Comparative Analysis of the Prognostic Significance of IDH,TERT, EGFR and MGMT Status in Patients with Adult Non-H3-Altered Grade 4 Gliomas: A Prospective Cohort Study.

INTRODUCTION: Gliomas continue to have a dismal prognosis. A myriad of genetic alterations has been described in this subset of tumors over the last decades. The integrative interpretation of the biomarker constellation for individual patients remains unclear. This study aims to evaluate the impact of some known genetic factors as prognostic biomarkers in grade 4 gliomas. METHODS: Adult non-H3-altered grade 4 gliomas who underwent maximal safe resection accompanied by adjuvant therapy were successively enrolled since January 2019 till January 2021. Patient data were documented preoperatively and during the follow-up visits. The genetic profiling of the tumors included Isocitrate Dehydrogenase (IDH)-1 and IDH-2 mutation, MGMT promoter methylation rate, EGFR gene amplification and telomerase reverse transcriptase gene promoter (TERTp) mutation. RESULTS: Mean Overall survival (OS) and Progression-free survival (PFS) were 14.45 ± 5.13 months (3-24 months) and 10.66 ± 4.87 months respectively. TERTp-mutant group had a significantly lower OS (10.9 vs. 15.9) and PFS (6.9 vs. 12.3) than TERTp wildtype group. In the TERT-mutant group, those with concomitant IDH wildtype tumor had higher OS and PFS, comparable to those with both TERTp and IDH wildtype tumors. In multivariate analysis, IDH mutation and TERTp wildtype status were predictive of longer OS and PFS. While IDH and absence of TERTp mutation were associated with KPS > 80 across the follow-ups, their predictive values were inferior to preoperative KPS scores. CONCLUSIONS: TERTp mutation and IDH-wildtype status were associated with worse OS and PFS and lower follow-up KPS score in surgically resected gliomas, while MGMT and EGFR status did not have considerable prognostic value in this study.

Investigation of the effect of Low-Level Laser Therapy on arm lymphedema in breast cancer patients: A noninvasive treatment for an intractable morbidity.

Purpose: This article aims to study the effect of Low-Level Laser Therapy (LLLT) on arm lymphedema in patients who have breast cancer. Methods and Materials: Twenty-three patients were selected in a nonrandomized phase-2 clinical trial. After measuring the circumference of the affected and unaffected limbs at 6-points, the volume of the limbs, the degree of mental symptoms on visual analog scale by the patient upon entering the study, and performing an ultrasound on the patient's axilla to locate the fibrotic areas, a low-level laser device at a therapeutic dose of 2 J/cm2 was used to treat the patients three times a week for 4 weeks, and after an 8-week gap, for another similar period. Measurement of circumference and volume of affected and unaffected limbs and mental symptoms were carried out at the end of the 4th week, the beginning of the 12th week, and the end of the 16th week, and the obtained results were compared with those before the treatment. Results: We noted that the average reductions in the circumference and volume of the affected limb, as compared with the unaffected limb, were about 16% and 21.7%, respectively, and improvement in the patient's mental symptoms was about 32%. Another notable observation was the great enthusiasm of most patients to continue their treatment, particularly from the second cycle onward. Conclusions: LLLT can, at least in association with current standard methods, be used for arm lymphedema to introduce further reductions in pain and volume.

Dual application of Polyvinyl Alcohol Glutaraldehyde Methylthymol Blue Fricke hydrogel in clinical practice: Surface dosimeter and bolus.

An essential issue is an accurate evaluation of surface dose distribution for such sensitive treatments. This work aimed to feasibility of the dual application of the Ferrous Polyvinyl Alcohol Glutaraldehyde Methylthymol Blue (PVA-GTA-MTB) gel as a bolus compensator and surface dosimeter in breast radiotherapy. The differences between the surface dose measured using PVA-GTA-MTB gel and film dosimetry in the medial and lateral parts of the breast were 3.74% and 4.18%, respectively. A qualitative comparison of the isodose curves showed that the PVA-GTA-MTB bolus creates a uniform dose distribution similar to the superflab bolus in the target volume.

