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Purpose: Stereotactic radiosurgery (SRS) has become an important modality in the treatment of brain metastases. The purpose of this study is to investigate the potential of radiomic features from planning magnetic resonance (MR) images and dose maps to predict local failure after SRS for brain metastases. Materials/Methods: Twenty‐eight patients who received Gamma Knife (GK) radiosurgery for brain metastases were retrospectively reviewed in this IRB‐approved study. 179 irradiated tumors included 42 that locally failed within one‐year follow‐up. Using SRS tumor volumes, radiomic features were calculated on T1‐weighted contrast‐enhanced MR images acquired for treatment planning and planned dose maps. 125 radiomic features regarding tumor shape, dose distribution, MR intensities and textures were extracted for each tumor. Logistic regression with automatic feature selection was built to predict tumor progression from local control after SRS. Feature selection and model evaluation using receiver operating characteristic (ROC) curves were performed in a nested cross validation (CV) scheme. The associations between selected radiomic features and treatment outcomes were statistically assessed by univariate analysis. Results: The logistic model with feature selection achieved ROC AUC of 0.82 ± 0.09 on 5‐fold CV, providing 83% sensitivity and 70% specificity for predicting local failure. A total of 10 radiomic features including 1 shape feature, 6 MR images and 3 dose distribution features were selected. These features were significantly associated with treatment outcomes (p < 0.05). The model was validated on independent holdout data with an AUC of 0.78. Conclusions: Radiomic features from planning MR images and dose maps provided prognostic information in SRS for brain metastases. A model built on the radiomic features shows promise for early prediction of tumor local failure after treatment, potentially aiding in personalized care for brain metastases. [ABSTRACT FROM AUTHOR]

Key points Central hypercapnic hypoventilation is highly prevalent in children suffering from congenital central hypoventilation syndrome (CCHS)., Mutations of the gene for paired-like homeobox 2b (Phox2b) are aetiologically associated with CCHS and Phox2b is present in central components of respiratory chemoreflex, such as the nucleus tractus solitarius (NTS)., Injection of the neurotoxin substance P-saporin into NTS destroys Phox2b-expressing neurons. Impaired hypercapnic ventilatory response caused by this neurotoxin is attributable to a loss of CO2-sensitive Phox2b-expressing NTS neurons., A subgroup of Phox2b-expressing neurons exhibits intrinsic chemosensitivity. A background K+ channel-like current is partially responsible for such chemosensitivity in Phox2b-expressing neurons., The present study helps us better understand the mechanism of respiratory deficits in CCHS and potentially locates a brainstem site for development of precise clinical intervention., Abstract The nucleus tractus solitarius (NTS) neurons have been considered to function as central respiratory chemoreceptors. However, the common molecular marker defined for these neurons remains unknown. The present study investigated whether paired-like homeobox 2b (Phox2b)-expressing NTS neurons are recruited in hypercapnic ventilatory response (HCVR) and whether these neurons exhibit intrinsic chemosensitivity. HCVR was assessed using whole body plethysmography and neuronal chemosensitivity was examined by patch clamp recordings in brainstem slices or dissociated neurons from Phox2b-EGFP transgenic mice. Injection of the neurotoxin substance P-saporin (SSP-SAP) into NTS destroyed Phox2b-expressing neurons. Minute ventilation and tidal volume were both reduced by 13% during exposure to 8% CO2 in inspired air when ∼13% of the Phox2b-expressing neurons were eliminated. However, a loss of ∼18% of these neurons was associated with considerable decreases in minute ventilation by ≥18% and in tidal volume by≥22% when challenged by ≥4% CO2. In both cases, breathing frequency was unaffected. Most CO2-activated neurons were immunoreactive to Phox2b. In brainstem slices, ∼43% of Phox2b-expressing neurons from Phox2b-EGFP mice displayed a sustained or transient increase in firing rate during physiological acidification (pH 7.0 or 8% CO2). Such a response was also present in dissociated neurons in favour of an intrinsic property. In voltage clamp recordings, a background K+ channel-like current was found in a subgroup of Phox2b-expressing neurons. Thus, the respiratory deficits caused by injection of SSP-SAP into the NTS are attributable to proportional lesions of CO2/H+-sensitive Phox2b-expressing neurons. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate a plastic scintillation detector for the measurement of small field dosimetry and to verify the accuracy of measured dose in comparison with Monte Carlo calculation in a heterogeneous medium. Methods The study is performed with CyberKnife planning and delivery system. The setup consists of a custom made solid lung phantom with the insert of an Exradin W1 scintillation detector or an Exradin A16 ion chamber. The measurement was done for a series of cone sizes from 5 mm to 60 mm, and the dose was calculated by Monte Carlo algorithm in MultiPlan workstation. The difference between measurement and calculation was reported. Results Our preliminary results demonstrated the applicability of plastic scintillation detectors in the measurement of small field dosimetry in a heterogeneous medium. The difference between the calculated and measured output factors was less than 3% for all cone sizes from 60 mm down to 5 mm. Without any corrections, the measured dose from the scintillation detector calibrated to the ion chamber reading was also within 3% of the Monte Carlo calculation in the lung phantom for cone sizes 20 mm or larger. Conclusions Small field dosimetry is particularly relevant to stereotactic radiation treatment. The accuracy of dose calculation for small static beams is critical to dose planning so would potentially affect the treatment outcomes in a heterogeneous medium. Our results have shown good agreement with plastic scintillation detector in both homogeneous and heterogeneous medium. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To study the impact of seed localization, as performed by different observers using linked 125I seeds, on postimplant dosimetry in prostate brachytherapy and, to compare transrectal ultrasound (TRUS)-based with CT-based approach for the dosimetric outcomes. Methods and Materials: Nineteen permanent prostate implants were conducted using linked 125I seeds. Postimplant TRUS and CT images were acquired and prostate glands were, after implantation, delineated on all images by a single oncologist, who had performed all 19 seeding procedures. Six observers independently localized the seeds on both TRUS and CT images, from which the principle dosimetric parameters V 100 (volume of prostate that received the prescribed dose), V 150 (volume of prostate that received 150% of the prescribed dose), and D 90 (minimal dose delivered to 90% of the prostate) were directly calculated for each patient. A single-factor analysis of variance was first applied to determine interobserver variability in seed localization. A nonparametric comparison of the approach using TRUS and CT was then carried out by the Wilcoxon paired-sample test. Results: Analysis from the analysis of variance for TRUS showed that the null hypothesis for equal means, could not be rejected for all six observers based on a significance level α =0.05. TRUS-based and CT-based approaches were then cross compared by the Wilcoxon paired-sample test, which suggested that the null hypothesis was insignificant for V 100 and D 90, but was significant for V 150. Conclusions: Both TRUS- and CT-imaging modalities provided indistinguishable postimplant dosimetry results as far as V 100 and D 90 were concerned. There was comparable observer independence between TRUS- and CT-based seed localization for linked-seed implant procedures. With other advantages that TRUS-imaging modality had over CT in the evaluation of postimplant dosimetry, TRUS would be a preferred choice in conjunction with linked seeds for intraoperative procedures in prostate brachytherapy. [Copyright &y& Elsevier]

