Analysis of X-ray irradiation effects on the mortality values and hemolymph immune cell composition of Apis mellifera and its parasite, Varroa destructor.

Varroa destructor is one of the most destructive enemies of the honey bee, Apis mellifera all around the world. Several control methods are known to control V. destructor, but the efficacy of several alternative control methods remains unexplored. Irradiation can be one of these unknown solutions but before practical application, the effectiveness, and the physiological effects of ionizing radiation on the host and the parasite are waiting to be tested. Therefore, the objective of our study was to investigate the effects of different doses (15, 50, 100, and 150 Gy) of high-energy X-ray irradiation through mortality rates and hemocyte composition changes in A. mellifera workers and record the mortality rates of the parasite. The mortality rate was recorded during short-term (12, 24, and 48 h) and long-term periods (3, 6, 12, 18, and 24d). The sensitivity of the host and the parasite in case of the higher doses of radiation tested (50, 100, and 150 Gy) been demonstrated by total mortality of the host and 90 % of its parasite has been observed on the 18th day after the irradiation. V. destructor showed higher sensitivity (1.52-times higher than the adult honey bee workers) at the lowest dose (15 Gy). A. mellifera hemocytes were influenced significantly by radiation dosage and the elapsed time after treatment. The higher radiation doses increased plasmatocyte numbers in parallel with the decrease in prohemocyte numbers. On the contrary, the numbers of granulocytes and oencoytes increased in the treated samples, but the putative effects of the different dosages on the recorded number of these hemocyte types could not be statistically proven. In summary, based on the outcome of our study X-ray irradiation can be deemed an effective tool for controlling phoretic V. destructor. However, further research is needed to understand the physiological response of the affected organisms.

Pancreatic SABR using peritumoral fiducials, triggered imaging and breath-hold.

Background: We aim to present our linear accelerator-based workflow for pancreatic stereotactic ablative radiotherapy (SABR) in order to address the following issues: intrafractional organ motion management, Cone Beam CT (CBCT) image quality, residual errors with dosimetric consequences, treatment time, and clinical results. Methods: Between 2016 and 2021, 14 patients with locally advanced pancreatic cancer were treated with induction chemotherapy and SABR using volumetric modulated arc therapy (VMAT). Internal target volume (ITV) concept (5), phase-gated (4), or breath hold (5) techniques were used. Treatment was verified by CBCT before and after irradiation, while tumor motion was monitored and controlled by kV triggered imaging and beam hold using peritumoral surgical clips. Beam interruptions and treatment time were recorded. The CBCT image quality was scored and supplemented by an agreement analysis (Krippendorff's-α) of breath-hold CBCT images to determine the position of OARs relative to the planning risk volumes (PRV). Residual errors and their dosimetry impact were also calculated. Progression free (PFS) and overall survival (OS) were assessed by the Kaplan-Meier analysis with acute and late toxicity reporting (CTCAEv4). Results: On average, beams were interrupted once (range: 0-3) per treatment session on triggered imaging. The total median treatment time was 16.7 ± 10.8 min, significantly less for breath-hold vs. phase-gated sessions (18.8 ± 6.2 vs. 26.5 ± 13.4, p < 0.001). The best image quality was achieved by breath hold CBCT. The Krippendorff's-α test showed a strong agreement among five radiation therapists (mean K-α value: 0.8 (97.5%). The mean residual errors were <0.2 cm in each direction resulting in an average difference of <2% in dosimetry for OAR and target volume. Two patients received offline adaptation. The median OS/PFS after induction chemotherapy and SABR was 20/12 months and 15/8 months. No Gr. ≥2 acute/late RT-related toxicity was noted. Conclusion: Linear accelerator based pancreatic SABR with the combination of CBCT and triggered imaging + beam hold is feasible. Peritumoral fiducials improve utility while breath-hold CBCT provides the best image quality at a reasonable treatment time with offline adaptation possibilities. In well-selected cases, it can be an effective alternative in clinics where CBCT/MRI-guided online adaptive workflow is not available.

