Stereotactic body radiotherapy of central lung tumours using a 1.5 T MR-linac: First clinical experiences.

Background: MRI-guidance may aid better discrimination between Organs at Risk (OARs) and target volumes in proximity of the mediastinum. We report the first clinical experiences with Stereotactic Body Radiotherapy (SBRT) of (ultra)central lung tumours on a 1.5 T MR-linac. Materials and Methods: Patients with an (ultra)central lung tumour were selected for MR-linac based SBRT treatment. A T2-weighted 3D sequence MRI acquired during free breathing was used for daily plan adaption. Prior to each fraction, contours of Internal Target Volume (ITV) and OARs were deformably propagated and amended by a radiation oncologist. Inter-fractional changes in volumes and coverage of target volumes as well as doses in OARs were evaluated in offline and online treatment plans. Results: Ten patients were treated and completed 60 Gy in 8 or 12 fractions. In total 104 fractions were delivered. The median time in the treatment room was 41 min with a median beam-on time of 8.9 min. No grade ≥3 acute toxicity was observed. In two patients, the ITV significantly decreased during treatment (58 % and 37 %, respectively) due to tumour shrinkage. In the other patients, 81 % of online ITVs were within ±15 % of the volume of fraction 1. Comparison with the pre-treatment plan showed that ITV coverage of the online plan was similar in 52 % and improved in 34 % of cases. Adaptation to meet OAR constraints, led to decreased ITV coverage in 14 %. Conclusions: We describe the workflow for MR-guided Radiotherapy and the feasibility of using 1.5 T MR-linac for SBRT of (ultra) central lung tumours.

Medical Students' Perspectives on Online Proctoring During Remote Digital Progress Test.

Remote teaching and assessment are essential for current education. During online examination, online proctoring is often used as a surveillance tool. Little is known about student perceptions on online proctoring. Using an online questionnaire, we found that medical students worry most about unjustified invalidation of their exam due to unstable internet connection, background noise or webcam issues, and privacy issues. It is important to be aware of these worries as they may influence test results.

[Chronic radiation enteritis after irradiation of the lesser pelvis: surgical (im)possibilities]. / Chronische radiatie-enteritis na bestraling op het kleine bekken: chirurgische (on)mogelijkheden.

Three women aged 74, 59 and 36 years, had chronic complaints of abdominal pain, nausea, vomiting and diarrhoea, 1 to 8 years after radiotherapy for pelvic malignancies. Mechanical ileus due to fibrotic adhesions was found to be the cause; all three patients recovered after one or more operations. The prevalence of chronic radiation injury correlates with both radiation factors (volume) and patient characteristics. If possible, tumour recurrence needs to be excluded. Chronic intermittent ileus is the predominant symptom of chronic radiation injury. It often occurs within 2 years, but sometimes as long as 10 to 20 years after radiotherapy. Resection is warranted when short segments are affected. In other cases an intestinal bypass or stoma is the treatment of choice.

[Children with craniopharyngioma, a 'benign' brain tumor with a high morbidity]. / Kinderen met een craniofaryngioom, een 'goedaardige' hersentumor met grote morbiditeit.

The craniopharyngioma is a histologically benign tumour, mainly occurring in childhood. Neurosurgical treatment, in some of these patients in combination with external radiotherapy, results in a fair prognosis for children with craniopharyngioma. However, the central localisation of this tumour in the brain, damage of surrounding structures due to tumour growth, as well as the adverse effects of treatment will result in substantial morbidity in many patients. The first patient, a 13-year-old boy, presented with symptoms and signs of increased intracranial pressure. Following operation he was treated with radiotherapy, and up to 4 years after the operation there was no tumour recurrence. However, he experienced endocrine, visual, hypothalamic and intellectual disturbances due to the disease and its treatment. The second patient, a 6-year-old girl, presented with hydrocephalus due to the tumour, but also had growth retardation. After operation and radiotherapy, she had visual, endocrine, and intellectual dysfunction, but there were no signs of tumor recurrence. The third patient, an 12-year-old boy, already had growth retardation several years before he presented with neurological dysfunction. He received no postoperative radiation, as all tumour tissue could be removed. He had visual, hypothalamic, endocrine and intellectual disturbances but until nearly 6 years after the operation, there was no tumour recurrence. The morbidity due to the tumour and its treatment has a negative impact on the patient's quality of life. A multidisciplinary treatment and follow-up of these children cannot avoid this morbidity but may result in a timely observation of problems and thereby prevent unnecessary damage.

The learning curve in prostate seed implantation.

OBJECTIVE: To describe the learning curve in prostate seed implantation, according to the experience with two groups of 100 patients. MATERIAL AND METHODS: A perineal, ultrasound-guided implantation technique with manual afterloading was used in all patients. Of a total of 255 patients treated over the period 1989 through 1998, the results of the first hundred patients were compared in relation to the last hundred patients. In the first group single seeds were used, while in the second group RAPID Strands were applied. RESULTS: Although there is a difference in the follow-up period, a significant difference is found in disease-free survival between the two groups. PSA progression was noticed in 39% of patients in the first group and in 12% in the other group. The strongest prognostic factor, however, is the initial PSA value. Toxicity is relatively low, though higher in the second group. CONCLUSIONS: The results obtained in the second hundred patients are in agreement with data from literature. Differences in outcome between the two groups are, however, not only explained by differences in technique, but also by selection and total number of implanted seeds.

