Mitochondrial Signaling, the Mechanisms of AKI-to-CKD Transition and Potential Treatment Targets.

Acute kidney injury (AKI) is increasing in prevalence and causes a global health burden. AKI is associated with significant mortality and can subsequently develop into chronic kidney disease (CKD). The kidney is one of the most energy-demanding organs in the human body and has a role in active solute transport, maintenance of electrochemical gradients, and regulation of fluid balance. Renal proximal tubular cells (PTCs) are the primary segment to reabsorb and secrete various solutes and take part in AKI initiation. Mitochondria, which are enriched in PTCs, are the main source of adenosine triphosphate (ATP) in cells as generated through oxidative phosphorylation. Mitochondrial dysfunction may result in reactive oxygen species (ROS) production, impaired biogenesis, oxidative stress multiplication, and ultimately leading to cell death. Even though mitochondrial damage and malfunction have been observed in both human kidney disease and animal models of AKI and CKD, the mechanism of mitochondrial signaling in PTC for AKI-to-CKD transition remains unknown. We review the recent findings of the development of AKI-to-CKD transition with a focus on mitochondrial disorders in PTCs. We propose that mitochondrial signaling is a key mechanism of the progression of AKI to CKD and potential targeting for treatment.

Using meta-analysis and CNN-NLP to review and classify the medical literature for normal tissue complication probability in head and neck cancer.

PURPOSE: The study aims to enhance the efficiency and accuracy of literature reviews on normal tissue complication probability (NTCP) in head and neck cancer patients using radiation therapy. It employs meta-analysis (MA) and natural language processing (NLP). MATERIAL AND METHODS: The study consists of two parts. First, it employs MA to assess NTCP models for xerostomia, dysphagia, and mucositis after radiation therapy, using Python 3.10.5 for statistical analysis. Second, it integrates NLP with convolutional neural networks (CNN) to optimize literature search, reducing 3256 articles to 12. CNN settings include a batch size of 50, 50-200 epoch range and a 0.001 learning rate. RESULTS: The study's CNN-NLP model achieved a notable accuracy of 0.94 after 200 epochs with Adamax optimization. MA showed an AUC of 0.67 for early-effect xerostomia and 0.74 for late-effect, indicating moderate to high predictive accuracy but with high variability across studies. Initial CNN accuracy of 66.70% improved to 94.87% post-tuning by optimizer and hyperparameters. CONCLUSION: The study successfully merges MA and NLP, confirming high predictive accuracy for specific model-feature combinations. It introduces a time-based metric, words per minute (WPM), for efficiency and highlights the utility of MA and NLP in clinical research.

Using machine learning algorithm to analyse the hypothyroidism complications caused by radiotherapy in patients with head and neck cancer.

Machine learning algorithms were used to analyze the odds and predictors of complications of thyroid damage after radiation therapy in patients with head and neck cancer. This study used decision tree (DT), random forest (RF), and support vector machine (SVM) algorithms to evaluate predictors for the data of 137 head and neck cancer patients. Candidate factors included gender, age, thyroid volume, minimum dose, average dose, maximum dose, number of treatments, and relative volume of the organ receiving X dose (X: 10, 20, 30, 40, 50, 60 Gy). The algorithm was optimized according to these factors and tenfold cross-validation to analyze the state of thyroid damage and select the predictors of thyroid dysfunction. The importance of the predictors identified by the three machine learning algorithms was ranked: the top five predictors were age, thyroid volume, average dose, V50 and V60. Of these, age and volume were negatively correlated with thyroid damage, indicating that the greater the age and thyroid volume, the lower the risk of thyroid damage; the average dose, V50 and V60 were positively correlated with thyroid damage, indicating that the larger the average dose, V50 and V60, the higher the risk of thyroid damage. The RF algorithm was most accurate in predicting the probability of thyroid damage among the three algorithms optimized using the above factors. The Area under the receiver operating characteristic curve (AUC) was 0.827 and the accuracy (ACC) was 0.824. This study found that five predictors (age, thyroid volume, mean dose, V50 and V60) are important factors affecting the chance that patients with head and neck cancer who received radiation therapy will develop hypothyroidism. Using these factors as the prediction basis of the algorithm and using RF to predict the occurrence of hypothyroidism had the highest ACC, which was 82.4%. This algorithm is quite helpful in predicting the probability of radiotherapy complications. It also provides references for assisting medical decision-making in the future.