Abstract: Purpose: To investigate interobserver variability in contouring the prostate on postimplant transrectal ultrasonography (TRUS) images and its effect on dosimetric parameters that quantify implant quality. Methods and materials: Twenty preplanned peripherally loaded prostate implants were performed using 125I seeds and spacers linked together in linear arrays that maintain precise seed spacing and prevent seeds from rotating about their longitudinal axis. A set of two-dimensional transverse images spaced at 0.50-cm intervals was obtained with a high-resolution TRUS probe at the conclusion of the procedure with the patient still under anesthesia. A high percentage of the seeds (>85%) were localized based on their visible echoes. The remaining seeds were identified based on the known locations of the “missing” seeds in the arrays. Two experienced ultrasonographers and a prostate brachytherapist independently contoured the prostate on the postimplant TRUS images. The prostate volumes defined by each observer were used to calculate the minimal dose received by 90% of the prostate volume (D 90) and the percentage of the prostate volume receiving 100% of the prescribed minimal peripheral dose (V 100). The observers also contoured the prostate on six preimplant TRUS studies to compare the variability in defining the prostate on pre- and postimplant TRUS images. Results: The mean postimplant prostate volumes ranged from 20.8 to 66.9cm3 (median: 45.7cm3). The standard deviations (SDs), which reflect the variation in the volumes of the three observers, ranged from 1.4% to 26.1% of the mean (median: 11%). Multiple pairwise comparisons showed that the prostate volumes delineated by observer 3 differed significantly from those of observers 1 and 2 (p <0.003). The volumes of observers 1 and 2 were not significantly different (p >0.5). The mean values of D 90 ranged from 124.2 to 171.1Gy (median: 154.7Gy) having SDs that ranged from 0.6% to 24.4% of the mean D 90 (median: 7.8%). The mean values of V 100 ranged from 82.3% to 95.1% (median: 92.8%) having SDs that ranged from 0.4% to 11.2% of the mean V 100 (median: 4.0%). The values of both D 90 and V 100 calculated from the volumes of observer 3 were significantly (p <0.003) different from those of observers 1 and 2, which did not differ significantly (p >0.5). There was less interobserver variability in contouring the preimplant TRUS volumes. The mean volumes ranged from 20.3 to 54.3cm3 having SDs that ranged from 1.9% to 14.1% (median: 8.6%). Conclusions: Significant interobserver differences in delineating the prostate volume on postimplant TRUS images were observed; however, these differences were less than generally reported for postimplant CT images. The interobserver differences in contouring the prostate in both TRUS and CT images produced significant differences in the dosimetric parameters, D 90 and V 100. [Copyright &y& Elsevier]

