90Y post-radioembolization clinical assessment with whole-body Biograph Vision Quadra PET/CT: image quality, tumor, liver and lung dosimetry.

PURPOSE: Evaluation of 90Y liver radioembolization post-treatment clinical data using a whole-body Biograph Vision Quadra PET/CT to investigate the potential of protocol optimization in terms of scan time and dosimetry. METHODS: 17 patients with hepatocellular carcinoma with median (IQR) injected activity 2393 (1348-3298) MBq were included. Pre-treatment dosimetry plan was based on 99mTc-MAA SPECT/CT with Simplicit90Y™ and post-treatment validation with Quadra using Simplicit90Y™ and HERMIA independently. Regarding the image analysis, mean and peak SNR, the coefficient of variation (COV) and lesion-to-background ratio (LBR) were evaluated. For the post-treatment dosimetry validation, the mean tumor, whole liver and lung absorbed dose evaluation was performed using Simplicit90Y and HERMES. Images were reconstructed with 20-, 15-, 10-, 5- and 1- min sinograms with 2, 4, 6 and 8 iterations. Wilcoxon signed rank test was used to show statistical significance (p < 0.05). RESULTS: There was no difference of statistical significance between 20- and 5- min reconstructed times for the peak SNR, COV and LBR. In addition, there was no difference of statistical significance between 20- and 1- min reconstructed times for all dosimetry metrics. Lung dosimetry showed consistently lower values than the expected. Tumor absorbed dose based on Simplicit90Y™ was similar to the expected while HERMES consistently underestimated significantly the measured tumor absorbed dose. Finally, there was no difference of statistical significance between expected and measured tumor, whole liver and lung dose for all reconstruction times. CONCLUSION: In this study we evaluated, in terms of image quality and dosimetry, whole-body PET clinical images of patients after having been treated with 90Y microspheres radioembolization for liver cancer. Compared to the 20-min standard scan, the simulated 5-min reconstructed images provided equal image peak SNR and noise behavior, while performing also similarly for post-treatment dosimetry of tumor, whole liver and lung absorbed doses.

Clinical benefits of deep inspiration breath-hold in postoperative radiotherapy for right-sided breast cancer: a meta-analysis.

OBJECTIVES: The study aims to emphasize the clinical importance of the Deep Inspiration Breath Hold (DIBH) technique by quantifying its dosimetric advantages over Free Breathing (FB) in reducing radiation exposure to the heart, liver, and lungs for right-sided breast cancer patients. This evidence supports its potential for routine clinical use to mitigate radiation-induced toxicity. METHODS: A systematic retrieval of controlled trials comparing DIBH and FB techniques in postoperative radiotherapy for right-sided breast cancer was conducted utilizing the PubMed, Embase, Cochrane Library, and Web of Science databases. The primary outcomes assessed included the doses of adjacent normal tissues (heart, liver, and lungs). Summary standardized mean differences (SMD) along with 95% confidence intervals (CI) were computed, respectively. StataMP 17 software was selected to perform data analysis. RESULTS: The study encompassed an analysis of 313 patients derived from seven online studies, comprising 168 individuals in the DIBH group and 269 individuals in the FB group. The findings indicated that the DIBH group received significantly lower irradiation doses to the heart, liver, and lungs in comparison to the FB group, with statistical significance (heart dose: SMD = -0.63, 95% CI -0.85 to -0.41, P < 0.05; liver dose: SMD = -1.15, 95% CI -1.91 to -0.38, P < 0.05; lung dose: SMD = -0.79, 95% CI -1.23 to -0.35, P < 0.05). CONCLUSION: This meta-analysis indicated that the application of DIBH during postoperative radiotherapy for right-sided breast cancer markedly decreases radiation exposure to the heart, liver, and lungs, while maintaining consistent tumor dose coverage. CLINICAL TRIAL NUMBER: Not applicable.

Metabolic profiling of murine radiation-induced lung injury with Raman spectroscopy and comparative machine learning.

