Dosimetric Comparison Between Helical Tomotherapy and Volumetric Modulated Arc Therapy in Patients With Malignant Pleural Mesothelioma.

AIMS: To carry out a dosimetric comparison and constraints feasibility proof of adjuvant radiotherapy through helical tomotherapy or volumetric modulated arc therapy (VMAT) for malignant pleural mesothelioma patients after pleurectomy/decortication. MATERIALS AND METHODS: Retrospective calculations were carried out on previously acquired simulations. A whole-pleura volume with 50.4 Gy in 28 fractions was prescribed, simulating a no residual tumour situation. Calculations were carried out using an anisotropic analytical algorithm with a 2.0 mm grid. Beam-on time, planning target volume (PTV) coverage, homogeneity index and organ at risk exposure were compared. RESULTS: Sixteen patient plans were calculated per device. Constraints were met overall by both modalities. For helical tomotherapy and VMAT plans, median beam-on times were 13.8 (11.6-16.1) min and 6.4 (6.1-7.0) min; P = 0.006. The median left-sided radiotherapy PTV D98 were 48.1 (48.0-48.8) Gy and 47.6 (46.5-48.3) Gy; P = 0.023. No significant difference for right-sided radiotherapy was found. PTV D2 for left-sided radiotherapy was higher with VMAT (P = 0.014). For right-sided radiotherapy, helical tomotherapy showed higher doses (P = 0.039). No homogeneity index differences for left-sided radiotherapy (P = 1.00) and right-sided radiotherapy (P = 0.598) were seen. Significant organ at risk exposure differences were found on left-sided radiotherapy whole-lung V20, as well as D50 (both P = 0.008). Higher contralateral lung and ipsilateral kidney exposures were found with VMAT plans for both treatment sides. CONCLUSION: Adjuvant radiotherapy after pleurectomy/decortication in malignant pleural mesothelioma patients, with a VMAT- or helical tomotherapy-based platform, is dosimetrically feasible. Lung sparing was mostly improved with helical tomotherapy. Technique selection must be carried out according to availability and clinical criteria.

[Multimodal document management in radiotherapy]. / Multimodales Dokumentenmanagement in der Strahlentherapie.

BACKGROUND AND PURPOSE: After incorporating treatment planning and the organisational model of treatment planning in the operating schedule system (BAS, "Betriebsablaufsystem"), complete document qualities were embedded in the digital environment. The aim of this project was to integrate all documents independent of their source (paper-bound or digital) and to make content from the BAS available in a structured manner. As many workflow steps as possible should be automated, e.g. assigning a document to a patient in the BAS. Additionally it must be guaranteed that at all times it could be traced who, when, how and from which source documents were imported into the departmental system. Furthermore work procedures should be changed that the documentation conducted either directly in the departmental system or from external systems can be incorporated digitally and paper document can be completely avoided (e.g. documents such as treatment certificate, treatment plans or documentation). It was a further aim, if possible, to automate the removal of paper documents from the departmental work flow, or even to make such paper documents superfluous. In this way patient letters for follow-up appointments should automatically generated from the BAS. Similarly patient record extracts in the form of PDF files should be enabled, e.g. for controlling purposes. METHOD: The available document qualities were analysed in detail by a multidisciplinary working group (BAS-AG) and after this examination and assessment of the possibility of modelling in our departmental workflow (BAS) they were transcribed into a flow diagram. The gathered specifications were implemented in a test environment by the clinical and administrative IT group of the department of radiation oncology and subsequent to a detailed analysis introduced into clinical routine. RESULTS: The department has succeeded under the conditions of the aforementioned criteria to embed all relevant documents in the departmental workflow via continuous processes. Since the completion of the concepts and the implementation in our test environment 15,000 documents were introduced into the departmental workflow following routine approval. Furthermore approximately 5000 appointment letters for patient aftercare per year were automatically generated by the BAS. In addition patient record extracts in the form of PDF files for the medical services of the healthcare insurer can be generated.

[Integration of the radiotherapy irradiation planning in the digital workflow]. / Integration der Bestrahlungsplanung in den volldigitalen Workflow.

BACKGROUND AND PURPOSE: At the Clinic of Radiotherapy at the University Hospital Freiburg, all relevant workflow is paperless. After implementing the Operating Schedule System (OSS) as a framework, all processes are being implemented into the departmental system MOSAIQ. Designing a digital workflow for radiotherapy irradiation planning is a large challenge, it requires interdisciplinary expertise and therefore the interfaces between the professions also have to be interdisciplinary. For every single step of radiotherapy irradiation planning, distinct responsibilities have to be defined and documented. All aspects of digital storage, backup and long-term availability of data were considered and have already been realized during the OSS project. METHOD: After an analysis of the complete workflow and the statutory requirements, a detailed project plan was designed. In an interdisciplinary workgroup, problems were discussed and a detailed flowchart was developed. The new functionalities were implemented in a testing environment by the Clinical and Administrative IT Department (CAI). After extensive tests they were integrated into the new modular department system. RESULTS AND CONCLUSION: The Clinic of Radiotherapy succeeded in realizing a completely digital workflow for radiotherapy irradiation planning. During the testing phase, our digital workflow was examined and afterwards was approved by the responsible authority.

