiated tumors. We detected A modest growth delay in both flank tumors and long-term survival after hypofraction treatments (16 Gy × 1F, 10 Gy × 2F). A single high RT dose increased CD8 + cells number in irradiated (p = 0.000) and non-irradiated (p = 0.002) tumors approximal up to 2 points along with significant induction of IFN-γ production by CD8 + cells in the spleen when combined with anti- programmed death ligand-1 (PDL-1) (p = 0.000). Combination therapy was also associated with bilateral tumor growth control and increased life span in mice. Hypofractionated RT schedules, especially single high dose, seem the most effective regimen for inducing an abscopal effect. Immune checkpoint inhibitors could promote RT-induced systemic effects.

Combining ablative radiotherapy and anti CD47 monoclonal antibody improves infiltration of immune cells in tumor microenvironments.

Radiotherapy as an anti-tumor treatment can stimulate the immune system. However, irradiated tumor cells express CD47 to escape the anti-tumor immune response. Anti- CD47 Immunotherapy is a possible way to tackle this problem. This study evaluated the effect of single high dose radiotherapy combined with an anti-CD47 monoclonal antibody (αCD47 mAb) in CT26 tumor-bearing BALB/c mice. We assessed the tumors volume and survival in mice 60 days after tumor implantation. Also, immune cell changes were analyzed by flow cytometry in tumors, lymph nodes, and spleen. Combination therapy enhanced the anti-tumor response in treated mice by increasing CD8+ T cells and M1 macrophages and decreasing M2 macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME). Also, our results showed that combination therapy increased survival time in mice compared to other groups. Furthermore, tumor volumes remarkably decreased in mice that received a single high dose RT plus αCD47 mAb. In conclusion, we showed that combining RT and αCD47 mAb improved the immune cell population in TME, regressed tumor growth, and increased survival in tumor-bearing mice.

Low-dose radiotherapy (LD-RT) for COVID-19-induced pneumopathy: a worth considering approach.

PURPOSE: It seems that 2020 would be always remembered by the name of novel coronavirus (designated as SARS-CoV-2), which exerted its deteriorating effects on the health care, economy, education, and political relationships. In August 2020 more than eight hundred thousand patients lost their lives due to acute respiratory syndrome. In the limited list of therapeutic approaches, the effectiveness of low-dose radiation therapy (LD-RT) for curing inflammatory-related diseases have sparkled a light that probably this approach would bring promising advantages for COVID-19 patients. LD-RT owns its reputation from its ability to modulate the host inflammatory responses by blocking the production of pro-inflammatory cytokines and hampering the activity of leukocytes. Moreover, the cost-effective and availability of this method allow it to be applied to a large number of patients, especially those who could not receive anti-IL-6 treatments in low-income countries. But enthusiasm for applying LD-RT for the treatment of COVID-19 patients has been muted yet. CONCLUSION: In this review, we take a look at LD-RT mechanisms of action in the treatment of nonmalignant diseases, and then through studying both the dark and bright sides of this approach, we provide a thorough discussion if LD-RT might be a promising therapeutic approach in COVID-19 patients.