Implications for driving based on the risk of seizures after ischaemic stroke.

BACKGROUND: In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. METHODS: We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs. RESULTS: Seizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0-6 points) had low COSY (0.7%-11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3-13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7-13 points) had the highest risk (14%-92%). CONCLUSIONS: Personalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

The AMP-Related Kinase (AMPK) Induces Ca2+-Independent Dilation of Resistance Arteries by Interfering With Actin Filament Formation.

RATIONALE: Decreasing Ca2+ sensitivity of vascular smooth muscle (VSM) allows for vasodilation without lowering of cytosolic Ca2+. This may be particularly important in states requiring maintained dilation, such as hypoxia. AMP-related kinase (AMPK) is an important cellular energy sensor in VSM. Regulation of Ca2+ sensitivity usually is attributed to myosin light chain phosphatase activity, but findings in non-VSM identified changes in the actin cytoskeleton. The potential role of AMPK in this setting is widely unknown. OBJECTIVE: To assess the influence of AMPK on the actin cytoskeleton in VSM of resistance arteries with regard to potential Ca2+ desensitization of VSM contractile apparatus. METHODS AND RESULTS: AMPK induced a slowly developing dilation at unchanged cytosolic Ca2+ levels in potassium chloride-constricted intact arteries isolated from mouse mesenteric tissue. This dilation was not associated with changes in phosphorylation of myosin light chain or of myosin light chain phosphatase regulatory subunit. Using ultracentrifugation and confocal microscopy, we found that AMPK induced depolymerization of F-actin (filamentous actin). Imaging of arteries from LifeAct mice showed F-actin rarefaction in the midcellular portion of VSM. Immunoblotting revealed that this was associated with activation of the actin severing factor cofilin. Coimmunoprecipitation experiments indicated that AMPK leads to the liberation of cofilin from 14-3-3 protein. CONCLUSIONS: AMPK induces actin depolymerization, which reduces vascular tone and the response to vasoconstrictors. Our findings demonstrate a new role of AMPK in the control of actin cytoskeletal dynamics, potentially allowing for long-term dilation of microvessels without substantial changes in cytosolic Ca2+.

NO Augments Endothelial Reactivity by Reducing Myoendothelial Calcium Signal Spreading: A Novel Role for Cx37 (Connexin 37) and the Protein Tyrosine Phosphatase SHP-2.

OBJECTIVE: Because of its strategic position between endothelial and smooth muscle cells in microvessels, Cx37 (Connexin 37) plays an important role in myoendothelial gap junctional intercellular communication. We have shown before that NO inhibits gap junctional intercellular communication through gap junctions containing Cx37. However, the underlying mechanism is not yet identified. APPROACH AND RESULTS: Using channel-forming Cx37 mutants exhibiting partial deletions or amino acid exchanges in their C-terminal loops, we now show that the phosphorylation state of a tyrosine residue at position 332 (Y332) in the C-terminus of Cx37 controls the gap junction-dependent spread of calcium signals. Mass spectra revealed that NO protects Cx37 from dephosphorylation at Y332 by inhibition of the protein tyrosine phosphatase SHP-2. Functionally, the inhibition of gap junctional intercellular communication by NO decreased the spread of the calcium signal (induced by mechanical stimulation of individual endothelial cells) from endothelial to smooth muscle cells in intact vessels, while, at the same time, augmenting the calcium signal spreading within the endothelium. Consequently, preincubation of small resistance arteries with exogenous NO enhanced the endothelium-dependent dilator response to acetylcholine in spite of a pharmacological blockade of NO-dependent cGMP formation by the soluable guanylyl cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one). CONCLUSIONS: Our results identify a novel mechanism by which NO can increase the efficacy of calcium, rising vasoactive agonists in the microvascular endothelium.

Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

Podosomes are dynamic cytoskeletal membrane structures with local adhesive and proteolytic activity. They are critically involved in angiogenesis and vascular adaptive growth. Here, we studied in HUVECs and murine small vessels whether shear stress controls podosome assembly and local proteolytic activity. Podosomes were characterized by immunohistochemistry, and their proteolytic activity was assessed as degradation imprints in fluorescent gelatin that was used as growth substrate. Compared with controls (10 dyn/cm(2)), the number of podosomes formed per time was doubled when cells were exposed to low shear stress (0.3 dyn/cm(2)) or even increased 5-fold under static conditions. This was a result of an enhanced expression of VEGF after reduction of shear stress. Consequently, enhanced podosome formation could be prevented by a VEGF receptor antagonist as well by interruption of VEGF signaling via inhibition of PI3K, Src, or p38. Increase of podosome assembly went along with significantly augmented cell motility. In vivo experiments in mouse arteries confirmed increased endothelial podosome numbers when shear stress was abolished by vessel occlusion. We conclude that shear stress, by reducing VEGF release, inhibits podosome assembly. Hence, endothelial cell-mediated matrix proteolysis and migratory activity are inhibited, thereby stabilizing the structure of the vessel wall.-Fey, T., Schubert, K. M., Schneider, H., Fein, E., Kleinert, E., Pohl, U., Dendorfer, A. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

Endothelial Dysfunction, and A Prothrombotic, Proinflammatory Phenotype Is Caused by Loss of Mitochondrial Thioredoxin Reductase in Endothelium.

OBJECTIVE: Although the investigation on the importance of mitochondria-derived reactive oxygen species (ROS) in endothelial function has been gaining momentum, little is known on the precise role of the individual components involved in the maintenance of a delicate ROS balance. Here we studied the impact of an ongoing dysregulated redox homeostasis by examining the effects of endothelial cell-specific deletion of murine thioredoxin reductase 2 (Txnrd2), a key enzyme of mitochondrial redox control. APPROACH AND RESULTS: We analyzed the impact of an inducible, endothelial cell-specific deletion of Txnrd2 on vascular remodeling in the adult mouse after femoral artery ligation. Laser Doppler analysis and histology revealed impaired angiogenesis and arteriogenesis. In addition, endothelial loss of Txnrd2 resulted in a prothrombotic, proinflammatory vascular phenotype, manifested as intravascular cellular deposits, as well as microthrombi. This phenotype was confirmed by an increased leukocyte response toward interleukin-1 in the mouse cremaster model. In vitro, we could confirm the attenuated angiogenesis measured in vivo, which was accompanied by increased ROS and an impaired mitochondrial membrane potential. Ex vivo analysis of femoral arteries revealed reduced flow-dependent vasodilation in endothelial cell Txnrd2-deficient mice. This endothelial dysfunction could be, at least partly, ascribed to inadequate nitric oxide signaling. CONCLUSIONS: We conclude that the maintenance of mitochondrial ROS via Txnrd2 in endothelial cells is necessary for an intact vascular homeostasis and remodeling and that Txnrd2 plays a vitally important role in balancing mitochondrial ROS production in the endothelium.

Intensity-modulated whole abdomen irradiation following adjuvant carboplatin/taxane chemotherapy for FIGO stage III ovarian cancer : four-year outcomes.

INTRODUCTION: A prospective study to assess toxicity and survival outcomes after intensity-modulated whole-abdominal irradiation (IM-WAI) following surgery and adjuvant intravenous carboplatin/taxane chemotherapy in advanced FIGO stage III ovarian cancer. PATIENTS AND METHODS: Between 2006 and 2009, 16 patients with optimally resected FIGO stage III ovarian cancer, who had received six cycles of adjuvant carboplatin/taxane chemotherapy were treated with consolidation IM-WAI. Radiotherapy was delivered to a total dose of 30 Gy in 1.5-Gy fractions, using step-and-shoot (n = 3) or helical tomotherapy (n = 13). The first 10 patients were treated within a phase I trial; the following patients received the same treatment modality. The target volume included the entire peritoneal cavity, the diaphragm, the liver capsule, and the pelvic and para-aortic node regions. Organs at risk were kidneys, liver, heart, and bone marrow. RESULTS: Median follow-up was 44 months (range 19.2-67.2 months). No grade 4 toxicities occurred during IM-WAI. Common Toxicity Criteria for Adverse Events (CTCAE) grade 3 toxicities were: diarrhea (25 %), leucopenia (19 %), nausea/vomiting (6 %), and thrombocytopenia (6 %). No toxicity-related treatment break was necessary. Small bowel obstruction occurred in a total of 6 patients: in 3 cases (19 %) due to postsurgical adhesions and in 3 cases due to local tumor recurrence (19 %). Median recurrence-free survival (RFS) was 27.6 months (95 % confidence interval, CI = 24-44 months) and median overall survival (OS) was 42.1 months (95 %CI = 17-68 months). The peritoneal cavity was the most frequent site of initial failure. CONCLUSION: Consolidation IM-WAI following surgery and adjuvant chemotherapy is feasible and can be performed with manageable acute and late toxicity. The favorable RFS outcome is promising and justifies further clinical trials.

