Intensity modulated radiation therapy with electrons using algorithm based energy/range selection methods.

BACKGROUND AND PURPOSE: In recent years photon intensity modulated radiation therapy (IMRT) has gained attention due to its ability to improve conformity of dose distributions. A potential advantage of electron-IMRT is that the dose fall off in the depth dose curve makes it possible to modulate the dose distribution in the direction of the beam by selecting different electron energies. This paper examines the use of a computer based energy selection in combination with the IMRT technique to optimise the electron dose distribution. MATERIALS AND METHODS: One centimetre square electron beamlets ranging from 2.5 to 50 MeV were pre-calculated in water using Monte Carlo methods. A modified IMRT optimisation tool was then used to find an optimum mix of electron energies and intensities. The main principles used are illustrated in some simple geometries and tested on two clinical cases of post-operated ca. mam. RESULTS: It is clearly illustrated that the energy optimisation procedure lowers the dose to lung and heart and makes the dose in the target more homogeneous. Increasing the energy at steep gradients compensates for lack of target coverage at beam edges and steep gradients. Comparison with a clinically acceptable four segment plan indicates the advantage of the used electron IMRT technique. CONCLUSIONS: Using an intensity optimised mix of computer selected electron energies has the potential to improve electron treatments for mastectomy patients with good target coverage and reduced dose to normal tissue such as lung and heart.     

Impact of target reproducibility on tumor dose in stereotactic radiotherapy of targets in the lung and liver.

BACKGROUND AND PURPOSE: Previous analyses of target reproducibility in extracranial stereotactic radiotherapy have revealed standard security margins for planning target volume (PTV) definition of 5mm in axial and 5-10mm in longitudinal direction. In this study the reproducibility of the clinical target volume (CTV) of lung and liver tumors within the PTV over the complete course of hypofractionated treatment is evaluated. The impact of target mobility on dose to the CTV is assessed by dose-volume histograms (DVH). MATERIALS AND METHODS: Twenty-two pulmonary and 21 hepatic targets were treated with three stereotactic fractions of 10 Gy to the PTV-enclosing 100%-isodose with normalization to 150% at the isocenter. A conformal dose distribution was related to the PTV, which was defined by margins of 5-10mm added to the CTV. Prior to each fraction a computed tomography (CT)-simulation over the complete target volume was performed resulting in a total of 60 CT-simulations for lung and 58 CT-simulations for hepatic targets. The CTV from each CT-simulation was segmented and matched with the CT-study used for treatment planning. A DVH of the simulated CTV was calculated for each fraction. The target coverage (TC) of dose to the simulated CTV was defined as the proportion of the CTV receiving at least the reference dose (100%). RESULTS: A decrease of TC to <95% was found in 3/60 simulations (5%) of pulmonary and 7/58 simulations (12%) of hepatic targets. In two of 22 pulmonary targets (9%) and in four of 21 hepatic targets (19%) a TC of <95% occurred in at least one fraction. At risk for a decreased TC <95% were pulmonary targets with increased breathing mobility and hepatic targets with a CTV exceeding 100 cm(3). CONCLUSIONS: Target reproducibility was precise within the reference isodose in 91% of lung and 81% of liver tumors with a TC of the complete CTV >or=95% at each fraction of treatment. Pulmonary targets with increased breathing mobility and liver tumors >100 cm(3) are at risk for target deviation exceeding the standard security margins for PTV-definition at least for one fraction and require individual evaluation of sufficient margins.     

The prevalence of respiratory symptoms and asthma among school children in three different areas of Norway

The role of exposure to ambient air pollution has been a topic of interest as a potential risk factor for respiratory symptoms and asthma. We expected that the prevalence rates would vary in Norway between the capital, Oslo, the mountainous area Hallingdal and the industrial area Odda. Surveys were conducted in school children, aged 6-16 years, in; Oslo (n=2577), Hallingdal (n=1177) and Odda (n=831). The parent-reported prevalence of wheeze in past year was almost similar in Oslo (13. 1 (95% CI 11. 7-14. 5)) and Upper Hallingdal (14. 2 (13. 1–15. 3)), but lower in Odda (9. 0 (7. 0–11. 0)). The findings for severe respiratory symptoms were almost equal. The age patters within each area differed. The risk of wheeze ever (p < 0.001) and wheeze in past year (p=0.04) decreased with increasing age in Odda, while there was an increase in the risk of exercise induced wheeze in Oslo (p=0.02) and Hallingdal (p < 0.001). The lifetime prevalence of asthma was lowest in Odda (5. 4 (3. 8–7. 0)) compared to Oslo (9. 4 (8. 2–10. 6)) and Hallingdal (8. 5 (6. 8–10. 2)). There was a positive association between physical activity and wheeze in past year. The results do not support the hypothesis that respiratory morbidity is more common in urban than rural areas, age and physical activity can influence the prevalence rates of respiratory symptoms in school children.     

In vitro T-lymphocyte function in head and neck cancer patients

T-lymphocyte cell function was studied in vitro in peripheral blood mononuclear cells (PBMC) from 61 male patients with head and neck squamous cell carcinomas compared to 46 control patients. Patients older than 80 years or with reduced tumor-related performance status as measured by Karnofsky score less than 75 were excluded. In contrast to previous similar studies, control subjects ensured a minimum stress load by sampling all patients on the day of either diagnostic or therapeutic surgery. PBMC were separated by density-gradient centrifugation and subsequently cultured with autologous sera in vitro. The mitogen concanavalin A (Con A), which stimulates all T-cell clones, was employed. Findings showed that increased Con A stimulation and PBMC proliferation occurred with PBMC from cancer patients compared to that from control patients. In contrast, no differences could be detected with respect to the stimulated supernatant level of interleukin-2, interleukin-4 or interferon-γ between the groups. These results suggest that T-lymphocytes from PBMC are generally affected by neoplastic disease through either a supporting cell or serum factor.     