Using deep learning models to analyze the cerebral edema complication caused by radiotherapy in patients with intracranial tumor.

Using deep learning models to analyze patients with intracranial tumors, to study the image segmentation and standard results by clinical depiction complications of cerebral edema after receiving radiotherapy. In this study, patients with intracranial tumors receiving computer knife (CyberKnife M6) stereotactic radiosurgery were followed using the treatment planning system (MultiPlan 5.1.3) to obtain before-treatment and four-month follow-up images of patients. The TensorFlow platform was used as the core architecture for training neural networks. Supervised learning was used to build labels for the cerebral edema dataset by using Mask region-based convolutional neural networks (R-CNN), and region growing algorithms. The three evaluation coefficients DICE, Jaccard (intersection over union, IoU), and volumetric overlap error (VOE) were used to analyze and calculate the algorithms in the image collection for cerebral edema image segmentation and the standard as described by the oncologists. When DICE and IoU indices were 1, and the VOE index was 0, the results were identical to those described by the clinician.The study found using the Mask R-CNN model in the segmentation of cerebral edema, the DICE index was 0.88, the IoU index was 0.79, and the VOE index was 2.0. The DICE, IoU, and VOE indices using region growing were 0.77, 0.64, and 3.2, respectively. Using the evaluated index, the Mask R-CNN model had the best segmentation effect. This method can be implemented in the clinical workflow in the future to achieve good complication segmentation and provide clinical evaluation and guidance suggestions.

Effect of natural garlic essential oil on chickens with artificially infected Eimeria tenella.

Chicken coccidiosis is a kind of parasitic protozoosis caused by Eimeria parasitizing in the chicken intestinal epithelial cells. Eimeria tenella is considered as a significantly virulent and harmful parasite. At present, drug resistance remains a major problem and a large number of drug residues have been found to be produced in the treatment of the disease. Hence, novel strategies are needed to avoid the harmful effects caused by the generation of various chemical drug residues to the human body and also reduce the economic loss caused by coccidiosis to the chicken industry. In this study, natural garlic essential oil was used to control Eimeria tenella infection. The anticoccidial index (ACI) was calculated according to the clinical symptoms, body weight gain, oocyst excretion and cecal lesions. The immune organ index and serum biochemical indexes were measured to verify the possible anticoccidial effects. The results showed that: compared with the infected group, continuous feeding of different doses of natural garlic essential oil could significantly reduce the clinical symptoms, cecal lesions, the number of oocysts, but increase the weight of sick chickens, and effectively improve the intestinal functions. Moreover, compared with diclazuril control group, 0.06 mL/L garlic essential oil exhibited similar anticoccidial index. The content of immune organ index, serum biochemical index IgM, IgG and IgA in 0.06 mL/L garlic essential oil group was the highest, which indicated that garlic essential oil had a significant tendency to improve the immune function of the chickens. This study also showed that the natural garlic essential oil exhibited the same beneficial effects as that of diclazuril on chicken coccidiosis, and the anti-coccidiosis index of 0.06 mL/L garlic essential oil was favorable. Thus based on the above evidences and its relatively low cost, garlic essential oil can be potentially be used as an efficient anti parasitic drug.

Whole blood gas and biochemical reference intervals for Lohmann Silver layers.