[Current requirements for image management in radiotherapy]. / Aktuelle Anforderungen an das Bildmanagement in der Strahlentherapie.

AIMS AND METHODS: Treatment techniques of increasing complexity such as dynamic/rotational techniques mandate digital management and increasingly image guidance. This constantly increases requirements for image management and archiving. This article discusses the current status of these requirements and will present potential image administration strategies. RESULTS: Fundamentals of image administration and storage/archiving are presented (DICOM Standard, radiotherapy-specific issues) along the typical patient pathway (demographic data, radiotherapy treatment planning, signatures/approval of plan and image data, archiving of plan and image data). Different strategies for image management are presented (archiving centered on individual application vs. integral approach with central archiving in a DICOM-RT-PACS governed by a radiation oncology information system (ROCIS)). Infrastructural requirements depending on the amount of image data generated in the department are discussed. CONCLUSION: Application-centered image management provides access to image data including all relevant RT-specific elements. This approach, however, is not migration-safe, requires significant administrative work to ensure a redundancy level that protects against data loss and does not provide datasets that are linked to respective therapeutic interventions. Therefore, centralized image management and archiving that links images to patients and individual steps in the treatment pathway within a standardized DICOM(-RT) environment is preferable despite occasional problems with visualization of specific data elements.

Influence of ionizing radiation on nucleus 24 cochlear implants.

HYPOTHESIS: To evaluate the influence of conventional or hyperfractionated radiotherapy on Nucleus CI24M or CI24R(CS) implant systems. BACKGROUND: As a consequence of more than 70,000 cochlear implant recipients worldwide, the potential need for radiotherapy is an issue requiring consideration by both implantees and implantation centers. Conditions requiring radiotherapy of the head may include head, neck, or brain tumors. METHODS: The study examines the effect of ionizing radiation on cochlear implant function. The implanted devices examined were the Nucleus CI24M and Nucleus CI24R(CS). In a modeled study, two implants of each type were treated with fraction schemes most frequently used in clinical routine (e.g., conventional fractionation [total dose, 120 Gy] and hyperfractionation [total dose, 116 Gy]). Parameters quantified were the implant output amplitude changes at high and low current level (current levels 255 and 100, respectively), the charge balance of the biphasic pulse, and the accuracy of the impedance telemetry function. RESULTS: Within the clinically relevant dose range (< 80 Gy), implant function in all four devices was normal. Failure occurred in one Nucleus CI24R(CS) device treated with hyperfractionation. A dramatic drop in the output amplitude at 106 Gy was observed, and the impedance measurement failed at a total dose of 111 Gy. CONCLUSION: The results suggest that conventional or hyperfractionated radiotherapy can be applied safely at Nucleus CI24M or CI24R(CS) implant systems in a patient-like setting. Therefore, the authors propose that the results of the study can be applicable in clinical practice.

Double allogeneic peripheral stem cell transplants for patients at high risk of relapse.

Patients with chronic myeloid leukemia (CML) relapsing in blast crisis after HLA-identical sibling bone marrow transplantation (BMT) are difficult to treat. Infusion of donor lymphocytes or retransplantation are unlikely to result in long-term disease-free survival. Treatment intensification with allogeneic double-BMT, made possible by using repeatedly mobilized peripheral blood stem cells, offers a new treatment option. We report two patients with Philadelphia chromosome positive CML transplanted in chronic phase, relapsing with CML in myeloid blast crisis. Both received intensive induction chemotherapy (ICE) followed by a first, T cell-depleted peripheral stem cell transplant from the initial donor. Both patients engrafted rapidly (day 15). Upon hematologic recovery, a second G-CSF mobilized non-T cell-depleted peripheral stem cell transplant from the same donor was given after pretransplant conditioning with busulphan and cyclophosphamide. Again, engraftment was rapid (days 18 and 16) and both patients are alive and disease-free 18 and 21 months after allogeneic double-BMT. G-CSF mobilized peripheral stem cells allow new ways of treatment intensification with double-BMT in refractory leukemias relapsing post-transplant. This approach warrants further study.

Quality assurance for non-invasive patient fixation during stereotactic convergent beam irradiation.