Accelerated tomotherapy delivery with TomoEdge technique.

TomoEDGE is an advanced delivery form of tomotherapy which uses a dynamic secondary collimator. This plan comparison study describes the new features, their clinical applicability, and their effect on plan quality and treatment speed. For the first 45 patients worldwide that were scheduled for a treatment with TomoEdge, at least two plans were created: one with the previous "standard"mode with static jaws and 2.5 cm field width (Reg 2.5) and one with TomoEdge technique and 5 cm field width (Edge 5). If, after analysis in terms of beam on time, integral dose, dose conformity, and organ at risk sparing the treating physician decided that the Edge 5 plan was not suitable for clinical treatment, a plan with TomoEdge and 2.5 cm field width was created (Edge 2.5) and used for the treatment. Among the 45 cases, 30 were suitable for Edge 5 treatment, including treatments of the head and neck, rectal cancer, anal cancer, malignancies of the chest, breast cancer, and palliative treatments. In these cases, the use of a 5 cm field width reduced beam on time by more than 30% without compromising plan quality. The 5 cm beam could not be clinically applied to treatments of the pelvic lymph nodes for prostate cancer and to head and neck irradiations with extensive involvement of the skull, as dose to critical organs at risk such as bladder (average dose 28 Gy vs. 29 Gy, Reg 2.5 vs. Edge 5), small bowel (29% vs. 31%, Reg 2.5 vs. Edge 5) and brain (average dose partial brain 19 Gy vs. 21 Gy, Reg 2.5 vs. Edge 5) increased to a clinically relevant, yet not statistically significant, amount. TomoEdge is an advantageous extension of the tomotherapy technique that can speed up treatments and thus increase patient comfort and safety in the majority of clinical settings.

Lung and liver SBRT using helical tomotherapy--a dosimetric comparison of fixed jaw and dynamic jaw delivery.

The purpose of the study was to evaluate the time effectiveness and dose distribution details of dynamic jaw delivery compared to the regular helical tomotherapy delivery mode in stereotactic body radiation therapy (SBRT) of liver and lung tumors. Ten patients with liver and ten patients with lung tumors were chosen to analyze the dose profiles and treatment times of regular helical tomotherapy delivery (2.5cm field width) and new helical tomotherapy mode using dynamic jaw delivery with 5 cm field width. A median dose between 24 and 30 Gy was delivered in a single fraction. Regular helical tomotherapy took an average of 31.9 ± 6.7 min (lung SBRT) and 41.7 ± 15.0 min (liver SBRT). A reduction in delivery duration of 38.8% to 19.5± 2.9 min could be accomplished for lung irradiation (p < 0.05) and by 50.8% to 20.5 ± 6.0 min for liver SBRT (p < 0.05). Target coverage, as well as conformity and uniformity indices, showed no significant differences. No significant increase in organs-at-risk exposure could be detected either for lung or liver tumors. Therefore, use of new delivery mode with dynamic jaws improves treatment efficiency by reducing beam-on time, while maintaining excellent planquality.

[Neuromuscular Practical Knowledge: Focus On Muscle Weakness]. / Neuromuskuläres Praxiswissen: Fokus Muskelschwäche.

