Cone beam CT-based adaptive intensity modulated proton therapy assessment using automated planning for head-and-neck cancer.

BACKGROUND: To assess the feasibility of CBCT-based adaptive intensity modulated proton therapy (IMPT) using automated planning for treatment of head and neck (HN) cancers. METHODS: Twenty HN cancer patients who received radiotherapy and had pretreatment CBCTs were included in this study. Initial IMPT plans were created using automated planning software for all patients. Synthetic CTs (sCT) were then created by deforming the planning CT (pCT) to the pretreatment CBCTs. To assess dose calculation accuracy on sCTs, repeat CTs (rCTs) were deformed to the pretreatment CBCT obtained on the same day to create deformed rCT (rCTdef), serving as gold standard. The dose recalculated on sCT and on rCTdef were compared by using Gamma analysis. The accuracy of DIR generated contours was also assessed. To explore the potential benefits of adaptive IMPT, two sets of plans were created for each patient, a non-adapted IMPT plan and an adapted IMPT plan calculated on weekly sCT images. The weekly doses for non-adaptive and adaptive IMPT plans were accumulated on the pCT, and the accumulated dosimetric parameters of two sets were compared. RESULTS: Gamma analysis of the dose recalculated on sCT and rCTdef resulted in a passing rate of 97.9% ± 1.7% using 3 mm/3% criteria. With the physician-corrected contours on the sCT, the dose deviation range of using sCT to estimate mean dose for the most organ at risk (OARs) can be reduced to (- 2.37%, 2.19%) as compared to rCTdef, while for V95 of primary or secondary CTVs, the deviation can be controlled within (- 1.09%, 0.29%). Comparison of the accumulated doses from the adaptive planning against the non-adaptive plans reduced mean dose to constrictors (- 1.42 Gy ± 2.79 Gy) and larynx (- 2.58 Gy ± 3.09 Gy). The reductions result in statistically significant reductions in the normal tissue complication probability (NTCP) of larynx edema by 7.52% ± 13.59%. 4.5% of primary CTVs, 4.1% of secondary CTVs, and 26.8% tertiary CTVs didn't meet the V95 > 95% constraint on non-adapted IMPT plans. All adaptive plans were able to meet the coverage constraint. CONCLUSION: sCTs can be a useful tool for accurate proton dose calculation. Adaptive IMPT resulted in better CTV coverage, OAR sparing and lower NTCP for some OARs as compared with non-adaptive IMPT.

CBCT-Based Adaptive Assessment Workflow for Intensity Modulated Proton Therapy for Head and Neck Cancer.

PURPOSE: Anatomical changes and patient setup uncertainties during intensity modulated proton therapy (IMPT) of head and neck (HN) cancers demand frequent evaluation of delivered dose. This work investigated a cone-beam computed tomography (CBCT) and deformable image registration based therapy workflow to demonstrate the feasibility of proton dose calculation on synthetic computed tomography (sCT) for adaptive IMPT treatment of HN cancer. MATERIALS AND METHODS: Twenty-one patients with HN cancer were enrolled in this study, a retrospective institutional review board protocol. They had previously been treated with volumetric modulated arc therapy and had daily iterative CBCT. For each patient, robust optimization (RO) IMPT plans were generated using ±3 mm patient setup and ±3% proton range uncertainties. The sCTs were created and the weekly delivered dose was recalculated using an adaptive dose accumulation workflow in which the planning computed tomography (CT) was deformably registered to CBCTs and Hounsfield units transferred from the planning CT. Accumulated doses from ±3 mm/±3% RO-IMPT plans were evaluated using clinical dose-volume constraints for targets (clinical target volume, or CTV) and organs at risk. RESULTS: Evaluation of weekly recalculated dose on sCTs showed that most of the patient plans maintained target dose coverage. The primary CTV remained covered by the V95 > 95% (95% of the volume receiving more than 95% of the prescription dose) worst-case scenario for 84.5% of the weekly fractions. The oral cavity accumulated mean dose remained lower than the worst-case scenario for all patients. Parotid accumulated mean dose remained within the uncertainty bands for 18 of the 21 patients, and all were kept lower than RO-IMPT worst-case scenario for 88.7% and 84.5% for left and right parotids, respectively. CONCLUSION: This study demonstrated that RO-IMPT plans account for most setup and anatomical uncertainties, except for large weight-loss changes that need to be tracked throughout the treatment course. We showed that sCTs could be a powerful decision tool for adaptation of these cases in order to reduce workload when using repeat CTs.