The blood gas and biochemical reference range established with i-STAT clinical analyzer in avian has become common, however, the reference value for various laying hen lines is limited. Therefore, blood gas and biochemical reference intervals will be established for Lohmann Silver layers in the pre- and post-laying periods. The blood sample was collected at a 4-wk interval. A total of 230 Lohmann Silver layers including 80 pullets (5-17 wk) and 150 laying hens (21-37 wk) were collected for whole blood measurement with the i-STAT clinical analyzer. The CG8+ cartridge provides values of the following 13 parameters: sodium (Na mmol/L), potassium (K mmol/L), ionized calcium (iCa mmol/L), glucose (Glu mg/dL), hematocrit (Hct% Packed Cell Volume [PCV]), pH, partial pressure carbon dioxide (PCO2 mm Hg), partial pressure oxygen (PO2 mm Hg), total concentration carbon dioxide (TCO2 mmol/L), bicarbonate (HCO3 mmol/L), base excess (BE mmol/L), oxygen saturation (sO2%), and hemoglobin (Hb g/dL). The correlation of these parameters and the effect of physiological status were investigated. The reference value interval was established with a reference value advisor for pre-laying and post-laying birds. Correlations were found to be statistically significant, especially between BE and HCO3 and TCO2. Besides, values in Na, iCa, K, Hct, Hb, sO2 differed significantly between the pre- and post-laying periods. Data in this study might serve as important information for facilitating the genetic selection and assessing the health of Lohmann Silver laying hens.

Outcomes of patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

Nasopharyngeal cancer shows a good response to intensity-modulated radiotherapy. However, there is no clear evidence for the benefits of routine use of image-guided radiotherapy. The purpose of this study was to perform a retrospective investigation of the treatment outcomes, treatment-related complications and prognostic factors for nasopharyngeal cancer treated with intensity-modulated radiotherapy and image-guided radiotherapy techniques. Retrospective analysis was performed on 326 consecutive nasopharyngeal cancer patients treated between 2004 and 2015. Potentially significant patient-related and treatment-related variables were analyzed. Radiation-related complications were recorded. The 5-year overall survival and disease-free survival rates of these patients were 77.9% and 70.5%, respectively. Age, AJCC (American Joint Committee on Cancer) stage, retropharyngeal lymphadenopathy, treatment interruption and body mass index were independent prognostic factors for overall survival. Age, AJCC stage, retropharyngeal lymphadenopathy, image-guided radiotherapy and body mass index were independent prognostic factors for disease-free survival. In conclusion, intensity-modulated radiotherapy significantly improves the treatment outcomes of nasopharyngeal cancer. With the aid of image-guided radiotherapy, the advantage of intensity-modulated radiotherapy might be further amplified.

Comparison of Intrafractional Motion in Head and Neck Cancer Between Two Immobilization Methods During Stereotactic Ablative Radiation Therapy by CyberKnife.

PURPOSE: Maintaining immobilization to minimize spine motion is very important during salvage stereotactic ablative radiation therapy (SABR) for recurrent head and neck cancer. This study aimed to compare the intrafractional motion between two immobilization methods. PATIENTS AND METHODS: With a spine tracking system for image guiding, 9094 records from 41 patients receiving SABR by CyberKnife were obtained for retrospective comparison. Twenty-one patients were immobilized with a thermoplastic mask and headrest (Group A), and another 20 patients used a thermoplastic mask and headrest together with a vacuum bag to support the head and neck area (Group B). The intrafractional motion in the X (superior-inferior), Y (right-left), Z (anterior-posterior) axes, 3D (three-dimensional) vector, Roll, Pitch and Yaw in the two groups was compared. The margins of the planning target volume (PTV) to cover 95% intrafractional motion were evaluated. RESULTS: The translational movements in the X-axis, Y-axis, and 3D vector in Group A were significantly smaller than in Group B. The rotational errors in the Roll and Yaw in Group A were also significantly smaller than those in Group B; conversely, those in the Pitch in Group A were larger. To cover 95% intrafractional motion, margins of 0.96, 1.55, and 1.51 mm in the X, Y and Z axes, respectively were needed in Group A, and 1.06, 2.86, and 1.34 mm, respectively were required in Group B. CONCLUSION: The immobilization method of thermoplastic mask and head rest with vacuum bag did not provide better immobilization than that without vacuum bag in most axes. The clinical use of 2 mm as a margin of PTV to cover 95% intrafractional motion was adequate in Group A but not in Group B.

ARC 118925XX stimulates cation influx in bEND.3 endothelial cells.