Radiation-induced lung injury (RILI) is a dose-limiting toxicity for cancer patients receiving thoracic radiotherapy. As such, it is important to characterize metabolic associations with the early and late stages of RILI, namely pneumonitis and pulmonary fibrosis. Recently, Raman spectroscopy has shown utility for the differentiation of pneumonitic and fibrotic tissue states in a mouse model; however, the specific metabolite-disease associations remain relatively unexplored from a Raman perspective. This work harnesses Raman spectroscopy and supervised machine learning to investigate metabolic associations with radiation pneumonitis and pulmonary fibrosis in a mouse model. To this end, Raman spectra were collected from lung tissues of irradiated/non-irradiated C3H/HeJ and C57BL/6J mice and labelled as normal, pneumonitis, or fibrosis, based on histological assessment. Spectra were decomposed into metabolic scores via group and basis restricted non-negative matrix factorization, classified with random forest (GBR-NMF-RF), and metabolites predictive of RILI were identified. To provide comparative context, spectra were decomposed and classified via principal component analysis with random forest (PCA-RF), and full spectra were classified with a convolutional neural network (CNN), as well as logistic regression (LR). Through leave-one-mouse-out cross-validation, we observed that GBR-NMF-RF was comparable to other methods by measure of accuracy and log-loss (p > 0.10 by Mann-Whitney U test), and no methodology was dominant across all classification tasks by measure of area under the receiver operating characteristic curve. Moreover, GBR-NMF-RF results were directly interpretable and identified collagen and specific collagen precursors as top fibrosis predictors, while metabolites with immune and inflammatory functions, such as serine and histidine, were top pneumonitis predictors. Further support for GBR-NMF-RF and the identified metabolite associations with RILI was found as CNN interpretation heatmaps revealed spectral regions consistent with these metabolites.

Note on dose conversion for radon exposure.

The epidemiological approach to converting radon exposure to effective dose is examined. Based on the definition of the effective dose, the dose conversion is obtained from the equivalence of lung-specific detriment associated with low-LET radiation and with radon exposure. This approach most reliably estimates effective dose per radon exposure on the basis of epidemiological data and implicitly includes the radiation weighting factor required to calculate the effective dose from radon exposure using the dosimetric approach, applying biokinetic and dosimetric models. Consistency between the results of the epidemiological and dosimetric approaches is achieved by using a radiation weighting factor of about 10 for alpha particles instead of the current ICRP value of 20. In contrast, the epidemiological approach implemented in ICRP 65, and referred to as dose conversion convention, was based on direct comparison of total radiation detriment with lung detriment from radon exposure. With the revision of radiation detriments in ICRP 103, this approach can be judged to overestimate the effective dose per radon exposure by about a factor of two because the tissue weighting factor for lung differs from the value of relative detriment to which it relates.

A genome-wide microRNA screen identifies the microRNA-183/96/182 cluster as a modulator of circadian rhythms.

The regulatory mechanisms of circadian rhythms have been studied primarily at the level of the transcription-translation feedback loops of protein-coding genes. Regulatory modules involving noncoding RNAs are less thoroughly understood. In particular, emerging evidence has revealed the important role of microRNAs (miRNAs) in maintaining the robustness of the circadian system. To identify miRNAs that have the potential to modulate circadian rhythms, we conducted a genome-wide miRNA screen using U2OS luciferase reporter cells. Among 989 miRNAs in the library, 120 changed the period length in a dose-dependent manner. We further validated the circadian regulatory function of an miRNA cluster, miR-183/96/182, both in vitro and in vivo. We found that all three members of this miRNA cluster can modulate circadian rhythms. Particularly, miR-96 directly targeted a core circadian clock gene, PER2. The knockout of the miR-183/96/182 cluster in mice showed tissue-specific effects on circadian parameters and altered circadian rhythms at the behavioral level. This study identified a large number of miRNAs, including the miR-183/96/182 cluster, as circadian modulators. We provide a resource for further understanding the role of miRNAs in the circadian network and highlight the importance of miRNAs as a genome-wide layer of circadian clock regulation.

Validation of Acuros for total body irradiation at extended distance.

PURPOSE: Standardized and accurately reported doses are essential in conventional total body irradiation (TBI), especially lung doses. This study evaluates the accuracy of the Acuros algorithm in predicting doses for extended-distance TBI. METHODS: Measurements and calculations were done with both 6 and 18 MV. Tissue Maximum Ratio (TMR), output and off axis ratios (OAR) were measured at 200 and 500 cm source to detector distance and compared to Acuros calculated values. Two end-to-end tests were carried out, one with an in-house phantom (solid water and Styrofoam) with inserted ion chambers and the other was with the Imaging and Radiation Oncology Core (IROC) TBI anthropomorphic phantom equipped with TLDs. The end-to-end test was done for 6 and 18 MV both with and without lung blocks. The source to midplane distance for both phantoms were at 518 and 508 cm respectively. Lung blocks were placed at the phantom surface and a beam spoiler was positioned 30 cm from the surface of the phantoms as per our clinical set up. RESULTS: The agreement between measured and calculated TMR, output and off axis ratios for both 6 and 18 MV were within 2%. Ion chamber measurements in both the Styrofoam and solid water for both energies carried out with and without lung blocks were within 2% of calculated values. TLD measured doses for both 6 and 18 MV in the IROC phantom were within 5% of calculated doses which is within the uncertainty of the TLD measurement. CONCLUSIONS: The results indicate that the clinical beam model for Acuros 16.1 commissioned at standard clinical distances is capable of calculating doses accurately at extended distances up to 500 cm.

