Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity. ^

Impact of a modified dietary plan on the health related quality of life of minority participants in the Women's Healthy Eating and Living (WHEL) Study

Advances in medical technology, in genetics, and in clinical research have led to early detection of cancer, precise diagnosis, and effective treatment modalities. Decline in cancer incidence and mortality due to cancer has led to increased number of long-term survivors. However, the ethnic minority population has not experienced this decline and still continues to carry a disparate proportion of the cancer burden. Majority of the clinical research including survivorship studies have recruited and continue to recruit a convenient sample of middle- to upper-class Caucasian survivors. Thus, minorities are underrepresented in cancer research in terms of both clinical studies and in health related quality of life (HRQOL) studies. ^ Life style and diet have been associated with increased risk of breast cancer. High vegetable low fat diet has been shown to reduce recurrence of breast cancer and early death. The Women's Healthy Eating and Living Study is an ongoing multi-site randomized controlled trial that is evaluating the high-vegetable low fat diet in reducing the recurrence of breast cancer and early death. The purpose of this dissertation was to (1) compare the impact of the modified diet on the HRQOL during the first 12-month period on specific Minorities and matched Caucasians; (2) identify predictors that significantly impact the HRQOL of the study participants; and (3) using the structural equation modeling assess the impact of nutrition on the HRQOL of the intervention group participants. Findings suggest that there are no significant differences in change in HRQOL between Minorities and Caucasians; between Minorities in the intervention group and those in the comparison group; and between women in the intervention group and those in the comparison group. Minority indicator variable and Intervention/Comparison group indicator variable were not found to be good predictors of HRQOL. Although the structural equation models suggested viable representation of the relationship between the antecedent variables, the mediating variables and the two outcome variables, the impact of nutrition was not statistically significant to be included in the model. This dissertation, by analyzing the HRQOL of minorities in the WHEL Study, attempted to add to the knowledge base specific to minority cancer survivors. ^

Sleep quality and quantity and associated factors among high school students from south Texas

Background. Insufficient and poor quality sleep among adolescents affects not only the cognitive functioning, but overall health of the individual. Existing research suggests that adolescents from varying ethnic groups exhibit differing sleep patterns. However, little research focuses on sleep patterns and associated factors (i.e. tobacco use, mental health indicators) among Hispanic youth. ^ Methods. The study population (n=2,536) included students in grades 9-12 who attended one of the three public high schools along the Texas-Mexico border in 2003. This was a cross sectional study using secondary data collected via a web-based, confidential, self-administered survey. Separate logistic regression models were estimated to identify factors associated with reduced (<9 hours/night) and poor quality sleep on average during weeknights. ^ Results. Of participants, 49.5% reported reduced sleep while 12.8% reported poor quality sleep. Factors significantly (p<0.05) associated with poor quality sleep were: often feeling stressed or anxious (OR=5.49), being born in Mexico (OR=0.65), using a computer/playing video games 15+ hours per week (OR=2.29), working (OR=1.37), being a current smoker (OR=2.16), and being a current alcohol user (OR=1.64). Factors significantly associated with reduced quantity of sleep were: often feeling stressed or anxious (OR=2.74), often having headaches/stomachaches (OR=1.77), being a current marijuana user (OR=1.70), being a current methamphetamine user (OR=4.92), and being a current alcohol user (OR=1.27). ^ Discussion. Previous research suggests that there are several factors that can influence sleep quality and quantity in adolescents. This paper discusses these factors (i.e. work, smoking, alcohol, etc.) found to be associated with poor sleep quality and reduced sleep quantity in the Hispanic adolescent population. A reduced quantity of sleep (81.20% of the participants) and a poor quality of sleep (12.80% of the participants) were also found in high school students from South Texas. ^

Concordance between medical records and personal interview in ascertaining breast cancer and diabetes status: Analysis of the south Texas women's health project

