Racial disparities in COVID-19 vaccination in Canada: results from the cross-sectional Canadian Community Health Survey.

BACKGROUND: Racial and ethnic disparities in COVID-19 vaccination coverage have been observed in Canada and in other countries. We aimed to compare vaccination coverage for at least 1 dose of a COVID-19 vaccine between First Nations people living off reserve and Métis, Black, Arab, Chinese, South Asian and White people. METHODS: We used data collected between June 2021 and June 2022 by Statistics Canada's Canadian Community Health Survey, a large, nationally representative cross-sectional study. The analysis included 64 722 participants aged 18 years or older from the 10 provinces. We used a multiple logistic regression model to determine associations between vaccination status and race, controlling for collection period, region of residence, age, gender and education. RESULTS: Nonvaccination against COVID-19 was more frequent in off-reserve First Nations people (adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 1.2-2.7) and Black people (adjusted OR 1.7, 95% CI 1.1-2.6), and less frequent among South Asian people (adjusted OR 0.3, 95% CI 0.1-0.7) compared to White people. INTERPRETATION: This analysis showed significant inequalities in COVID-19 vaccine uptake between racial/ethnic populations in Canada. Further research is needed to understand the sociocultural, structural and systemic facilitators of and barriers to vaccination across racial groups, and to identify strategies that may improve vaccination uptake among First Nations and Black people.

Toward Systematic Assessment and Improvement of Radiation Therapy Plan Quality of Cooperative Group Trial Submissions: A Report From the Children's Oncology Group.

PURPOSE: This study evaluates the quality of plans used for the treatment of patients in the Children's Oncology Group study ACNS1123. Plan quality is quantified based on a scoring system specific to the protocol. In this way, the distribution of plan quality scores is determined that can be used to identify plan quality issues for this study and for future plan quality improvement. METHODS AND MATERIALS: ACNS1123 stratum 1 patients (70) were evaluated. This included 50 photon and 20 proton plans. Digital Imaging and Communications in Medicine (DICOM) structure and dose data were obtained from the Children's Oncology Group. A commercially available plan quality scoring algorithm was used to create a scoring system we designed using the protocol dosimetric requirements. The whole ventricle and boost planning target volumes (PTVs) could earn a maximum of 70 points, whereas the organs at risk could earn 30 points (total maximum score of 100 points). The scoring algorithm adjusted scores based on the difficulty in achieving the structure dose requirements, which depended on the proximity of the PTVs and the dose gradients achieved relative to the organs at risk. The distribution of plan scores was used to determine the mean, median, and range of scores. RESULTS: The median adjusted plan quality scores for the 20 proton and 50 photon plans were 83.3 and 86.9, respectively. The range of adjusted scores (maximum to minimum) was 50 points. The average score adjustment was 7.4 points. Photon and proton plans performed almost equally. Average plan quality by individual structure revealed that the brain stem, PTV boost, and cochlea lost the most points. CONCLUSIONS: This report is the first to systematically analyze overall radiation therapy plan quality scores for an entire cohort of patients treated in a cooperative group clinical trial. The methodology demonstrated a large variation in plan quality in this trial. Future clinical trials could potentially use this method to reduce plan quality variability, which may improve outcomes.

Measuring inequalities in COVID-19 vaccination uptake and intent: results from the Canadian Community Health Survey 2021.