Purpose: To demonstrate that (125)I seeds can be localized in transrectal ultrasound (TRUS) images obtained with a high-resolution probe when the implant is performed with linked seeds and spacers. Adequate seed localization is essential to the implementation of TRUS-based intraoperative dosimetry for prostate brachytherapy. Methods and Materials: Thirteen preplanned peripherally loaded prostate implants were performed using (125)I seeds and spacers linked together in linear arrays that prevent seed migration and maintain precise seed spacing. A set of two-dimensional transverse images spaced at 0.50-cm intervals were obtained with a high-resolution TRUS probe at the conclusion of the procedure with the patient still under anesthesia. The image set extended from 1.0 cm superior to the base to 1.0 cm inferior to the apex. The visible echoes along each needle track were first localized and then compared with the known construction of the implanted array. The first step was to define the distal and proximal ends of each array. The visible echoes were then identified as seeds or spacers from the known sequence of the array. The locations of the seeds that did not produce a visible echo were interpolated from their known position in the array. A CT scan was obtained after implantation for comparison with the TRUS images. Results: On average, 93% (range, 86-99%) of the seeds were visible in the TRUS images. However, it was possible to localize 100% of the seeds in each case, because the locations of the missing seeds could be determined from the known construction of the arrays. Two factors complicated the interpretation of the TRUS images. One was that the spacers also produced echoes. Although weak and diffuse, these echoes could be mistaken for seeds. The other was that the number of echoes along a needle track sometimes exceeded the number of seeds and spacers implanted. This was attributed to the overall length of the array, which was approximately 0.5 cm longer than the center-to-center distance between the first and last seed owing to the finite length of the seeds at the ends of the array. When this occurred, it was necessary to disregard either the most distal or most proximal echo, which produced a 0.5-cm uncertainty in the location of the array in the axial direction. For these reasons, simply localizing the visible echoes in the TRUS images did not guarantee the reliable identification of the seeds. Conclusion: Our results have demonstrated that a high percentage (>85%) of the implanted (125)I seeds can be directly visualized in postimplant TRUS images when the seeds and spacers are linked to preclude seed migration and rotation and when the images are obtained with a high-resolution TRUS probe. Moreover, it is possible to localize 100% of the seeds with the mechanism of linked seeds because the locations of the missing seeds can be determined from the known construction of the arrays. [ABSTRACT FROM AUTHOR]

Fault diagnosis of wind turbines is of great importance to reduce operating and maintenance costs of wind farms. At present, most wind turbine fault diagnosis methods are focused on single faults, and the methods for combined faults usually depend on inefficient manual analysis. Filling the gap, this paper proposes a low-pass filtering empirical wavelet transform (LPFEWT) machine learning based fault diagnosis method for combined fault of wind turbines, which can identify the fault type of wind turbines simply and efficiently without human experience and with low computation costs. In this method, low-pass filtering empirical wavelet transform is proposed to extract fault features from vibration signals, LPFEWT energies are selected to be the inputs of the fault diagnosis model, a grey wolf optimizer hyperparameter tuned support vector machine (SVM) is employed for fault diagnosis. The method is verified on a wind turbine test rig that can simulate shaft misalignment and broken gear tooth faulty conditions. Compared with other models, the proposed model has superiority for this classification problem. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) expression analysis is very important for investigating its functions. To date, no research on reference genes (RGs) for miRNAs in gymnosperms, including Cryptomeria fortunei, has been reported. Here, ten miRNAs (i.e., pab-miR159a, cln-miR162, cas-miR166d, pab-miR395b, ppt-miR894, cln-miR6725, novel1, novel6, novel14 and novel16) and three common RGs (U6, 5S and 18S) were selected as candidate RGs. qRT-PCR was used to analyse their expressions in C. fortunei under various experimental conditions, including multiple stresses (cold, heat, drought, salt, abscisic acid and gibberellin) and in various tissues (roots, stems, tender needles, cones and seeds). Four algorithms (delta Ct, geNorm, NormFinder and BestKeeper) were employed to assess the stability of candidate RG expression; the geometric mean and RefFinder program were used to comprehensively evaluate RG stability. According to the results, novel16, cln-miR6725, novel1 and U6 were the most stable RGs for studying C. fortunei miRNA expression. In addition, the expression of three target miRNAs (aly-miR164c-5p, aly-miR168a-5p and smo-miR396) was examined to verify that the selected RGs are suitable for miRNA expression normalisation. This study may aid further investigations of miRNA expression/function in the response of C. fortunei to abiotic stress and provides an important basis for the standardisation of miRNA expression in other gymnosperm species. [ABSTRACT FROM AUTHOR]