Assessment of Oropharyngeal and Laryngeal Cancer Treatment Delay in a Private and Safety Net Hospital System.

Objective To examine the impact of treatment setting and demographic factors on oropharyngeal and laryngeal cancer time to treatment initiation (TTI). Study Design Retrospective case series. Setting Safety net hospital and adjacent private academic hospital. Subjects and Methods Demographic, staging, and treatment details were retrospectively collected for 239 patients treated from January 1, 2014, to June 30, 2016. TTI was defined as days between diagnostic biopsy and initiation of curative treatment (defined as first day of radiotherapy [RT], surgery, or chemotherapy). Results On multivariable analysis, safety net hospital treatment (vs private academic hospital treatment), initial diagnosis at outside hospital, and oropharyngeal cancer (vs laryngeal cancer) were all associated with increased TTI. Surgical treatment, severe comorbidity, and both N1 and N2 status were associated with decreased TTI. Conclusion Safety net hospital treatment was associated with increased TTI. No differences in TTI were found when language spoken and socioeconomic status were examined in the overall cohort.

Intrathoracic extensive-stage small cell lung cancer: assessment of the benefit of thoracic and brain radiotherapy using the SEER database.

BACKGROUND: Extensive-stage small cell lung cancer (ESCLC) includes metastatic disease and locally advanced disease confined to the thorax that cannot be encompassed in a typical radiation portal. We assessed and then compared the benefits of thoracic radiotherapy (TRT) and/or brain radiotherapy (BRT) on overall survival (OS) between the intrathoracic (T-ESCLC) and metastatic (M-ESCLC) groups using the Surveillance Epidemiology and End Results database. METHODS: TRT and BRT data were available for 10150 patients treated from 1988-1997. The T-ESCLC group included 1774 patients. The Kaplan-Meier method was used to estimate OS and the proportional hazards model was used to estimate OS hazard ratios for prognostic factors including age, gender, race, tumor size, T/N stage, TRT, and BRT. RESULTS: The 2-year OS for T-ESCLC was 7.8 % compared to 3 % in the M-ESCLC group (p < 0.001). In the T-ESCLC group, TRT and BRT were delivered to 750 and 102 patients, respectively. The 2-year OS was 13 % in the TRT group compared to 4.1 % in the no-TRT group (p ≤ 0.001) and 22.5 % in the BRT group compared to 7 % in the no-BRT group (p < 0.001). In the M-ESCLC group, TRT and BRT were delivered to 3093 and 1887 patients, respectively. The 2-year OS was 4.4 % in the TRT group compared to 2.8 % in the no-TRT group (p < 0.001) and 4.3 % in the BRT compared to 2.6 % in the no-BRT group (p < 0.001). Age, gender, TRT and BRT were significant OS prognostic factors in both groups. CONCLUSIONS: Our study suggests that T-ESCLC is a disease entity distinct from M-ESCLC. Prospective studies to determine whether TRT should be recommended for the thoracic-only subgroup are warranted.

Physician attitudes and practices related to voluntary error and near-miss reporting.

PURPOSE: Incident learning systems are important tools to improve patient safety in radiation oncology, but physician participation in these systems is poor. To understand reporting practices and attitudes, a survey was sent to staff members of four large academic radiation oncology centers, all of which have in-house reporting systems. METHODS: Institutional review board approval was obtained to send a survey to employees including physicians, dosimetrists, nurses, physicists, and radiation therapists. The survey evaluated barriers to reporting, perceptions of errors, and reporting practices. The responses of physicians were compared with those of other professional groups. RESULTS: There were 274 respondents to the survey, with a response rate of 81.3%. Physicians and other staff agreed that errors and near-misses were happening in their clinics (93.8% v 88.7%, respectively) and that they have a responsibility to report (97% overall). Physicians were significantly less likely to report minor near-misses (P = .001) and minor errors (P = .024) than other groups. Physicians were significantly more concerned about getting colleagues in trouble (P = .015), liability (P = .009), effect on departmental reputation (P = .006), and embarrassment (P < .001) than their colleagues. Regression analysis identified embarrassment among physicians as a critical barrier. If not embarrassed, participants were 2.5 and 4.5 times more likely to report minor errors and major near-miss events, respectively. CONCLUSIONS: All members of the radiation oncology team observe errors and near-misses. Physicians, however, are significantly less likely to report events than other colleagues. There are important, specific barriers to physician reporting that need to be addressed to encourage reporting and create a fair culture around reporting.