INTRODUCTION: Muscle weakness is a common symptom in the general practice. The diagnostic work-up starts with distinguishing true muscle weakness from fatigue. The localization, time course and severity of muscle weakness as well as associated symptoms, concomitant diseases, medication and family history can help classify the weakness into certain main categories. These are genetic, inflammatory, infectious, neoplastic, toxic and metabolic/endocrine causes. Further laboratory investigations, ENMG, MRI, muscle biopsy and genetic testing can help to further narrow the differential diagnosis. Due to recent advances, particularly in the field of genetics and targeted immunomodulatory therapies, a growing number of diseases which present with muscular weakness can be treated successfully.

Sleep spindle and slow wave activity in Parkinson disease with excessive daytime sleepiness.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a common and devastating symptom in Parkinson disease (PD), but surprisingly most studies showed that EDS is independent from nocturnal sleep disturbance measured with polysomnography. Quantitative electroencephalography (EEG) may reveal additional insights by measuring the EEG hallmarks of non-rapid eye movement (NREM) sleep, namely slow waves and spindles. Here, we tested the hypothesis that EDS in PD is associated with nocturnal sleep disturbance revealed by quantitative NREM sleep EEG markers. METHODS: Patients with PD (n = 130) underwent polysomnography followed by spectral analysis to calculate spindle frequency activity, slow-wave activity (SWA), and overnight SWA decline, which reflects the dissipation of homeostatic sleep pressure. We used the Epworth Sleepiness Scale (ESS) to assess subjective daytime sleepiness and define EDS (ESS > 10). All examinations were part of an evaluation for deep brain stimulation. RESULTS: Patients with EDS (n = 46) showed reduced overnight decline of SWA (p = 0.036) and reduced spindle frequency activity (p = 0.032) compared with patients without EDS. Likewise, more severe daytime sleepiness was associated with reduced SWA decline (ß= -0.24 p = 0.008) and reduced spindle frequency activity (ß= -0.42, p < 0.001) across all patients. Reduced SWA decline, but not daytime sleepiness, was associated with poor sleep quality and continuity at polysomnography. CONCLUSIONS: Our data suggest that daytime sleepiness in PD patients is associated with sleep disturbance revealed by quantitative EEG, namely reduced overnight SWA decline and reduced spindle frequency activity. These findings could indicate that poor sleep quality, with incomplete dissipation of homeostatic sleep pressure, may contribute to EDS in PD.

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model.

Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. Design, Setting, and Participants: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. Exposures: Type of acute symptomatic seizure. Main Outcomes and Measures: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). Results: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. Conclusions and Relevance: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

High-risk patients with locally advanced non-small cell lung cancer treated with stereotactic body radiation therapy to the peripheral primary combined with conventionally fractionated volumetric arc therapy to the mediastinal lymph nodes.

Introduction: A very narrow therapeutic window exists when delivering curative chemoradiotherapy for inoperable locally advanced non-small cell lung cancer (NSCLC), particularly when large distances exist between areas of gross disease in the thorax. In the present study, we hypothesize that a novel technique of stereotactic body radiation therapy (SBRT) to the primary tumor in combination with volumetric arc therapy (VMAT) to the mediastinal lymph nodes (MLN) is a suitable approach for high-risk patients with large volume geographically distant locally advanced NSCLC. Patients and methods: In this single institutional review, we identified high-risk patients treated between 2014 and 2017 with SBRT to the parenchymal lung primary as well as VMAT to the involved MLN using conventional fractionation. Dosimetrically, comparative plans utilizing VMAT conventionally fractionated delivered to both the primary and MLN were analyzed. Clinically, toxicity (CTCAE version 5.0) and oncologic outcomes were analyzed in detail. Results: A total of 21 patients were identified, 86% (n=18) of which received chemotherapy as a portion of their treatment. As treatment phase was between 2014 and 2017, none of the patients received consolidation immunotherapy. Target volume (PTV) dose coverage (99 vs. 87%) and CTV volume (307 vs. 441 ml) were significantly improved with SBRT+MLN vs. for VMAT alone (p<0.0001). Moreover, low-dose lung (median V5Gy [%]: 71 vs. 77, p<0.0001), heart (median V5Gy [%]: 41 vs. 49, p<0.0001) and esophagus (median V30Gy [%]: 54 vs. 55, p=0.03) dose exposure were all significantly reduced with SBRT+MLN. In contrast, there was no difference observed in high-dose exposure of lungs, heart, and spinal cord. Following SBRT+MLN treatment, we identified only one case of high-grade pneumonitis. As expected, we observed a higher rate of esophagitis with a total of seven patients experience grade 2+ toxicity. Overall, there were no grade 4+ toxicities identified. After a median 3 years follow up, disease progression was observed in 70% of patients irradiated using SBRT+MLN, but never in the spared 'bridging' tissue between pulmonary SBRT and mediastinal VMAT. Conclusion: For high risk patients, SBRT+MLN is dosimetrically feasible and can provide an alternative to dose reductions necessitated by otherwise very large target volumes.