Fully automated clinical target volume segmentation for glioblastoma radiotherapy using a deep convolutional neural network.

Purpose: Target volume delineation is a crucial step prior to radiotherapy planning in radiotherapy for glioblastoma. This step is performed manually, which is time-consuming and prone to intra- and inter-rater variabilities. Therefore, the purpose of this study is to evaluate a deep convolutional neural network (CNN) model for automatic segmentation of clinical target volume (CTV) in glioblastoma patients. Material and methods: In this study, the modified Segmentation-Net (SegNet) model with deep supervision and residual-based skip connection mechanism was trained on 259 glioblastoma patients from the Multimodal Brain Tumour Image Segmentation Benchmark (BraTS) 2019 Challenge dataset for segmentation of gross tumour volume (GTV). Then, the pre-trained CNN model was fine-tuned with an independent clinical dataset (n = 37) to perform the CTV segmentation. In the process of fine-tuning, to generate a CT segmentation mask, both CT and MRI scans were simultaneously used as input data. The performance of the CNN model in terms of segmentation accuracy was evaluated on an independent clinical test dataset (n = 15) using the Dice Similarity Coefficient (DSC) and Hausdorff distance. The impact of auto-segmented CTV definition on dosimetry was also analysed. Results: The proposed model achieved the segmentation results with a DSC of 89.60 ± 3.56% and Hausdorff distance of 1.49 ± 0.65 mm. A statistically significant difference was found for the Dmin and Dmax of the CTV between manually and automatically planned doses. Conclusions: The results of our study suggest that our CNN-based auto-contouring system can be used for segmentation of CTVs to facilitate the brain tumour radiotherapy workflow.

Alteration of anxiety and depression after awake craniotomy: a prospective study on patients with language eloquent high-grade glioma.

BACKGROUND: Awake craniotomy (AC) is considered to achieve maximal safe resection of language eloquent gliomas. Impact of AC on the psychological status of patients (mainly anxiety, and post-traumatic stress disorder [PTSD]) is a potential concern. Despite the studies reporting the early postoperative patient's perception after AC, this study has been performed to quantitatively evaluate the long-term influence of AC on the level of anxiety/depression after surgery. METHODS: Patients who underwent AC for suspected language eloquent high-grade glioma were enrolled in this study. The anxiety, depression and PTSD of the patients were evaluated via hospital anxiety and depression scale (HADS) one week before and 1 and 6 months after the operation. PTSD symptoms were assessed according to the DSM-V checklist and confirmed by a structured clinical interview for DSM-V. RESULTS: Twenty-eight patients (22 men, six women) with the mean age of 39.2 years were enrolled. The mean preoperative depressive and anxiety score was 4.9±5.9 and 7.7±5.8 respectively. One month after surgery they were 6±4.9 and 7.4±6.2 and at 6 months' follow-up 5.5±5.1 and 5.4±4.2 respectively. There was no statistically significant trend for alterations of the anxiety/depression levels before and after surgery. Female patients, those suspected to have glioblastoma and patients presenting with speech disturbance had remarkably higher preoperative anxiety levels. Three patients had PTSD symptoms 3 months after AC while at 6 months there was no indication of PTSD. The decremental trend of PTSD score within 6 months was statistically significant. CONCLUSIONS: Judicious application of AC is not associated with an escalation of the anxiety/depression level among the patients. Even patients with high preoperative anxiety levels could be managed with AC without severe psychological deterioration.

Dosimetric comparison of AP/PA and bilateral geometries for total body irradiation treatment.