[Linac-based stereotactic ablative radiotherapy for pancreatic cancer with intrafractional triggered imaging]. / Hasnyálmirigyrák lineáris gyorsító alapú sztereotaxiás sugárterápiája kezelés alatti tumorkövetéssel.

Our aim was to present different treatment strategies (non-gated [NG], respiratory-gated [RG] and deep inspiration breath-hold [DIBH] technique) of linac-based stereotaxic ablative radiotherapy (SABR) for pancreatic cancer in terms of use of marker, abdominal compression, image quality, and time efficiency. From October 2016 to October 2020 14 patients were treated with VMAT-based SABR (NG: 6/14, 8/14 RG RT including 3/8 DIBH SABR). Treatment verification consisted of 3D/4D CBCTs. For intrafractional tumor visualization (11/14) different type of fiducials were used. The average treatment time was the shortest with NG RT, followed by DIBH and RG RT. However, the best image quality was achieved with DIBH technique. The Krippendorff's agreement test among three independent RTTs showed that DIBH CBCT (Cone Beam CT) can produce sufficient image quality for OARs and can be used to reliably determine OARs position related to safety zone (PRV). Overall, marker-based DIBH SABR with intrafractional tumor visualization appears to be the best technique on linac at present.

Triggered Imaging With Auto Beam Hold and Pre-/Posttreatment CBCT During Prostate SABR: Analysis of Time Efficiency, Target Coverage, and Normal Volume Changes.

PURPOSE: Our purpose was to investigate time efficiency and target coverage for prostate stereotactic ablative radiation therapy (SABR) using triggered imaging (TI) and auto beam hold. METHODS AND MATERIALS: A total of 20 patients were treated with volumetric modulated arc-based SABR. Treatment verification consisted of pre- and post-radiation therapy cone beam computed tomography (CBCT) with gold marker-based TI every 3 seconds. In case of ≥3 mm (deviation limit) displacement, the treatment was interrupted and imaging-based correction was performed. Beam interruptions, intrafractional shifts, and treatment times were recorded. Prostate, rectum, and bladder were delineated on each CBCT. Target coverage was evaluated by comparing the individual prostate delineations with 98% isodose contour volumes (% of the evaluated volumes exceeding the reference). Both inter- and intrafractional changes of bladder and rectal volumes were assessed. RESULTS: The average overall treatment time (±standard deviation) was 18 ± 11 min, with a radiation delivery time of 6 ± 3 min if no intrafractional CBCT acquisitions were necessary (91% of fractions). On average, 1.2 beam interruptions per fraction were required with 0/1 correction in 71% of the fractions. The mean residual 3-dimensional shift was 1.6 mm, exceeding the deviation limit in 8%. In the case of intrafractional CBCT and/or ≥2 corrections the treatment time dramatically increased. The 98% isodose lines did not encompass the prostate in only 8/180 (4%) evaluations in 6 different patients, leading to a loss of D98 between 0.1%-6% as a worst case scenario. The bladder volumes showed significant increases during treatment (P < .01) while rectal volumes were stable. CONCLUSIONS: Time efficiency of TI + auto beam hold with 3 mm/3 sec threshold during prostate SABR is comparable with competitive techniques, resulting in minimal 3-dimensional residual errors with maintained target coverage. Technical developments are necessary to further reduce radiation delivery time. Use of CBCT allowed full control of rectal volumes, while bladder volumes showed significant increases over time.

OAR sparing 3D radiotherapy planning supported by fMRI brain mapping investigations.