Molecular Regulation of Cell Death and Therapeutic Strategies for Cell Death Induction in Prostate Carcinoma

Many of the common molecular alterations associated with prostate cancer progression involve genes known to regulate cell death susceptibility. The significance of these molecular events is discussed in the context of developing and implementing new strategies designed to restore cell death susceptibility in prostate cancer cells and overcome therapeutic resistance.     

Quality of Life in the General Norwegian Population, Measured by the Quality of Life Scale (QOLS-N)

The main aim of the present study was to derive norms or reference values from the general Norwegian population for the Norwegian version of the Quality of Life Scale (QOLS-N). In addition, associations between socio-demographic and health variables on the level of quality of life were examined. The sample consisted of 1893 subjects from a total of 4000 randomly selected Norwegian citizens representative of the entire Norwegian population, aged 19-81. The subjects received a mailed questionnaire containing the QOLS-N. Results show that the mean quality of life score was 84.1 (SD 12.5). Women reported a higher quality of life than men. People with higher levels of education reported a higher quality of life. Those who were married or cohabitating reported the highest quality of life and those who were unemployed reported a lower quality of life than those who worked. In addition, people reporting long-term diseases or health problems scored significantly lower on quality of life. These results could serve as reference values for the level of quality of life, as measured by the QOLS-N in the Norwegian population.     

Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.     

Risk-Adjusted Cancer Screening and Prevention (RiskAP): Complementing Screening for Early Disease Detection by a Learning Screening Based on Risk Factors

BackgroundRisk-adjusted cancer screening and prevention is a promising and continuously emerging option for improving cancer prevention. It is driven by increasing knowledge of risk factors and the ability to determine them for individual risk prediction. However, there is a knowledge gap between evidence of increased risk and evidence of the effectiveness and efficiency of clinical preventive interventions based on increased risk. This gap is, in particular, aggravated by the extensive availability of genetic risk factor diagnostics, since the question of appropriate preventive measures immediately arises when an increased risk is identified. However, collecting proof of effective preventive measures, ideally by prospective randomized preventive studies, typically requires very long periods of time, while the knowledge about an increased risk immediately creates a high demand for action.SummaryTherefore, we propose a risk-adjusted prevention concept that is based on the best current evidence making needed and appropriate preventive measures available, and which is constantly evaluated through outcome evaluation, and continuously improved based on these results. We further discuss the structural and procedural requirements as well as legal and socioeconomical aspects relevant for the implementation of this concept.     

Changes in socioeconomic differentials in old age life expectancy in four Nordic countries: the impact of educational expansion and education-specific mortality

Overall progress in life expectancy (LE) depends increasingly on survival in older ages. The birth cohorts now reaching old age have experienced considerable educational expansion, which is a driving force for the social change and social inequality. Thus, this study examines changes in old age LE by educational attainment in the Nordic countries and aims to find out to what extent the change in national LEs is attributable to education-specific mortality and the shifting educational composition. We used national register data comprising total 65 + populations in Denmark, Finland, Norway and Sweden to create period life tables stratified by five-year age groups (65–90 +), sex and educational attainment. Difference in LE between 2001 and 2015 was decomposed into the contributions of mortality changes within each educational group and changes in educational composition. Increasing LE at all ages and in all educational groups coincided with persistent and growing educational inequalities in all countries. Most of the gains in LE at age 65 could be attributed to decreased mortality (63–90%), especially among those with low education, the largest educational group in most countries. The proportion of the increase in LE attributable to improved education was 10–37%, with the highest contributions recorded for women in Norway and Sweden. The rising educational levels in the Nordic countries still carry potential for further gains in national LEs. However, the educational expansion has contributed to uneven gains in LE between education groups, which poses a risk for the future increase of inequalities in LE.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10433-022-00698-y.     

Software-Automated Implant Detection for Intraoperative 3D Imaging—First Clinical Evaluation on 214 Data Sets

Previous studies have demonstrated a frequent occurrence of screw/K-wire malpositioning during surgical fracture treatment under 2D fluoroscopy and a correspondingly high revision rate as a result of using intraoperative 3D imaging. In order to facilitate and accelerate the diagnosis of implant malpositioning in 3D data sets, this study investigates two versions of an implant detection software for mobile 3D C-arms in terms of their detection performance based on comparison with manual evaluation. The 3D data sets of patients who had received surgical fracture treatment at five anatomical regions were extracted from the research database. First, manual evaluation of the data sets was performed, and the number of implanted implants was assessed. For 25 data sets, the time required by four investigators to adjust each implant was monitored. Subsequently, the evaluation was performed using both software versions based on the following detection parameters: true-positive-rate, false-negative-rate, false-detection-rate and positive predictive value. Furthermore, the causes of false positive and false negative detected implants depending on the anatomical region were investigated. Two hundred fourteen data sets with overall 1767 implants were included. The detection parameters were significantly improved (p<.001) from version 1 to version 2 of the implant detection software. Automatic evaluation required an average of 4.1±0.4 s while manual evaluation was completed in 136.15±72.9 s (p<.001), with a statistically significant difference between experienced and inexperienced users (p=.005). In summary, version 2 of the implant detection software achieved significantly better results. The time saved by using the software could contribute to optimizing the intraoperative workflow.