In a previous publication when we studied the purinergic receptor with which ATP interacted in mouse brain bEND.3 endothelial cells, we observed addition of 3 µm ARC 118925XX (ARC; selective P2Y2 antagonist) strongly suppressed ATP-triggered Ca2+ release, suggesting the response was mediated via P2Y2 receptors. We here report ARC unexpectedly promoted substantial Ca2+ influx even when ATP-triggered Ca2+ release was largely inhibited. Since this large Ca2+ influx may have important pharmacological significance, we proceeded to investigate its mechanism. ARC did not trigger intracellular Ca2+ release thus suggesting Ca2+ influx triggered by ARC was not store-operated. ARC-triggered Ca2+ influx could be blocked by 1 mm Ni2+ , a general Ca2+ channel blocker, but not by SK&F 96365, a nonselective TRP channel blocker. Unexpectedly, ARC promoted influx of Na+ and La3+ , but not Mn2+ . This is a surprising finding, since Mn2+ is conventionally used as a Ca2+ surrogate ion (as it permeates Ca2+ channel), and La3+ is classically used as a potent Ca2+ channel antagonist. Electrophysiological examination showed ARC did not stimulate any cation currents. Therefore, ARC opened, rather than a cation channel pore, an unidentified Ca2+ influx pathway which was Na+ - and La3+ -permeable but Mn2+ -impermeable.

Relationships among patient characteristics, irradiation treatment planning parameters, and treatment toxicity of acute radiation dermatitis after breast hybrid intensity modulation radiation therapy.

To evaluate the relationships among patient characteristics, irradiation treatment planning parameters, and treatment toxicity of acute radiation dermatitis (RD) after breast hybrid intensity modulation radiation therapy (IMRT). The study cohort consisted of 95 breast cancer patients treated with hybrid IMRT. RD grade ≥2 (2+) toxicity was defined as clinically significant. Patient characteristics and the irradiation treatment planning parameters were used as the initial candidate factors. Prognostic factors were identified using the least absolute shrinkage and selection operator (LASSO)-based normal tissue complication probability (NTCP) model. A univariate cut-off dose NTCP model was developed to find the dose-volume limitation. Fifty-two (54.7%) of ninety-five patients experienced acute RD grade 2+ toxicity. The volume of skin receiving a dose >35 Gy (V35) was the most significant dosimetric predictor associated with RD grade 2+ toxicity. The NTCP model parameters for V35Gy were TV50 = 85.7 mL and γ50 = 0.77, where TV50 was defined as the volume corresponding to a 50% incidence of complications, and γ50 was the normalized slope of the volume-response curve. Additional potential predictive patient characteristics were energy and surgery, but the results were not statistically significant. To ensure a better quality of life and compliance for breast hybrid IMRT patients, the skin volume receiving a dose >35 Gy should be limited to <85.7 mL to keep the incidence of RD grade 2+ toxicities below 50%. To avoid RD toxicity, the volume of skin receiving a dose >35 Gy should follow sparing tolerance and the inherent patient characteristics should be considered.

An innovative method to acquire the location of point A for cervical cancer treatment by HDR brachytherapy.

Brachytherapy of local cervical cancer is generally accomplished through film-based treatment planning with the prescription directed to point A, which is invisible on images and is located at a high-dose gradient area. Through a standard reconstruction method by digitizing film points, the location error for point A would be 3mm with a condition of 30° curvature tandem, which is 10° away from the gantry rotation axis of a simulator, and has an 8.7 cm interval between the flange and the isocenter. To reduce the location error of the reconstructed point A, this paper proposes a method and demonstrates its accuracy. The Cartesian coordinates of point A were derived by acquiring the locations of the cervical os (tandem flange) and a dummy seed located in the tandem above the flange. To verify this analytical method, ball marks in a commercial "Isocentric Beam Checker" were selected to simulate the two points A, the os, and the dummies. The Checker was placed on the simulator couch with its center ball coincident with the simulator isocenter and its rotation axis perpendicular to the gantry rotation axis. With different combinations of the Checker and couch rotation angles, the orthogonal films were shot and all coor-dinates of the selected points were reconstructed through the treatment planning system and compared with that calculated through the analytical method. The position uncertainty and the deviation prediction of point A were also evaluated. With a good choice of the reference dummy point, the position deviations of point A obtained through this analytical method were found to be generally within 1 mm, with the standard uncertainty less than 0.5 mm. In summary, this new method is a practical and accurate tool for clinical usage to acquire the accurate location of point A for the treatment of cervical cancer patient.

