Thorough design and pre-trial quality assurance (QA) decrease dosimetric impact of delineation and dose planning variability in the STRICTLUNG and STARLUNG trials for stereotactic body radiotherapy (SBRT) of central and ultra-central lung tumours.

INTRODUCTION: SBRT of central lung tumours implies significant risk of toxicity. We are initiating two phase II trials prescribing 56 Gy/eight fractions to PTV, allowing for dose escalation of GTV. We prioritize organs at risk (OAR) constraints over target coverage, making the treatment plans very sensitive to OAR delineation variations. The aim of this study is to quantify the dosimetric impact of contouring variations and to provide a thorough description of pre-trial quality assurance to be used in upcoming trials to provide consistent clinical care. MATERIALS AND METHODS: Delineation: Seven physicians delineated OAR in three rounds, with evaluations in-between. For each patient case, seven treatment plans, repeatedly using each of the OAR structure sets from the seven physicians, were made and compared to evaluate the dosimetric effect of delineation variability. Treatment planning: Treatment plans for seven cases were made at six departments in two rounds, with discussion in-between. RESULTS: OAR delineation variation between centres resulted in high variabilities in OAR dose for simulated plans and led to potential overdosage of the lobar bronchus (constraint: D0.03cc < 45 Gy), with maximum doses ranging between 58 Gy (first round), and 50 Gy (third round). For mediastinal tissue, the constraint (D0.03cc < 45 Gy) was violated for the majority of the delineations in all three rounds, with maximum doses of 84 Gy (first round), and 72 Gy (third round).For the treatment planning study, the range of the standard deviation for GTV mean dose was 12.8-18.5 Gy (first round) and 2.8-3.5 Gy (second round). CONCLUSIONS: Even small variations in OAR delineation led to high OAR overdosage. The study demonstrates the importance of having extensive QA procedures in place before initiating clinical trials on dose escalation in SBRT.

Paws without claws? Ecological effects of large carnivores in anthropogenic landscapes.

Large carnivores are frequently presented as saviours of biodiversity and ecosystem functioning through their creation of trophic cascades, an idea largely based on studies coming primarily out of relatively natural landscapes. However, in large parts of the world, particularly in Europe, large carnivores live in and are returning to strongly human-modified ecosystems. At present, we lack a coherent framework to predict the effects of large carnivores in these anthropogenic landscapes. We review how human actions influence the ecological roles of large carnivores by affecting their density or behaviour or those of mesopredators or prey species. We argue that the potential for density-mediated trophic cascades in anthropogenic landscapes is limited to unproductive areas where even low carnivore numbers may impact prey densities or to the limited parts of the landscape where carnivores are allowed to reach ecologically functional densities. The potential for behaviourally mediated trophic cascades may be larger and more widespread, because even low carnivore densities affect prey behaviour. We conclude that predator-prey interactions in anthropogenic landscapes will be highly context-dependent and human actions will often attenuate the ecological effects of large carnivores. We highlight the knowledge gaps and outline a new research avenue to study the role of carnivores in anthropogenic landscapes.

Effects of limited concentrate feeding on growth and blood and serum variables, and on nutrient digestibility and gene expression of hepatic gluconeogenic enzymes in dairy calves.

This study elucidated the effects of limited concentrate feeding on growth, nutrient digestibility, blood profile and gene expression of gluconeogenic enzymes in the liver of dairy calves. The study utilized 36 German Holstein dairy calves (5-7 days of age) divided into two groups of 18 calves each for 150 days. Control group calves received 2 kg/(calf × day) of concentrate, whereas calves in the restricted group received only 1 kg/(calf × day). Good quality forage (mixture of maize and grass silages) was available for ad libitum consumption to both groups. The intake of milk replacer before weaning, and of concentrate were recorded daily per calf; however, the consumption of forages was quantified as daily average of the group. Body weights (BW) were recorded at start and on days 35, 70, 112 and 150. Blood and serum samples and spot urinary and faecal samples were also collected at similar time points. On days 70 and 150, liver biopsies were collected from seven animals in each group. The BW was not different between the groups at all times. Total BW gain in the control group was 124 kg as opposed to 111 kg in restricted group that led to average BW gain of 827 g/day and 739 g/day in respective groups, and the differences were significant (p = 0.018). As planned, the control group had higher concentrate and lower forage intake than the restricted group. The blood haemoglobin, haematocrit and serum variables (glucose, total protein, albumin and urea) were within the normal range in both groups, but serum glucose was higher (p < 0.05) in control than in restricted group at 70 days. There was no difference between groups in organic matter (OM) digestibility which declined (p < 0.001) with increasing age in both groups. Microbial crude protein (MCP) synthesis estimated from urinary allantoin excretion increased (p < 0.001) in both groups with increasing age but was not different between groups. The mRNA expressions for the gluconeogenic enzymes, cytosolic and mitochondrial phosphoenol pyruvate carboxykinase (EC 4.1.1.32) and pyruvate carboxylase (EC 6.4.1.1) measured by quantitative real-time PCR in liver biopsies showed no differences between groups. Overall, restricting concentrate moderately reduced the growth intensity without affecting the normal serum and blood indices, and MCP synthesis and OM digestibility showed no differences between groups, indicating that both concentrate feeding schemes can be successfully applied.

