Volumetric response of intracranial meningioma after photon or particle irradiation.

BACKGROUND: Meningiomas are usually slow growing, well circumscribed intracranial tumors. In symptom-free cases observation with close follow-up imaging could be performed. Symptomatic meningiomas could be surgically removed and/or treated with radiotherapy. The study aimed to evaluate the volumetric response of intracranial meningiomas at different time points after photon, proton, and a mixed photon and carbon ion boost irradiation. PATIENTS AND METHODS: In Group A 38 patients received proton therapy (median dose: 56 GyE in 1.8-2 GyE daily fractions) or a mixed photon/carbon ion therapy (50 Gy in 2 Gy daily fractions with intensity modulated radiotherapy (IMRT) and 18 GyE in 3 GyE daily dose carbon ion boost). Thirty-nine patients (Group B) were treated by photon therapy with IMRT or fractionated stereotactic radiotherapy technique (median dose: 56 Gy in 1.8-2 Gy daily fractions). The delineation of the tumor volume was based on the initial, one- and two-year follow-up magnetic resonance imaging and these volumes were compared to evaluate the volumetric tumor response. RESULTS: Significant tumor volume shrinkage was detected at one- and at two-year follow-up both after irradiation by particles and by photons. No significant difference in tumor volume change was observed between photon, proton or combined photon plus carbon ion boost treated patients. WHO grade and gender appear to be determining factors for tumor volume shrinkage. CONCLUSION: Significant volumetric shrinkage of meningiomas could be observed independently of the applied radiation modality. Long-term follow-up is recommended to evaluate further dynamic of size reduction and its correlation with outcome data.

Lipidomic analysis reveals a radiosensitizing role of gamma-linolenic acid in glioma cells.

Previous studies have demonstrated that gamma-linolenic acid (GLA) is effective against glioma cells under both in vitro and in vivo conditions. In the present study we determined how GLA alone or in combination with irradiation alters the fatty acid (FA) and lipid profiles, the lipid droplet (LD) content, the lipid biosynthetic gene expression and the apoptosis of glioma cells. In GLA-treated cells direct correlations were found between the levels of various FAs and the expression of the corresponding FA biosynthetic genes. The total levels of saturated and monosaturated FAs decreased in concert with the down-regulation of FASN and SCD1 gene expression. Similarly, decreased FADS1 gene expression was paralleled by lowered arachidonic acid (20:4 n-6) and eicosapentaenoic acid (20:5 n-3) contents, while the down-regulation of FADS2 expression was accompanied by a diminished docosahexaenoic acid (22:6 n-3) content. Detailed mass spectrometric analyses revealed that individual treatments gave rise to distinct lipidomic fingerprints. Following uptake, GLA was subjected to elongation, resulting in dihomo-gamma-linolenic acid (20:3 n-6, DGLA), which was used for the synthesis of the LD constituent triacylglycerols and cholesteryl esters. Accordingly, an increased number of LDs were observed in response to GLA administration after irradiation. GLA increased the radioresponsiveness of U87 MG cells, as demonstrated by an increase in the number of apoptotic cells determined by FACS analysis. In conclusion, treatment with GLA increased the apoptosis of irradiated glioma cells, and GLA might therefore increase the therapeutic efficacy of irradiation in the treatment of gliomas.

Evaluation of the good tumor response of embryonal tumor with abundant neuropil and true rosettes (ETANTR).

The embryonal tumor with abundant neuropil and true rosettes is a rare and highly malignant variant of embryonal brain tumors. It usually affects infants and young children under the age of 4 years and exhibits a very aggressive course with a dismal prognosis. For the 68 cases reported to date the mean age at diagnosis was 25.42 months (range 3-57 months). Survival data are available for 48 children (including our case): the median overall survival is 13.0 months, though 6 (9%) of the children have had a relative long survival (>30 months). The aggressive combined treatment, involving primary surgical tumor removal, adjuvant polychemotherapy, including high-dose chemotherapy with stem cell transplantation, radiotherapy and radiochemotherapy, might play an important role in the longer survival. We have performed a literature review and we present here a multimodal-treated case of a 2- year-old girl with a long survival, who was reoperated when recurrence occurred. The residual tumor demonstrated a good response to temozolomide radiochemotherapy (craniospinal axis + boost) and followed by maintenance temozolomide. The described complex aggressive treatment option might be considered for future cases of this tumor entity.