BACKGROUND: By July 2021, Canada had received enough COVID-19 vaccines to fully vaccinate every eligible Canadian. However, despite the availability of vaccines, some eligible individuals remain unvaccinated. Differences in vaccination uptake can be driven by health inequalities which have been exacerbated and amplified by the pandemic. This study aims to assess inequalities in COVID-19 vaccination uptake and intent in adults 18 years or older across Canada by identifying sociodemographic factors associated with non-vaccination and low vaccination intent using data drawn from the June to August 2021 Canadian Community Health Survey (CCHS). METHODS: The CCHS is an annual cross-sectional and nationally representative survey conducted by Statistics Canada, which collects health-related information. Since September 2020, questions about the COVID-19 pandemic are asked. Adjusted logistic regression models were fitted to examine associations between vaccination uptake or intent and sociodemographic and health related variables. Region, age, gender, level of education, Indigenous status, visible minority status, perceived health status, and having a regular healthcare provider were considered as predictors, among other factors. RESULTS: The analysis included 9,509 respondents. The proportion of unvaccinated was 11%. Non-vaccination was associated with less than university education (aOR up to 3.5, 95% CI 2.1-6.1), living with children under 12 years old (aOR 1.6, 95% CI 1.1-2.4), not having a regular healthcare provider (aOR 1.6, 95% CI 1.1-2.2), and poor self-perceived health (aOR 1.8, 95% CI 1.3-2.4). Only 5% of the population had low intention to get vaccinated. Being unlikely to get vaccinated was associated with the Prairies region (aOR 2.2, 95% CI 1.2-4.1), younger age groups (aOR up to 4.0, 95% CI 1.3-12.3), less than university education (aOR up to 3.8, 95% CI 1.9-7.6), not being part of a visible minority group (aOR 3.0, 95% CI 1.4-6.4), living with children under 12 years old (aOR 1.8, 95% CI 1.1-2.9), unattached individuals (aOR 2.6, 95% CI 1.1-6.1), and poor self-perceived health (aOR 2.0, 95% CI 1.3-2.9). CONCLUSIONS: Disparities were observed in vaccination uptake and intent among various sociodemographic groups. Awareness of inequalities in COVID-19 vaccination uptake and intent is needed to determine the vaccination barriers to address in vaccination promotion strategies.

Using Health Economics to Inform Immunization Policy Across All Levels of Government.

Publicly funded immunization programs have grown in both complexity and scope, resulting in increased costs and more complex programmatic decision making. Economic evaluations can provide crucial information to support informed decision making. While very few countries have National Immunization Technical Advisory Groups that analyze economic information, many have started to develop processes for this purpose. Since these guidelines are being developed at the national level, we propose that regional jurisdictions, especially those responsible for healthcare (e.g., provinces, territories, states), need clear processes for incorporating this information into their immunization decision making and program implementation. We interviewed Canadian vaccine experts involved in provincial vaccine policy decision making to identify current practices, perceptions, and recommendations around incorporating economic analysis into that process. Based on these interviews, we make five recommendations: (1) economic evidence should be routinely incorporated into the decision making process; (2) economic experts should sit on, or be available to, regional advisory committees; (3) efforts should be made to build on regional expertise by increasing educational opportunities on economic evaluation; (4) processes should include guidelines for when economic analysis is not required; and (5) clarification on the role of regional advisory groups in economic analysis is needed in relation to national expertise. The information presented here provides a starting point for regional health policy experts and decision makers to work collaboratively with national partners to create transparent and effective approaches to incorporating economic analysis into vaccine decision making.

Evaluating the Individual Healthcare Costs and Burden of Disease Associated with RSV Across Age Groups.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of acute respiratory infection (ARI), with high morbidity and mortality worldwide. RSV costing and burden estimates can highlight the potential benefits of future vaccination programs and are essential for economic evaluations. OBJECTIVE: We aimed to determine RSV healthcare costs across age groups and the overall disease burden of medically attended RSV in Canada. METHODS: We conducted a retrospective case-control study to estimate the attributable healthcare costs per RSV case in Alberta. We used two case definitions to capture diversity in case severity: laboratory-confirmed RSV and ARI attributable to RSV. Matching occurred on five criteria: (1) age, (2) urban/rural status, (3) sex, (4) prematurity and (5) Charlson Comorbidity Index score. We calculated the age-specific burden of medically attended RSV in Canada from 2010 to 2019 by multiplying the weekly age-specific incidence of medically attended ARI with the RSV positivity rate. RESULTS: Costs per laboratory-confirmed RSV case were (in Canadian dollars [CAD], year 2020 values) $CAD12,713 and 40,028 in the first 30 and 365 days following diagnosis, respectively, whereas a case of ARI potentially attributable to RSV cost $CAD316 and 915, in 30 and 365 days, respectively. Older (aged ≥ 65 years) and younger (aged < 90 days) age groups had the highest case costs. The average medically attended RSV incidence rate across nine seasons was 1743 cases per 100,000 people per year. CONCLUSIONS: RSV is a common and expensive infection at the extremes of life, and the development of immunization programs targeting older and younger ages may be important for the reduction of RSV burden and cost.