The human brain as an organ has numerous functions; some of them can be visualized by functional imaging techniques (e.g., functional MRI [fMRI] or positron emission tomography). The localization of the appropriate activity clusters requires sophisticated instrumentation and complex measuring protocol. As the inclusion of the activation pattern in modern self-tailored 3D based radiotherapy has notable advantages, this method is applied frequently. Unfortunately, no standardized method has been published yet for the integration of the fMRI data into the planning process and the detailed description of the individual applications is usually missing. Thirteen patients with brain tumors, receiving fMRI based RT planning were enrolled in this study. The delivered dose maps were exported from the treatment planning system and processed for further statistical analysis. Two parameters were introduced to measure the geometrical distance Hausdorff Distance (HD), and volumetric overlap Dice Similarity Coefficient (DSC) of fMRI corrected and not corrected dose matrices as calculated by 3D planning to characterize similarity and/or dissimilarity of these dose matrices. Statistical analysis of bootstrapped HD and DSC data was performed to determine confidence intervals of these parameters. The calculated confidence intervals for HD and DSC were (5.04, 7.09), (0.79, 0.86), respectively for the 40 Gy and (5.2, 7.85), (0.74, 0.83), respectively for the 60 Gy dose volumes. These data indicate that in the case of HD < 5.04 and/or DSC > 0.86, the 40 Gy dose volumes obtained with and without fMRI activation pattern do not show a significant difference (5% significance level). The same conditions for the 60 Gy dose volumes were HD < 5.2 and/or DSC > 0.83. At the same time, with HD > 7.09 and/or DSC < 0.79 for 40 Gy and HD > 7.85 and/or DSC < 0.74 for 60 Gy the impact of fMRI utilization in RT planning is excessive. The fMRI activation clusters can be used in daily RT planning routine to spare activation clusters as critical areas in the brain and avoid their high dose irradiation. Parameters HD (as distance) and DSC (as overlap) can be used to characterize the difference and similarity between the radiotherapy planning target volumes and indicate whether the fMRI delivered activation patterns and consequent fMRI corrected planning volumes are reliable or not.

[Multimodal imaging during lung and abdominal stereotactic ablative radiotherapy: from cine MRI through 3D/4D CBCT to intrafractional kV verification]. / Multimodális képalkotás tüdõ- és hasi sztereotaxiás ablatív radioterápia során: a cine MRI-mérésektõl a 3D/4D CBCT-n át a kezelés alatti kV-os képi verifikációig.

Our aim was to present our treatment and verification protocols of linear accelerator-based lung and abdominal stereotactic ablative radiotherapy (SABR). During our treatments both the volumetric imaging (3D/4D CBCT/CT) and triggered kV intrafractional tumor motion control could be combined allowing a full control on the whole workflow. The most optimal kV directions from which the tumor is well detectable were defined. Tumor movements measured on cine MRI in treatment position correlated well with the ones on 4D CBCT, thus cine MRI is considered an excellent device to pre-select the appropriate image/treatment verification SABR protocol. In abdominal targets implanted markers and cine MRI are preferred due to limited image quality of CBCT with the current version. In selected lung SABR cases (≥8mm motion) the dose delivery of organs at risk (lungs - GTV, chest wall) could be reduced compared to free breathing conditions, however, the treatment time is at least two-folds higher.

Changes in functional MRI signals after 3D based radiotherapy of glioblastoma multiforme.

The purpose of our study was to examine the potential effects of conventional 3D based radiotherapy on functional MRI activation areas following the treatment of glioblastoma multiforme. Seventeen patients with a histologically proven glioblastoma multiforme were enrolled in this study. A functional MRI examination was performed alongside the planning CT and conventional MRI prior to the delivery of conventional 3D based radiotherapy. All patients received 3D based postoperative radiotherapy (up to 60 Gy) combined with temozolomide. Follow-up fMRI examinations were performed after completion of the treatment in the 6th week and in 3 months time. Changes of the task related activation areas were registered and analyzed. The difference in changes of high dose and low dose areas of the brain were also registered and analyzed. The comparison of the pretreatment and 6th week control fMRI activation areas revealed significant changes in motor activation and listening tasks in the case of brain areas which received a high dose (over 40 Gy). Based on the population level statistical parametric images (motor activation tasks) acquired at the 6th week control examination, a significant increase of signal was registered in the precuneus region and in the globus pallidus region. When comparing the 6th week and 3rd month activation signals, no significant changes were registered. Our results demonstrate the influence of radiotherapy on functional MRI signals within the human brain. Based on our findings, functional activation transfers from high dose areas to low dose areas. In case of the motor activation tasks, activations of the secondary motor area were observed following radiotherapy.