Regional hyperthermia of pelvic tumours using the Utrecht 'Coaxial TEM' system: a feasibility study.

Between August 1989 and July 1992 a total of 22 patients (64 treatments) with inoperable or recurrent deep seated pelvic tumours were treated with regional hyperthermia and radiotherapy. The 70 Mhz Coaxial TEM applicator with its characteristic open waterbolus was used as heating device. The main objective of this pilot study was to evaluate the feasibility, toxicity and temperature data. The results showed that the major treatment limiting factors were insufficient power and systemic stress. Local pain was observed in only 10% of all treatments. Most of the treatments resulted in elevated systemic temperatures with the overall mean maximum oesophagus temperature reaching 38.9 +/- 0.7 degrees C, however, in only 6% of these treatments this was found to be treatment limiting. From the measured data the following intratumoral temperatures were calculated: T90 = 39.9 +/- 1.0 degrees C; T50 = 40.7 +/- 1.0 degrees C; T10 = 41.4 +/- 1.0 degrees C. In addition, the overall mean average normal tissue temperatures were determined: Trectum = 40.8 +/- 0.7 degrees C; Tvagina = 41.3 +/- 0.9 degrees C; Turethra = 40.8 +/- 0.9 degrees C. The temperatures in normal tissue were frequently higher than in tumour, indicating that a large volume was heated. The open waterbolus allows strong cooling, but the strategy was changed during the study: higher systemic temperatures were allowed to improve the pelvic temperatures. This pilot study proved that the open waterbolus is clinically a success, because it offers patient comfort and SAR-steering by patient repositioning, and that regional hyperthermia with the Coaxial TEM is feasible.

Purification and comparative studies of alcohol dehydrogenases.

Alcohol dehydrogenases from various animal and plant sources were purified by a common procedure which employed DEAE, Sephadex-G100 and affinity chromatographies. The procedure achieves an 80-130 fold purification for animal enzymes. However, only a 5-15 fold purification for plant enzymes was attained because of the instability of these enzymes. Purified alcohol dehydrogenases from animal and plant sources differ in coenzyme and substrate specificities. The enzymes from mammalian, avian and fish livers display aldehyde oxidizing and esterolytic activities in addition to alcohol oxidizing activity. However, the enzymes from plants and yeast show only the oxidative activity toward alcohols. Chemical modifications have been performed to identify amino acid residues which are essential to the oxidative and esterolytic activities of alcohol dehydrogenases.

Immunoradiometric assays for human coagulation factor VII using polyclonal antibodies against the Ca(II)-dependent and Ca(II)-independent conformation.

Human coagulation factor VII is a trace plasma protein belonging to the vitamin K-dependent factors. Two specific and sensitive immunoradiometric assays for factor VII were developed using immunopurified rabbit antibodies against the Ca(II)-independent and Ca(II)-dependent conformation of factor VII. Both assays were insensitive to the activation state of factor VII. The distribution of factor VII antigen was studied in 40 healthy individuals and the antigen level in normal plasma was calculated to be 0.52-0.62 micrograms/ml. The two assays were used in a comparative study of factor VII procoagulant activity and factor VII antigen in patients treated with oral anticoagulants.

Rabbit polyclonal antibodies against the calcium-dependent conformation of factor IX and their application in solid phase immunoradiometric assays.

Two subpopulations of antibodies were isolated from rabbit polyclonal antiserum directed against human factor IX: one against the Ca(II)-dependent conformation of factor IX and one against the Ca(II)-independent conformation of factor IX. The two subpopulations were used for the development of immunoradiometric assays (IRMA's) for factor IX:Ca(II)Ag and factor IX:NonCa(II)Ag respectively. Ranges for the concentration of factor IX:Ca(II)Ag and factor IX:NonCa(II)Ag were established in plasmas of healthy volunteers, patients treated with oral anticoagulants and hemophilia B patients. In the group of patients using oral anticoagulant therapy a progressively reduced ratio of factor IX:Ca(II)Ag to factor IX:NonCa(II)Ag was observed with increasing intensity of oral anticoagulant treatment. Variant factor IX molecules from hemophilia B patients (CRM-, CRM(Red) and CRM+) with a defective Ca(II) binding or defective conformational transition induced by Ca(II) binding, were identified. These defects are absent in variant factor IX molecules from one hemophilia Bm patient and from patients with hemophilia B Leyden.

The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency.

Protein C is a vitamin K dependent protein involved in blood coagulation. A congenital deficiency in protein C antigen - which inherits as an autosomal dominant disorder - has been reported to be associated with a high risk for thrombo-embolic disease at relatively young age. In the present paper we report on the development of a functional assay for plasma protein C. In this assay protein C is adsorbed to Al(OH)3, eluted and activated by thrombin, after which the concentration of the activated protein C is measured with a peptide substrate (S2366). Normal values for protein C activity and protein C antigen were determined in healthy volunteers and patients on stable oral anticoagulant treatment. Protein C activity and antigen levels were compared in 28 patients from 9 different pedigrees with both congenital protein C deficiency and thrombotic disease. Two types of protein C deficiency could be recognized: in type I the deficiency is due to the absence or reduced presence of protein C molecules, while in type II the deficiency is caused by the presence of an abnormal protein C molecule with strongly reduced functional activity.