Imaging response assessment for CNS germ cell tumours: consensus recommendations from the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group.

Homogeneous and common objective disease assessments and standardised response criteria are important for better international clinical trials for CNS germ cell tumours. Currently, European protocols differ from those of North America (the USA and Canada) in terms of criteria to assess radiological disease response. An international working group of the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group was therefore established to review existing literature and current practices, identify major challenges regarding imaging assessment, and develop consensus recommendations for imaging response assessment for patients with CNS germ cell tumours. New clinical imaging standards were defined for the most common sites of CNS germ cell tumour and for the definition of locoregional extension. These new standards will allow the evaluation of response to therapy in patients with CNS germ cell tumours to be more consistent, and facilitate direct comparison of treatment outcomes across international studies.

Background incidence rates of hospitalisations and emergency department visits for thromboembolic and coagulation disorders in Ontario, Canada for COVID-19 vaccine safety assessment: a population-based retrospective observational study.

OBJECTIVE: The objective of this study was to estimate background rates of selected thromboembolic and coagulation disorders in Ontario, Canada. DESIGN: Population-based retrospective observational study using linked health administrative databases. Records of hospitalisations and emergency department visits were searched to identify cases using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada diagnostic codes. PARTICIPANTS: All Ontario residents. PRIMARY OUTCOME MEASURES: Incidence rates of ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, deep vein thrombosis, pulmonary embolism, idiopathic thrombocytopaenia, disseminated intravascular coagulation and cerebral venous thrombosis during five prepandemic years (2015-2019) and 2020. RESULTS: The average annual population was 14 million with 51% female. The mean annual rates per 100 000 population during 2015-2019 were 127.1 (95% CI 126.2 to 127.9) for ischaemic stroke, 22.0 (95% CI 21.6 to 22.3) for intracerebral haemorrhage, 9.4 (95% CI 9.2 to 9.7) for subarachnoid haemorrhage, 86.8 (95% CI 86.1 to 87.5) for deep vein thrombosis, 63.7 (95% CI 63.1 to 64.3) for pulmonary embolism, 6.1 (95% CI 5.9 to 6.3) for idiopathic thrombocytopaenia, 1.6 (95% CI 1.5 to 1.7) for disseminated intravascular coagulation, and 1.5 (95% CI 1.4 to 1.6) for cerebral venous thrombosis. Rates were lower in 2020 than during the prepandemic years for ischaemic stroke, deep vein thrombosis and idiopathic thrombocytopaenia. Rates were generally consistent over time, except for pulmonary embolism, which increased from 57.1 to 68.5 per 100 000 between 2015 and 2019. Rates were higher for females than males for subarachnoid haemorrhage, pulmonary embolism and cerebral venous thrombosis, and vice versa for ischaemic stroke and intracerebral haemorrhage. Rates increased with age for most of these conditions, but idiopathic thrombocytopaenia demonstrated a bimodal distribution with incidence peaks at 0-19 years and ≥60 years. CONCLUSIONS: Our estimated background rates help contextualise observed events of these potential adverse events of special interest and to detect potential safety signals related to COVID-19 vaccines.

Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee.

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research.

End-of-Range Radiobiological Effect on Rib Fractures in Patients Receiving Proton Therapy for Breast Cancer.