Most conventional wind turbine fault diagnosis techniques only use a single type of signal as fault feature and their performance could be limited to such signal characteristics. In this paper, multiple types of signals including vibration, temperature, and stator current are used simultaneously for wind turbine misalignment diagnosis. The model is constructed by integrated methods based on Dempster–Shafer (D–S) evidence theory. First, the time domain, frequency domain, and time–frequency domain features of the collected vibration, temperature, and stator current signal are respectively taken as the inputs of the least square support vector machine (LSSVM). Then, the LSSVM outputs the posterior probabilities of the normal, parallel misalignment, angular misalignment, and integrated misalignment of the transmission systems. The posterior probabilities are used as the basic probabilities of the evidence fusion, and the fault diagnosis is completed according to the D–S synthesis and decision rules. Considering the correlation between the inputs, the vibration and current feature vectors' dimensionalities are reduced by t-distributed stochastic neighbor embedding (t-SNE), and the improved artificial bee colony algorithm is used to optimize the parameters of the LSSVM. The results of the simulation and experimental platform demonstrate the accuracy of the proposed model and its superiority compared with other models. [ABSTRACT FROM AUTHOR]

Purpose: We sought to investigate the tumor control probability (TCP) of vestibular schwannomas after single-fraction stereotactic radiosurgery (SRS) or hypofractionated SRS over 2 to 5 fractions (fSRS).Methods and Materials: Studies (PubMed indexed from 1993-2017) were eligible for data extraction if they contained dosimetric details of SRS/fSRS correlated with local tumor control. The rate of tumor control at 5 years (or at 3 years if 5-year data were not available) were collated. Poisson modeling estimated the TCP per equivalent dose in 2 Gy per fraction (EQD2) and in 1, 3, and 5 fractions.Results: Data were extracted from 35 publications containing a total of 5162 patients. TCP modeling was limited by the absence of analyzable data of <11 Gy in a single-fraction, variability in definition of "tumor control," and by lack of significant increase in TCP for doses >12 Gy. Using linear-quadratic-based dose conversion, the 3- to 5-year TCP was estimated at 95% at an EQD2 of 25 Gy, corresponding to 1-, 3-, and 5-fraction doses of 13.8 Gy, 19.2 Gy, and 21.5 Gy, respectively. Single-fraction doses of 10 Gy, 11 Gy, 12 Gy, and 13 Gy predicted a TCP of 85.0%, 88.4%, 91.2%, and 93.5%, respectively. For fSRS, 18 Gy in 3 fractions (EQD2 of 23.0 Gy) and 25 Gy in 5 fractions (EQD2 of 30.2 Gy) corresponded to TCP of 93.6% and 97.2%. Overall, the quality of dosimetric reporting was poor; recommended reporting guidelines are presented.Conclusions: With current typical SRS doses of 12 Gy in 1 fraction, 18 Gy in 3 fractions, and 25 Gy in 5 fractions, 3- to 5-year TCP exceeds 91%. To improve pooled data analyses to optimize treatment outcomes for patients with vestibular schwannoma, future reports of SRS should include complete dosimetric details with well-defined tumor control and toxicity endpoints. [ABSTRACT FROM AUTHOR]

NAC transcription factor (TF), the most prominent plant-specific gene family, is involved in various metabolic pathways during the growth and development of the plant. However, few reports have been published concerning the NAC gene family in gymnosperms such as Cryptomeria fortunei Hooibrenk. As an essential native coniferous timber tree, C. fortunei is widely cultivated in southern China due to its significant economic and ecological value. Here, we aimed to identify and characterize the CfNACs in C. fortunei vascular development. A total of 33 CfNACs were identified from C. fortunei vascular cambium. They all shared the conserved NAC motifs. Phylogenetic evolutionary indicated that CfNACs were classified into various evolutionary branches, including secondary xylem development, lignin and secondary cell wall (SCW) biosynthesis, and various stress response. In addition, the expression profiles of CfNACs under diverse developmental stages suggested that several CfNACs were involved in multiple metabolic pathways during C. fortunei cambium development. Moreover, the co-expression network revealed that numerous CfNACs were involved in vascular and xylem development, and lignin biosynthesis as key upstream regulators. There were significant correlations between CfNACs and lignin biosynthetic genes, phytohormone synthase genes. Transient expression analysis implied that CfNAC5 and CfNAC16, targeted to the nucleus, acted as activators. Genetic transformation analysis demonstrated that overexpression of CfNAC5 dramatically affected the secondary xylem development and elevated the lignin biosynthesis and SCW thickness in transgenic plants. Furthermore, the expression levels of lignin biosynthetic genes were markedly increased in transgenic plants. In conclusion, these findings would help provide insight into the functional differentiation and evolutionary relationships of CfNACs and elucidate the regulatory roles of CfNACs during C. fortunei vascular development and wood formation. • A total of 33 CfNACs were retrieved from the RNA-seq data of C. fortunei cambium. • These genes were grouped into different clades, including lignin biosynthesis and stress response. • CfNACs were differentially expressed during the diverse growth stages of C. fortunei cambium. • CfNAC5 and CfNAC16 were nucleus localization factors and transcriptional activators. • CfNAC5 played a positive role in regulating the lignin biosynthesis and secondary cell wall formation in transgenic tobacco. [ABSTRACT FROM AUTHOR]

