[en] Purpose: To develop a framework with which to evaluate locations of radiation therapy (RT) centers in a region based on geographic access. Methods and Materials: Patient records were obtained for all external beam radiation therapy started in 2011 for the province of British Columbia, Canada. Two metrics of geographic access were defined. The primary analysis was percentage of patients (coverage) within a 90-minute drive from an RT center (C90), and the secondary analysis was the average drive time (ADT) to an RT center. An integer programming model was developed to determine optimal center locations, catchment areas, and capacity required under different scenarios. Results: Records consisted of 11,096 courses of radiation corresponding to 161,616 fractions. Baseline geographic access was estimated at 102.5 minutes ADT (each way, per fraction) and 75.9% C90. Adding 2 and 3 new centers increased C90 to 88% and 92%, respectively, and decreased ADT by between 43% and 61%, respectively. A scenario in which RT was provided in every potential location that could support at least 1 fully utilized linear accelerator resulted in 35.3 minutes' ADT and 93.6% C90. Conclusions: The proposed framework and model provide a data-driven means to quantitatively evaluate alternative configurations of a regional RT system. Results suggest that the choice of location for future centers can significantly improve geographic access to RT

[en] The effects of acute benzene (BZ) exposure on hematopoietic progenitor cells (HPCs) derived from bone marrow cells were studied using homozygous male v-Ha-ras Tg.AC mice at 8-10 weeks of age. The mice were given 0.02% BZ in their drinking water for 28 days with the dose rate estimated to be 34 mg benzene/kg BW/day. Analysis of cultured HPCs indicated that BZ suppressed the proliferation of the multilineage colony forming unit-granulocyte, erythrocyte, macrophage, megakaryocyte (CFU-GEMM); colony forming unit-granulocyte, macrophage (CFU-GM); and blast forming unit erythrocyte/colony forming unit erythrocyte (BFUE/CFUE). A gene expression profile was generated using nylon arrays spotted with 23 cDNAs involved in selected signal pathways involved in cell distress, inflammation, DNA damage, cell cycle arrest, and apoptosis. Of the 23 marker genes, 6 (bax, c-fos, E124, hsf1, ikBa, and p57) were significantly (Mann-Whitney U tests, P < 0.05) overexpressed in BZ-exposed mice. Two genes (c-myc and IL-2) approached significance (at P = 0.053). The pattern of gene expression was consistent with BZ toxicity and the suppression of HPCs

[en] Purpose: To investigate the impact of γ-irradiation on cyclooxygenase-2 (COX-2) expression and its enzymatic activity in PC-3 cells. Cell cycle redistribution, viability, and apoptosis were quantitated in control and irradiated cells with or without the COX-2 inhibitor NS-398. Methods and Materials: Western blot analysis was used to assess COX-2 protein expression. Prostaglandin (PGE₂) was measured after addition of arachidonic acid (AA) using a Monoclonal Immunoassay Kit. Cell cycle and apoptosis were assessed using flow cytometry. Results: We observed a dose-dependent increase in COX-2 of 37.0%, 79.7%, and 97.5% following irradiation with 5, 10, and 15 Gy, respectively. The PGE₂ level of irradiated cells was higher than in controls (1512 ± 157.5 vs. 973.7 ± 54.2 ρg PGE₂/mL; p < 0.005, n 4) while cells irradiated in the presence of NS-398 had reduced PGE₂ levels (218.8 ± 80.1 ρg PGE₂/mL; p < 0.005; n = 4). We found no differences in cell cycle distribution or apoptosis between cells irradiated in the presence or absence of NS-398. Conclusions: COX-2 protein is upregulated and enzymatically active after irradiation, resulting in elevated levels of PGE₂. This effect can be suppressed by NS-398, which has clinical implications for therapies combining COX-2 inhibitors with radiation therapy