Total body irradiation (TBI) is an external radiotherapy technique. Its aim is to deliver a therapeutic dose uniformly within ± 10% of the absorbed dose to the prescription point. In the present study, the TBI technique was implemented in anterior/posterior (AP/PA), and bilateral geometry with photons from a 6 [Formula: see text] and 18 [Formula: see text] accelerator. The TBI technique was implemented on an Alderson Rando phantom at 312 [Formula: see text] source surface distance. During bilateral fraction, rice bags were applied as tissue compensators. To reduce the lung's absorbed dose to the acceptance level, in AP/PA geometry lung blocks made of Cerrobend were used. The required monitor unit (MU) for each fraction was calculated regarding depending on the prescribed dose and beam output. Gafchromic EBT3 films were used for dosimetry between the phantom layers in eight selected points. It is demonstrated that dose uniformity for AP/PA geometry with 6 [Formula: see text] and 18 [Formula: see text] photons was within ± 10%. In contrast, for the bilateral geometry the dose uniformity was not acceptable for both studied energies; However, the results for 18 [Formula: see text] were better than those for 6 [Formula: see text]. Dose accuracy for all measurements was within ± 5 of the prescribed dose. The absorbed dose to the lungs was successfully reduced using the lung blocks. By combining different therapeutic geometries and energies over six fractions, the results of uniformity and accuracy of dose delivery could be improved. It is concluded that the introduced TBI method achieved good dose accuracy and acceptable dose uniformity. Lungs absorbed dose was lower than 10 [Formula: see text] using the lungs blocks. Based on these results, the TBI technique can now be implemented in radiotherapy at Tehran's Imam Hospital. The approach developed in the present study can be used and adapted to match with the conditions at other hospitals.

A rapid review of influential factors and appraised solutions on organ delineation uncertainties reduction in radiotherapy.

Background and purpose.Accurate volume delineation plays an essential role in radiotherapy. Contouring is a potential source of uncertainties in radiotherapy treatment planning that could affect treatment outcomes. Therefore, reducing the degree of contouring uncertainties is crucial. The role of utilized imaging modality in the organ delineation uncertainties has been investigated. This systematic review explores the influential factors on inter-and intra-observer uncertainties of target volume and organs at risk (OARs) delineation focusing on the used imaging modality for these uncertainties reduction and the reported subsequent histopathology and follow-up assessment.Methods and materials.An inclusive search strategy has been conducted to query the available online databases (Scopus, Google Scholar, PubMed, and Medline). 'Organ at risk', 'target', 'delineation', 'uncertainties', 'radiotherapy' and their relevant terms were utilized using every database searching syntax. Final article extraction was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Included studies were limited to the ones published in English between 1995 and 2020 and that just deal with computed tomography (CT) and magnetic resonance imaging (MRI) modalities.Results.A total of 923 studies were screened and 78 were included of which 31 related to the prostate 20 to the breast, 18 to the head and neck, and 9 to the brain tumor site. 98% of the extracted studies performed volumetric analysis. Only 24% of the publications reported the dose deviations resulted from variation in volume delineation Also, heterogeneity in studied populations and reported geometric and volumetric parameters were identified such that quantitative synthesis was not appropriate.Conclusion.This review highlightes the inter- and intra-observer variations that could lead to contouring uncertainties and impede tumor control in radiotherapy. For improving volume delineation and reducing inter-observer variability, the implementation of well structured training programs, homogeneity in following consensus and guidelines, reliable ground truth selection, and proper imaging modality utilization could be clinically beneficial.

Mixed malignant glioblastoma and schwannoma in spinal cord with metachronous ependymoma: A case report.

Here, we report a very rare case of mixed spinal tumor comprising of malignant glioblastoma and schwannoma, who was initially treated with tumor resection and adjuvant chemoradiation, but relapsed three years later with grade 3 ependymoma.

Investigation of the Scaling Formula Accuracy for Poly-energetic Kernel Calculation in 6 MV Photon Beam.