[Role of 18FDG-PET/CT in the management and gross tumor volume definition for radiotherapy of head and neck cancer; single institution experiences based on long-term follow-up]. / 18FDG-PET/CT szerepe fej-nyak daganatok kezelésében és a sugárterápiás tumortérfogat meghatározásában - Az SZTE Onkoterápiás Klinika eredményeinek értékelése.

The purpose of our work is evaluation of the impact of 18FDG-PET/CT on the complex management of locoregionally advanced (T3-4N1-3) head and neck squamous cell cancer (LAHNSC), and on the target definition for 3D conformal (3DCRT) and intensity-modulated radiotherapy (IMRT). 18FDG-PET/CT were performed on 185 patients with LAHNSC prior to radiotherapy/chemoradiation in the treatment position between 2006 and 2011. Prior to it 91 patients received induction chemotherapy (in 20 cases of these, baseline PET/CT was also available). The independently delineated CT-based gross tumor volume (GTVct) and PET/CT based ones (GTVpet) were compared. Impact of PET/CT on the treatment strategy, on tumor response evaluation to ICT, on GTV definition furthermore on overall and disease-specific survival (OS, DSS) was analysed. PET/CT revealed 10 head and neck, 2 lung cancers for 15 patients with carcinoma of unknown primary (CUP) while 3 remained unknown. Second tumors were detected in 8 (4.4%), distant metastasis in 15 (8.2%) cases. The difference between GTVct and GTVpet was significant (p=0.001). In 16 patients (14%) the GTVpet were larger than GTVct due to multifocal manifestations in the laryngo-pharyngeal regions (4 cases) or lymph node metastases (12 cases). In the majority of the cases (82 pts, 72%) PET/CT-based conturing resulted in remarkable decrease in the volume (15-20%: 4 cases, 20-50%: 46 cases, >50%: 32 cases). On the basis of the initial and post-ICT PET/CT comparison in 15/20 patients more than 50% volume reduction and in 6/20 cases complete response were achieved. After an average of 6.4 years of follow-up the OS (median: 18.3±2.6 months) and DSS (median: 25.0±4.0 months) exhibited close correlation (p=0.0001) to the GTVpet. In cases with GTVpet <10 cm3 prior to RT, DSS did not reach the median, the mean is 82.1±6.1 months, while in cases with GTVpet 10-40 cm3 the median of the DSS was 28.8±4.9 months (HR = 3.57; 95% CI: 1.5-8.3), and in those with GTVpet >40 cm3 the median DSS was 8.4±0.96 months (HR= 11.48; 95% CI: 5.3-24.9). Our results suggest that 18FDG-PET/CT plays an important role for patient with LAHNSC, by modifying the treatment concept and improving the target definition for selective RT modalities. Volumetric PET/CT-based assessment of the tumor response after ICT gives valuable contribution to further therapy planning.

Radio-neuroprotective effect of L-alpha-glycerylphosphorylcholine (GPC) in an experimental rat model.

Ionizing radiation plays a major role in the treatment of brain tumors, but side-effects may restrict the efficacy of therapy. In the present study, our goals were to establish whether the administration of L-alpha-glycerylphosphorylcholine (GPC) can moderate or prevent any of the irradiation-induced functional and morphological changes in a rodent model of hippocampus irradiation. Anesthetized adult (6-weeks-old) male Sprague-Dawley rats were subjected to 40 Gy irradiation of one hemisphere of the brain, without or with GPC treatment (50 mg/kg bw by gavage), the GPC treatment continuing for 4 months. The effects of this partial rat brain irradiation on the spatial orientation and learning ability of the rats were assessed with the repeated Morris water maze (MWM) test. Histopathologic (HP) evaluation based on hematoxylin-eosin and Luxol blue staining was performed 4 months after irradiation. The 40 Gy irradiation resulted in a moderate neurological deficit at the levels of both cognitive function and morphology 4 months after the irradiation. The MWM test proved to be a highly sensitive tool for the detection of neurofunctional impairment. The site navigation of the rats was impaired by the irradiation, but the GPC treatment markedly decreased the cognitive impairment. HP examination revealed lesser amounts of macrophage density, reactive gliosis, calcification and extent of demyelination in the GPC-treated group. GPC treatment led to significant protection against the cognitive decline and cellular damage, evoked by focal brain irradiation at 40 Gy dose level. Our study warrants further research on the protective or mitigating effects of GPC on radiation injuries.