Ir-192 Calibration in Air with Farmer Chamber for HDR Brachytherapy.

A comprehensive review for the in-air calibration of an Ir-192 high-dose-rate brachytherapy source in terms of air kerma strength (AKS) and reference air kerma rate (RAKR) using the Farmer chamber was conducted. The reviewed calibration methods include the National Physical Laboratory (NPL) calibration standard in the UK, the 7-distance technique with the standard calibration of the National Institute of Standards and Technology and Accredited Dosimetry Calibration Laboratory in the US, the calibration conducted in Australia following recommendations of the International Atomic Energy Agency with the chamber primarily calibrated by the Australian Radiation Protection and Nuclear Safety Agency, the calibration conducted in India following the Deutsche Gesellschaft fur Medizinische Physik recommendation, and the convenient empirical method used in Taiwan. The calibrated AKS (or RAKR) and uncertainty obtained using Farmer chambers are similar to those obtained using well chambers. All reported differences (between measurements obtained using Farmer and well chambers, respectively) and uncertainties (k = 2) were generally less than 1.5 and 2.5 %, respectively. The standard uncertainty of the NPL calibration is approximately half that of all the other proposed approaches, and may become the gold standard calibration procedure. Almost all techniques follow the 7-distance technique basis; however, the services at NPL can calibrate the source with lower uncertainty. Users can calibrate the Ir-192 source more conveniently using the empirical method with only one source-chamber distance.

Geometric error of cervical point A calculated through traditional reconstruction procedures for brachytherapy treatment.

Brachytherapy used in local cervical cancer is still widely based on 2D standard dose planning with the prescription to point A, which is invisible on imaging and located at a high-dose gradient. In this study, the geometric location error of point A was investigated. It is traditionally reconstructed in the treatment planning system after carefully digitizing the point marks that were previously drawn on the orthogonal radiographs into the system. Two Cartesian coordinates of point A were established and compared. One was built up based on the geometric definition of point A and would be taken as the true coordinate, while the other was built up through traditional clinical treatment procedures and named as the practical coordinate. The orthogonal-film reconstruction technique was used and the location error between the practical and the true coordinate introduced from the variations of, first, the angle between the tandem and the simulator gantry-rotation-axis, and second, the interval between the tandem flange and the simulator isocenter, was analyzed. The location error of point A was higher if the tandem was rotated away from the gantry-rotation-axis or if the location of the tandem flange was set away from the isocenter. If a tandem with a 30-degree curvature was rotated away from the gantry-rotation-axis 10 degrees in the anterior-posterior (AP) view, and there was an 8.7 cm interval between the flange and the isocenter, the location error of point A would be greater than 3 mm without including other errors from simulator calibration, data input, patient setup and movements. To reduce the location error of point A calculated for traditional reconstruction procedures, it is suggested to move the couch or patient to make the mid-point of two points A near the isocenter and the tandem in the AP view parallel to the gantry-rotation-axis as much as possible.

Calibration of EBT2 film using a red-channel PDD method in combination with a modified three-channel technique.