Factors associated with cavity formation after stereotactic body radiation therapy for peripheral early-stage lung cancer.

PURPOSE: This retrospective study aimed to identify the factors associated with cavity formation after SBRT in peripheral early-stage lung cancer patients. We analyzed the occurrence of cavity changes after SBRT. MATERIALS AND METHODS: We examined 99 cases with T1-T2aN0 peripheral non-small cell lung cancer treated with SBRT from 2004 to 2021. Patients underwent respiratory function tests, including diffusing capacity for carbon monoxide (DLco), before treatment. The median observation period was 35 months (IQR 18-47.5 months). Treatment involved fixed multi-portal irradiation in 67% of cases and VMAT in 33%. The total radiation doses ranged from 42 to 55 Gy, delivered over 4 to 5 fractions. RESULTS: Cavity formation occurred in 14 cases (14.1%), appearing a median of 8 months after SBRT. The cavity disappeared in a median of 4 months after formation. High DLco and total radiation dose were identified as factors significantly associated with cavity formation. There have been no confirmed recurrences to date, but one patient developed a lung abscess. CONCLUSION: Although cavity formation after SBRT for peripheral early-stage lung cancer is infrequent, it can occur. This study showed high DLco and total radiation dose to be factors significantly associated with cavity formation. These findings can be applied to optimizing radiation therapy (RT) and improving patient outcomes. Further research is needed to determine the optimal radiation dose for patients with near-normal DLco for whom surgery is an option. This study provides valuable insights into image changes after RT.

Assessment of tracheobronchial and lung dose due to radon and thoron inhalation.

The main sources of natural background radiation are radon, thoron and their progeny, which may cause health risks to humans. Keeping in mind the importance of the subject, three samples each from 10 selected residential areas, including the centre of Babylon Governorate, Iraq, and its districts, were collected. Concentration of radon and thoron was measured using solid-state track detectors (CR-39). The arithmetic means of the concentration of radon and thoron were 47.367±19.56 and 133.246±16.585 Bqm-3, respectively; these values are considered safe when compared with the upper reference level of 200-600 Bqm-3 recommended by the International Commission for Radiological Protection (ICRP). The value of the inhalation equivalent dose from radon gas discovered in these areas with rate 37.893 nSv is less than the value of the global average of 1.15 mSv. This indicates that the risks related to inhalation of radon are low as the lung dose rate (DLung), tracheobronchial region (DT-B), annual effective dose (AED) and excess lifetime cancer risk (ELCR) is (1.894 nGyh-1, 22.736 nSv, 0.236 mSvy-1 and 0.835 x10-3), respectively. While the value of the inhalation equivalent dose (IED) from thoron as effective dose to lung DLung, AED and ELCR are equal to (0.133 nSv, 0.167 mSvy-1 and 0.587 x 10-3), respectively. To conclude, the rates in the study area are less than the ICRP recommended level of 3 mSv; therefore, the studied areas are safe from the health risks of inhalation of radon and thoron.

4DCT ventilation function image-based functional lung protection for esophageal cancer radiotherapy.