CT-myelography for high-dose irradiation of spinal and paraspinal tumors with helical tomotherapy: revival of an old tool.

BACKGROUND AND PURPOSE: High-dose irradiation or reirradiation of spinal and paraspinal tumors is a challenge particularly in the presence of metal artifacts after surgery. Image-guided advanced intensity-modulated radiotherapy delivers high-dose radiation to the tumor sparing the spinal cord. Precise delineation of the spinal cord is necessary treating para- and intraspinal tumors with a sufficient dose. PATIENTS AND METHODS: The use of myelo-CT was evaluated in 23 patients with spinal and paraspinal tumors. All patients had had previous surgery with metal implants in the radiation area. All patients had an indication for high-dose irradiation. Treatment planning was performed using nonenhanced and contrast-enhanced myelo-CT in the same position and immobilization and both CT scans were matched. Treatment was performed by using a tomotherapy treatment unit. RESULTS: Contouring of the myelon in all slices of the myelo-CT was possible in 20 of 23 patients. All these patients were treated with doses of median 69.4 Gy in 2 Gy/1.8 Gy single doses using daily image guidance. One patient received an integrated boost with a TD/SD of 70/2.3 Gy. No side effects have been observed so far during a median follow-up of 15.5 months. No separation between tumor and myelon could be observed in 3 patients. CONCLUSION: Myelo-CT offers a distinct delineation of the myelon and the paraspinal tumor in case of artifacts due to metal implants after surgery. Using this tool in combination with advanced image guidance and IMRT techniques, patients with relatively radioresistent paraspinal tumors might have the chance of improved local control using higher target doses.

Impact of FAPI-PET/CT on Target Volume Definition in Radiation Therapy of Locally Recurrent Pancreatic Cancer.

(1) Background: A new radioactive positron emission tomography (PET) tracer uses inhibitors of fibroblast activation protein (FAPI) to visualize FAP-expressing cancer associated fibroblasts. Significant FAPI-uptake has recently been demonstrated in pancreatic cancer patients. Target volume delineation for radiation therapy still relies on often less precise conventional computed tomography (CT) imaging, especially in locally recurrent pancreatic cancer patients. The need for improvement in precise tumor detection and delineation led us to innovatively use the novel FAPI-PET/CT for radiation treatment planning. (2) Methods: Gross tumor volumes (GTVs) of seven locally recurrent pancreatic cancer cases were contoured by six radiation oncologists. In addition, FAPI-PET/CT was used to automatically delineate tumors. The interobserver variability in target definition was analyzed and FAPI-based automatic GTVs were compared to the manually defined GTVs. (3) Results: Target definition differed significantly between different radiation oncologists with mean dice similarity coefficients (DSCs) between 0.55 and 0.65. There was no significant difference between the volumes of automatic FAPI-GTVs based on the threshold of 2.0 and most of the manually contoured GTVs by radiation oncologists. (4) Conclusion: Due to its high tumor to background contrast, FAPI-PET/CT seems to be a superior imaging modality compared to the current gold standard contrast-enhanced CT in pancreatic cancer. For the first time, we demonstrate how FAPI-PET/CT could facilitate target definition and increases consistency in radiation oncology in pancreatic cancer.

The influence of different IMRT techniques on the peripheral dose: a comparison between sMLM-IMRT and helical tomotherapy.