Emerging technologies in extracellular vesicle-based molecular diagnostics.

Extracellular vesicles (EVs), including exosomes and microvesicles, have been shown to carry a variety of biomacromolecules including mRNA, microRNA and other non-coding RNAs. Within the past 5 years, EVs have emerged as a promising minimally invasive novel source of material for molecular diagnostics. Although EVs can be easily identified and collected from biological fluids, further research and proper validation is needed in order for them to be useful in the clinical setting. In addition, innovative and more efficient means of nucleic acid profiling are needed to facilitate investigations into the cellular and molecular mechanisms of EV function and to establish their potential as useful clinical biomarkers and therapeutic tools. In this article, we provide an overview of recent technological improvements in both upstream EV isolation and downstream analytical technologies, including digital PCR and next generation sequencing, highlighting future prospects for EV-based molecular diagnostics.

Rural-urban differences in health insurance coverage and patterns among working-age adults in Kentucky.

CONTEXT: Past studies show that rural populations are less likely than urban populations to have health insurance coverage, which may severely limit their access to needed health services. PURPOSE: To examine rural-urban differences in various aspects of health insurance coverage among working-age adults in Kentucky. METHODS: Data are from a household survey conducted in Kentucky in 2005. The respondents include 2,036 individuals ages 18-64. Bivariate analyses were used to compare the rural-urban differences in health insurance coverage by individual characteristics. Logistic regression analyses were used to examine the independent impact of rural-urban residence on the various aspects of health insurance coverage, while controlling for the individuals' health status and sociodemographic characteristics. FINDINGS: The overall rate of working-age adults with health insurance did not differ significantly between the rural and urban areas of Kentucky. However, there were significant rural-urban differences in insurance for specific types of health care and in patterns of insurance coverage. Rural adults were less likely than urban adults to have coverage for vision care, dental care, mental health care, and drug abuse treatment. Rural adults were also less likely to obtain insurance through employment, and their current insurance coverage was, on average, of shorter duration than that of urban adults. CONCLUSIONS: In Kentucky, the overall health insurance rate of working-age adults is influenced more by employment status and income than by whether these individuals reside in rural or urban areas. However, coverage for specific types of care, and coverage patterns, differ significantly by place of residence.

Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity.

We describe a highly efficient microfluidic fluorescence-activated droplet sorter (FADS) combining many of the advantages of microtitre-plate screening and traditional fluorescence-activated cell sorting (FACS). Single cells are compartmentalized in emulsion droplets, which can be sorted using dielectrophoresis in a fluorescence-activated manner (as in FACS) at rates up to 2000 droplets s(-1). To validate the system, mixtures of E. coli cells, expressing either the reporter enzyme beta-galactosidase or an inactive variant, were compartmentalized with a fluorogenic substrate and sorted at rates of approximately 300 droplets s(-1). The false positive error rate of the sorter at this throughput was <1 in 10(4) droplets. Analysis of the sorted cells revealed that the primary limit to enrichment was the co-encapsulation of E. coli cells, not sorting errors: a theoretical model based on the Poisson distribution accurately predicted the observed enrichment values using the starting cell density (cells per droplet) and the ratio of active to inactive cells. When the cells were encapsulated at low density ( approximately 1 cell for every 50 droplets), sorting was very efficient and all of the recovered cells were the active strain. In addition, single active droplets were sorted and cells were successfully recovered.

Functional protein arrays to facilitate drug discovery and development.

Protein microarrays are miniaturized formats for studying proteins. This technology is empowering investigators with the ability to profile numerous types of interactions to progress basic science research and to advance drug discovery and development. Protein microarrays are poised to make significant contributions to our understanding of biology and disease because: (i) both covalent and non-covalent interactions can be reconstituted on solid-state supports; and (ii) a wealth of knowledge can be generated rapidly from such simple experiments. This feature focuses on applications of protein microarrays that have tremendous potential for addressing bottlenecks in disease-focused discovery efforts.

The impact of states' small group health insurance reforms on uninsurance rates.