PURPOSE: A prospective trial of proton therapy for breast cancer revealed an increased rib fracture rate of 7%, which is higher than the expected rate based on the literature on photon therapies. We aim to evaluate the hypothesis that the increased relative biological effectiveness (RBE) at the distal edge of proton beams is the cause. METHODS AND MATERIALS: We combined the cohort from the prospective clinical trial and a retrospective cohort from a database. Monte Carlo simulations were performed to recalculate the physical dose and dose-averaged linear energy transfer (LETd). The first 10 ribs and fracture areas in patients with fractures were contoured and deformably registered. The LETd-weighted dose was used as a surrogate for biological effectiveness and compared with the conventional fixed RBE of 1.1. Dose to 0.5 cm3 of the ribs (D0.5) was selected to analyze the dose-response relationship using logistic regression. We chose an alpha/beta ratio of 3 to calculate the biological effective dose in Gy3(RBE). RESULTS: Thirteen of 203 patients in the cohorts exhibited a total of 25 fractures. The LETd in fractured areas is increased (6.1 ± 2.0 keV/µm, mean ± standard deviation), suggesting possible end-of-range radiobiological effects with increased RBE. The D0.5 of the fractured ribs is 80.3 ± 9.4 Gy3(RBE) with a generic factor of 1.1 and is relatively low compared with historical photon results. On the other hand, the D0.5 of the fractured ribs is 100.0 ± 12.5 Gy3(RBE) using the LETd-based model with a dose-response curve that is more consistent with historical photon data. CONCLUSIONS: The increased rib fracture rate seen in our trial is probably associated with the increased LETd and RBE at the distal edge of proton beams. This phenomenon warrants further investigation and possible integration of LETd into treatment planning and optimization in proton therapy.

Immunization Coverage of Children in Care of the Child Welfare System in High-Income Countries: A Systematic Review.

CONTEXT: Children in care of the child welfare system tend to underutilize preventive health services compared with other children. The purpose of this systematic review was to assess current knowledge regarding immunization coverage levels for children in the child welfare system and to determine barriers and supports to them utilizing immunization services. EVIDENCE ACQUISITION: Articles published in Medline, Embase, Cochrane Library, CINAHL, SocINDEX, and ERIC from January 1, 2000 to October 13, 2017 were searched. Thesis and conference databases and relevant websites were also examined. Studies were included if written in English, from high-income countries, and addressed immunizations for children in the child welfare system. Independent dual screening, extraction, and quality appraisal were conducted between October 2016 and December 2017, followed by narrative synthesis. EVIDENCE SYNTHESIS: Of 2,906 records identified, 33 met inclusion criteria: 21 studied coverage, two studied barriers/supports, and ten studied both. Nineteen studies were moderate or high quality and thus included in the narrative synthesis; 15 studied coverage, one studied barriers/supports, and three studied both. Most studies found lower coverage among children in child welfare. The few studies that explicitly studied barriers/supports to immunization identified that a collaborative and coordinated approach between health and social services was key to service delivery to this population. CONCLUSIONS: This review highlights that children in care of the child welfare system are at risk of poor immunization coverage. There is a need for high-quality studies on this issue, with a focus on assessing supports/barriers to immunization in this population.

Quality of life in patients with proton-treated pediatric medulloblastoma: Results of a prospective assessment with 5-year follow-up.

BACKGROUND: To the authors' knowledge, health-related quality of life (HRQOL) outcomes are not well described in patients with medulloblastoma. The use of proton radiotherapy (RT) may translate into an improved HRQOL. In the current study, the authors report long-term HRQOL in patients with proton-treated pediatric medulloblastoma. METHODS: The current study was a prospective cohort HRQOL study of patients with medulloblastoma who were treated with proton RT and enrolled between August 5, 2002, and October 8, 2015. Both child report and parent-proxy report Pediatric Quality of Life Inventory (PedsQL) surveys were collected at baseline during RT and annually thereafter (score range on surveys of 0-100, with higher scores indicating better HRQOL). Patients were dichotomized by clinical/treatment variables and subgroups were compared. Mixed-model analysis was performed to determine the longitudinal trajectory of PedsQL scores. The Student t test was used to compare long-term HRQOL measures with published means from a healthy child population. RESULTS: Survey data were evaluable for 116 patients with a median follow-up of 5 years (range, 1-10.6 years); the median age at the time of diagnosis was 7.6 years (range, 2.1-18.1 years). At baseline, children reported a total core score (TCS) of 65.9, which increased by 1.8 points annually (P<.001); parents reported a TCS of 59.1, which increased by 2.0 points annually. Posterior fossa syndrome adversely affected baseline scores, but these scores significantly improved with time. At the time of last follow-up, children reported a TCS of 76.3, which was 3.3 points lower than that of healthy children (P = .09); parents reported a TCS of 69, which was 11.9 points lower than that of parents of healthy children (P<.001). Increased follow-up time from diagnosis correlated with improved HRQOL scores. CONCLUSIONS: HRQOL scores appear to increase over time after treatment in children treated with proton RT for medulloblastoma but remain lower compared with those of parent-proxy reports as well as published means from a healthy normative sample of children. Additional follow-up may translate into continued improvements in HRQOL. Cancer 2018. © 2018 American Cancer Society.