Introduction. Brachytherapy plays a key role in the treatment of many gynecologic cancers. However, some patients are unable to tolerate brachytherapy for medical or other reasons. For these patients, stereotactic body radiotherapy (SBRT) offers an alternative form of treatment. Methods. Retrospective review of patients prospectively collected on SBRT database is conducted. A total of 11 gynecologic patients who could not have brachytherapy received SBRT for treatment of their malignancies. Five patients have been candidates for interstitial brachytherapy, and six have required tandem and ovoid brachytherapy. Median SBRT dose was 25 Gy in five fractions. Results. At last followup, eight patients were alive, and three patients had died of progressive disease. One patient had a local recurrence. Median followup for surviving patients was 420 days (median followup for all patients was 120 days). Two patients had acute toxicity (G2 dysuria and G2 GI), and one patient had late toxicity (G3 GI, rectal bleeding requiring cauterization). Conclusions. Our data show acceptable toxicity and outcome for gynecologic patients treated with SBRT who were unable to receive a brachytherapy boost. This treatment modality should be further evaluated in a phase II study. [ABSTRACT FROM AUTHOR]

ICE1, a regulator of the cold-inducible transcriptome and freezing tolerance, is currently widely believed to be involved in plant resistance to cold stress. In this study, CfICE1 from Cryptomeria fortunei was transformed into poplar. Physiological indicators of transgenic, empty vector and wild-type poplar after abiotic stress (cold, drought and salt) were determined. Transgenic lines had a higher chlorophyll content, antioxidant enzyme activity and soluble protein content, as well as a lower malondialdehyde and hydrogen peroxide content. The ultrastructure of the plant was observed by transmission electron microscopy, and after stress, the cell structure of the transgenic line was more complete than that of the wild type. CfICE1 was upregulated in transgenic poplar trees after abiotic stress (cold, drought and salt). The CfICE1 transgenic plants improved plant resistance by regulating the CBF gene of poplar under cold and salt stress. In terms of plant responses to abiotic stress, this study showed that overexpression of CfICE1 improved the cold, drought and salt tolerance of poplars. [ABSTRACT FROM AUTHOR]

Purpose: Patients with poor performance status (PS), usually defined as a Karnofsky Performance Status of 60 or less, were not eligible for randomized stereotactic radiosurgery (SRS) studies, and many guidelines suggest that whole-brain radiation therapy (WBRT) is the most appropriate treatment for poor PS patients.Methods and Materials: In this retrospective review of our SRS database, we identified 36 patients with PS of 60 or less treated with SRS for central nervous system (CNS) metastatic disease. PS, as defined by the Karnofsky Performance Status, was 60 (27 patients), 50 (8 patients), or 40 (1 patient). The median number of CNS lesions treated was 3.Results: Median overall survival (OS) was 7.2 months (range, 0.73-25.6 months). Fifteen patients (41%) were alive at 6 months, and 6 patients (16.6%) were alive at 1 year. There was no difference in OS in patients who underwent previous WBRT. There were no local failures or cases of radiation toxicity. Distant CNS failures were seen in 9 patients (25%).Conclusions: Our patients with poor PS had reasonable median OS and relatively low distant CNS failure rates. Patients in this patient population may be ideal candidates for SRS compared with WBRT given the low incidence of distant failure over their remaining lives and the favorable logistics of single-fraction treatment for these patients with debility and their caregivers. [ABSTRACT FROM AUTHOR]

Cryptomeria fortunei has become one of the main timber afforestation species in subtropical high-altitude areas of China due to its fast growth, good material quality, and strong adaptability, showing broad application prospects. Quantitative real-time PCR (qRT-PCR) is the most accurate and widely used gene expression evaluation technique, and selecting appropriate reference genes (RGs) is essential for normalizing qRT-PCR results. However, suitable RGs for gene expression normalization in C. fortunei have not been reported. Here, we tested the expression stability for 12 RGs in C. fortunei under various experimental conditions (simulated abiotic stresses (cold, heat, drought, and salinity) and hormone treatments (methyl jasmonate, abscisic acid, salicylic acid, and gibberellin) and in different tissues (stems, tender needles, needles, cones, and seeds) using four algorithms (delta Ct, geNorm, NormFinder, and BestKeeper). Then, geometric mean rankings from these algorithms and the RefFinder program were used to comprehensively evaluate RG stability. The results indicated CYP, actin, UBC, and 18S as good choices for studying C. fortunei gene expression. qRT-PCR analysis of the expression patterns of three target genes (CAT and MAPK1/6) further verified that the selected RGs were suitable for gene expression normalization. This study provides an important basis for C. fortunei gene expression standardization and quantification. [ABSTRACT FROM AUTHOR]