BACKGROUND: Dose distribution can be obtained from total energy released per unit mass (TERMA) and inhomogeneous energy deposition kernel (EDK) convolution. Since inhomogeneous EDK data is location-dependent, it is calculated by employing the density scaling method rather than Monte Carlo based user code EDKnrc. OBJECTIVE: The present study aimed at investigating EDK scaling formula accuracy in the presence of lung and bone inhomogeneities. MATERIAL AND METHODS: In this theoretical-practical study, six EDKs datasets with lung and bone inhomogeneity in different radii were generated using EDKnrc user code and density scaling formula. Then the scaling method data and corresponding EDKnrc-generated ones were compared to enhance the calculations, and some correction factors for error reduction were also derived to create more consistency between these data. RESULTS: The study has shown that the errors in the theoretical method for calculating inhomogeneous EDKs were significantly reduced based on the attenuation coefficient and ρα rel parameter, with α equal to 1.2 and 0.8 for bone and lung voxels, respectively. CONCLUSION: Although the density scaling method has acceptable accuracy, the error values are significant at the location of lung or bone voxels. By using the mentioned correction factors, the calculation inaccuracy of heterogeneous EDKs can be reduced down to 5%. However, the lung heterogeneity results corrected by the method are not as good as the bone cases.

Novel method of combined photon beam radiotherapy and brachytherapy for treatment of extensive advanced scalp squamous cell carcinoma.

Radiotherapy of extensive malignant scalp lesions has always been a challenge for radiation oncologists considering the proximity of critical structures. We treated a 39-year-old patient with extensive scalp squamous cell carcinoma with application of adjuvant concurrent chemoradiation and external beam radiation therapy (EBRT), followed by high-dose-rate (HDR) surface brachytherapy boost using an exclusively designed mould, and assessed the radiation dose reaching planning target volume, brain, and optic structures. Comparison between conventional planning with sole EBRT and combined treatment planning with EBRT and brachytherapy, assured the use of the latter treatment to avoid high radiation doses from reaching critical organs at risk without compromising the required dose for planning target volume.

Dosimetric effect of nanoparticles in the breast cancer treatment using INTRABEAM®system with spherical applicators in the presence of tissue heterogeneities: A Monte Carlo study.

Using the 50 kV INTRABEAM®IORT system after breast-conserving surgery: tumor recurrence and organs at risk (OARs), such as the lung and heart, long-term complications remain the challenging problems for breast cancer patients. So, the objective of this study was to address these two problems with the help of high atomic number nanoparticles (NPs). A Monte Carlo (MC) Simulation type EGSnrc C++ class library (egspp) with its Easy particle propagation (Epp) user code was used. The simulation was validated against the measured depth dose data found in our previous study (Tegaw,et al2020 Dosimetric characteristics of the INTRABEAM®system with spherical applicators in the presence of air gaps and tissue heterogeneities,Radiat. Environ. Biophys. (10.1007/s00411-020-00835-0)) using the gamma index and passed 2%/2 mm acceptance criteria in the gamma analysis. Gold (Au) NPs were selected after comparing Dose Enhancement Ratios (DERs) of bismuth (Bi), Au, and platinum (Pt) NPs which were calculated from the simulated results. As a result, 0.02, 0.2, 2, 10, and 20 mg-Au/g-breast tissue were used throughout this study. These particles were not distributed in discrete but in a uniform concentration. For 20 mg-Au/g-breast tissue, the DERs were 3.6, 0.420, and 0.323 for breast tissue, lung, heart, respectively, using the 1.5 cm-diameter applicator (AP) and 3.61, 0.428, and 0.335 forbreast tissue, lung, and heart using the 5 cm-diameter applicator, respectively. DER increased with the decrease in the depth of tissues and increase in the effective atomic number (Zeff) and concentration of Au NPs, however, there was no significant change as AP sizes increased. Therefore, Au NPs showed dual advantages such as dose enhancement within the tumor bed and reduction in the OARs (heart and lung).

Evaluation of ferrous benzoic methylthymol-blue gel as a dosimeter via magnetic resonance imaging.

