Monte Carlo dosimetry of a novel Yttrium-90 disc source for episcleral brachytherapy.

PURPOSE: To calculate the dose distribution using Monte Carlo simulations for a novel high-dose-rate Yttrium-90 (Y-90) disc source recently developed for episcleral brachytherapy and provide a lookup table for treatment planning. METHODS: Monte Carlo simulations were performed to calculate the in-water dose distribution of the Y-90 disc source using the "GATE", a software based on the "Geant4" Monte Carlo simulation toolkit developed by the international OpenGATE collaboration. The geometry of this novel beta source, its capsule, and the surrounding water medium were accurately modeled in the simulation input files. The standard Y-90 element beta spectrum from ICRU 72 was used, and the physics processes for beta and photon interactions with matters were all included. The dose distribution of this Y-90 disc source was measured in a separate study using Gafchromic EBT-3 films and the results were reported elsewhere. To match the setup of the experiment, a Gafchromic EBT-3 film was also included in the simulation geometry. The simulated dose profiles were exported from the 3D dose distribution results and compared with the measured dose profiles. Transverse dose profiles at different distances from the seed surface were also obtained to study the lateral coverage of the source. RESULTS: The measured percent depth dose (PDD) curves along the central axis perpendicular to the surface of the Y-90 disc were constructed from the experimental and simulated data, and normalized to the reference point at 1 mm from the source capsule. Both PDD curves agreed well up to 4 mm from the source surface (maximum difference ± 10%) but deviated from each other beyond 4 mm. The deviation might be caused by the increased measurement uncertainty in the low-dose region. The dose rate at the reference point calculated from the Monte Carlo simulation was 1.09 cGy/mCi-s and agreed very well with the measured dose rate of 1.05 cGy/mCi-s. If the 80% isodose line is selected as the lateral coverage, the lateral dose coverage is maximal (∼4.5 mm) at the plane next to the source surface, and gradually decreases with the increasing distance, approaching 3.5 mm when the plane is 5 mm from the 6-mm diameter source surface. CONCLUSION: Monte Carlo simulations were successfully performed to confirm the measured PDD curve of the novel Y-90 disc source. This simulation work laid a solid foundation for characterizing the full dosimetry parameters of this source for episcleral brachytherapy applications.

Does Size Matter? On the Role of Stereotactic Radiosurgery for Large Vestibular Schwannomas as Seen in an Institutional Experience of Gamma Knife Radiosurgery for High-Grade Tumors.

OBJECTIVE: Management of large vestibular schwannoma (VS) is controversial. Surgery has historically been the treatment of choice, but emerging literature suggests that definitive stereotactic radiosurgery is feasible. We report our institutional experience of control and morbidity outcomes treating Koos grade 3-4 VS with Gamma Knife radiosurgery (GKRS). METHODS: An institutional review board-approved database compiled outcomes of Koos grade 3-4 VS treated by GKRS from March 2014 to January 2021 with >6 months' follow-up. Baseline symptoms per Common Terminology Criteria for Adverse Events definitions were recorded. Control rates, toxicities, and post-treatment volumetric changes were analyzed. Aggregate impairment scores (AIs) were defined by the sum of relevant Common Terminology Criteria for Adverse Events grades to categorize symptomatic burdens. Baseline and post-treatment AIs were tested for association with definitive versus adjuvant strategies. RESULTS: In total, 34 patients with Koos grade 3-4 VS were identified, 19 treated with definitive GKRS (GKRS-D) and 15 with adjuvant GKRS (GKRS-A). Median follow-up was 34.2 months for GKRS-D and 48.8 months for GKRS-A. Patients who received GKRS-A had greater AIs at presentation (3.73 vs. 2.11, P = 0.017). Irrespective of treatment approach, tumor control rates were 100% without instances of brainstem necrosis or shunt placement. Six of 19 patients who received GKRS-D had improved post-treatment AI, and 63% of patients who received GKRS-D and 66% of patients who received GKRS-A had tumor shrinkage >20%. CONCLUSIONS: In well-selected patients with Koos grade 3-4 VS, definitive stereotactic radiosurgery may be an appropriate strategy with excellent control and minimal toxicity. Our data suggest that the need for surgical decompression should be considered based on pretreatment symptom burden rather than tumor size.