Purpose: Dose-volume data for injury to carotid artery and other major vessels in stereotactic body radiation therapy (SBRT)/SABR head and neck reirradiation were reviewed, modeled, and summarized.Methods and Materials: A PubMed search of the English-language literature (stereotactic and carotid and radiation) in April 2018 found 238 major vessel maximum point doses in 6 articles that were pooled for logistic modeling. Two subsequent studies with dose-volume major vessel data were modeled separately for comparison. Attempts were made to separate carotid blowout syndrome from other bleeding events (BE) in the analysis, but we acknowledge that all except 1 data set has some element of BE interspersed.Results: Prior radiation therapy (RT) dose was not uniformly reported per patient in the studies included, but a course on the order of conventionally fractionated 70 Gy was considered for the purposes of the analysis (with an approximately ≥6-month estimated interval between prior and subsequent treatment in most cases). Factors likely associated with reduced risk of BE include nonconsecutive daily treatment, lower extent of circumferential tumor involvement around the vessel, and no surgical manipulation before or after SBRT.Conclusions: Initial data pooling for reirradiation involving the carotid artery resulted in 3 preliminary models compared in this Hypofractionated Treatment Effects in the Clinic (HyTEC) report. More recent experiences with alternating fractionation schedules and additional risk-reduction strategies are also presented. Complications data for the most critical structures such as spinal cord and carotid artery are so limited that they cannot be viewed as strong conclusions of probability of risk, but rather, as a general guideline for consideration. There is a great need for better reporting standards as noted in the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic introductory paper. [ABSTRACT FROM AUTHOR]

Purpose: We sought to investigate the tumor control probability (TCP) of spinal metastases treated with stereotactic body radiation therapy (SBRT) in 1 to 5 fractions.Methods and Materials: PubMed-indexed articles from 1995 to 2018 were eligible for data extraction if they contained SBRT dosimetric details correlated with actuarial 2-year local tumor control rates. Logistic dose-response models of collected data were compared in terms of physical dose and 3-fraction equivalent dose.Results: Data were extracted from 24 articles with 2619 spinal metastases. Physical dose TCP modeling of 2-year local tumor control from the single-fraction data were compared with data from 2 to 5 fractions, resulting in an estimated α/β = 6 Gy, and this was used to pool data. Acknowledging the uncertainty intrinsic to the data extraction and modeling process, the 90% TCP corresponded to 20 Gy in 1 fraction, 28 Gy in 2 fractions, 33 Gy in 3 fractions, and (with extrapolation) 40 Gy in 5 fractions. The estimated TCP for common fractionation schemes was 82% at 18 Gy, 90% for 20 Gy, and 96% for 24 Gy in a single fraction, 82% for 24 Gy in 2 fractions, and 78% for 27 Gy in 3 fractions.Conclusions: Spinal SBRT with the most common fractionation schemes yields 2-year estimates of local control of 82% to 96%. Given the heterogeneity in the tumor control estimates extracted from the literature, with variability in reporting of dosimetry data and the definition of and statistical methods of reporting tumor control, care should be taken interpreting the resultant model-based estimates. Depending on the clinical intent, the improved TCP with higher dose regimens should be weighed against the potential risks for greater toxicity. We encourage future reports to provide full dosimetric data correlated with tumor local control to allow future efforts of modeling pooled data. [ABSTRACT FROM AUTHOR]

Purpose: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature.Methods and Materials: PubMed-indexed studies published between January 1995 and September 2017 were used to evaluate dosimetric and clinical predictors of TCP after SRS or fSRS for brain metastases. Eligible studies had ≥10 patients and included detailed dose-fractionation data with corresponding ≥1-year local control (LC) data, typically evaluated as a >20% increase in diameter of the targeted lesion using the pre-SRS diameter as a reference.Results: Of 2951 potentially eligible manuscripts, 56 included sufficient dose-volume data for analyses. Accepting that necrosis and pseudoprogression can complicate the assessment of LC, for tumors ≤20 mm, single-fraction doses of 18 and 24 Gy corresponded with >85% and 95% 1-year LC rates, respectively. For tumors 21 to 30 mm, an 18 Gy single-fraction dose was associated with 75% LC. For tumors 31 to 40 mm, a 15 Gy single-fraction dose yielded ∼69% LC. For 3- to 5-fraction fSRS using doses in the range of 27 to 35 Gy, 80% 1-year LC has been achieved for tumors of 21 to 40 mm in diameter.Conclusions: TCP for SRS and fSRS are presented. For small lesions ≤20 mm, single doses of ≈18 Gy appear generally associated with excellent rates of LC; for melanoma, higher doses seem warranted. For larger lesions >20 mm, local control rates appear to be ≈ 70% to 75% with usual doses of 15 to 18 Gy, and in this setting, fSRS regimens should be considered. Greater consistency in reporting of dosimetric and LC data is needed to facilitate future pooled analyses. As systemic and biologic therapies evolve, updated analyses will be needed to further assess the necessity, efficacy, and toxicity of SRS and fSRS. [ABSTRACT FROM AUTHOR]