PURPOSE: In previous studies, methylthymol-blue and benzoic acid have been introduced as a diffuser limiter and sensitivity enhancer in the gel dosimeter composition, respectively. This work focused on analyzing a formulation of the Fricke gel dosimeter consisting of methylthymol-blue and benzoic acid through magnetic resonance imaging. METHODS: The gel dosimeter samples were irradiated using 6, 10, and 15 MV photons with different levels of doses and read using a 1.5 T scanner in order to evaluate the dose-response sensitivity and to study the effect of benzoic acid concentration, diffusion coefficient and temperature and to determine the temporal stability of the gel dosimeter. RESULTS: Inspection of radiological properties revealed that this gel dosimeter can be considered as a tissue equivalent medium. Within the dose range 0 to 1000 cGy, the R1 sensitivity and R2 sensitivity of the gel dosimeter equaled 0.058 ± 0.003 and 0.092 ± 0.004 s-1Gy-1, respectively. The diffusion coefficient was less than 0.85 ± 0.02mm2h-1 for doses higher than 200 cGy. In addition, by changing the temperature from 15C to 25, the R1 sensitivity and R2 sensitivity decreased about 5 and 11%, respectively. Further, no significant energy and dose rate dependence were observed over photon energies of 6, 10, and 15 MV and over the range 65 to 525 cGy min-1. CONCLUSIONS: Based on our observation, the ferrous benzoic acid methylthymol-blue gel dosimeter can be suggested to measure the dose distribution. Further analysis is required to clarify its performance in clinical situations.

Evaluation of contrast agent dose and diffusion coefficient measurement on vessel size index estimation.

OBJECTIVES: The goal of this study is to examine the effect of contrast agent (CA) dose and diffusion coefficient on the estimation of vessel size index (VSI). MATERIALS AND METHODS: Three groups of four participants were enrolled in this study and two different experiments were performed. Different dose of CA, namely 0.1 mmol/kg and 0.05 mmol/kg were assessed in two groups of normal subjects. Diffusion coefficient effect was assessed in the third group with high-grade glioma. Imaging included gradient echo and spin-echo DSC and DTI on a 3-T MR Scanner. RESULTS: VSI estimation using half of standard dose of CA showed higher values compared to the application of standard, with a ratio of 2 for the WM and 1.5 for the GM. VSI estimates for tumor tissues (22 µm) were considerably higher compared to contra-lateral Normal-Appearing WM (NAWM, 4 µm, P < 0.01) and Normal-Appearing GM (NAGM, 8 µm, P < 0.04). DISCUSSION: Application of standard dose for CA injection and also taking into account the effect of diffusion coefficient can lead to a better correlation of VSI with previous theoretically predicted values and improvement of individual diagnostics in tumor evaluations.

Clinical outcome after high-precision radiotherapy for skull base meningiomas: Pooled data from three large German centers for radiation oncology.

PURPOSE: To evaluate outcome in patients with base of skull meningiomas treated with modern high precision radiation therapy (RT) techniques. PATIENTS AND METHODS: 927 patients from three centers were treated with either radiosurgery or fractionated high-precision RT for meningiomas. Treatment planning was based on CT and MRI following institutional guidelines. For radiosurgery, a median dose of 13 Gy was applied, for fractionated treatments, a median dose of 54 Gy in 1.8 Gy single fractions was prescribed. Follow-up included a clinical examination as well as contrast-enhanced imaging. All patients were followed up prospectively after radiotherapy in the three departments within a strict follow-up regimen. The median follow-up time was 81 months (range 1-348 months). RESULTS: Median local control was 79 months (range 1-348 months). Local control (LC) was 98% at 1 year, 94% at 3 years, 92% at 5 years and 86% at 10 years. There was no difference between radiosurgery and fractionated RT. We analyzed the influence of higher doses on LC and could show that dose did not impact LC. Moreover, there was no difference between 54 Gy and 57.6 Gy in the fractionated group. Side effects were below 5% in both groups without any severe treatment-related complications. DISCUSSION: Based on the pooled data analysis this manuscript provides a large series of meningiomas of the skull base treated with modern high precision RT demonstrating excellent local control and low rates of side effects. Such data support the recommendation of RT for skull base meningiomas in the interdisciplinary tumor board discussions. The strong role of RT must influence treatment recommendations keeping in mind the individual risk-benefit profile of treatment alternatives.

Optic toxicity in radiation treatment of meningioma: a retrospective study in 213 patients.