Accurate ascertainment of risk factors and disease status is vital in public health research for proper classification of research subjects. The two most common ways of obtaining this data is by self-report and review of medical records (MRs). South Texas Women’s Health Project was a case-control study looking at interrelationships between hormones, diet, and body size and breast cancer among Hispanic women 30-79 years of age. History of breast cancer, diabetes mellitus (DM) and use of DM medications was ascertained from a personal interview. At the time of interview, the subject identified her major health care providers and signed the medical records release form, which was sent to the designated providers. The MRs were reviewed to confirm information obtained from the interview.^ Aim of this study was to determine the sensitivity and specificity between MRs and personal interview in diagnosis of breast cancer, DM and DM treatment. We also wanted to assess how successful our low-cost approach was in obtaining pertinent MRs and what factors influenced the quality of MR or interview data. Study sample was 721 women with both self-report and MR data available by June 2007. Overall response rate for MR requests was 74.5%. MRs were 80.9% sensitive and 100% specific in confirming breast cancer status. Prevalence of DM was 22.7% from the interviews and 16% from MRs. MRs did not provide definite information about DM status of 53.6% subjects. Sensitivity and specificity of MRs for DM status was 88.9% and 90.4% respectively. Disagreement on DM status from the two sources was seen in 15.9% subjects. This discordance was more common among older subjects, those who were married and were predominantly Spanish speaking. Income and level of education did not have a statistically significantly association with this disagreement.^ Both self-report and MRs underestimate the prevalence of DM. Relying solely on MRs leads to greater misclassification than relying on self-report data. MRs have good to excellent specificity and thus serve as a good tool to confirm information obtained from self-report. Self-report and MRs should be used in a complementary manner for accurate assessment of DM and breast cancer status.^

Physical activity among breast and prostate cancer survivors: Barriers, facilitators and maintenance following the FRESH START trial

Research provides evidence of the positive health effects associated with regular physical activity participation in all populations. Activity may prove to be especially beneficial in those with chronic conditions such as cancer. However, the majority of cancer patients and survivors do not participate in the recommended amount of physical activity. The purpose of this dissertation was to identify factors associated with physical activity participation, describe how these factors change as result of a diet and exercise intervention, and to evaluate correlates of long term physical activity maintenance. ^ For this dissertation, I analyzed data from the FRESH START trial, a randomized, single-blind, phase II clinical trial focused on improving diet and physical activity among recently diagnosed breast and prostate cancer survivors. Analyses included both parametric and non-parametric statistical tests. Three separate studies were conducted, with sample sizes ranging from 400 to 486. ^ Common barriers to exercise, such as “no willpower,” “too busy,” and “I have pain,” were reported among breast and prostate cancer survivors; however, these barriers were not significantly associated with minutes of physical activity. Breast cancer survivors reported a greater number of total barriers to exercise as well as higher proportions reporting individual barriers, compared to prostate cancer survivors. Just less than half of participants reduced their total number of barriers to exercise from baseline to 1-year follow-up, and those who did reduce barriers reported greater increases in minutes of physical activity compared to those who reported no change in barriers to exercise. Participants in both the tailored and standardized intervention groups reported greater minutes of physical activity at 2-year follow-up compared to baseline. Overall, twelve percent of participants reached recommended levels of physical activity at both 1- and 2-year follow-up. Self-efficacy was positively associated with physical activity maintenance, and the number of total barriers to exercise was inversely associated with physical activity maintenance. ^ Results from this dissertation are novel and informative, and will help to guide future physical activity interventions among cancer survivors. Thoughtfully designed interventions may encourage greater participation in physical activity and ultimately improve overall quality of life in this population. ^

Long Term Follow-up of Morbidity and Quality of Life Associated with Isolated Gastroschisis

Gastroschisis is a birth defect in which an opening in the abdominal wall allows herniation of the viscera. Prenatal counseling regarding gastroschisis typically discusses that, although these infants often endure a difficult neonatal course, they experience few long-term complications. However, information regarding long-term outcomes is based on limited studies that lack specificity. Therefore, we aimed to study the long-term morbidity and quality of life in children born with gastroschisis in a large and diverse population drawn from the Texas Birth Defects Registry (TBDR). Study packets with informed consent, a questionnaire, and the Pediatric Quality of Life Inventory Generic Core Scale 4.0 (PedsQL 4.0) in English and Spanish were mailed to 1,112 parents of children born with isolated gastroschisis in Texas between 1999 and 2008 via the TBDR. Information was abstracted from the TBDR for 58 mothers of children with gastroschisis who returned study materials. Three hundred fifty five packets were returned to sender, giving a response rate of 7.7%. Children born with gastroschisis had quality of life scores that were not significantly different than expected (p = 0.981). However, factors such as having a learning disability (p = 0.001) and missing school due to gastrointestinal issues (p = 0.020) were found to significantly decrease quality of life. Overall, children with gastroschisis had a significantly increased risk for learning disabilities regardless of whether they were preterm (p = 0.021) or full term (p = 0.021). Additionally, there appeared to be an increased risk for auditory impairment in Caucasian children (p < 0.0005). Therefore, while overall long-term quality of life is not significantly altered for children born with gastroschisis, the previously unreported increased risk for learning disabilities and possible association with hearing impairment are important findings that should be conveyed to prospective parents.