The impact of states' small group market reforms on uninsurance rates was examined. Reform status was quantified on five reform dimensions: Access Improvement, Premium Reduction, Premium Differential Reduction, Continuity of Coverage, and Enhancing Valued Plan Features. These reform indices were calculated based on actuarial judgment of the market impact potential of each regulation. Regression analysis showed no association between uninsurance rates and the depth of reforms on any dimension, while controlling for income, foreign-born population, black population, and employment in the smallest businesses. Possible reasons for the lack of impact are discussed.

Reducing the numbers of the uninsured: policy implications from state-level data analysis.

The objective of the study described in this article was to identify a model that best predicts state uninsurance rates and quantifies the contribution of socio-economic factors to enable targeted state programs to reduce uninsurance. Linear regression analysis was carried out using state uninsurance rate as the dependent variable and state-level data on demographic, employment, income, and health care environment data (independent variables). For 2000 data, the model R is 0.77, indicating that 77% of the variation in uninsurance rates is explained by the percentage of immigrant population, the workforce in very small businesses, the Black population, the state's median income, and the Medicare-aged population (model R = 0.77 for 1999 and 0.68 for 1998 data). A 1% increase in immigrant population is associated with 0.18% increase in uninsurance rate. A 1% increase in workforce employed in very small businesses associates with 0.79% increase in uninsurance. The findings indicate substantial potential for reducing uninsurance through targeted state policies. Policy recommendations are made to alleviate the insurance hurdles faced by immigrant and small business employee populations.

Socioeconomic differences in health: how much do health behaviors and health insurance coverage account for?

As evidence accumulates that both unhealthy behaviors and inadequate access to health care are responsible in part for poor health, there is a tendency to attribute the differences in health status between the poor and the affluent to the higher prevalence of unhealthy behaviors and inadequate access to health care among people of low socioeconomic status (SES). The purpose of this study is to determine quantitatively how much health behaviors and health insurance coverage account for the SES disparity in health. The study employed secondary analysis of data collected through the Kentucky Behavioral Risk Factor Surveillance System for 2000. After adjusting for health behaviors and health insurance coverage, the differences in health among different levels of SES (measured by education and income) remained strong and significant. Health behaviors and health insurance coverage accounted for 10-16% of the socioeconomic differences in health.

Person and place: the compounding effects of race/ethnicity and rurality on health.

Rural racial/ethnic minorities constitute a forgotten population. The limited research addressing rural Black, Hispanic, and American Indian/Alaska Native populations suggests that disparities in health and in health care access found among rural racial/ethnic minority populations are generally more severe than those among urban racial/ethnic minorities. We suggest that disparities must be understood as both collective and contextual phenomena. Rural racial/ethnic minority disparities in part stem from the aggregation of disadvantaged individuals in rural areas. Disparities also emerge from a context of limited educational and economic opportunity. Linking public health planning to the education and economic development sectors will reduce racial/ethnic minority disparities while increasing overall well-being in rural communities.

Disparities in access to care among rural working-age adults.

CONTEXT: Nationally, minority population disparities in health and in the receipt of health services are well documented but are infrequently examined within rural populations. PURPOSE: The purpose of this study is to provide a national picture of health insurance coverage and access to care among rural minorities. METHODS: A cross-sectional analysis using the 1999-2000 National Health Interview Surveys examined insurance status and receipt of ambulatory care during the past year. Multiple logistic regression was used to measure factors influencing the odds of insurance coverage and a provider visit. FINDINGS: Among rural minority adults, 32% of blacks, 35% of "other" race persons, and 45% of Hispanics were uninsured compared to 18% of whites. Differences in insurance status were not significant for rural blacks and Hispanics after resources such as education, income, and employment were held constant. Examining use, 37% of rural Hispanics and 27% of blacks, versus 20% of whites and 19% of persons of other race, had not made a health care visit in the past year. When resources were held constant, blacks and persons of other race/ethnicity no longer differed from whites, but differences among Hispanics persisted. CONCLUSIONS: A comprehensive approach to the health needs of rural working age adults must consider the unique characteristics of rural communities and populations, requiring cultural as well as financial creativity in the design of health delivery systems. The importance of resources such as education and employment points to the need to link health problems to area-specific rural economic development.

Small group health insurance: ranking the states on the depth of reform, 1999.