BACKGROUND: 4DCT (four-dimensional computed tomography) can effectively obtain functional lung ventilation images for patients and integrate them into radiotherapy treatment planning. Studies have not been performed on esophageal cancer, and there is no clear consensus on the optimal functional lung threshold for functional lung. METHODS: Functional lung images were generated for 11 patients with esophageal cancer. The correlation between the dose-volume parameters of functional lung (FL) as defined by different thresholds and the change of PFT/PDFT (pulmonary [diffusion] function test) metrics before and after radiotherapy were evaluated. FL-sparing planning was generated for each patient to preserve the functional lung and compared to conventional anatomical CT (non-sparing) planning. RESULTS: There was a significant positive correlation between the FL0.8 (defined Jacobian value ≤ 0.8), FL0.84, and FL0.9 dose-volume parameters and ΔFEV1/FVC (reduction before and after radiotherapy), and the FL0.8­V30 correlation was the strongest (r = 0.819, P < 0.01). The FL-sparing planning had a target area conformity index and homogeneity index comparable to the non-sparing planning (P > 0.05). For FL, the FL-sparing planning achieved lower FL-MLD (6.30 ±â€¯2.14 Gy vs. 7.83 ± 2.70 Gy), V10 (17.13 ±â€¯7.70% vs. 27.40 ± 9.48%), and V20 (6.96 ±â€¯3.85% vs. 11.63 ± 7.19%) compared to the non-sparing planning (P < 0.05), while heart and spinal cord doses were not significantly different between the two planning groups. CONCLUSION: The 4DCT-based FL irradiation dose for esophageal cancer was significantly associated with a decrease in FEV1/FVC. The optimal FL defined as a Jacobian value ≤ 0.8 or about 21% of the whole lung volume may be a good choice. FL-sparing planning significantly reduced the FL dose without compromising target area coverage.

Correlation between AI-based CT organ features and normal lung dose in adjuvant radiotherapy following breast-conserving surgery: a multicenter prospective study.

BACKGROUND: Radiation pneumonitis (RP) is one of the common side effects after adjuvant radiotherapy in breast cancer. Irradiation dose to normal lung was related to RP. We aimed to propose an organ features based on deep learning (DL) model and to evaluate the correlation between normal lung dose and organ features. METHODS: Patients with pathology-confirmed invasive breast cancer treated with adjuvant radiotherapy following breast-conserving surgery in four centers were included. From 2019 to 2020, a total of 230 patients from four nationwide centers in China were screened, of whom 208 were enrolled for DL modeling, and 22 patients from another three centers formed the external testing cohort. The subset of the internal testing cohort (n = 42) formed the internal correlation testing cohort for correlation analysis. The outline of the ipsilateral breast was marked with a lead wire before the scanning. Then, a DL model based on the High-Resolution Net was developed to detect the lead wire marker in each slice of the CT images automatically, and an in-house model was applied to segment the ipsilateral lung region. The mean and standard deviation of the distance error, the average precision, and average recall were used to measure the performance of the lead wire marker detection model. Based on these DL model results, we proposed an organ feature, and the Pearson correlation coefficient was calculated between the proposed organ feature and ipsilateral lung volume receiving 20 Gray (Gy) or more (V20). RESULTS: For the lead wire marker detection model, the mean and standard deviation of the distance error, AP (5 mm) and AR (5 mm) reached 3.415 ± 4.529, 0.860, 0.883, and 4.189 ± 8.390, 0.848, 0.830 in the internal testing cohort and external testing cohort, respectively. The proposed organ feature calculated from the detected marker correlated with ipsilateral lung V20 (Pearson correlation coefficient, 0.542 with p < 0.001 in the internal correlation testing cohort and 0.554 with p = 0.008 in the external testing cohort). CONCLUSIONS: The proposed artificial Intelligence-based CT organ feature was correlated with normal lung dose in adjuvant radiotherapy following breast-conserving surgery in patients with invasive breast cancer. TRIAL REGISTRATION: NCT05609058 (08/11/2022).

Effects of reconstruction methods on dose distribution for lung stereotactic body radiotherapy treatment plans.