Proton therapy for pediatric malignancies: Fact, figures and costs. A joint consensus statement from the pediatric subcommittee of PTCOG, PROS and EPTN.

Radiotherapy plays an important role in the management of childhood cancer, with the primary aim of achieving the highest likelihood of cure with the lowest risk of radiation-induced morbidity. Proton therapy (PT) provides an undisputable advantage by reducing the radiation 'bath' dose delivered to non-target structures/volume while optimally covering the tumor with tumoricidal dose. This treatment modality comes, however, with an additional costs compared to conventional radiotherapy that could put substantial financial pressure to the health care systems with societal implications. In this review we assess the data available to the oncology community of PT delivered to children with cancer, discuss on the urgency to develop high-quality data. Additionally, we look at the advantage of combining systemic agents with protons and look at the cost-effectiveness data published so far.

Can differences in linear energy transfer and thus relative biological effectiveness compromise the dosimetric advantage of intensity-modulated proton therapy as compared to passively scattered proton therapy?

PURPOSE: To investigate the effect of differences in linear energy transfer (LET) and thus the relative biological effectiveness (RBE) between passively scattered proton therapy (PS) and pencil-beam scanning intensity-modulated proton therapy (IMPT). METHODS: IMPT treatment plans were generated for six ependymoma patients, originally treated with PS, using the original plan's computed tomography image sets and beam directions, and its dose-volume values as optimization constraints. Two beam spot sizes and both single-field optimization (SFO) and multi-field optimization (MFO) techniques were used for each patient. Three-dimensional variable-RBE-weighted dose distributions were computed, using Monte Carlo calculated dose and LET distributions, and a linear dose and LET-based RBE model, and were compared between the two delivery methods. RESULTS: Increased target dose coverage and decreased mean and maximum dose to the OARs was achieved with IMPT compared to PS, for constant RBE value of 1.1. Nevertheless, the maximum variable-RBE-weighted dose to the brainstem, was increased up to 6% for the IMPT plans compared to the corresponding PS plans. CONCLUSIONS: IMPT can be dosimetrically superior to PS for ependymoma patients. However, caution should be exercised so that the increased dose conformity is not counteracted by an increase in radiobiological effect in adjacent critical structures.

Methods used for immunization coverage assessment in Canada, a Canadian Immunization Research Network (CIRN) study.

Accurate and complete immunization data are necessary to assess vaccine coverage, safety and effectiveness. Across Canada, different methods and data sources are used to assess vaccine coverage, but these have not been systematically described. Our primary objective was to examine and describe the methods used to determine immunization coverage in Canada. The secondary objective was to compare routine infant and childhood coverage estimates derived from the Canadian 2013 Childhood National Immunization Coverage Survey (cNICS) with estimates collected from provinces and territories (P/Ts). We collected information from key informants regarding their provincial, territorial or federal methods for assessing immunization coverage. We also collected P/T coverage estimates for select antigens and birth cohorts to determine absolute differences between these and estimates from cNICS. Twenty-six individuals across 16 public health organizations participated between April and August 2015. Coverage surveys are conducted regularly for toddlers in Quebec and in one health authority in British Columbia. Across P/Ts, different methodologies for measuring coverage are used (e.g., valid doses, grace periods). Most P/Ts, except Ontario, measure up-to-date (UTD) coverage and 4 P/Ts also assess on-time coverage. The degree of concordance between P/T and cNICS coverage estimates varied by jurisdiction, antigen and age group. In addition to differences in the data sources and processes used for coverage assessment, there are also differences between Canadian P/Ts in the methods used for calculating immunization coverage. Comparisons between P/T and cNICS estimates leave remaining questions about the proportion of children fully vaccinated in Canada.

Evaluating Intensity Modulated Proton Therapy Relative to Passive Scattering Proton Therapy for Increased Vertebral Column Sparing in Craniospinal Irradiation in Growing Pediatric Patients.