Combination of unsaturated fatty acids and ionizing radiation on human glioma cells: cellular, biochemical and gene expression analysis.

BACKGROUND: Based on previous observations a potential resort in the therapy of the particularly radioresistant glioma would be its treatment with unsaturated fatty acids (UFAs) combined with irradiation. METHODS: We evaluated the effect of different UFAs (arachidonic acid (AA), docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and oleic acid (OA)) on human U87 MG glioma cell line by classical biochemical end-point assays, impedance-based, real-time cellular and holographic microscopic analysis. We further analyzed AA, DHA, and GLA at morphological, gene and miRNA expression level. RESULTS: Corresponding to LDH-, MTS assays and real-time cytoxicity profiles AA, DHA, and GLA enhanced the radio sensitivity of glioma cells. The collective application of polyunsaturated fatty acids (PUFAs) and irradiation significantly changed the expression of EGR1, TNF-α, NOTCH1, c-MYC, TP53, HMOX1, AKR1C1, NQO1, while up-regulation of GADD45A, EGR1, GRP78, DDIT3, c-MYC, FOSL1 were recorded both in response to PUFA treatment or irradiation alone. Among the analyzed miRNAs miR-146 and miR-181a were induced by DHA treatment. Overexpression of miR-146 was also detected by combined treatment of GLA and irradiation. CONCLUSIONS: Because PUFAs increased the radio responsiveness of glioma cells as assessed by biochemical and cellular assays, they might increase the therapeutic efficacy of radiation in treatment of gliomas. We demonstrated that treatment with DHA, AA and GLA as adjunct to irradiation up-regulated the expression of oxidative-stress and endoplasmic reticulum stress related genes, and affected NOTCH1 expression, which could explain their additive effects.

Single dose irradiation of defined region of rat brain with stereotactic brainlab system.

UNLABELLED: Background and purpose of our study was to develop a precise dose delivery technique for partial brain irradiation of two rats simultaneously. METHODS: Using a self-developed frame stereotactic radiotherapy with single doses of 30-90 Gy was delivered to the frontal lobe of 22 animals. Tolerability and reproducibility of the method were evaluated and dosimetric measurements were conducted to verify the treatment plans. 2, 4 and 6 months after the irradiation magnetic resonance imaging (MRI) scans and histopathological examinations were performed to detect late radiation induced biological changes. RESULTS: Immobilization device provided excellent reproducibility and tolerability. Dosimetry revealed good correspondence with planned dose distribution, but the measured absorbed dose was 30% lower than the planned dose. During the 6 months follow-up period the procedure related death of subject animals after 30 Gy, 70 Gy and 90 Gy were 0%, 20% and 100% respectively. T2 signal and structural changes on MRI scans found to be dose and time dependent. While 30 Gy caused no detectable structural changes, 70 Gy lead to cystic necrosis in 2 cases after 4 month. Histopathology revealed signs of necrosis on macroscopic examination after 70 Gy in the high dose region involving both frontal lobes, and no obvious microscopic changes in the surrounding area were detectable. CONCLUSION: Our technique of rat cranial irradiation using human stereotactic system provided high accuracy of single dose delivery for a pair of small animals, resulting in brain injury in the defined area. This method proved to be a reproducible model for preclinical studies on radiation effects.

Individual benefit in heart sparing during DIBH-supported left breast radiotherapy.