[en] Background and purpose: The planning portion of the radiation therapy treatment process at the British Columbia Cancer Agency is efficient but nevertheless contains room for improvement. The purpose of this study is to show how a discrete-event simulation (DES) model can be used to represent this complex process and to suggest improvements that may reduce the planning time and ultimately reduce overall waiting times. Materials and methods: A simulation model of the radiation therapy (RT) planning process was constructed using the Arena simulation software, representing the complexities of the system. Several types of inputs feed into the model; these inputs come from historical data, a staff survey, and interviews with planners. Results: The simulation model was validated against historical data and then used to test various scenarios to identify and quantify potential improvements to the RT planning process. Conclusions: Simulation modelling is an attractive tool for describing complex systems, and can be used to identify improvements to the processes involved. It is possible to use this technique in the area of radiation therapy planning with the intent of reducing process times and subsequent delays for patient treatment. In this particular system, reducing the variability and length of oncologist-related delays contributes most to improving the planning time.

[en] Purpose: To model and quantify the relationship between radiation therapy (RT) use and travel time to RT services. Methods and Materials: Population-based registries and databases were used to identify both incident cancer patient and patients receiving RT within 1 year of diagnosis (RT1y) in British Columbia, Canada, between 1992 and 2011. The effects of age, gender, diagnosis year, income, prevailing wait time, and travel duration for RT on RT1y were assessed. Significant factors from univariate analyses were included in a multivariable logistic regression model. The shape of the travel time–RT1y curve was represented by generalized additive and segmented regression models. Analyses were conducted for breast, lung, and genitourinary cancer separately and for all cancer sites combined. Results: After adjustment for age, gender, diagnosis year, income, and prevailing wait times, increasing travel time to the closest RT facility had a negative impact RT1y. The shape of the travel time–RT1y curve varied with cancer type. For breast cancer, the odds of RT1y were constant for the first 2 driving hours and decreased at 17% per hour thereafter. For lung cancer, the odds of RT1y decreased by 16% after 20 minutes and then decreased at 6% per hour. Genitourinary cancer RT1y was relatively independent of travel time. For all cancer sites combined, the odds of RT1y were constant within the first 2 driving hours and decreased at 7% per hour thereafter. Conclusions: Travel time to receive RT has a different impact on RT1y for different tumor sites. The results provide evidence-based insights for the configuration of catchment areas for new and existing cancer centers providing RT.

[en] Purpose: Comparing radiation therapy utilization rates (RTUR) to those predicted by best evidence is a useful measure of the equity and accessibility of service delivery. In this study the RTUR for melanoma was established for British Columbia, Canada, and compared with the rate suggested by the evidence. Demographic variables, specifically age, gender, and geography that influenced the RTUR were examined with a view to identifying methods of improving underutilization. Methods and Materials: The RTUR in the management of malignant melanoma was taken from British Columbia Cancer registry data for 1986 to 1998. Variations in utilization based on age, gender, health authority, stage of disease, and referral patterns were analyzed. Results: An RTUR of 11% was identified. This was consistent over time. Referral rates decreased between 1986 and 1998. RT is used mostly for later stage disease. Males were more likely to receive RT than females, related to later stage of disease in men. Referral rates decreased, but RTUR for referred cases increased, in health authorities that did not have a cancer center. Conclusions: Use of RT is influenced by age and by stage of disease. Overall RTUR in British Columbia is lower than suggested by best evidence. Referral patterns are influenced by geography. RTUR was higher in males, consistent with a different pattern of disease in males compared with females