PURPOSE: At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. METHODS AND MATERIALS: Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (-35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4 Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system. RESULTS: IMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10 Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20 Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher. CONCLUSIONS: Advanced proton techniques can sufficiently reduce the dose to the vertebral body and allow for vertebral column growth for children with central nervous system tumors requiring CSI. This was true even when considering variable RBE values. A clinical trial is planned for VBS to the thoracic and lumbosacral spine in growing children.

Individual Preferences for Child and Adolescent Vaccine Attributes: A Systematic Review of the Stated Preference Literature.

BACKGROUND: Discrete choice experiments are increasingly used to assess preferences for vaccines and vaccine service delivery. OBJECTIVES: To synthesize and critically assess the application of discrete choice experiments in childhood/adolescent vaccines, to describe how discrete choice experiments have been applied to understand preferences, and to evaluate the use of discrete choice experiment data to inform estimates of vaccine uptake. METHODS: We conducted a systematic review of six electronic databases. Included studies were discrete choice experiments and conjoint analyses published from 2000 to 2016 related to childhood/adolescent vaccines where respondents were parents, children/adolescents, or service providers. Validity assessment was used to assess study quality and risk of bias. RESULTS: In total, 27 articles were included, representing 21 different studies. A majority of articles were published between 2011 and 2016. Vaccines studied included human papillomavirus (24%), influenza (19%), meningococcal vaccines (14%), childhood vaccines (14%), hypothetical vaccines (10%), hepatitis B (5%), and diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae type b (5%). Most studies assessed parent preferences (67%). The most common attributes were risk (24%), degree/duration of protection (21%), and cost (15%). Commonly reported outcome measures were estimates of uptake (33%), willingness-to-pay (22%), and other marginal rates of substitution (14%). Validity assessments yielded high scores overall. Areas of weakness included low response rates, inefficient experimental design, and failure to conduct formative qualitative work and a pilot of the discrete choice experiment. CONCLUSION: This is the first systematic review of childhood/adolescent vaccine-related discrete choice experiments. In future, special attention should be paid to ensuring that choice context and discrete choice experiment design are compatible to generate reliable estimates of uptake.

Proton Treatment Techniques for Posterior Fossa Tumors: Consequences for Linear Energy Transfer and Dose-Volume Parameters for the Brainstem and Organs at Risk.

PURPOSE: In proton therapy of posterior fossa tumors, at least partial inclusion of the brainstem in the target is necessary because of its proximity to the tumor and required margins. Additionally, the preferred beam geometry results in directing the field distal edge toward this critical structure, raising concerns for brainstem toxicity. Some treatment techniques place the beam's distal edge within the brainstem (dose-sparing techniques), and others avoid elevated linear energy transfer (LET) of the proton field by placing the distal edge beyond it (LET-sparing techniques). Hybrid approaches are also being used. We examine the dosimetric efficacy of these techniques, accounting for LET-dependent and dose-dependent variable relative biologic effectiveness (RBE) distributions. METHODS: Six techniques were applied in ependymoma cases: (a) 3-field dose-sparing; (b) 3-field LET-sparing; (c) 2-field dose-sparing, wide angles; (d) 2-field LET-sparing, wide angles; (e) 2-field LET-sparing, steep angles; and (f) 2-field LET-sparing with feathered distal end. Monte Carlo calculated dose, LET, and RBE-weighted dose distributions were compared. RESULTS: Decreased LET values in the brainstem by LET-sparing techniques were accompanied by higher, not statistically significant, median dose: 53.6 Gy(RBE), 53.4 Gy(RBE), and 54.3 Gy(RBE) for techniques (b), (d), and (e) versus 52.1 Gy(RBE) for technique (a). Accounting for variable RBE distributions, the brainstem volume receiving at least 55 Gy(RBE) increased from 72.5% for technique (a) to 80.3% for (b) (P<.01) and from 70.7% for technique (c) to 77.6% for (d) (P<.01). Less than 2%, but statistically significant, decrease in maximum variable RBE-weighted brainstem dose was observed for the LET-sparing techniques compared with the corresponding dose-sparing (P=.03 and .004). CONCLUSIONS: Extending the proton range beyond the brainstem to reduce LET results in clinically comparable maximum radiobiologic effective dose to this sensitive structure. However this method significantly increasing the brainstem volume receiving RBE-weighted dose higher than 55 Gy(RBE) with possible consequences based on known dose-volume parameters for increased toxicity.