The aim of the present study was to investigate the effect of tumour motion on various imaging strategies as well as on treatment plan accuracy for lung stereotactic body radiotherapy treatment (SBRT) cases. The ExacTrac gating phantom and paraffin were used to investigate respiratory motion and represent a lung tumour, respectively. Four-dimensional computed tomography (4DCT) imaging was performed, while the phantom was moving sinusoidally with 4 s cycling time with three different amplitudes of 8, 16, and 24 mm. Reconstructions were done with maximum (MIP) and average intensity projection (AIP) methods. Comparisons of target density and volume were performed using two reconstruction techniques and references values. Volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) were planned based on reconstructed computed tomography (CT) sets, and it was examined how density variations affect the dose-volume histogram (DVH) parameters. 4D cone beam computed tomography (CBCT) was performed with the Elekta Versa HD linac imaging system before irradiation and compared with 3D CBCT. Thus, various combinations of 4DCT reconstruction methods and treatment alignment methods have been investigated. Point measurements as well as 2 and 3D dose measurements were done by optically stimulated luminescence (OSL), gafchromic films, and electronic portal imaging devices (EPIDs), respectively. The mean volume reduction was 7.8% for the AIP and 2.6% for the MIP method. The obtained Hounsfield Unit (HU) values were lower for AIP and higher for MIP when compared with the reference volume density. In DVH analysis, there were no statistical differences for D95%, D98%, and Dmean (p > 0.05). However, D2% was significantly affected by HU changes (p < 0.01). A positional variation was obtained up to 2 mm in moving direction when 4D CBCT was applied after 3D CBCT. Dosimetric measurements showed that the main part of the observed dose deviation was due to movement. In lung SBRT treatment plans, D2% doses differ significantly according to the reconstruction method. Additionally, it has been observed that setups based on 3D imaging can cause a positional error of up to 2 mm compared to setups based on 4D imaging. It is concluded that MIP has advantages over AIP in defining internal target volume (ITV) in lung SBRT applications. In addition, 4D CBCT and 3D EPID dosimetry are recommended for lung SBRT treatments.

Benchmarking halcyon ring delivery system for hypofractionated breast radiotherapy: Validation and clinical implementation of the fast-forward trial.

PURPOSE: The aim of this study was to demonstrate the feasibility and efficacy of an iterative CBCT-guided breast radiotherapy with Fast-Forward trial of 26 Gy in five fractions on a Halcyon Linac. This study quantifies Halcyon plan quality, treatment delivery accuracy and efficacy by comparison with those of clinical TrueBeam plans. MATERIALS AND METHODS: Ten accelerated partial breast irradiation (APBI) patients (four right, six left) who underwent Fast-Forward trial at our institute on TrueBeam (6MV beam) were re-planned on Halcyon (6MV-FFF). Three site-specific partial coplanar VMAT arcs and an Acuros-based dose engine were used. For benchmarking, PTV coverage, organs-at-risk (OAR) doses, beam-on time, and quality assurance (QA) results were compared for both plans. RESULTS: The average PTV was 806 cc. Compared to TrueBeam plans, Halcyon provided highly conformal and homogeneous plans with similar mean PTVD95 (25.72  vs. 25.73 Gy), both global maximum hotspot < 110% (p = 0.954) and similar mean GTV dose (27.04  vs. 26.80 Gy, p = 0.093). Halcyon provided lower volume of ipsilateral lung receiving 8 Gy (6.34% vs. 8.18%, p = 0.021), similar heart V1.5 Gy (16.75% vs. 16.92%, p = 0.872), V7Gy (0% vs. 0%), mean heart dose (0.96  vs. 0.9 Gy, p = 0.228), lower maximum dose to contralateral breast (3.2  vs. 3.6 Gy, p = 0.174), and nipple (19.6  vs. 20.1 Gy, p = 0.363). Compared to TrueBeam, Halcyon plans provided similar patient-specific QA pass rates and independent in-house Monte Carlo second check results of 99.6% vs. 97.9% (3%/2 mm gamma criteria) and 98.6% versus 99.2%, respectively, suggesting similar treatment delivery accuracy. Halcyon provided shorter beam-on time (1.49  vs. 1.68 min, p = 0.036). CONCLUSION: Compared to the SBRT-dedicated TrueBeam, Halcyon VMAT plans provided similar plan quality and treatment delivery accuracy, yet potentially faster treatment via one-step patient setup and verification with no patient collision issues. Rapid delivery of daily APBI on Fast-Forward trial on Halcyon with door-to-door patient time < 10 min, could reduce intrafraction motion errors, and improve patient comfort and compliance. We have started treating APBI on Halcyon. Clinical follow-up results are warranted. We recommend Halcyon users consider implementing the protocol to remote and underserved APBI patients in Halcyon-only clinics.

Biomarkers to Predict Lethal Radiation Injury to the Rat Lung.