Introduction: Deep-inspirational breath hold (DIBH) is an option for heart protection in breast radiotherapy; we intended to study its individual benefit. Materials and Methods: 3DCRT treatment planning was performed in a cohort of 103 patients receiving radiotherapy of the whole breast (WBI)/chest wall (CWI) ± nodal regions (NI) both under DIBH and free breathing (FB) in the supine position, and in the WBI only cases prone (n = 45) position, too. A series of patient-related and heart dosimetry parameters were analyzed. Results: The DIBH technique provided dramatic reduction of all heart dosimetry parameters the individual benefit, however, varied. In the whole population the best predictor of benefit was the ratio of ipsilateral lung volume (ILV)FB and ILVDIBH. In the WBI cohort 9-11 patients and 5-8 patients received less dose to selected heart structures with the DIBH and prone positioning, respectively; based on meeting various dose constraints DIBH was the only solution in 6-13 cases, and prone positioning in 5-6 cases. In addition to other excellent predictors, a small ILVFB or ILVDIBH with outstanding predicting performance (AUC ≥ 0.90) suggested prone positioning. Detailed analysis consistently indicated the outstanding performance of ILVFB and ILVDIBH in predicting the benefit of one over the other technique in lowering the mean heart dose (MHD), left anterior descending coronary artery (LAD) mean dose and left ventricle(LV)-V5Gy. The preference of prone positioning was further confirmed by anatomical parameters measured on a single CT scan at the middle of the heart. Performing spirometry in a cohort of 12 patients, vital capacity showed the strongest correlation with ILVFB and ILVDIBH hence this test could be evaluated as a clinical tool for patient selection. Discussion: Individual lung volume measures estimated by spirometry and anatomical data examined prior to acquiring planning CT may support the preference of DIBH or prone radiotherapy for optimal heart protection.

Survival Benefit of Stereotactic Radiotherapy in the Complex Management of Metastatic Melanoma.

BACKGROUND/AIM: Targeted therapy and immunotherapy, with additional stereotactic radiation therapy (SRT) have revolutionized the management of metastatic malignant melanoma (mMM). We aimed to analyze the effectiveness and safety of SRT and determine its role in the complex management of mMM. PATIENTS AND METHODS: We treated 24 patients with solitary metastasis, 15 with oligometastatic disease and one with multiple metastases. The primary endpoint was to investigate the possible effect of stereotactic radiotherapy for metastatic lesions on patients' survival taking the systemic therapy into consideration. RESULTS: The median overall survival (OS) for the entire group was 30.07 months; 50% of them received immunotherapy, 32% received targeted therapy. Complete remission of the irradiated lesions was observed in six patients, partial tumor response was achieved in 13, while stable disease was detected in 10; tumor progression occurred in four cases. Compartmental recurrence (recurrence in the brain in a not previously irradiated region) developed in seven patients. OS was significantly longer in those with extracranial metastases treated with stereotactic body radiotherapy in comparison to brain SRT. We found a strong correlation between tumor response and mean OS (42.5 months after complete or partial remission versus 11.8 months in those with stable or progressive disease). No OS difference was observed according to the number of irradiated lesions or type of systemic therapy before SRT (no therapy: 43.6 months, with therapy: 25.7 months). Significant OS advantage was shown when immunotherapy was administered post-SRT (mean OS: with immunotherapy: 39.6 months, no immunotherapy: 18.5 months). CONCLUSION: In the case of oligometastatic MM, SRT can be used safely and with good efficiency in addition to targeted therapy/anti-programmed cell death protein 1 therapy. Improved survival warrants including SRT in the complex management of mMM, however, further studies are needed for SRT optimization.

Post-operative management of primary glioblastoma multiforme in patients over 60 years of age.

BACKGROUND AND PURPOSE: Optimal treatment for elderly patients with glioblastoma multiforme is not well defined. We evaluated the efficacy of post-operative radiotherapy with or without concomitant and/or adjuvant temozolomide in patient, aged > or = 60 years to assess survival and identify prognostic factors of survival. METHODS: A retrospective analysis of overall survival and progression-free survival in patients with newly diagnosed glioblastoma multiforme aged > or = 60 years treated with post-operative radiotherapy with or without temozolomide chemotherapy was conducted at our institutions. Prognostic factors were determined by univariate and multivariate analyses. RESULTS: Of 75 study participants (54.7% male; median age at first diagnosis, 65.1 years), 29 (38.7%) underwent gross total resection, whereas others underwent partial resection or biopsy only. All but 1 patient received radiotherapy. Twenty patients received concomitant temozolomic e only. Adjuvant temozolomide (1-50 cycles) was administered in 42 patients; 16 received > or = 6 cycles. Median overall survival was 10.3 months. One- and 2-year overall survival rates were 42.6% and 6.7%, respectively. Median progression-free survival was 4.1 months. Radiochemotherapy was generally well tolerated. Median overall survival was 15.3 and 29.6 months for patients who received 6-12 cycles and >12 cycles of adjuvant temozolomide, respectively. There were no significant differences in overall survival between age groups (60-64, 65-69, and > or = 70 years). Adjuvant temozolomide, Karnofsky performance status > or = 70, and additional surgery after progression were significant prognostic factors of longer overall survival (p<0.05). CONCLUSIONS: Radiochemotherapy, including > or = 6 cycles of adjuvant temozolomide, was safe and prolonged survival of glioblastoma patients aged > or = 60 years. Aggressive therapy should not be withheld from patients aged > or = 60 years with good performance status because of age.