[en] The primary objective of this research was to assess the relationship between FPs’ knowledge of palliative radiotherapy (RT) and referral for palliative RT. 1001 surveys were sent to FPs who work in urban, suburban, and rural practices. Respondents were tested on their knowledge of palliative radiotherapy effectiveness and asked to report their self-assessed knowledge. The response rate was 33%. FPs mean score testing their knowledge of palliative radiotherapy effectiveness was 68% (SD = 26%). The majority of FPs correctly identified that painful bone metastases (91%), airway obstruction (77%), painful local disease (85%), brain metastases (76%) and spinal cord compression (79%) can be effectively treated with RT, though few were aware that hemoptysis (42%) and hematuria (31%) can be effectively treated. There was a linear relationship between increasing involvement in palliative care and both self-assessed (p < 0.001) and tested (p = 0.02) knowledge. FPs had higher mean knowledge scores if they received post-MD training in palliative care (12% higher; p < 0.001) or radiotherapy (15% higher; p = 0.002). There was a strong relationship between FPs referral for palliative radiotherapy and both self-assessed knowledge (p < 0.001) and tested knowledge (p = 0.01). Self-assessed and tested knowledge of palliative RT is positively associated with referral for palliative RT. Since palliative RT is underutilized, further research is needed to assess whether family physician educational interventions improve palliative RT referrals. The current study suggests that studies could target family physicians already in practice, with educational interventions focusing on hemostatic and other less commonly known indications for palliative RT

[en] Recent technological advances have led to rapid progress in the characterization of epigenetic modifications that control gene expression in a generally heritable way, and are likely involved in defining cellular phenotypes, developmental stages and disease status from one generation to the next. On November 18, 2013, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) held a symposium entitled “Advances in Assessing Adverse Epigenetic Effects of Drugs and Chemicals” in Washington, D.C. The goal of the symposium was to identify gaps in knowledge and highlight promising areas of progress that represent opportunities to utilize epigenomic profiling for risk assessment of drugs and chemicals. Epigenomic profiling has the potential to provide mechanistic information in toxicological safety assessments; this is especially relevant for the evaluation of carcinogenic or teratogenic potential and also for drugs that directly target epigenetic modifiers, like DNA methyltransferases or histone modifying enzymes. Furthermore, it can serve as an endpoint or marker for hazard characterization in chemical safety assessment. The assessment of epigenetic effects may also be approached with new model systems that could directly assess transgenerational effects or potentially sensitive stem cell populations. These would enhance the range of safety assessment tools for evaluating xenobiotics that perturb the epigenome. Here we provide a brief synopsis of the symposium, update findings since that time and then highlight potential directions for future collaborative efforts to incorporate epigenetic profiling into risk assessment

[en] Purpose: To assess the impact of a population-based intervention to increase the consistency and use of single-fraction radiation therapy (SFRT) for bone metastases. Methods and Materials: In 2012, an audit of radiation therapy prescriptions for bone metastases in British Columbia identified significant interphysician and -center (26%-73%) variation in the use of SFRT. Anonymous physician-level and identifiable regional cancer center SFRT use data were presented to all radiation oncologists, together with published guidelines, meta-analyses, and recommendations from practice leaders. The use of SFRT for bone metastases from 2007 through 2011 was compared with use of SFRT in 2013, to assess the impact of the audit and educational intervention. Multilevel logistic regression was used to assess the relationship between the usage of SFRT and the timing of the radiation while controlling for potentially confounding variables. Physician and center were included as group effects to account for the clustered structure of the data. Results: A total of 16,898 courses of RT were delivered from 2007 through 2011, and 3200 courses were delivered in 2013. The rates of SFRT use in 2007, 2008, 2009, 2010, 2011, and 2013 were 50.5%, 50.9%, 48.3%, 48.5%, 48.0%, and 59.7%, respectively (P<.001). Use of SFRT increased in each of 5 regional centers: A: 26% to 32%; B: 36% to 56%; C: 39% to 57%; D: 49% to 56%; and E: 73% to 85.0%. Use of SFRT was more consistent; 3 of 5 centers used SFRT for 56% to 57% of bone metastases RT courses. The regression analysis showed strong evidence that the usage of SFRT increased after the 2012 intervention (odds ratio 2.27, 95% confidence interval 2.06-2.50, P<.0001). Conclusion: Assessed on a population basis, an audit-based intervention increased utilization of SFRT for bone metastases. The intervention reversed a trend to decreasing SFRT use, reduced costs, and improved patient convenience. This suggests that dissemination of programmatic quality indicators in oncology can lead to increased utilization of evidence-based practice.