Currently, there are no biomarkers to predict lethal lung injury by radiation. Since it is not ethical to irradiate humans, animal models must be used to identify biomarkers. Injury to the female WAG/RijCmcr rat has been well-characterized after exposure to eight doses of whole thorax irradiation: 0-, 5-, 10-, 11-, 12-, 13-, 14- and 15-Gy. End points such as SPECT imaging of the lung using molecular probes, measurement of circulating blood cells and specific miRNA have been shown to change after radiation. Our goal was to use these changes to predict lethal lung injury in the rat model, 2 weeks post-irradiation, before any symptoms manifest and after which a countermeasure can be given to enhance survival. SPECT imaging with 99mTc-MAA identified a decrease in perfusion in the lung after irradiation. A decrease in circulating white blood cells and an increase in five specific miRNAs in whole blood were also tested. Univariate analyses were then conducted on the combined dataset. The results indicated that a combination of percent change in lymphocytes and monocytes, as well as pulmonary perfusion volume could predict survival from radiation to the lungs with 88.5% accuracy (95% confidence intervals of 77.8, 95.3) with a p-value of < 0.0001 versus no information rate. This study is one of the first to report a set of minimally invasive endpoints to predict lethal radiation injury in female rats. Lung-specific injury can be visualized by 99mTc-MAA as early as 2 weeks after radiation.

Pooled analysis on image-guided moderately hypofractionated thoracic irradiation in inoperable node-positive/recurrent patients with non-small cell lung cancer with poor prognostic factors and severely limited pulmonary function and reserve.

BACKGROUND: The objective of this study was to investigate the feasibility and efficacy of image-guided moderately hypofractionated thoracic radiotherapy (hypo-IGRT) in patients with non-small cell lung cancer (NSCLC) with poor performance status and severely limited pulmonary function and reserve. METHODS: Consecutive inoperable patients who had node-positive, stage IIB-IIIC (TNM, 8th edition) or recurrent NSCLC, had an Eastern Cooperative Oncology Group performance status ≥1, and had a forced expiratory volume in 1 second (FEV1 ) ≤1.0 L, had a single-breath diffusing capacity of the lung for carbon monoxide (DLCO-SB) ≤40% and/or on long-term oxygen therapy were analyzed. All patients received hypofractionated IGRT to a total dose of 42.0 to 49.0 Gy/13 to 16 fractions (2.8-3.5 Gy/fraction) (equivalent dose in 2-Gy fractions/biologically effective dose [α/ß = 10] = 45.5-55.1 Gy/54.6-66.2 Gy) alone. Patients were monitored closely for nonhematological toxicity, which was classified per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Between 2014 and 2021, 47 consecutive patients with a median age of 72 years (range, 52.2-88 years) were treated. At baseline, the median FEV1 , vital capacity, and DLCO-SB were 1.17 L (range, 0.69-2.84 L), 2.34 L (range, 1.23-3.74 L), and 35% predicted (range, 13.3%-69.0%), respectively. The mean and median planning target volumes were 410.8 cc (SD, 267.1 cc) and 315.4 cc (range, 83.4-1174.1 cc). With a median follow-up of 28.9 months (range, 0.5-90.6 months) after RT, the median progression-free survival (PFS)/overall survival (OS) and 6- and 12-month PFS/OS rates were 10.4 months (95% CI, 7-13.8 months)/18.3 months (95% CI, 9.2-27.4 months), 70%/89.4%, and 38.8%/66%, respectively. Treatment was well tolerated with only 1 case each of grade 3 pneumonitis and esophagitis. No toxicity greater than grade 3 was observed. CONCLUSIONS: Patients with inoperable node-positive NSCLC, a poor performance status, and severely limited lung function can be safely and effectively treated with individualized moderately hypofractionated IGRT. The achieved survival rates for this highly multimorbid group of patients were encouraging.

Efferocytosis and enhanced FPR2 expression following apoptotic cell instillation attenuate radiation-induced lung inflammation and fibrosis.

Lung inflammation and fibrosis are common side effects of radiotherapy that can lead to serious reduction in the quality of life of patients. However, no effective treatment is available, and the mechanisms underlying its pathophysiology are poorly understood. Irradiation increases formyl peptide receptor 2 (FPR2) expression in lung tissue, and FPR2 agonists are known to promote the uptake of apoptosis cells, referred to as efferocytosis that is a hallmark of the resolution of inflammation. Herein, in a mouse model of radiation-induced lung injury (RILI), efferocytosis was induced by injecting apoptotic cells into the lung through the trachea, and its correlation with FPR expression and the effect of efferocytosis and FPR expression on RILI were assessed. Interestingly, when apoptotic cells were injected into the lung, the radiation-induced increase in FPR2 expression was further amplified. In the mouse model of RILI, apoptotic cell instillation reduced the volume of the damaged lung and prevented the decrease in lung function. Additionally, the expression of inflammatory cytokines, fibrosis-related markers, and oxidative stress-related markers was reduced by apoptotic cell instillation. Co-administration of apoptotic Jurkat cells and WRW4, the FPR2 antagonist, reversed these effects. These findings suggest that efferocytosis induced by apoptotic cell instillation and enhanced FPR2 expression attenuate RILI, thereby alleviating lung inflammation and fibrosis.