Prostate-specific membrane antigen-based imaging for stereotactic irradiation of low-volume progressive prostate cancer: a single-center experience.

Introduction: Prostate-specific membrane antigen (PSMA) is a transmembrane protein that may be expressed on the surface of prostate cancer (PC) cells. It enables a more sensitive and specific diagnosis PC, compared to conventional anatomical imaging. Aim: The integration of PSMA-based imaging in the personalized radiotherapy of PC patients and the evaluation of its impact on target volume definition if stereotactic body radiotherapy (SBRT) is planned for locally recurrent or oligometastatic disease. Patients and methods: The data from 363 examinations were analyzed retrospectively. Inclusion criteria were histologically verified PC and clinical data suggesting local recurrence or distant metastasis. Whole-body 99mTc-PSMA-I&S single-photon emission computed tomography (SPECT)/CT or 18F-JK-PSMA-7 positron emission tomography/computer tomography (PET/CT) was carried out, and the evaluation of the scans and biological tumor volume contouring was performed at the Department of Nuclear Medicine. The target volume delineation on topometric CT (TCT) scan was performed at the Department of Oncotherapy. The comparison of the two volumes was performed by image fusion and registration. Results: From 363 PSMA isotope-based examinations, 84 lesions of 64 patients were treated with SBRT. In 50 patients, 70 lesions were examined for intermodality comparison. The target volume defined by the PSMA density was significantly smaller than the tumor size defined by the TCT scan: GTVCT (gross tumor volume on the TCT), 27.58 ± 46.07 cm3; BTVPSMA (biological target volume on the PSMA-based examination), 16.14 ± 29.87 cm3. During geometrical analyses, the Dice similarity coefficient (DSC) was 0.56 ± 0.20 (0.07-0.85). Prostate-specific antigen (PSA) control was performed to evaluate the response: mean pre-radiotherapy (pre-RT) PSA was 16.98 ng/ml ( ± SD: 33.81), and post-RT PSA at 3 months after SBRT was 11.19 ng/ml ( ± SD: 32.85). Three-month post-therapy PSMA-based imaging was performed in 14 cases, in which we observed a decrease or cessation of isotope uptake. Conventional imaging control was performed in 42 cases (65.6% of all cases): 22 (52.4%) complete remissions, 14 (33.3%) partial remissions, four (9.5%) stable diseases, and two (4.8%) progressive diseases were described. Conclusion: PSMA-based imaging is a promising diagnostic method for specifying the stage and detecting the low-volume progression. Our results suggest that PSMA-based hybrid imaging can influence treatment decisions and target volume delineation for SBRT.

Magnetic Resonance Imaging-Based Delineation of Organs at Risk in the Head and Neck Region.

Purpose: The aim of this article is to establish a comprehensive contouring guideline for treatment planning using only magnetic resonance images through an up-to-date set of organs at risk (OARs), recommended organ boundaries, and relevant suggestions for the magnetic resonance imaging (MRI)-based delineation of OARs in the head and neck (H&N) region. Methods and Materials: After a detailed review of the literature, MRI data were collected from the H&N region of healthy volunteers. OARs were delineated in the axial, coronal, and sagittal planes on T2-weighted sequences. Every contour defined was revised by 4 radiation oncologists and subsequently by 2 independent senior experts (H&N radiation oncologist and radiologist). After revision, the final structures were presented to the consortium partners. Results: A definitive consensus was reached after multi-institutional review. On that basis, we provided a detailed anatomic and functional description and specific MRI characteristics of the OARs. Conclusions: In the era of precision radiation therapy, the need for well-built, straightforward contouring guidelines is on the rise. Precise, uniform, delineation-based, automated OAR segmentation on MRI may lead to increased accuracy in terms of organ boundaries and analysis of dose-dependent sequelae for an adequate definition of normal tissue complication probability.

