Gender differences in colorectal cancer screening and incidence in large nationwide, population-based cohorts

Background. A few studies have reported gender differences along the colorectal cancer (CRC) continuum but none has done so longitudinally to compare a cancer and a non-cancer populations.^ Objectives and Methods. To examine gender differences in colorectal cancer screening (CRCS); to examine trends in gender differences in CRC screening among two groups of patients (Medicare beneficiaries with and without cancer); to examine gender differences in CRC incidence; and to examine for any differences over time. In Paper 1, the study population consisted of men and women, ages 67–89 years, with CRC (73,666) or without any cancer (39,006), residing in 12 U.S. Surveillance Epidemiology and End-Results (SEER) regions. Crude and age-adjusted percentages and odds ratios of receiving fecal occult blood test (FOBT), sigmoidoscopy (SIG), or colonoscopy (COL) were calculated. Multivariable logistic regression was used to assess gender on the odds of receiving CRC screening over time.^ In Paper 2, age-adjusted incidence rates and proportions over time were reported across race, CRC subsite, CRC stage and SEER region for 373,956 patients, ages 40+ years, residing in 9 SEER regions and diagnosed with malignant CRC. ^ Results. Overall, women had higher CRC screening rates than men and screening rates in general were higher in the SEER sample of persons with CRC diagnosis. Significant temporal divergence in FOBT screening was observed between men and women in both cohorts. Although the largest temporal increases in screening rates were found for COL, especially among the cohort with CRC, little change in the gender gap was observed over time. Receipt of FOBT was significantly associated with female gender especially in the period of full Medicare coverage. Receipt of COL was also significantly associated with male gender, especially in the period of limited Medicare coverage.^ Overall, approximately equal numbers of men (187,973) and women (185,983) were diagnosed with malignant CRC. Men had significantly higher age-adjusted CRC incidence rates than women across all categories of age, race, subsite, stage and SEER region even though rates declined in all categories over time. Significant moderate increases in rate difference occurred among 40-59 year olds; significant reductions occurred among patients age 70+, within subsite rectum, unstaged and distant stage CRC, and eastern and western SEER regions. ^ Conclusions. Persistent gender differences in CRC incidence across time may have implications for gender-based interventions that take age into consideration. A shift toward proximal cancer was observed over time for both genders, but the high proportion of men who develop rectal cancer suggests that a greater proportion of men may need to be targeted with newer screening methods such as fecal DNA or COL. Although previous reports have documented higher CRC screening among men, higher incidence of CRC observed among men suggests that higher risk categories of men are probably not being reached. FOBT utilization rates among women have increased over time and the gender gap has widened between 1998 and 2005. COL utilization is associated with male gender but the differences over time are small.^

Goals, plans, and behavior changes: A relevant part of the post-treatment cancer experience

Background. Colorectal cancer (CRC) survivors have to manage treatment side effects, psychosocial issues, and co-morbidities, as well as modify their lifestyles to decrease risk of recurrence and prolong life. Identifying survivors’ goals and key factors that influence their goals will highlight the issues cancer survivors face post-treatment and the resources needed to help them engage in health-promoting behaviors.^ Objectives and methods. This dissertation examines the health-related goals of post-treatment CRC survivors using two studies: (1) a qualitative study to identify and describe the health goals of CRC survivors during the transition from active treatment to post-treatment survivorship and follow-up care; and (2) a cross-sectional survey to identify CRC survivors’ goals, and key factors that influence their goals.^ Results. (1) The 41 qualitative interviews indicated participants’ health-related goals were to be healthy, get back to normal, and not have a cancer recurrence. Most of the CRC survivors reported they maintained healthy behaviors, made healthy behavior changes, or had goals to change their behavior. Respondents were empowered to improve their health by maintaining follow-up care and regular health screenings, and many were managing treatment side effects in an effort to improve functional abilities. (2) The cross-sectional study found that CRC survivors’ most prevalent goals were related to healthy behaviors (i.e., eat a healthy diet and engage in physical activity), and cancer care or disease management (i.e., keep up with health screenings and monitor symptoms). Goals that survivors identified as important were similar to goals they perceived were important to their providers (i.e., goals related to cancer care, disease management). Certain goals were statistically associated with age, barriers to achieving goals, social support and health-related quality of life.^ Conclusions. CRC survivors have health-promoting goals post-treatment and are interested in making health behavior changes. Goals ranged from cancer care/surveillance and disease management to healthy lifestyle modifications. Patients may need help resolving or managing treatment side effects or co-morbidities prior to implementing health promoting behaviors. Healthcare providers’ recommendations may be a powerful resource to encourage survivors to engage in health-promoting behaviors. Self-management and goal setting support could be an appropriate strategy to assist patients with achieving their post-treatment health goals.^

Assessment of cancer incidence in Titus County, Texas, 1977--1984

The purpose of this study was to determine the incidence of cancer in Titus County, Texas, through the identification of all cases of cancer that occurred in residents of the county during the period from 1977 to 1984. Data gathered from Texas Cancer Registry, hospital records, and death certificates were analyzed with regard to anatomic site, race, sex, age, city of residence, and place of birth. Adjustment of incidence rates by sex and race allowed comparisons with U.S. rates provided by the Surveillance, Epidemiology, and End Results Program (SEER).^ Seven hundred sixty-six (766) cancer cases were identified for the eight year period during 171,536 person-years of observation. In whites, statistically significant standardized incidence ratios (SIR) were found for leukemia (males SIR = 2.70 and females SIR = 2.26), melanoma (males SIR = 1.90 and females SIR = 2.25), lung (males SIR = 1.45) and for multiple myeloma (both sexes combined SIR = 1.86). In blacks, significant excess numbers of cases were found for Hodgkin's disease (males SIR = 8.33 and females SIR = 13.3) and for esophagus and bone considering both sexes together (SIR = 2.68 and 12.54, respectively). Rates for blacks were based on a small population and therefore unstable. A statistically significant excess number of cases for all sites combined was found in Mount Pleasant residents (age-adjusted incidence rate = 563.6 per 100,000 per year).^ A review of possible environmental risk factors in the area: hazardous waste disposal site, lignite deposits, and petrochemical and poultry industries are presented. A need for further epidemiological and environmental studies to identify etiological factors that could be responsible for the excess number of leukemia cases are recommended. For melanoma, a public health educational program to teach the population methods of protection from sun exposure is also suggested. ^