States are ranked based on the potential of their small group health insurance reforms to enhance health insurance uptake. Reforms were quantified based on their market impact potential. Five dimensions of reforms were identified, Access Improvement, Premium Reduction, Premium Differential Reduction, Continuity of Coverage, and Enhancing Valued Plan Features. The reform indices representing these dimensions were developed based on document review of state statutes, combined with actuarial judgment to identify and assign scores to market-relevant regulations in line with their impact potential. The distribution of the states' reform scores and rankings show wide variation in the depth and focus of their reforms. Only seven of the top ten states on the Total Reform index had consistently higher scores on two or more reform dimensions. The conceptual linkages between specific regulations and the documented small group market problems lead to normative expectations of an association between the depth of state reforms and the prevalence of uninsurance.

The National Health Service Corps and Medicaid inpatient care: experience in a southern state.

BACKGROUND: Since 1970, the National Health Service Corps (NHSC) has worked to increase primary care access among underserved groups. This study examined whether NHSC alumni physicians were likely to treat a high proportion of Medicaid patients in their practices. METHODS: Using licensure files and hospital discharge data, we identified all physicians practicing in South Carolina who attended at least one discharge in 1998, excluding physicians who graduated before 1969, residents, and current NHSC-obligated physicians. The outcome studied was ranking in the highest quartile for Medicaid participation. RESULTS: Former NHSC participants, after adjustment for personal characteristics, education, and specialty, were nearly twice as likely to fall into the category of high Medicaid participation. NHSC physicians were more likely to practice in community health centers and to locate in areas with a health professions shortage and counties with high percentages of minorities and people living in poverty. CONCLUSION: NHSC alumni make career choices leading them to serve low-income patients.

Potentially preventable care: ambulatory care-sensitive pediatric hospitalizations in South Carolina in 1998.

OBJECTIVE: We examined pediatric hospitalizations to assess personal and community factors affecting potentially preventable ambulatory care-sensitive condition (ACSC) hospitalizations. METHODS: Data came from the South Carolina 1998 Hospital Inpatient Encounter Database, which yielded 10,156 ACSC discharges among 81,808 pediatric hospitalizations. Analyses were performed at three levels: ACSC as a percentage of all hospitalizations, ACSC patients compared with other patients, and county ACSC rates. RESULTS: Younger, male, and nonwhite children; children with Medicaid insurance coverage; and children living in rural areas, health professional shortage area-designated counties, and poorer counties with fewer heath care resources were more likely to be hospitalized with ACSCs. A high percentage of children living in poverty and an absence of federally qualified community health centers were predictive of high county ACSC rates. CONCLUSION: Poverty and the absence of a provider serving low-income children increase ACSC rates. Monitoring changes in ACSC rates can be a tool for studying the effects of policy change.

Prenatal care and infant birth outcomes among Medicaid recipients.

Infant morbidity due to low birth weight and preterm births results in emotional suffering and significant direct and indirect costs. African American infants continue to have worse birth outcomes than white infants. This study examines relationships between newborn hospital costs, maternal risk factors, and prenatal care in Medicaid recipients in an impoverished rural county in South Carolina. Medicaid African American mothers gave birth to fewer preterm infants than did non-Medicaid African American mothers. No differences in the rates of preterm infants were noted between white and African American mothers in the Medicaid group. Access to Medicaid services may have contributed to this reduction in disparities due to race. Early initiation of prenatal care compared with later initiation did not improve birth outcomes. Infants born to mothers who initiated prenatal care early had increased morbidity with increased utilization of hospital services, suggesting that high-risk mothers are entering prenatal care earlier.

Dietary behavior in relation to socioeconomic characteristics and self-perceived health status.

The purposes of this study were to examine the relationship between dietary behavior and self-perceived health status and to demonstrate the relative significance of people's socioeconomic characteristics in relation to their dietary behavior. Data came from the 1994 Behavioral Risk Factor Surveillance System of South Carolina. Descriptive statistics were performed to provide a profile of the general characteristics of the sample. Multivariate linear regression modeling was used to examine the relative significance of socioeconomic status in relation to dietary behavior and the association between dietary behavior and self-perceived general, physical, and mental health status, controlling for other behavioral risk factors, such as smoking and sedentary lifestyle. Socioeconomically disadvantaged individuals with low income and low educational level were more likely to engage in poor dietary practice than were their counterparts. Dietary behavior was found strongly associated with self-perceived general and mental health status.