Primary radiotherapy of carcinoma of the supraglottic larynx--a multivariate analysis of prognostic factors.

PURPOSE: The aim of this study was to analyze the importance of different possible prognostic factors in cancer of the supraglottic larynx. METHODS AND MATERIALS: Nine hundred thirty-two patients with carcinoma of the supraglottic larynx were consecutively treated at The Finseninstitute in Copenhagen between 1966 and 1991. Of the patients, 768 treated with radiotherapy only were eligible for a multivariate Cox regression analysis of prognostic factors with local-regional control as endpoint. Of these, 73% (561) were men and 27% (207) women. Twelve factors: Age; gender; tumor size; site; T category (UICC78); nodal involvement (UICC 78); stage (UICC78); treatment period; tumor surface appearance; histopathologic differentiation; cord mobility; and hemoglobin level were tested. RESULTS: Only gender, T, N, and size proved to have independent significant prognostic importance in the multivariate analysis. A hazard index including these four factors for each patient was calculated, and eight risk groups formed. When the relative risks (RR) for these groups were plotted against the corresponding 5-year local-regional control failure rates, a very simple equation for the risk of failure could be derived as: 5-year local failure risk = 0.2 + 0.1 RR. CONCLUSION: We recommend that this estimation of an individual patient's risk of failure should be implemented in future clinical decision making.

Squamous cell carcinoma of the oropharynx. Results of primary radiotherapy.

During the six-year period in 1979 through 1985, 226 patients (67 females and 159 males) with squamous cell carcinoma of the oropharynx were treated at the Finsen Institute in Copenhagen. Ages ranged from 35 to 86 years with an average of 64 years for females and 61 years for males. The primary tumour was most often situated in the lateral wall (55%) and the anterior wall (25%). Thirty-nine per cent of the tumours were in stage III and 40% in stage IV. The primary treatment was radiotherapy, in this period given with three different treatment schedules, one continuous and two split-course. The 5-year crude survival rate in the total material was 36% and the corrected 5-year survival rate 45%. Females had a higher loco-regional control rate than males, but there was no significant differences between the sexes concerning survival. The tumour stage (IUCC, 1978) was an important prognostic factor for both loco-regional control and survival. No significant differences could be found between the three treatment schedules concerning loco-regional control or survival.

Ultrasonic diagnosis of placenta praevia.

741 women suspected of placenta praevia were submitted to ultrasonic scanning during the second and/or third trimesterr of pregnancy. In 61 an abnormal placental site was diagnosed. During Caesarean section, carried out in 46 of these cases, the location was compared with the ultrasound findings. The scanning diagnosis during the last trimester correlated with the findings at delivery. At scanning after the 35th week the diagnosis differed in only 4 cases. In all 4 there was a question of a low-lying placenta versus partial placenta praevia. During the second trimester diagnosis of low-lying placenta were revised in several cases at later scans. It is discussed whether these early diagnoses of an abnormal placental site, which later becomes normal, indicate a migrating placenta and/or an uncertainty of the scanning method. Early diagnosis of low-lying placentae should be checked by repeat scans.

Prenatal diagnosis of soft-tissue malformations by ultrasound and X-ray.

This study presents four cases of fetal soft-tissue malformations diagnosed during pregnancy by ultrasonic scanning and amniography. The series comprises two fetal teratomas, one case of fetal ascites, and one case of a partial mole with coexistent fetus. Diagnostic and differential diagnostic problems are illustrated by a fifth case where the final diagnosis was a big maternal ovarian cyst-adenoma coexistent with a normal fetus.