Comprehensive dose evaluation of a Deep Learning based synthetic Computed Tomography algorithm for pelvic Magnetic Resonance-only radiotherapy.

BACKGROUND AND PURPOSE: Magnetic Resonance (MR)-only radiotherapy enables the use of MR without the uncertainty of MR-Computed Tomography (CT) registration. This requires a synthetic CT (sCT) for dose calculations, which can be facilitated by a novel Zero Echo Time (ZTE) sequence where bones are visible and images are acquired in 65 seconds. This study evaluated the dose calculation accuracy for pelvic sites of a ZTE-based Deep Learning sCT algorithm developed by GE Healthcare. MATERIALS AND METHODS: ZTE and CT images were acquired in 56 pelvic radiotherapy patients in the radiotherapy position. A 2D U-net convolutional neural network was trained using pairs of deformably registered CT and ZTE images from 36 patients. In the remaining 20 patients the dosimetric accuracy of the sCT was assessed using cylindrical dummy Planning Target Volumes (PTVs) positioned at four different central axial locations, as well as the clinical treatment plans (for prostate (n = 10), rectum (n = 4) and anus (n = 6) cancers). The sCT was rigidly and deformably registered, the plan recalculated and the doses compared using mean differences and gamma analysis. RESULTS: Mean dose differences to the PTV D98% were ≤ 0.5% for all dummy PTVs and clinical plans (rigid registration). Mean gamma pass rates at 1%/1 mm were 98.0 ± 0.4% (rigid) and 100.0 ± 0.0% (deformable), 96.5 ± 0.8% and 99.8 ± 0.1%, and 95.4 ± 0.6% and 99.4 ± 0.4% for the clinical prostate, rectum and anus plans respectively. CONCLUSIONS: A ZTE-based sCT algorithm with high dose accuracy throughout the pelvis has been developed. This suggests the algorithm is sufficiently accurate for MR-only radiotherapy for all pelvic sites.

Predicting the true extent of glioblastoma based on probabilistic tractography.

Glioblastoma is the most frequent type of primary brain tumors. Despite the advanced therapy, most of the patients die within 2 years after the diagnosis. The tumor has a typical appearance on MRI: a central hypointensity surrounded by an inhomogeneous, ring-shaped contrast enhancement along its border. Too small to be recognized by MRI, detached individual tumor cells migrate along white matter fiber tracts several centimeters away from the edge of the tumor. Usually these cells are the source of tumor recurrence. If the infiltrated brain areas could be identified, longer survival time could be achieved through supratotal resection and individually planned radiation therapy. Probabilistic tractography is an advanced imaging method that can potentially be used to identify infiltrated pathways, thus the real extent of the glioblastoma. Our study consisted of twenty high grade glioma patients. Probabilistic tractography was started from the tumor. The location of tumor recurrence on follow-up MRI was considered as the primary infiltrated white matter tracts. The results of probabilistic tractography were evaluated at thirteen different thresholds. The overlap with the tumor recurrence of each threshold level was then defined to calculate the sensitivity and specificity. In the group level, sensitivity (81%) and specificity (90%) were the most reliable at 5% threshold level. There were two outliers in the study group, both with high specificity and very low sensitivity. According to our results, probabilistic tractography can help to define the true extent of the glioblastoma at the time of diagnosis with high sensitivity and specificity. Individually planned surgery and irradiation could provide a better chance of survival in these patients.

Application of Lacunarity for Quantification of Single Molecule Localization Microscopy Images.

The quantitative analysis of datasets achieved by single molecule localization microscopy is vital for studying the structure of subcellular organizations. Cluster analysis has emerged as a multi-faceted tool in the structural analysis of localization datasets. However, the results it produces greatly depend on the set parameters, and the process can be computationally intensive. Here we present a new approach for structural analysis using lacunarity. Unlike cluster analysis, lacunarity can be calculated quickly while providing definitive information about the structure of the localizations. Using simulated data, we demonstrate how lacunarity results can be interpreted. We use these interpretations to compare our lacunarity analysis with our previous cluster analysis-based results in the field of DNA repair, showing the new algorithm's efficiency.

Beam pulse structure and dose rate as determinants for the flash effect observed in zebrafish embryo.