In this retrospective evaluation, we correlated radiation dose parameters with occurrence of optical radiation-induced toxicities. 213 meningioma patients received radiation between 2000 and 2013. Radiation dose and clinical data were extracted from planning systems and patients' files. The range of follow-up period was 2-159 months (median 75 months). Median age of patients was 60 years (range 23-86). There were 163 female and 50 male patients. In 140 cases, at least one of the neuro-optic structures (optic nerves and chiasm) was inside the irradiated target volumes. We found 15 dry eye (7 %) and 24 cataract (11.2 %) cases. Median dose to affected lachrymal glands was 1.47 Gy and median dose to affected lenses was 1.05 Gy. Age and blood cholesterol level in patients with cataract were significantly higher. Patients with dry eye were significantly older. Only two patients with visual problems attributable to radiation treatment were seen. They did not have any risk factors. Maximum and median delivered doses to neuro-optic structures were not higher than 57.30 and 54.60 Gy respectively. Low percentages of cases with radiation induced high grade optic toxicities show that modern treatment techniques and doses are safe. In very few patients with optic side effects, doses to organs at risk were higher than the defined constraint doses. This observation leads to the problem of additional risk factors coming into play. The role of risk factors and safety of higher radiation doses in high grade meningiomas should be investigated in more comprehensive studies.

Simultaneous integrated vs. sequential boost in VMAT radiotherapy of high-grade gliomas.

BACKGROUND: In 20 patients with high-grade gliomas, we compared two methods of planning for volumetric-modulated arc therapy (VMAT): simultaneous integrated boost (SIB) vs. sequential boost (SEB). The investigation focused on the analysis of dose distributions in the target volumes and the organs at risk (OARs). METHOD: After contouring the target volumes [planning target volumes (PTVs) and boost volumes (BVs)] and OARs, SIB planning and SEB planning were performed. The SEB method consisted of two plans: in the first plan the PTV received 50 Gy in 25 fractions with a 2-Gy dose per fraction. In the second plan the BV received 10 Gy in 5 fractions with a dose per fraction of 2 Gy. The doses of both plans were summed up to show the total doses delivered. In the SIB method the PTV received 54 Gy in 30 fractions with a dose per fraction of 1.8 Gy, while the BV received 60 Gy in the same fraction number but with a dose per fraction of 2 Gy. RESULTS: All of the OARs showed higher doses (Dmax and Dmean) in the SEB method when compared with the SIB technique. The differences between the two methods were statistically significant in almost all of the OARs. Analysing the total doses of the target volumes we found dose distributions with similar homogeneities and comparable total doses. CONCLUSION: Our analysis shows that the SIB method offers advantages over the SEB method in terms of sparing OARs.

A multicentre cross-sectional study of arm lymphedema four or more years after breast cancer treatment in Iranian patients.

BACKGROUND: We performed a cross-sectional multicentre study to assess the prevalence of lymphedema after breast cancer treatment in Iran. PATIENTS AND METHODS: All female breast cancer patients who attended our follow-up clinics four or more years after their surgery with no sign of disease were asked to participate in this study. Lymphedema was defined as an increase of 10% in the circumference of the arm on the involved side compared to the opposite arm. RESULTS: The total number of patients participating in this study was 355. The prevalence of lymphedema in the study patients was 17.5%, with the rate varying significantly (between 4 and 21%) among the three study centres (p = 0.007). The mean number of months post surgery was larger for patients with lymphedema (84 months) than for those without (79 months), though this was not statistically significant (p > 0.1). The relationships of various treatment factors and the education levels of the patients to the presence of lymphedema were also evaluated. None of the observed differences were statistically significant aside from those for the type of surgery (mastectomy vs. conservative surgery, p = 0.055), treatment with radiotherapy (p = 0.099), and prescription of a supraclavicular radiation field (p = 0.057), which were only just significant. CONCLUSION: The rate of lymphedema in our patients was 17.5%, ranging from 4 to 21% in different study centres. Time post surgery, treatment with radiotherapy and the technique used, and nodal radiation seem to be factors that are related to this large variation.