Purpose: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).Methods and Materials: Eligible studies provided NTCPs for the endpoints of radionecrosis, edema, or symptoms after cranial SRS/fSRS and quantitative dose-volume metrics. Studies of patients with only glioma, meningioma, vestibular schwannoma, or brainstem targets were excluded. The data summary and analyses focused on arteriovenous malformations (AVM) and brain metastases.Results: Data from 51 reports are summarized. There was wide variability in reported rates of radionecrosis. Available data for SRS/fSRS for brain metastases were more amenable to NTCP modeling than AVM data. In the setting of brain metastases, SRS/fSRS-associated radionecrosis can be difficult to differentiate from tumor progression. For single-fraction SRS to brain metastases, tissue volumes (including target volumes) receiving 12 Gy (V12) of 5 cm3, 10 cm3, or >15 cm3 were associated with risks of symptomatic radionecrosis of approximately 10%, 15%, and 20%, respectively. SRS for AVM was associated with modestly lower rates of symptomatic radionecrosis for equivalent V12. For brain metastases, brain plus target volume V20 (3-fractions) or V24 (5-fractions) <20 cm3 was associated with <10% risk of any necrosis or edema, and <4% risk of radionecrosis requiring resection.Conclusions: The risk of radionecrosis after SRS and fSRS can be modeled as a function of dose and volume treated. The use of fSRS appears to reduce risks of radionecrosis for larger treatment volumes relative to SRS. More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses that can refine predictive models of brain toxicity risks. [ABSTRACT FROM AUTHOR]

Purpose: Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation.Methods and Materials: Eligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION).Results: Thirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in <1% RION risks include 12 Gy in 1 fraction (which is greater than our recommendation of 10 Gy in 1 fraction), 20 Gy in 3 fractions, and 25 Gy in 5 fractions. Omitting multi-fraction data (and thereby eliminating uncertainties associated with dose conversions), a single-fraction dose of 10 Gy was associated with a 1% RION risk. Insufficient details precluded modeling of NTCP risks after prior radiation therapy.Conclusions: Optic apparatus NTCP and tolerance doses after single- and multi-fraction stereotactic radiosurgery are presented. Additional standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP after SRS/fSRS. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) has emerged as a viable reirradiation strategy for locally recurrent previously-irradiated head and neck cancer. Doses in the literature have varied, which challenges clinical application of SBRT as well as clinical trial design.Material& Methods: A working group was formed through the American Association of Physicists in Medicine to study tumor control probabilities for SBRT in head and neck cancer. We herein present a systematic review of the available literature addressing the dose/volume data for tumor control probability with SBRT in patients with locally recurrent previously-irradiated head and neck cancer. Dose-response models are generated that present tumor control probability as a function of dose.Results: Data from more than 300 cases in 8 publications suggest that there is a dose-response relationship, with superior local control and possibly improved overall survival for doses of 35 to 45 Gy (in 5 fractions) compared with <30 Gy.Conclusion: Stereotactic body radiation therapy doses equivalent to 5-fraction doses of 40 to 50 Gy are suggested for retreatment. [ABSTRACT FROM AUTHOR]

As the most abundant renewable energy source, wood comprises the secondary cell wall (SCW). SCW biosynthesis involves lignin and cellulose deposition. Increasing studies have illustrated that R2R3-MYB transcription factors (TFs) play pivotal roles in affecting lignin accumulation and SCW formation. Nevertheless, the regulatory roles of R2R3-MYBs are still unresolved in Cryptomeria fortunei Hooibrenk cambium and wood formation. To dissect the potentials of CfMYBs , we successfully cloned and intensively studied the functions of CfMYB4 and CfMYB5 in SCW formation and abiotic stress response. They both contained the conserved MYB domain capable of forming a special structure that could bind to the core motifs of downstream genes. The phylogenetic tree implied that two CfMYBs clustered into different evolutionary branches. They were predominantly expressed in the stem and were localized to the nucleus. Furthermore, CfMYB4 functioned as an activator to enhance lignin and cellulose accumulation, and increase the SCW thickness by elevating the expression levels of SCW-related genes. By contrast, CfMYB5 negatively regulated lignin and cellulose biosynthesis, and decreased SCW formation by reducing the expression of SCW biosynthetic genes. Our data not only highlight the regulatory functions of CfMYBs in lignin deposition but also provide critical insights into the development of strategies for the genetic improvement of Cryptomeria fortunei wood biomass. • According to previous study, we successfully isolated CfMYB4 and CfMYB5 from Chinese cedar vascular cambium. • CfMYB4 and CfMYB5 are localized in the nucleus. • CfMYB4 functions as a transcriptional activator to enhance lignin biosynthesis and cell wall thickness. • CfMYB5 negatively regulates the lignin biosynthesis and secondary xylem formation. [ABSTRACT FROM AUTHOR]