Establishing Cost-Effective Allocation of Proton Therapy for Breast Irradiation.

PURPOSE: Cardiac toxicity due to conventional breast radiation therapy (RT) has been extensively reported, and it affects both the life expectancy and quality of life of affected women. Given the favorable oncologic outcomes in most women irradiated for breast cancer, it is increasingly paramount to minimize treatment side effects and improve survivorship for these patients. Proton RT offers promise in limiting heart dose, but the modality is costly and access is limited. Using cost-effectiveness analysis, we provide a decision-making tool to help determine which breast cancer patients may benefit from proton RT referral. METHODS AND MATERIALS: A Markov cohort model was constructed to compare the cost-effectiveness of proton versus photon RT for breast cancer management. The model was analyzed for different strata of women based on age (40 years, 50 years, and 60 years) and the presence or lack of cardiac risk factors (CRFs). Model entrants could have 1 of 3 health states: healthy, alive with coronary heart disease (CHD), or dead. Base-case analysis assumed CHD was managed medically. No difference in tumor control was assumed between arms. Probabilistic sensitivity analysis was performed to test model robustness and the influence of including catheterization as a downstream possibility within the health state of CHD. RESULTS: Proton RT was not cost-effective in women without CRFs or a mean heart dose (MHD) <5 Gy. Base-case analysis noted cost-effectiveness for proton RT in women with ≥1 CRF at an approximate minimum MHD of 6 Gy with a willingness-to-pay threshold of $100,000/quality-adjusted life-year. For women with ≥1 CRF, probabilistic sensitivity analysis noted the preference of proton RT for an MHD ≥5 Gy with a similar willingness-to-pay threshold. CONCLUSIONS: Despite the cost of treatment, scenarios do exist whereby proton therapy is cost-effective. Referral for proton therapy may be cost-effective for patients with ≥1 CRF in cases for which photon plans are unable to achieve an MHD <5 Gy.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury.

BACKGROUND: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. METHODS AND MATERIALS: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. RESULTS: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). CONCLUSIONS: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE): epidemiology, emerging organisms, and economics.

BACKGROUND: Each year in Canada there are 5 million episodes of acute gastroenteritis (AGE) with up to 70% attributed to an unidentified pathogen. Moreover, 90% of individuals with AGE do not seek care when ill, thus, burden of disease estimates are limited by under-diagnosing and under-reporting. Further, little is known about the pathogens causing AGE as the majority of episodes are attributed to an "unidentified" etiology. Our team has two main objectives: 1) to improve health through enhanced enteric pathogen identification; 2) to develop economic models incorporating pathogen burden and societal preferences to inform enteric vaccine decision making. METHODS/DESIGN: This project involves multiple stages: 1) Molecular microbiology experts will participate in a modified Delphi process designed to define criteria to aid in interpreting positive molecular enteric pathogen test results. 2) Clinical data and specimens will be collected from children aged 0-18 years, with vomiting and/or diarrhea who seek medical care in emergency departments, primary care clinics and from those who contact a provincial medical advice line but who do not seek care. Samples to be collected will include stool, rectal swabs (N = 2), and an oral swab. Specimens will be tested employing 1) stool culture; 2) in-house multiplex (N = 5) viral polymerase chain reaction (PCR) panel; and 3) multi-target (N = 15) PCR commercially available array. All participants will have follow-up data collected 14 days later to enable calculation of a Modified Vesikari Scale score and a Burden of Disease Index. Specimens will also be collected from asymptomatic children during their well child vaccination visits to a provincial public health clinic. Following the completion of the initial phases, discrete choice experiments will be conducted to enable a better understanding of societal preferences for diagnostic testing and vaccine policy. All of the results obtained will be integrated into economic models. DISCUSSION: This study is collecting novel samples (e.g., oral swabs) from previously untested groups of children (e.g., those not seeking medical care) which are then undergoing extensive molecular testing to shed a new perspective on the epidemiology of AGE. The knowledge gained will provide the broadest understanding of the epidemiology of vomiting and diarrhea of children to date.