Using a non-invasive mask this patient fixation system for stereotactic radiotherapy allows one to perform fractionated irradiation. Measuring the statistical quantities of patient motion and positioning uncertainties and calculating its effect on a spherically symmetric dose distribution showed that there is no severe disadvantage in most cases. Only if small field-size, excentric target volume localisation and extreme proximity to an organ at risk coincides have the statistical effects to be taken into account. The greatest measured standard deviation for positioning uncertainty was 2.3 mm. Its effect on the dose distribution with a field size of 9.1 mm increases the diameter of the 80% isodose to about 115%.

The influence of extracorporeal circulation on erythrocytes and flow properties of blood.

The influence of extracorporeal circulation on red blood cells and flow properties of blood was studied in 10 patients undergoing aorta-coronary bypass grafting. Blood samples were drawn on admission, under general anesthesia before the operation, during extracorporeal circulation, immediately after extracorporeal circulation, and 24 hours after extracorporeal circulation. Echinocytes were found during and shortly after extracorporeal circulation, but disappeared within 24 hours. Washing the cells in buffer restored the normal discocytic shape, which indicated that a plasma factor was responsible. Red cell membrane lipids were not affected. Analysis of the membrane proteins revealed a decrease of ankyrin after extracorporeal circulation, which was prevented by protease inhibitors during preparation. This suggests an increased proteolytic activity of the plasma after extracorporeal circulation. Red cell deformability was not altered. Plasma viscosity and hematocrit were markedly reduced by hemodilution with the priming solution. Their low levels resulted in a low blood viscosity during extracorporeal circulation, which was even lower at 26 degrees C than before or after the operation at 37 degrees C. We conclude that the red cell is affected by extracorporeal circulation. The flow properties of blood, however, are not impaired, but are improved by hemodilution.

Effect of amiodarone on erythrocyte shape and membrane properties.

1. Amiodarone is a potent anti-arrhythmic drug with lipophilic properties. The intercalation of such a drug into the membrane of erythrocytes may alter their shape and have an impact on the flow properties of blood. We therefore studied the influence of amiodarone on erythrocyte shape and deformability in vitro and in vivo. 2. Incubation in vitro with increasing amiodarone concentrations led to a progressive stomatocytic shape transformation and a decreased deformability of the erythrocytes. 3. Amiodarone treatment in eight patients did not affect erythrocyte morphology and deformability. However, an increase in the membrane cholesterol/phospholipid ratio was found. 4. The stomatocytic shape transformation of erythrocytes in vitro indicates that amiodarone intercalates in the inner hemileaflet of the lipid bilayer leading to membrane internalization. These results shed light on the interaction of amiodarone with biomembranes.

Gel filtration: a new method to analyze and separate red blood cells with different deformabilities.

Filtration of red blood cells through agarose gels (Sephadex, Sepharose, and Superose) was used to assess red cell deformability and simultaneously obtain fractions of red cells with different properties. The hemoglobin concentration in each fraction was used to define a filtration profile of red cells. It was found that gel filtration was a reproducible process. A gel filtration index (GFI) was derived from the height and the width of the filtration curve at half the maximum height. Osmotically treated red cells, red cells partially hardened with increasing glutaraldehyde concentrations, and mixtures of normal and hardened red cells were used to test the method. Changes in red cell deformability were sensitively detected by the GFI. The first fractions eluted from the column contained red cells with normal deformability, whereas the later fractions contained primarily less deformable cells with an increased membrane elastic modulus. By repeated filtration of late fractions it was possible to enrich the suspensions with less deformable cells. Patients with chronic renal failure had a decreased filterability; their GFI was 1.04 +/- 0.27 (n = 15) compared with 1.18 +/- 0.17 in controls (n = 20, p less than 0.05). We conclude that gel filtration is useful to detect and isolate abnormal red cell subpopulations. It could be a valuable tool for the investigation of disorders such as sickle cell anemia.

Mechanisms of the haematological changes induced by hyperventilation.

During voluntary hyperventilation an increase in the lymphocyte and thrombocyte counts occurs, paralleled by an increase in plasma epinephrine and norepinephrine. All these changes are rapidly reversible after hyperventilation and are followed by an increase in the neutrophil granulocyte count. The pathophysiological mechanisms of these changes were investigated by comparison of the hyperventilation-induced changes of the blood picture in 11 normal, 9 splenectomized and 12 beta-blocked volunteers. Splenectomy did not affect the hyperventilation-induced mobilization of lymphocytes and neutrophils but totally suppressed the change in the thrombocyte count. beta-blockade by 80 mg propranolol did not suppress the hyperventilation-induced increase in neutrophils. It reduced the absolute increase of lymphocytes and thrombocytes by half, but it also increased the baseline counts of these cells. The study shows that hyperventilation mobilizes thrombocytes from the spleen but not from extralienal pools, and that lymphocytes and neutrophils are mobilized from extralienal pools. Whereas neutrophil mobilization is not suppressed by beta-blockade, the reduction of hyperventilation-induced mobilization of lymphocytes and thrombocytes may be due to a reduction in the size of the mobilizable cell pools, and therefore cannot be interpreted as a sure indication that adrenergic mechanisms are involved in their hyperventilation-induced mobilization.