Atypical Adams-Oliver syndrome with typical ocular signs of familial exudative vitreoretinopathy.

AIM: To report an atypical Adams-Oliver syndrome (AOS) family with typical ocular signs of familial exudative vitreoretinopathy (FEVR). METHODS: A patient with visible avascular area and obvious non-perfusion zone in the peripheral retina with systemic signs of AOS was reported. Familial and personal characteristics were collected for the patient and his sister. Gene sequencing and ophthalmic examinations including fluorescein angiography were all performed for the whole family. RESULTS: Two novel mutations of DOCK6 (c.1396C>T and c.4796G>A) were identified in the proband and his family, and two compound heterozygous mutations were revealed in the proband and his sister. The patient and his sister showed physical deformities and mental abnormalities while FEVR mimicking retinal disorder can also be defined. No remarkable ocular or systemic abnormality can be observed for their parents. Peripheral retinal non-perfusion area, obvious abnormal vascularization or even retinal fold were observed in the proband and his sister, while only small avascular zone was identified for their parents. CONCLUSION: This is the first genetic authenticated AOS case mimicked as FEVR with genetic sequencing of a family. For the patients with ocular phenotype of FEVR, further examination should be performed if the systemic or mental abnormalities exist.

A novel mutation of CYP4V2 gene associated with Bietti crystalline dystrophy complicated by choroidal neovascularization.

AIM: To investigate the clinical characteristics and genetic features of a Bietti crystalline dystrophy (BCD) proband in a Chinese family. METHODS: A Chinese female diagnosed with BCD complicated by bilateral choroidal neovascularization (CNV) and her parents underwent complete ophthalmic examinations, including fundus autofluorescence (AF), fundus photography (FP), fundus fluorescein angiography (FFA), visual field testing, full-field electroretinography (ERG), optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The sequencing of the CYP4V2 gene was performed to the whole family. RESULTS: Bilateral tiny glittering crystal-like deposits and differing extent of atrophy of the retinal pigment epithelium (RPE) were found in the posterior pole of her fundus. The diffuse hypo-fluorescence shown on AF images and window defects shown on FFA both indicated the atrophy of the RPE and choriocapillaris. OCT showed the thinning of the RPE and choriocapillaris layer, ellipsoid zone (EZ) band defect and CNV in both eyes. OCTA images proofed bilateral type 2 CNV. The visual field test showed central and paracentral scotoma. ERG showed a slightly decreased b-wave in scotopic ERG. Gene sequencing identified three mutations of the CYP4V2 gene, c.802_807del, c.810delT, and c.1388G>A. The mutation c.1388G>A was a novel substitution mutation. CONCLUSION: The novel mutation c.1388G>A may be a possible cause that could induce the clinical phenotype of BCD.

Evaluating dosimetric accuracy of the 6 MV calibration on EBT3 film in the use of Ir-192 high dose rate brachytherapy.

PURPOSE: To evaluate the dosimetric accuracy of EBT3 film calibrated with a 6 MV beam for high dose rate brachytherapy and propose a novel method for direct film calibration with an Ir-192 source. METHODS: The 6 MV calibration was performed in water on a linear accelerator (linac). The Ir-192 calibration was accomplished by irradiating the film wrapped around a cylinder applicator with an Ir-192 source. All films were scanned 1-day post-irradiation to acquire calibration curves for all three (red, blue, and green) channels. The Ir-192 calibration films were also used for single-dose comparison. Moreover, an independent test film under a H.A.M. applicator was irradiated and the 2D dose distribution was obtained separately for each calibration using the red channel data. Gamma analysis and point-by-point profile comparison were performed to evaluate the performance of both calibrations. The uncertainty budget for each calibration system was analyzed. RESULTS: The red channel had the best performance for both calibration systems in the single-dose comparison. We found a significant 4.89% difference from the reference for doses <250 cGy using the 6 MV calibration, while the difference was only 0.87% for doses >600 cGy. Gamma analysis of the 2D dose distribution showed the Ir-192 calibration had a higher passing rate of 91.9% for the 1 mm/2% criterion, compared to 83.5% for the 6 MV calibration. Most failing points were in the low-dose region (<200 cGy). The point-by-point profile comparison reported a discrepancy of 2%-3.6% between the Ir-192 and 6 MV calibrations in this low-dose region. The linac- and Ir-192-based dosimetry systems had an uncertainty of 4.1% (k = 2) and 5.66% (k = 2), respectively. CONCLUSIONS: Direct calibration of EBT3 films with an Ir-192 source is feasible and reliable, while the dosimetric accuracy of 6 MV calibration depends on the dose range. The Ir-192 calibration should be used when the measurement dose range is below 250 cGy.