PURPOSE: Ashland Inc. EBT2 and EBT3 films are widely used in quality assurance for radiation therapy; however, there remains a relatively high degree of uncertainty [B. Hartmann, M. Martisikova, and O. Jakel, "Homogeneity of Gafchromic EBT2 film," Med. Phys. 37, 1753-1756 (2010)]. Micke et al. (2011) recently improved the spatial homogeneity using all color channels of a flatbed scanner; however, van Hoof et al. (2012) pointed out that the corrected nonuniformity still requires further investigation for larger fields. To reduce the calibration errors and the uncertainty, the authors propose a new red-channel percentage-depth-dose method in combination with a modified three-channel technique. METHODS: For the ease of comparison, the EBT2 film image used in the authors' previous study (2012) was reanalyzed using different approaches. Photon beams of 6-MV were delivered to two different films at two different beam on times, resulting in the absorption doses of ranging from approximately 30 to 300 cGy at the vertical midline of the film, which was set to be coincident with the central axis of the beam. The film was tightly sandwiched in a 30(3)-cm(3) polystyrene phantom, and the pixel values for red, green, and blue channels were extracted from 234 points on the central axis of the beam and compared with the corresponding depth doses. The film was first calibrated using the multichannel method proposed by Micke et al. (2010), accounting for nonuniformities in the scanner. After eliminating the scanner and dose-independent nonuniformities, the film was recalibrated via the dose-dependent optical density of the red channel and fitted to a power function. This calibration was verified via comparisons of the dose profiles extracted from the films, where three were exposed to a 60° physical wedge field and three were exposed to composite fields, and all of which were measured in a water phantom. A correction for optical attenuation was implemented, and treatment plans of intensity modulated radiation therapy and volumetric modulated arc therapy were evaluated. RESULTS: The method described here demonstrated improved accuracy with reduced uncertainty. The relative error compared with the measurements of a water phantom was less than 1%, and the overall calibration uncertainty was less than 2%. Verification tests revealed that the results were close to those of the authors' previous study, and all differences were within 3%, except those with a high-dose gradient. The gamma pass rates (2%/2 mm) of the treatment plan evaluated using the method described here were greater than 99%, and no obvious stripe patterns were observed in the dose-difference maps. CONCLUSIONS: Spatial homogeneity was significantly improved via the calibration method described here. This technique is both convenient and time-efficient because it does not require cutting the film, and only two exposures are necessary.

The Major Prognostic Features of Nuclear Receptor NR5A2 in Infiltrating Ductal Breast Carcinomas.

Background. Gene expression profiles of 181 breast cancer samples were analyzed to identify prognostic features of nuclear receptors NR5A1 and NR5A2 based upon their associated transcriptional networks. Methods. A supervised network analysis approach was used to build the NR5A-mediated transcriptional regulatory network. Other bioinformatic tools and statistical methods were utilized to confirm and extend results from the network analysis methodology. Results. NR5A2 expression is a negative factor in breast cancer prognosis in both ER(-) and ER(-)/ER(+) mixed cohorts. The clinical and cohort significance of NR5A2-mediated transcriptional activities indicates that it may have a significant role in attenuating grade development and cancer related signal transduction pathways. NR5A2 signature that conditions poor prognosis was identified based upon results from 15 distinct probes. Alternatively, the expression of NR5A1 predicts favorable prognosis when concurrent NR5A2 expression is low. A favorable signature of eight transcription factors mediated by NR5A1 was also identified. Conclusions. Correlation of poor prognosis and NR5A2 activity is identified by NR5A2-mediated 15-gene signature. NR5A2 may be a potential drug target for treating a subset of breast cancer tumors across breast cancer subtypes, especially ER(-) breast tumors. The favorable prognostic feature of NR5A1 is predicted by NR5A1-mediated 8-gene signature.

Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy.

BACKGROUND: Radiation-induced tinnitus is a side effect of radiotherapy in the inner ear for cancers of the head and neck. Effective dose constraints for protecting the cochlea are under-reported. The aim of this study is to determine the cochlea dose limitation to avoid causing tinnitus after head-and-neck cancer (HNC) intensity-modulated radiation therapy (IMRT). METHODS: In total 211 patients with HNC were included; the side effects of radiotherapy were investigated for 422 inner ears in the cohort. Forty-nine of the four hundred and twenty-two samples (11.6%) developed grade 2+ tinnitus symptoms after IMRT, as diagnosed by a clinician. The Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) criteria were used for tinnitus evaluation. The logistic and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models were used for the analyses. RESULTS: The NTCP-fitted parameters were TD 50 = 46.31 Gy (95% CI, 41.46-52.50), γ 50 = 1.27 (95% CI, 1.02-1.55), and TD 50 = 46.52 Gy (95% CI, 41.91-53.43), m = 0.35 (95% CI, 0.30-0.42) for the logistic and LKB models, respectively. The suggested guideline TD 20 for the tolerance dose to produce a 20% complication rate within a specific period of time was TD 20 = 33.62 Gy (95% CI, 30.15-38.27) (logistic) and TD 20 = 32.82 Gy (95% CI, 29.58-37.69) (LKB). CONCLUSIONS: To maintain the incidence of grade 2+ tinnitus toxicity <20% in IMRT, we suggest that the mean dose to the cochlea should be <32 Gy. However, models should not be extrapolated to other patient populations without further verification and should first be confirmed before clinical implementation.