PURPOSE: To investigate how segmented multileaf modulation-(sMLM-)based intensity-modulated radiotherapy (IMRT) and dynamic helical tomotherapy (ToTh) affect the peripheral dose (PD) outside the treated region. MATERIAL AND METHODS: A cuboid Perspex phantom was scanned in a computed tomograph. Different artificial cases were contoured consisting of OARs surrounded by cylindrically shaped planning target volumes (PTVs) with different dimensions. Radiotherapy plans were generated with the sMLM system Konrad (Siemens) and with the ToTh planning system. The plans were optimized in such a way that the dose-volume histograms showed comparable results. The sMLM plans were applied with a linac Primus (Siemens OCS), the ToTh plans with the HiArt system (TomoTherapy); both with 6 MV. Measurements of PDs were performed along the longitudinal axis of the phantom outside the primary beam at different distances from the edge of the PTV (horizontal PD) and also at different depths at a fixed distance from the isocenter (vertical PD). Additional experiments to separate the scatter dose caused by the phantom were performed. This was realized by removing the part of the phantom lying in the primary beam, then applying the same plans like before. RESULTS: All PD values were normalized to the median dose of the PTV. The PD values for the different PTVs decrease with decreasing PTV size. They also decrease with increasing distance from the isocenter. The horizontal values are in a range of 7% for the largest PTV (diameter = 15 cm) near the primary dose region to 0.2% for the smallest PTV (diameter = 5 cm) far from the primary dose region. The ToTh values are higher than the sMLM values by a maximal factor of 2 near the primary dose region. They become more similar with increasing distance from the edge of the PTV in longitudinal direction. The PD values are nearly equal at a distance of 25 cm from the edge of the PTV. The vertical PDs are higher for the ToTh at depths of > 1 cm but higher for sMLM close to the surface. By removing the scatter cube, the horizontal PD values at middle distances are reduced to one third of the PD values with scatter cube for ToTh (0.5%) and to one half for sMLM (0.8%). This means that without scatter cube the PD for ToTh is lower than that for sMLM. The measured PD values without scatter cube are in the same dimension as published data. CONCLUSION: The increasing PDs and their trend with increasing PTV size can be explained by Compton scattering of photons from the irradiated volume toward the off-axis measuring points. The further increase of the PD in case of ToTh relative to sMLM is not easy to explain. Different presumptions are possible. The larger field length (in longitudinal direction) of the ToTh plans (consisting of the "real" field length and the overlap) relative to the sMLM plans could be one reason for the higher PD values. The softer energy spectrum of the HiArt machine with more sideward Compton scattering contributions could be another reason.

Dosimetric comparison of image guidance by megavoltage computed tomography versus bone alignment for prostate cancer radiotherapy.

BACKGROUND AND PURPOSE: Daily image guidance in irradiation of prostate cancer can be based on simple portal images or on soft-tissue imaging. This study compares daily bone alignment with daily pretreatment megavoltage computed tomography (MVCT). PATIENTS AND METHODS: Ten patients with a total of 356 fractions were analyzed. Before each fraction, the patient was positioned to match the prostate on pretreatment MVCT and planning CT. In seven fractions, rectum distension prevented a satisfactory match and the fraction was restarted after the patient went to the restroom. After treatment, organs were manually contoured on each daily MVCT and doses recalculated. Bone alignment was simulated by a software that matches the bones on MVCT and planning CT. RESULTS: In the seven interrupted fractions, median improvement of rectum volume receiving full fraction dose was 14 cm(3) between simulated treatment before and actual treatment after the patient went to the restroom. In the 349 noninterrupted fractions, the average difference of the isodose that covers 95% of the prostate between actual treatment position and simulated bone match position was < 1% and there was no significant change in the rectum volume with a fraction dose > or = 2 Gy. CONCLUSION: Full fraction dose rectum irradiation can be avoided with daily MVCT by interruption of single fractions. There was no relevant benefit of daily MVCT in the noninterrupted fractions with the margins used in this study.

Reirradiation of multiple brain metastases with helical tomotherapy. A multifocal simultaneous integrated boost for eight or more lesions.