Assessment of a Radiomic Signature Developed in a General NSCLC Cohort for Predicting Overall Survival of ALK-Positive Patients With Different Treatment Types.

BACKGROUND: The purpose of the study was to investigate the potential of a radiomic signature developed in a general non-small-cell lung cancer (NSCLC) cohort for predicting the overall survival of anaplastic lymphoma kinase (ALK)-positive (ALK+) patients with different treatment types. MATERIALS AND METHODS: After test-retest in the Reference Image Database to Evaluate Therapy Response data set, 132 features (intraclass correlation coefficient > 0.9) were selected in the least absolute shrinkage and selection operator Cox regression model with a leave-one-out cross-validation. The NSCLC radiomics collection from The Cancer Imaging Archive was randomly divided into a training set (n = 254) and a validation set (n = 63) to develop a general radiomic signature for NSCLC. In our ALK+ set, 35 patients received targeted therapy and 19 patients received nontargeted therapy. The developed signature was tested later in this ALK+ set. Performance of the signature was evaluated with the concordance index (C-index) and stratification analysis. RESULTS: The general signature had good performance (C-index > 0.6; log rank P < .05) in the NSCLC radiomics collection. It includes 5 features: Geom_va_ratio, W_GLCM_Std, W_GLCM_DV, W_GLCM_IM2, and W_his_mean. Its accuracy of predicting overall survival in the ALK+ set achieved 0.649 (95% confidence interval [CI], 0.640-0.658). Nonetheless, impaired performance was observed in the targeted therapy group (C-index = 0.573; 95% CI, 0.556-0.589) whereas significantly improved performance was observed in the nontargeted therapy group (C-index = 0.832; 95% CI, 0.832-0.852). Stratification analysis also showed that the general signature could only identify high- and low-risk patients in the nontargeted therapy group (log rank P = .00028). CONCLUSION: This preliminary study suggests that the applicability of a general signature to ALK+ patients is limited. The general radiomic signature seems to be only applicable to ALK+ patients who had received nontargeted therapy, which indicates that developing special radiomics signatures for patients treated with tyrosine kinase inhibitors might be necessary.

Application of radiomics signature captured from pretreatment thoracic CT to predict brain metastases in stage III/IV ALK-positive non-small cell lung cancer patients.