Patient- and therapy-related factors associated with the incidence of xerostomia in nasopharyngeal carcinoma patients receiving parotid-sparing helical tomotherapy.

We investigated the incidence of moderate to severe patient-reported xerostomia among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT) and identified patient- and therapy-related factors associated with acute and chronic xerostomia toxicity. The least absolute shrinkage and selection operator (LASSO) normal tissue complication probability (NTCP) models were developed using quality-of-life questionnaire datasets from 67 patients with NPC. For acute toxicity, the dosimetric factors of the mean doses to the ipsilateral submandibular gland (Dis) and the contralateral submandibular gland (Dcs) were selected as the first two significant predictors. For chronic toxicity, four predictive factors were selected: age, mean dose to the oral cavity (Doc), education, and T stage. The substantial sparing data can be used to avoid xerostomia toxicity. We suggest that the tolerance values corresponded to a 20% incidence of complications (TD20) for Dis = 39.0 Gy, Dcs = 38.4 Gy, and Doc = 32.5 Gy, respectively, when mean doses to the parotid glands met the QUANTEC 25 Gy sparing guidelines. To avoid patient-reported xerostomia toxicity, the mean doses to the parotid gland, submandibular gland, and oral cavity have to meet the sparing tolerance, although there is also a need to take inherent patient characteristics into consideration.

Developing Multivariable Normal Tissue Complication Probability Model to Predict the Incidence of Symptomatic Radiation Pneumonitis among Breast Cancer Patients.

PURPOSE: Symptomatic radiation pneumonitis (SRP), which decreases quality of life (QoL), is the most common pulmonary complication in patients receiving breast irradiation. If it occurs, acute SRP usually develops 4-12 weeks after completion of radiotherapy and presents as a dry cough, dyspnea and low-grade fever. If the incidence of SRP is reduced, not only the QoL but also the compliance of breast cancer patients may be improved. Therefore, we investigated the incidence SRP in breast cancer patients after hybrid intensity modulated radiotherapy (IMRT) to find the risk factors, which may have important effects on the risk of radiation-induced complications. METHODS: In total, 93 patients with breast cancer were evaluated. The final endpoint for acute SRP was defined as those who had density changes together with symptoms, as measured using computed tomography. The risk factors for a multivariate normal tissue complication probability model of SRP were determined using the least absolute shrinkage and selection operator (LASSO) technique. RESULTS: Five risk factors were selected using LASSO: the percentage of the ipsilateral lung volume that received more than 20-Gy (IV20), energy, age, body mass index (BMI) and T stage. Positive associations were demonstrated among the incidence of SRP, IV20, and patient age. Energy, BMI and T stage showed a negative association with the incidence of SRP. Our analyses indicate that the risk of SPR following hybrid IMRT in elderly or low-BMI breast cancer patients is increased once the percentage of the ipsilateral lung volume receiving more than 20-Gy is controlled below a limitation. CONCLUSIONS: We suggest to define a dose-volume percentage constraint of IV20< 37% (or AIV20< 310cc) for the irradiated ipsilateral lung in radiation therapy treatment planning to maintain the incidence of SPR below 20%, and pay attention to the sequelae especially in elderly or low-BMI breast cancer patients. (AIV20: the absolute ipsilateral lung volume that received more than 20 Gy (cc).

Correction to: Prognostic Features of Signal Transducer and Activator of Transcription 3 in an ER(+) Breast Cancer Model System.

[This corrects the article on p. 21 in vol. 13, PMID: 24526833.].