BACKGROUND AND PURPOSE: Continuing recent experiments at the research electron accelerator ELBE at the Helmholtz-Zentrum Dresden-Rossendorf the influence of beam pulse structure on the Flash effect was investigated. MATERIALS AND METHODS: The proton beam pulse structure of an isochronous cyclotron (UHDRiso) and a synchrocyclotron (UHDRsynchro) was mimicked at ELBE by quasi-continuous electron bunches at 13 MHz delivering mean dose rates of 287 Gy/s and 177 Gy/s and bunch dose rates of 106Gy/s and 109 Gy/s, respectively. For UHDRsynchro, 40 ms macro pulses at a frequency of 25 Hz superimposed the bunch delivery. For comparison, a maximum beam intensity (2.5 × 105 Gy/s mean and ∼109 Gy/s bunch dose rate) and a reference irradiation (of ∼8 Gy/min mean dose rate) were applied. Radiation induced changes were assessed in zebrafish embryos over four days post irradiation. RESULTS: Relative to the reference a significant protecting Flash effect was observed for all electron beam pulse regimes with less severe damage the higher the mean dose rate of the electron beam. Accordingly, the macro pulsing induced prolongation of treatment time at UHDRsynchro regime reduces the protecting effect compared to the maximum regime delivered at same bunch but higher mean dose rate. The Flash effect of the UHDRiso regime was confirmed at a clinical isochronous cyclotron comparing the damage induced by proton beams delivered at 300 Gy/s and ∼9 Gy/min. CONCLUSION: The recent findings indicate that the mean dose rate or treatment time are decisive for the normal tissue protecting Flash effect in zebrafish embryo.

Clinical considerations of bleomycin based electrochemotherapy with variable electrode geometry electrodes for inoperable, deep-seated soft tissue sarcomas.

The aim of the current prospective pilot study exclusively for deep-seated soft tissue sarcomas (STS) was to evaluate efficacy and safety of bleomycin-based ECT using VEG (variable electrode geometry) electrodes. During a 2-year period, seven surgically inoperable STSs were treated at the University of Szeged, Department of Surgery in Hungary. Electrode placement was determined by software planning using preoperative imaging (CT/MRI) and intraoperative ultrasound. Intravenous bleomycin (15.000 IU/m2) was administered 8 min before first pulse generation which lasted up to 40 min. Tumour response was evaluated through CT/MRI 2 months after treatment as per RECIST v.1.1. Five male- and 2 female patients were treated with fibromyxoid sarcoma (n = 2), epitheloid sarcoma (n = 3), liposarcoma (n = 1) and myofibroblastic sarcoma (n = 1) with median age of 54 years (49-88). Median tumour diameter, tumour volume and tumour depth was 5.9 cm (3.7-22.5), 131.13 cm3 (35.6-2456.22) and 6.18 cm (3.74-18.18), respectively. Median operative time was 75 min (35-180), median hospital stay 2 days (2-20). Two month follow-up confirmed partial response in 5 patients, while stable disease in 1 patient, and progressive disease in 1 case as per RECIST v.1.1. Grade 2 ulceration was experienced in four cases, and a transient left musculus quadriceps femoris plegia occured in one patient. Local control of deep-seated STSs with BLM-based VEG ECT holds a promising perspective and our results may serve as a practical guide for further investigation and treatment planning.

ß-Endorphin mediates radiation therapy fatigue.

Fatigue is a common adverse effect of external beam radiation therapy in cancer patients. Mechanisms causing radiation fatigue remain unclear, although linkage to skin irradiation has been suggested. ß-Endorphin, an endogenous opioid, is synthesized in skin following genotoxic ultraviolet irradiation and acts systemically, producing addiction. Exogenous opiates with the same receptor activity as ß-endorphin can cause fatigue. Using rodent models of radiation therapy, exposing tails and sparing vital organs, we tested whether skin-derived ß-endorphin contributes to radiation-induced fatigue. Over a 6-week radiation regimen, plasma ß-endorphin increased in rats, paralleled by opiate phenotypes (elevated pain thresholds, Straub tail) and fatigue-like behavior, which was reversed in animals treated by the opiate antagonist naloxone. Mechanistically, all these phenotypes were blocked by opiate antagonist treatment and were undetected in either ß-endorphin knockout mice or mice lacking keratinocyte p53 expression. These findings implicate skin-derived ß-endorphin in systemic effects of radiation therapy. Opioid antagonism may warrant testing in humans as treatment or prevention of radiation-induced fatigue.