Acceleration of the PanIN Development in Mice Expressing Oncogenic K-Ras Due to a High Fat Diet

Obesity is postulated to be one of the major risk factors for pancreatic cancer, and recently it was indicated that an elevated body mass index (BMI correlates strongly with a decrease in patient survival. Despite the evident relationship, the molecular mechanisms involved are unclear. Oncogenic mutation of K-Ras is found early and is universal in pancreatic cancer. Extensive evidence indicates oncogenic K-Ras is not entirely active and it requires a triggering event to surpass the activity of Ras beyond the threshold necessary for a Ras-inflammation feed-forward loop. We hypothesize that high fat intake induces a persistent low level inflammatory response triggering increased K-Ras activity and that Cox-2 is essential for this inflammatory reaction. To determine this, LSL-K-Ras mice were crossed with Ela-CreER (Acinar-specific) or Pdx-1-Cre (Pancreas-specific) to “knock-in” oncogenic K-Ras. Additionally, these animals were crossed with Cox-2 conditional knockout mice to access the importance of Cox-2 in the inflammatory loop present. The mice were fed isocaloric diets containing 60% energy or 10% energy from fat. We found that a high fat diet increased K-Ras activity, PanIN formation, and fibrotic stroma significantly compared to a control diet. Genetic deletion of Cox-2 prevented high fat diet induced fibrosis and PanIN formation in oncogenic K-Ras expressing mice. Additionally, long term consumption of high fat diet, increased the progression of PanIN lesions leading to invasive cancer and decreased overall survival rate. These findings indicate that a high fat diet can stimulate the activation of oncogenic K-Ras and initiate an inflammatory feed forward loop requiring Cox-2 leading to inflammation, fibrosis, and PanINs. This mechanism could explain the relationship between a high fat diet and elevated risk for pancreatic cancer.

Data quality in trauma transfusion studies and the impact of missing data on predicting massive transfusion

Maximizing data quality may be especially difficult in trauma-related clinical research. Strategies are needed to improve data quality and assess the impact of data quality on clinical predictive models. This study had two objectives. The first was to compare missing data between two multi-center trauma transfusion studies: a retrospective study (RS) using medical chart data with minimal data quality review and the PRospective Observational Multi-center Major Trauma Transfusion (PROMMTT) study with standardized quality assurance. The second objective was to assess the impact of missing data on clinical prediction algorithms by evaluating blood transfusion prediction models using PROMMTT data. RS (2005-06) and PROMMTT (2009-10) investigated trauma patients receiving ≥ 1 unit of red blood cells (RBC) from ten Level I trauma centers. Missing data were compared for 33 variables collected in both studies using mixed effects logistic regression (including random intercepts for study site). Massive transfusion (MT) patients received ≥ 10 RBC units within 24h of admission. Correct classification percentages for three MT prediction models were evaluated using complete case analysis and multiple imputation based on the multivariate normal distribution. A sensitivity analysis for missing data was conducted to estimate the upper and lower bounds of correct classification using assumptions about missing data under best and worst case scenarios. Most variables (17/33=52%) had <1% missing data in RS and PROMMTT. Of the remaining variables, 50% demonstrated less missingness in PROMMTT, 25% had less missingness in RS, and 25% were similar between studies. Missing percentages for MT prediction variables in PROMMTT ranged from 2.2% (heart rate) to 45% (respiratory rate). For variables missing >1%, study site was associated with missingness (all p≤0.021). Survival time predicted missingness for 50% of RS and 60% of PROMMTT variables. MT models complete case proportions ranged from 41% to 88%. Complete case analysis and multiple imputation demonstrated similar correct classification results. Sensitivity analysis upper-lower bound ranges for the three MT models were 59-63%, 36-46%, and 46-58%. Prospective collection of ten-fold more variables with data quality assurance reduced overall missing data. Study site and patient survival were associated with missingness, suggesting that data were not missing completely at random, and complete case analysis may lead to biased results. Evaluating clinical prediction model accuracy may be misleading in the presence of missing data, especially with many predictor variables. The proposed sensitivity analysis estimating correct classification under upper (best case scenario)/lower (worst case scenario) bounds may be more informative than multiple imputation, which provided results similar to complete case analysis.^

Baseline quality of life as a predictor of exercise intervention adherence among endometrial cancer survivors