Effect of plan complexity on the dosimetry, delivery accuracy, and interplay effect in lung VMAT SBRT with 6 MV FFF beam.

PURPOSE: The purpose of this study is to investigate the effect of plan complexity on the dosimetry, delivery accuracy, and interplay effect in lung stereotactic body radiation therapy (SBRT) using volumetric modulated arc therapy (VMAT) with 6 MV flattening-filter-free (FFF) beam. METHODS: Twenty patients with early stage non-small cell lung cancer were included. For each patient, high-complexity (HC) and low-complexity (LC) three-partial-arc VMAT plans were optimized by adjusting the normal tissue objectives and the maximum monitoring units (MUs) for a Varian TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, CA, USA) using 6 MV FFF beam. The effect of plan complexity was comprehensively evaluated in three aspects: (1) The dosimetric parameters, including CI, D2cm, R50, and dose-volume parameters of organs at risk were compared. (2) The delivery accuracy was assessed by pretreatment quality assurance for two groups of plans. (3) The motion-induced dose deviation was evaluated based on point dose measurements near the tumor center by using a programmable phantom. The standard deviation (SD) and maximum dose difference of five measurements were used to quantify the interplay effect. RESULTS: The dosimetry of HC and LC plans were similar except the CI (1.003 ± 0.032 and 1.026 ± 0.043, p = 0.030) and Dmax to the spinal cord (10.6 ± 3.2 and 9.9 ± 3.0, p = 0.012). The gamma passing rates were significantly higher in LC plans for all arcs (p < 0.001). The SDs of HC and LC plans ranged from 0.5-16.6% and 0.03-2.9%, respectively, under the conditions of one-field, two-field, and three-field delivery for each plan with 0.5, 1, 2, and 3 cm motion amplitudes. The maximum dose differences of HC and LC plans were 34.5% and 9.1%, respectively. CONCLUSION: For lung VMAT SBRT, LC plans have a higher delivery accuracy and a lower motion-induced dose deviation with similar dosimetry compared with HC plans.

Estimation of secondary cancer projected risk after partial breast irradiation at the 1.5 T MR-linac.

PURPOSE: For patients treated with partial breast irradiation (PBI), potential long-term treatment-related toxicities are important. The 1.5 T magnetic resonance guided linear accelerator (MRL) offers excellent tumor bed visualization and a daily treatment plan adaption possibility, but MRL-specific electron stream and return effects may cause increased dose deposition at air-tissue interfaces. In this study, we aimed to investigate the projected risk of radiation-induced secondary malignancies (RISM) in patients treated with PBI at the 1.5 T MRL. METHODS: Projected excess absolute risk values (EARs) for the contralateral breast, lungs, thyroid and esophagus were estimated for 11 patients treated with PBI at the MRL and compared to 11 patients treated with PBI and 11 patients treated with whole breast irradiation (WBI) at the conventional linac (CTL). All patients received 40.05 Gy in 15 fractions. For patients treated at the CTL, additional dose due to daily cone beam computed tomography (CBCT) was simulated. The t­test with Bonferroni correction was used for comparison. RESULTS: The highest projected risk for a radiation-induced secondary cancer was found for the ipsilateral lung, without significant differences between the groups. A lower contralateral breast EAR was found for MRL-PBI (EAR = 0.89) compared to CTL-PBI (EAR = 1.41, p = 0.01), whereas a lower thyroid EAR for CTL-PBI (EAR = 0.17) compared to MRL-PBI (EAR = 0.33, p = 0.03) and CTL-WBI (EAR = 0.46, p = 0.002) was observed. Nevertheless, when adding the CBCT dose no difference between thyroid EAR for CTL-PBI compared to MRL-PBI was detected. CONCLUSION: Better breast tissue visualization and the possibility for daily plan adaption make PBI at the 1.5 T MRL particularly attractive. Our simulations suggest that this treatment can be performed without additional projected risk of RISM.

Low-power infrared laser modulates mRNA levels from genes of base excision repair and genomic stabilization in heart tissue from an experimental model of acute lung injury.