[The use of PET/CT in radiotherapy of patients with non-small cell lung cancer]. / PET/CT alkalmazása nem-kissejtes tüdodaganatos betegek sugárkezeléséhez.

The goal of this paper was to investigate the influence of FDG-PET/CT scan on the modification of staging and irradiation planning in patients suffering from non-small cell lung cancer (NSCLC). Fifteen patients suffering from NSCLC were analyzed by the authors from January, 2008 to July, 2009. The aim of the analysis was to examine the influence of FDG-PET/CT on irradiation planning and on decision-making of the complex oncologic therapy. The FDG-PET/CT scan was carried out in the position of irradiation performed later. For irradiation planning, planning target volumes (PTV) and the organs of risk were contoured on the patients' topometric CT slides as well as on the fused FDG-PET/CT slides. We evaluated how the application of PET/CT modified the stage of the illness, the complex oncologic therapeutic plan, the volume and the localization of the PTV, and the irradiation doses of the organs at risk. The mean and maximum dose of the spinal cord, the mean and V20 dose load of the lungs and the mean dose loads of the heart as well as of the left ventricle were measured. In 8 of 15 cases the stage of the disease and the treatment strategy was modified, since distant metastases were detected by the PET/CT. We evaluated the modification of the PTV and dose load of the organs at risk in 7 cases. According to the PET/CT the PTV was reduced in 5 cases (mean: 393.6 cm3) and was increased in 2 cases (mean: 250.8 cm3). Concerning the risk organs we found that the average (8.8 Gy/9.5 Gy) and maximum (33.4 Gy/36.4 Gy) dose load of the spinal cord increased, while the average (24.5 Gy/13.8 Gy) and V20 (33.7%/22.1%) dose load of the lungs decreased. We likewise found a decrease in the mean dose load of the heart (17.3 Gy/16.8 Gy) and left ventricle (12.9 Gy/9.6 Gy). In the majority of the cases the FDG-PET/CT scan modified the therapeutic decision, the size of the irradiated volume, and the dose load of the lung, the organ at risk causing the most difficulties at irradiation planning, was also reduced. The PET/CT scan plays an essential role in the complex oncologic treatment and irradiation therapy of NSCLC.

Comparison of Shear Wave Elastography and Dynamometer Test in Muscle Tissue Characterization for Potential Medical and Sport Application.

Skeletal muscle status and its dynamic follow up are of particular importance in the management of several diseases where weight and muscle mass loss and, consequently, immobilization occurs, as in cancer and its treatment, as well as in neurodegenerative disorders. But immobilization is not the direct result of body and muscle mass loss, but rather the loss of the maximal tension capabilities of the skeletal muscle. Therefore, the development of a non-invasive and real-time method which can measure muscle tension capabilities in immobile patients is highly anticipated. Our aim was to introduce and evaluate a special ultrasound measurement technique to estimate a maximal muscle tension characteristic which can be used in medicine and also in sports diagnostics. Therefore, we determined the relationship between the results of shear wave elastography measurements and the dynamometric data of individuals. The measurements were concluded on the m. vastus lateralis. Twelve healthy elite athletes took part in our preliminary proof of principle study-five endurance (S) and seven strength (F) athletes showing unambiguously different muscle composition features, nine healthy subjects (H) without prior sports background, and four cancer patients in treatment for a stage 3 brain tumor (T). Results showed a high correlation between the maximal dynamometric isometric torque (Mmax) and mean elasticity value (E) for the non-athletes [(H + T), (r = 0.795)] and for the athletes [(S + F), (r = 0.79)]. For the athletes (S + F), the rate of tension development at contraction (RTDk) and E correlation was also determined (r = 0.84, p < 0.05). Our measurements showed significantly greater E values for the strength athletes with fast muscle fiber dominance than endurance athletes with slow muscle fiber dominance (p < 0.05). Our findings suggest that shear wave ultrasound elastography is a promising method for estimating maximal muscle tension and, also, the human skeletal muscle fiber ratio. These results warrant further investigations with a larger number of individuals, both in medicine and in sports science.