Purpose: To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiation therapy (SBRT) of the thorax.Methods and Materials: Published studies on lung toxicity in patients with early-stage non-small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT, including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2 to 5 (G2+) and grade 3 to 5 (G3+) RILT were computed. Patient, tumor, and dosimetric factors were analyzed for their correlation with RILT.Results: Eighty-eight studies (7752 patients) that reported RILT incidence were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% confidence interval [CI]: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range, 1.4-4.1) cm. Among the factors analyzed, older patient age (P=.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P=.049) and G3+ RILT (P=.001). Patients with stage IA versus stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, odds ratio = 0.43, 95% CI: 0.29-0.64, P<.0001). Among studies that provided detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P=.027) and V20 (P=.019) in patients with G2+ RILT than in those with grade 0 to 1 RILT.Conclusions: The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD, also significantly affect RILT risk. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the dosimetric feasibility of accelerated partial breast irradiation (APBI) using CyberKnife. Methods: Fourteen previously treated patients with early-stage breast cancer were selected for a retrospective study. Six of these patients had been treated to 38.5 Gy in 10 fractions in a phase III accelerated partial breast trial and the rest of the patients were treated to 50.4 Gy in 28 fractions. In this planning study, the guidelines in the protocol for the phase III partial breast trial were followed for organ delineation and CyberKnife planning. The achievable dosimetric parameters from all CyberKnife plans were compared to Intensity-modulated radiation therapy (IMRT) and 3D-CRT methods. The reproducibility of the dose delivery with and without respiratory motion was assessed through delivering a patient plan to a breast phantom. Different dose calculation algorithms were also compared between ray tracing and Monte Carlo. Results: For all the patients in the study, the dosimetric parameters met the guidelines from the NSABP B39/RTOG 0413 protocol strictly. The mean PTV volume covered by 100% of the prescription dose was 95.7 ± 0.7% (94.7%-97.1%). The mean maximal dose was 104 ± 2% of the prescription dose. The mean V50% and mean V100% to the ipsilateral normal breast were 23.1 ± 11.6% and 9.0 ± 5.8%, respectively. The conformity index of all plans was 1.14 ± 0.04. The maximum dose to the contralateral breast varied from 1.3 cGy to 111 cGy. The mean V5% and mean V30% to the contralateral and ipsilateral lungs were 1.0 ± 1.6% and 1.3 ± 1.2%, respectively. In our study, the mean V5% to the heart was 0.2 ± 0.5% for right-sided tumors and 9.4 ± 10.1% for left-sided tumors. Compared with IMRT and 3D-CRT planning, the PTV coverage from CyberKnife planning was the highest, and the ratio of V20% to V100% of the breast from CyberKnife planning was the smallest. The heart and lung doses were similar in all the techniques except that the V5% for the lung and heart in CyberKnife planning was slightly higher. Conclusions: The dosimetric feasibility of APBI using CyberKnife was investigated in this retrospective study. All the dosimetric parameters strictly met the guidelines from the NSABP B39/RTOG 0413 protocol. With advanced real-time tracking capability, CyberKnife should provide better target coverage and spare nearby critical organs for APBI treatment. [ABSTRACT FROM AUTHOR]

Radiobiological models have been used to calculate the outcomes of treatment plans based on dose–volume relationship. This study examines several radiobiological models for the calculation of tumor control probability (TCP) of intensity modulated radiotherapy plans for the treatment of lung, prostate, and head and neck (H&N) cancers. Dose volume histogram (DVH) data from the intensity modulated radiotherapy plans of 36 lung, 26 prostate, and 87 H&N cases were evaluated. The Poisson, Niemierko, and Marsden models were used to calculate the TCP of each disease group treatment plan. The calculated results were analyzed for correlation and discrepancy among the three models, as well as different treatment sites under study. The median value of calculated TCP in lung plans was 61.9% (34.1–76.5%), 59.5% (33.5–73.9%) and 32.5% (0.0–93.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in prostate plans was 85.1% (56.4–90.9%), 81.2% (56.1–88.7%) and 62.5% (28.2–75.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in H&N plans was 94.0% (44.0–97.8%) and 94.3% (0.0–97.8%) with the Poisson and Niemierko models, respectively. There were significant differences between the calculated TCPs with the Marsden model in comparison with either the Poisson or Niemierko model (p < 0.001) for both lung and prostate plans. The TCPs calculated by the Poisson and Niemierko models were significantly correlated for all three tumor sites. There are variations with different radiobiological models. Understanding of the correlation and limitation of a TCP model with dosimetric parameters can help develop the meaningful objective functions for plan optimization, which would lead to the implementation of outcome-based planning. More clinical data are needed to refine and consolidate the model for accuracy and robustness. This study has tested three radiobiological models with varied disease sites. It is significant to compare different models with the same data set for better understanding of their clinical applicability. [ABSTRACT FROM AUTHOR]