The aim of this study was to evaluate photobiomodulation effects on mRNA relative levels from genes of base excision repair and genomic stabilization in heart tissue from an experimental model of acute lung injury by sepsis. For experimental procedure, animals were randomly assigned to six main groups: (1) control group was animals treated with intraperitoneal saline solution; (2) LASER-10 was animals treated with intraperitoneal saline solution and exposed to an infrared laser at 10 J cm-2; (3) LASER-20 was animals treated with intraperitoneal saline solution and exposed to an infrared laser at 20 J cm-2; (4) acute lung injury (ALI) was animals treated with intraperitoneal LPS (10 mg kg-1); (5) ALI-LASER10 was animals treated with intraperitoneal LPS (10 mg kg-1) and, after 4 h, exposed to an infrared laser at 10 J cm-2 and (6) ALI-LASER20 was animals treated with intraperitoneal LPS (10 mg kg-1) and, after 4 h, exposed to an infrared laser at 20 J cm-2. Irradiation was performed only once and animal euthanasias for analysis of mRNA relative levels by RT-qPCR. Our results showed that there was a reduction of mRNA relative levels from ATM gene and an increase of mRNA relative levels from P53 gene in the heart of animals with ALI when compared to the control group. In addition, there was an increase of mRNA relative levels from OGG1 and APE1 gene in hearts from animals with ALI when compared to the control group. After irradiation, an increase of mRNA relative levels from ATM and OGG1 gene was observed at 20 J cm-2. In conclusion, low-power laser modulates the mRNA relative levels from genes of base excision repair and genomic stabilization in the experimental model of acute lung injury evaluated.

Transcutaneous systemic photobiomodulation reduced lung inflammation in experimental model of asthma by altering the mast cell degranulation and interleukin 10 level.

Asthma is a chronic inflammatory disease characterized by recurrent and reversible episodes of wheezing, dyspnea, chest stiffness, and cough. Its treatment includes several drugs, high cost, and considerable side effects. Photobiomodulation (PBM) emerges as an alternative treatment, showing good results, and it can be applied locally or systemically. Here, we aim to evaluate the effect of transcutaneous systemic photobiomodulation (TSPBM) by red diode light. Therefore, adult rats were sensitized and challenged with ovalbumin (OVA) plus alum for induction of asthma and irradiated or not with TSPBM in the caudal vein (wavelength 660 ± 10 nm; total radiant emission 15 J; area 2.8 cm2; energy density 5.35 J/cm2; irradiance 33.3 mW/cm2; exposure time 150 s). Our investigations prioritized the cell migration into the alveolar space and lung, tracheal responsiveness, release and gene expression of cytokines, mast cell degranulation, and anaphylactic antibodies. Our results showed that TSPBM reduced the cell migration and mast cell degranulation without altering the tracheal responsiveness and ovalbumin antibody titers. Indeed, TSPBM increased the levels of interleukin 10 (IL-10) in the BAL fluid without altering the gene expression of cytokines in the lung tissue. Thus, this study showed that transcutaneous systemic irradiation reduced lung inflammation by altering mast cells degranulation and IL-10 level. Considering that this study is a pioneer in the used of light by the systemic route to treat asthma, the data are interesting and instigate future investigations, mainly in relation to the mechanisms involved and in dosimetry.

New strategy of a lung compensating technique with STR for total body irradiation.

PURPOSE: To determine the thickness of a soft variable shape tungsten rubber (STR) as a lung compensating filter in total body irradiation. METHODS: A tough water (TW) phantom and tough lung (TL) phantom were used as water and lung-equivalent phantoms. The TW with a thickness of 3 cm simulating the thoracic wall was used (upper layer). The TW or TL with a thickness from 1 to 15 cm (1 cm increments) was placed beneath the upper layer (middle layer). The TW with a thickness of 5 cm simulating the mediastinum was placed beneath the middle layer (lower layer), and a farmer ionization chamber was placed beneath this layer. The relative doses of a 10 MV X-rays were then measured. The TL was compensated in 1 mm increments from 1 to 11 mm of the STR, and the thickness of the STR at the same dose of TW (water equivalent) was obtained. RESULTS: The compensating ability of STR increased as the thickness of the TL increased, and an STR with a thickness of 1 mm reduced the dose by 2%-4%, depending on the thickness of lung. The STR thickness as an equivalent dose of TW per cm of TL was approximately linear, and the thickness was 0.62 mm/cm of TL. CONCLUSION: The STR can be used as a lung compensating filter for a water equivalent dose with 0.62 mm of STR per cm of lung.