BACKGROUND: The purpose of this study is to develop a radiomics approach to predict brain metastasis (BM) for stage III/IV ALK-positive non-small cell lung cancer (NSCLC) patients. METHODS: Patients with ALK-positive III/IV NSCLC from 2014 to 2017 were enrolled retrospectively. Their pretreatment thoracic CT images were collected, and the gross tumor volume (GTV) was defined by two experienced radiation oncologists. An in-house feature extraction code-set was performed based on MATLAB 2015b (Mathworks, Natick, MA, USA) in patients' CT images to extract features. Patients were randomly divided into training set and test set (4:1) by using createDataPartition function in caret package. A test-retest in RIDER NSCLC dataset was performed to identify stable radiomics features. LASSO Cox regression and a leave-one-out cross-validation were conducted to identify optimal features for the logistic regression model to evaluate the predictive value of radiomics feature(s) for BM. Furthermore, extended validation for the radiomics feature(s) and Cox regression analyses which combined radiomics feature(s) and treatment elements were implemented to predict the risk of BM during follow-up. RESULTS: In total, 132 patients were included, among which 27 patients had pretreatment BM. The median follow-up time was 11.8 (range, 0.1-65.2) months. In the training set, one radiomics feature (W_GLCM_LH_Correlation) showed discrimination ability of BM (P value =0.014, AUC =0.687, 95% CI: 0.551-0.824, specificity =83.5%, sensitivity =57.1%). It also exhibited reposeful performance in the test set (AUC =0.642, 95% CI: 0.501-0.783, specificity =60.0%, sensitivity =83.3%). Those 105 patients without pretreatment BM were divided into stage III (n=57) and stage IV (n=48) groups. The radiomics feature (W_GLCM_LH_Correlation) had moderate performance to predict BM during/after treatment in separate groups (stage III: AUC =0.682, 95% CI: 0.537-0.826, specificity =64.4%, sensitivity =75.0%; stage IV: AUC =0.653, 95% CI: 0.503-0.804, specificity =70.4%, sensitivity =75.0%). Meanwhile, stage III patients could be divided into low risk and high risk groups for BM during surveillance according to Cox regression analysis (log-rank P value =0.021). CONCLUSIONS: We identified one wavelet texture feature derived from pretreatment thoracic CT that presented potential in predicting BM in stage III/IV ALK-positive NSCLC patients. This could be beneficial to risk stratification for such patients. Further investigation is necessary to include expanded sample size investigation and external multicenter validation.

Association between endogenous cortisol level and the risk of central serous chorioretinopathy: a Meta-analysis.

AIM: To assess the association between endogenous cortisol level and the risk of central serous chorioretinopathy (CSC). METHODS: Case-control studies were systematically searched on PubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI) for publishes between January 1990 and July 2017 to assess the association between endogenous cortisol level and CSC. The main endpoints were serum cortisol level at 8 a.m. and 24-hour urine 17-hydroxysteroids level. We assessed pooled data using a random-effects model. RESULTS: Of 86 identified studies, 5 were eligible included in our analysis. The 5 studies included a total of 315 participants, of whom 187 had CSC. Statistically significant association was observed between serum cortisol level (summary SMD=0.77, 95%CI=0.55-0.99), 24-hour urine 17-hydroxysteroids level (summary SMD=0.95, 95%CI=0.61-1.30), and the risk of CSC. CONCLUSION: Endogenous cortisol level is associated with an increased risk of CSC. Combined treatment targeting the serum cortisol level at 8 a.m. and 24-hour urine 17-hydroxysteroids level can be a potential preventive strategy for individuals who are at risk of CSC and therapeutic strategy for patients with CSC.

Expression of Total Vascular Endothelial Growth Factor and the Anti-angiogenic VEGF 165 b Isoform in the Vitreous of Patients with Retinopathy of Prematurity.

BACKGROUND: This study was to examine the expression of total vascular endothelial growth factor (VEGF) and the anti-angiogenic VEGF 165 b isoform in the vitreous body of retinopathy of prematurity (ROP) patients, and to further study the role of the VEGF splicing in the development of ROP. METHODS: This was a prospective clinical laboratory investigation study. All patients enrolled received standard ophthalmic examination with stage 4 ROP that required vitrectomy to collect the vitreous samples. The control samples were from congenital cataract patients. The expression of total VEGF and the anti-angiogenic VEGF 165 b were measured by enzyme-linked immunosorbent assay. Results were analyzed statistically using nonparametric tests. RESULTS: The total VEGF level was markedly elevated in ROP samples while VEGF 165 b was markedly decreased compared to control group. The relative protein expression level of VEGF 165 b isoform was significantly decreased in ROP patients which were correlated with the ischemia-induced neovascularization. CONCLUSIONS: There was a switch of VEGF splicing from anti-angiogenic to pro-angiogenic family in ROP patients. A specific inhibitor that more selectively targets VEGF 165 and controls the VEGF splicing between pro- and anti-angiogenic families might be a more effective therapy for ROP.