Plasma volume and proteins in voluntary hyperventilation.

In a controlled study the changes of the plasma volume and plasma proteins induced by voluntary hyperventilation (HV) were investigated in nine splenectomized volunteers. The plasma volume changes were calculated from the changes of the hemoglobin and hematocrit. After 20 min of HV in supine position, which lead to a decrease of the venous CO2 partial pressure by 19 Torr and to an increase of plasma epinephrine and norepinephrine levels, the plasma volume was reduced by 12.9%. The intravascular masses of total protein, albumin, and several other proteins decreased during HV but a similar decrease of these proteins was also observed during the control study (C), i.e., rest in supine position without HV. The differences between changes during HV and C were not significant, indicating that the loss of protein was not due to HV. It is concluded that acute HV leads to a rapidly reversible loss of a virtually protein-free solution from the vascular space. The red cell compartment participated in fluid shifts in that the mean red cell volume decreased by 2.2% (P less than 0.02 compared with C). Comparison with earlier work shows that addition of erythrocytes from the normal spleen does not play a part in the HV-induced increase of hemoglobin and hematocrit.

Longitudinal radiographical study on the rate of alveolar bone loss in patients of a dental school.

Two sets of radiographs, taken at an interval of 4-14 years in 105 patients of a dental school, were examined in order to determine the rate of resorption of alveolar bone. The percentage loss of maximum alveolar bone height was measured in the interproximal and interradicular sites by means of the Schei ruler. The average percentage of interproximal bone resorption was 0.51% (0.07 mm) per year. Age, sex, professional status, type of periodontal treatment and general state of health did not seem to affect the annual resorption rate. However, crowned teeth had a significantly greater rate of resorption than uncrowned teeth. Loss of bone tended to be more rapid in interdental as compared to interradicular areas. A positive and statistically significant correlation was found between initial resorption and annual tooth loss.

Immediate effect of lesion of the ventromedial hypothalamic area upon glucose-induced insulin secretion in anaesthetized rats.

Insulin secretion, measured in vivo following an intravneous load of glucose to anaesthetized rats, was markedly increased ten minutes after bilateral electrolytic lesions of the ventromedial hypothalamic (VMH) area when compared to both sham-operated and unoperated controls. The successful lesioning of the VMH area was assessed by the subsequent occurrence of hyperphagia, as estimated by the increase in body weight. It is concluded that the ventromedial hypothalamic area exerts an inhibitory influence upon the secretory activity of the B-cells. Furthermore, the rapid disappearance of such inhibitory influence following lesions of the VMH suggests that this area of the brain may be of importance in the minute to minute regulation of insulin secretion. The precise anatomical location of the hypothalamic "nucleus" (or "nuclei") involved, as well as the neural or humoral nature of its inhibitory effect upon the endocrine pancreas remain to be elucidated.

Idiopathic respiratory distress syndrome (IRDS): intermittent positive pressure ventilation (IPPV) versus continuous positive pressure ventilation (CPPV), a comparative study.

59 patients with IRDS treated with CPPV in 1973-1974 are compared with 59 patients treated with IPPV in 1971-1972. With CPPV there was a reduction in mortality from 40.7% to 32.2%. CPPV as compared to IPPV reduced right to left shunting from the 6th hour of life onwards. Elevated oxygen supply was needed for shorter time and time of mechanical ventilation as well as duration of intubation could be reduced. The frequency of pneumothorax during ventilation was unchanged. The frequency of bronchopulmonary dysplasia could be reduced. One third of the surviving patients had neurological symptoms at the age of one year, the frequency was lower in the CPPV group. One patient in the IPPV group was severely damaged. The results obtained are in favour of CPPV as compared to IPPV for mechanical ventilation in patients with IRDS.

Cardiomegaly in neonatal hypoglycemia.

Chest X-rays of 24 hypoglycemic newborns were compared with those of a matched control group of newborns with normal blood glucose levels. In the hypoglycemic group heart size was found to be significantly greater than in the control group. No correlation could be established between the degree of cardiomegaly and the severity of hypoglycemia. 19 of the 24 hypoglycemic children were prematures or small for dates and it is postulated that the low glycogen stores in these infants do not meet the metabolic demands of the myocardium during its postpartum circulatory adaptation.