Integrating functional MRI information into conventional 3D radiotherapy planning of CNS tumors. Is it worth it?

The purpose of our study was to examine the potential benefits of integrating functional MRI (fMRI) information into the 3D-based planning process for central nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2009, ten patients with astrocytoma (both low and high-grade histological type) were enrolled in this study. Before the planning process, conventional CT planning, postoperative MR, and individual functional MRI examinations were conducted. For the functional MRI examination four types of conventional stimuli were applied: acoustic, visual, somatosensory, and numeric. To examine the potential benefits of using fMRI-based information, three different types of theoretical planning were applied and compared: 3D conformal plan without fMRI information, 3D conformal plan with fMRI information, and IMRT plan with fMRI information. DVH analysis and the NTCP model were used for plan comparison. When comparing planning methods, distance-related subgroups were generated and studied. By using the additional fMRI information, a significantly higher sparing effect can be achieved on these ORs (both with conventional 3D-based planning and IMRT). In cases when the OR-PTV distance is less than 1 cm, IMRT seems to be a significantly better choice than conventional 3D-based techniques. IMRT also has an additional sparing effect on the optic tract and brainstem, especially for locations close to the midline. Our results demonstrated that using fMRI information in conventional 3D-based treatment planning has the potential benefit of significant dose reduction for the critical organs, with no compromise in PTV coverage even when using conventional 3D planning. fMRI can be widely used in low-grade cases (long life expectancy, lower acute and late toxicity) and also in cases with high-grade astrocytomas or distant metastases (higher dose to PTV with better sparing of risk organs). In cases when the OR-PTV distance is less than 1 cm, IMRT should be the choice of treatment for a higher sparing effect on functional active areas. Longer imaging and clinical follow up are needed to confirm the real sparing effect on these functional areas.

Integrating functional MRI information into radiotherapy planning of CNS tumors-early experiences.

The purpose of our study was to examine the integration of functional MRI (fMRI) information into 3D based planning process of the central nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2008 four patients with astrocytoma were enrolled to this study. Before the planning process conventional planning CT, postoperative MR and individual functional MRI examinations were delivered. For the functional MRI examination the following four types of stimulus were applied: acoustic, visual, somatosensory and numeral. Three different theoretical planning situations were applied and compared: 3D conformal plan without fMRI information, 3D conformal plan with fMRI information and IMRT plan with fMRI information. For plan comparison DVH analysis, and NTCP model were used. fMRI based OR definition resulted in 4 additional OR's in the contouring process. As these cases demonstrate, an average of 50% dose reduction was achieved in OR, OR2 and OR3 with IMRT and fMRI based 3D planning, especially in case of midline localization and big tumor extent. IMRT provides additional sparing effect in the optic tract and brainstem, especially for localizations close to the midline. Our results demonstrated that using fMRI information in conventional 3D based treatment planning potentially benefits significant dose reduction in critical organs, with no compromise in PTV coverage. fMRI can be widely used even in low grade cases (long life expectancies, lower acute and late toxicity in radiotherapy) and in cases with high grade astrocytomas or metastases (higher dose to PTV with better risk organ sparing in radiotherapy).

3-D conformal photon boost in the treatment of early stage breast cancer: four year follow up results.