BACKGROUND AND PURPOSE: : Recurrent brain metastases or new brain lesions after whole-brain radiotherapy represent a therapeutic challenge. While several treatment methods for single or few lesions have been described, options for multiple lesions are limited. This case report is intended to show an approach of whole-brain reirradiation with a simultaneous multifocal integrated boost using helical tomotherapy. Technique, feasibility, and acute side effects are presented. PATIENTS AND METHODS: : Two patients with multiple relapsed brain metastases (eight and eleven lesions) were reirradiated after previous whole-brain radiotherapy (total dose of 40 Gy 18 months before). Whole-brain reirradiation was performed using helical tomotherapy with a total dose of 15 Gy (single dose 1.5 Gy) and a multifocal simultaneous integrated boost with a total dose of 30 Gy (single dose 3 Gy) to the brain lesions. The boost planning target volume was delineated around the lesions visible on MRI plus a 2-mm margin. Follow-up of these patients was 6 and 12 months. RESULTS: : Radiation plans with excellent conformity and homogeneity were obtained. High dose exposure to normal brain tissue was kept minimal. Mean radiation time was 13 min. The only acute side effect observed was a mild headache over 2 days at the end of treatment. So far, no further side effects and no signs of recurrence have been observed. CONCLUSION: : Helical tomotherapy offers new treatment options for the reirradiation of multiple brain metastases. The number of cases treated with the described protocol is very limited but it is considered a promising option for patients that have responded well to the initial radiotherapy and are in a good performance status.

Surface dose in the treatment of breast cancer with helical tomotherapy.

PURPOSE: Investigation of the effects of breathing motion- and misregistration-induced errors on the superficial dose in the treatment of breast cancer using helical tomotherapy (HT). MATERIAL AND METHODS: Surface dose measurements were performed with thermoluminescence dosimetry (TLD). Two treatment plans with different planning target volume (PTV) definitions of the left breast were used: PTVskin had its ventral border exactly on skin level, while PTVair included also a 10-mm extension ventral to the PTVskin. With a thoracic static phantom, misregistration errors in an HT were simulated. A dynamic phantom was used to simulate a breathing patient during HT. Surface doses of breast cancer patients were measured both for an HT (179 points) and a conventional three-dimensional conformal treatment (70 points). RESULTS: In the static phantom misregistration setup, dose deviations of -31.9% for PTVskin to +35.4% for PTVair could be observed. The dynamic phantom measurements resulted in surface dose deviations from those in a static position between 0.8% and 3.8% without a significant difference for the PTV definitions. The measured surface doses on patients averaged (mean +/- standard deviation) 1.65 +/- 0.13 Gy for the HT and 1.42 +/- 0.11 Gy for the three-dimensional conformal treatment. CONCLUSION: HT enables a homogeneous and reproducible surface dose with small dose deviations in the treatment of breast cancer. HT is a feasible method to treat breast cancer under free shallow breathing of the patient using a treatment plan with a ventral PTV border on the skin level.

Comparison of arc-modulated cone beam therapy and helical tomotherapy for three different types of cancer.

PURPOSE: Arc-modulated cone beam therapy (AMCBT) is a fast treatment technique deliverable in a single rotation with a conventional C-arm shaped linac. In this planning study, the authors assess the dosimetric properties of single-arc therapy in comparison to helical tomotherapy for three different tumor types. METHODS: Treatment plans for three patients with prostate carcinoma, three patients with anal cancer, and three patients with head and neck cancer were optimized for helical tomotherapy and AMCBT. The dosimetric comparison of the two techniques is based on physical quantities derived from dose-volume histograms. RESULTS: For prostate cancer, the quality of dose distributions calculated for AMCBT was of equal quality as that generated for tomotherapy with the additional benefits of a faster delivery and a lower integral dose. For highly complex geometries, the plan quality achievable with helical tomotherapy could not be achieved with arc-modulated cone beam therapy. CONCLUSIONS: Rotation therapy with a conventional linac in a single arc is capable to deliver a high and homogeneous dose to the target and spare organs at risk. Advantages of this technique are a fast treatment time and a lower integral dose in comparison to helical tomotherapy. For highly complex cases, e.g., with several target regions, the dose shaping capabilities of AMCBT are inferior to those of tomotherapy. However, treatment plans for AMCBT were also clinically acceptable.