Background: The objective of this analysis is to test whether baseline quality of life (QOL) measurements, body mass index (BMI) and prior exercise behavior are significantly associated with (1) telephone counseling adherence, and (2) activity at the final assessment, in a physical activity promoting intervention among endometrial cancer survivors.^ Methods: One hundred endometrial cancer survivors not currently meeting physical activity guidelines completed baseline QOL and anthropometric assessments to measure general physical and mental health [Medical Outcomes Survey (SF-36)], sleep patterns and sleep quality [Pittsburgh Sleep Quality Index (PSQI)], perceived stress [Perceived Stress Scale (PSS)], cancer-specific concerns of long-term survivors [Quality of Life in Adult Cancer Survivors (QLACS)], and psychological distress [Brief Symptom Inventory-18 (BSI-18)]. Survivors were counseled by telephone during the 6-month intervention and their completion rate determined their adherence. The primary variables of interest included age, baseline BMI, baseline activity level, time since diagnosis, education, treatment received, and the SF-36 physical and mental component scores.^ Results: Final activity was most closely linked with baseline activity (p<.001) and less invasive surgery, being leaner and older, and experiencing less pain and more vitality. Telephone counseling was also predicted well by baseline activity, working less and having better overall cancer-related functioning.^ Conclusion: Above and beyond the QOL measures, baseline activity was the strongest predictor of both final activity and telephone counseling adherence. While education, surgery treatment type and bodily pain were important predictors for final exercise and employment status and cancer-related quality of life were important predictors for telephone counseling adherence, considering adaptive exercise interventions that focus heavily on engaging inactive participants may be a way to produce better exercise-related outcomes in the endometrial cancer survivor population.^

Efficiency from pharmacy inventory technology: A means to improving quality in non-profit hospitals

Hospitals, like all organizations, have both a mission and a finite supply of resources with which to accomplish that mission. Because the inventory of therapeutic drugs is among the more expensive resources needed by a hospital to achieve its mission, a conceptual model of structure plus process equals outcome posits that adequate emphasis should be placed on optimization of the organization's investment in this important structural resource to provide highest quality outcomes. Therefore emphasis should be placed on the optimization of pharmacy inventory because lowering the financial investment in drug inventory and associated costs increases productive efficiency, a key element of quality. ^ In this study, a post-intervention analysis of a hospital pharmacy inventory management technology implementation at The University of Texas M.D. Anderson Cancer Center was conducted to determine if an intervention which reduced a hospital's financial investment in pharmaceutical inventory provided an opportunity to incrementally optimize the organization's mix of structural resources thereby improving quality of care. The results suggest that hospital pharmacies currently lacking technology to support automated purchasing logistics and perpetual, real-time inventory management for drugs may achieve measurable benefits from the careful implementation of such technology, enabling the hospital to lower its investment in on-hand inventory and, potentially, to reduce overall purchasing expenditures. ^ The importance of these savings to the hospital and potentially to the patient should not be underestimated for their ability to generate funding for previously unfunded public health programs or in their ability to provide financial relief to patients in the form of lower drug costs given the current climate of escalating healthcare costs and tightening reimbursements.^

Quality of life and functional status in a low -income, multiethnic HIV -positive population

The introduction of new medical treatments in recent years, commonly referred to as highly active antiretroviral therapy, has greatly increased the survival of patients with HIV/AIDS. As patients with HIV/AIDS continue to live longer, other important health-related outcomes, such as quality of life (QOL), should be thoroughly studied. There is also evidence that racial/ethnic minorities are disproportionately affected by HIV/AIDS, but potential health disparities among individuals already infected with HIV/AIDS have not been adequately examined in ethnically diverse populations. The purpose of this dissertation was to: (1) examine the impact of both demographic and behavioral variables on functional status and overall QOL among a population of ethnically diverse and economically disadvantaged HIV/AIDS patients; (2) examine the psychometric properties of a functional status measure—the Household and Leisure Time Activities questionnaire (HLTA); and (3) assess a proximal-distal theoretical framework for QOL using a full structural equation model in a population of patients with HIV/AIDS. Analyses were performed using data collected in the fall of 2000 from the project, Health and Work-Related Quality of Life and Health Risk Behaviors in a Multiethnic HIV-positive Population . Investigators from The University of Texas M.D. Anderson Cancer Center, The University of Texas-Houston Medical School, and The University of Texas School of Public Health conducted this project. The study site was the Thomas Street Clinic (TSC), a comprehensive HIV/AIDS care facility funded by the Harris County Hospital District (HCHD). TSC provides HIV/AIDS care to a diverse population of approximately 4000 medically indigent residents of Harris County. A systematic, consecutive sampling procedure yielded a sample size of 348 patients. Findings suggested that overall QOL, work-role functioning, household functioning, and leisure time functioning were impaired in this patient population. Results from the psychometric evaluation indicated that the HLTA was a reliable and valid measure of household and leisure time functioning status in a low-income multiethnic HIV-positive population. Finally, structural equation modeling of the proximal-distal QOL model suggested that this model was not a viable representation of the relationship between the study variables in this patient population. ^