In the treatment of early stage breast cancer, breast conserving surgery (BCS) followed by whole breast irradiation (WBI) is the standard treatment. The impact of the tumor bed boost following WBI is well-defined, but there are various delivery methods. In this study we demonstrate our 4 year experience with the 3-D conformal boost technique. Between January 2004 and June 2005, 77 early stage (Stage I-II) breast cancer patients were treated in our institute with whole breast irradiation (WBI, 50.4 Gy in 28 fractions) after breast conserving surgery. Following WBI, 3-D conformal photon boost was delivered (10-16 Gy in five to eight fractions) for all patients. The clinical outcome was retrospectively recorded in terms of survival and local control. The side effect profile (fibrosis, fat necrosis and cosmetic outcome) was also recorded and studied. In our patient group the mean follow up time was 46.8 months (median: 52, range: 17-71, SD: 14.4) The 4-year probability of local tumor control was 96% (crude rate: 74/77-96.1%), the 4-year probability of overall survival was 96% (crude rate: 74/77-96.1%) in this patient group. In case of the distant metastasis free survival the probability was 89, 5% (crude rate: 70/77-90, 1%). Probability of disease specific survival was 98% (crude rate: 76/77-98. 7%). Local relapse occurred in three cases (3.9%). In ten cases (12.9%) asymptomatic grade I-II breast fibrosis, in eight cases (10.4%) asymptomatic breast fat necrosis were registered. For 14 patients (18.2%) asymptomatic lung fibrosis was recorded on the control CT scans. In term of the relapse free survival, the close resection margin and the nodal positivity resulted in significant difference in favor of the clear resection margin group and the node negative group. In this study the 3-D conformal photon boost resulted in good local control and side effect profile. The presence of tumor bed clips resulted in significantly lower boost PTV volumes, but no correlation was found between the irradiated boost volume and the breast fibrosis. In the relapse free survival analysis, nodal negativity and clear margin status resulted in significantly better RFS.

Comparison of photon with electron boost in treatment of early stage breast cancer.

In the treatment of early stage breast cancer breast conserving surgery (BCS) followed by whole breast irradiation (WBI) is a standard method. The impact of the tumor bed boost following WBI is well-defined, but there are various delivery methods. In this study the electron and the photon boost techniques were compared. For 78 early stage breast cancer patients both CT based 3D conformal photon boost and electron boost plans were created. For dosimetric comparison coverage index (CI), external volume index (EI) and conformality index (COIN) were studied. Lung volume receiving a dose of 2 Gy was also reviewed. Seventy-eight patients with 156 plans were compared. The mean tumor bed volume was measured as 61.39 cm3 the mean tumor bed-skin distance was 3.13 cm. In the case of CI and COIN significant differences were found in favor of the photon boost. In the comparison of EI no significant difference was detected between the two techniques. The mean lung volume receiving 2 Gy were 42.3 and 168.35 cm3, for photons and electrons respectively. In the adjuvant treatment of early stage breast cancer WBI followed by conformal photon boost showed to be superior to electron boost in focus of the COIN and CI.

[Radiotherapy of MALT-lymphoma of the stomach]. / A gyomor MALT-lymphomák sugárkezelése.

INTRODUCTION: The stomach is the most common extranodal site of the low-grade MALT lymphoma. This lymphoma usually appears in elderly patients, with typically indolent signs. At the time of the diagnosis, the lymphoma is usually localized in the stomach and/or the adjacent lymph nodes. The choice in these cases is local treatment, which in the past involved only a surgical approach (total/partial gastrectomy), whereas more recently radiotherapy is preferred. PURPOSE: The radiation fields cover the whole stomach and the paragastric lymph nodes. The radiation doses range from 30 to 40 Gy, given in 1.5 Gy fractions 5 days a week. An adequate dose distribution to the target volume can be achieved by 3D treatment planning and conformal irradiation. METHODS: At our institute, 5 patients were treated with this method, the intention was curative in 3 cases, and palliative in 2 cases. The median dose in the 4 cases completed as initially planned was 33.6 Gy, delivered at 1.5 Gy per fraction. The adjacent critical organs do not exceed the tolerance doses by this method. RESULTS: In these 4 cases, complete regression was achieved, as determined by endoscopy and biopsy. In the fifth, locally advanced case, irradiation had to be terminated because of gastric bleeding. During irradiation, no other severe acute side-effects were detected. CONCLUSION: The literature and our preliminary results confirm that radiation therapy for early, localized MALT lymphoma of the stomach, or in disseminated cases, can be not only effective and safe, but offers the significant advantages of low treatment-related morbidity and preservation of the gastric function.