Bayesian and survival model for tumor relapse status and disease-specific survival, with applications to breast cancer

Breast cancer is the most common non-skin cancer and the second leading cause of cancer-related death in women in the United States. Studies on ipsilateral breast tumor relapse (IBTR) status and disease-specific survival will help guide clinic treatment and predict patient prognosis.^ After breast conservation therapy, patients with breast cancer may experience breast tumor relapse. This relapse is classified into two distinct types: true local recurrence (TR) and new ipsilateral primary tumor (NP). However, the methods used to classify the relapse types are imperfect and are prone to misclassification. In addition, some observed survival data (e.g., time to relapse and time from relapse to death)are strongly correlated with relapse types. The first part of this dissertation presents a Bayesian approach to (1) modeling the potentially misclassified relapse status and the correlated survival information, (2) estimating the sensitivity and specificity of the diagnostic methods, and (3) quantify the covariate effects on event probabilities. A shared frailty was used to account for the within-subject correlation between survival times. The inference was conducted using a Bayesian framework via Markov Chain Monte Carlo simulation implemented in softwareWinBUGS. Simulation was used to validate the Bayesian method and assess its frequentist properties. The new model has two important innovations: (1) it utilizes the additional survival times correlated with the relapse status to improve the parameter estimation, and (2) it provides tools to address the correlation between the two diagnostic methods conditional to the true relapse types.^ Prediction of patients at highest risk for IBTR after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The goals of the second part of this dissertation were to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center, to determine the risk of IBTR in patients with DCIS treated with local excision, and to determine whether there is a subset of patients at low risk of IBTR. Patients who had undergone local excision from 1990 through 2007 at MD Anderson Cancer Center with a final diagnosis of DCIS (n=794) were included in this part. Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients with complete data. Nomogram for prediction of 5- and 10-year IBTR probabilities were found to demonstrate imperfect calibration and discrimination, with an area under the receiver operating characteristic curve of .63 and a concordance index of .63. In conclusion, predictive models for IBTR in DCIS patients treated with local excision are imperfect. Our current ability to accurately predict recurrence based on clinical parameters is limited.^ The American Joint Committee on Cancer (AJCC) staging of breast cancer is widely used to determine prognosis, yet survival within each AJCC stage shows wide variation and remains unpredictable. For the third part of this dissertation, biologic markers were hypothesized to be responsible for some of this variation, and the addition of biologic markers to current AJCC staging were examined for possibly provide improved prognostication. The initial cohort included patients treated with surgery as first intervention at MDACC from 1997 to 2006. Cox proportional hazards models were used to create prognostic scoring systems. AJCC pathologic staging parameters and biologic tumor markers were investigated to devise the scoring systems. Surveillance Epidemiology and End Results (SEER) data was used as the external cohort to validate the scoring systems. Binary indicators for pathologic stage (PS), estrogen receptor status (E), and tumor grade (G) were summed to create PS+EG scoring systems devised to predict 5-year patient outcomes. These scoring systems facilitated separation of the study population into more refined subgroups than the current AJCC staging system. The ability of the PS+EG score to stratify outcomes was confirmed in both internal and external validation cohorts. The current study proposes and validates a new staging system by incorporating tumor grade and ER status into current AJCC staging. We recommend that biologic markers be incorporating into revised versions of the AJCC staging system for patients receiving surgery as the first intervention.^ Chapter 1 focuses on developing a Bayesian method to solve misclassified relapse status and application to breast cancer data. Chapter 2 focuses on evaluation of a breast cancer nomogram for predicting risk of IBTR in patients with DCIS after local excision gives the statement of the problem in the clinical research. Chapter 3 focuses on validation of a novel staging system for disease-specific survival in patients with breast cancer treated with surgery as the first intervention. ^

Trastuzumab use and risk of congestive heart failure in older breast cancer patients

Trastuzumab is a humanized-monoclonal antibody, developed specifically for HER2-neu over-expressed breast cancer patients. Although highly effective and well tolerated, it was reported associated with Congestive Heart Failure (CHF) in clinical trial settings (up to 27%). This leaves a gap where, Trastuzumab-related CHF rate in general population, especially older breast cancer patients with long term treatment of Trastuzumab remains unknown. This thesis examined the rates and risk factors associated with Trastuzumab-related CHF in a large population of older breast cancer patients. A retrospective cohort study using the existing Surveillance, Epidemiology and End Results (SEER) and Medicare linked de-identified database was performed. Breast cancer patients ≥ 66 years old, stage I-IV, diagnosed in 1998-2007, fully covered by Medicare but no HMO within 1-year before and after first diagnosis month, received 1st chemotherapy no earlier than 30 days prior to diagnosis were selected as study cohort. The primary outcome of this study is a diagnosis of CHF after starting chemotherapy but none CHF claims on or before cancer diagnosis date. ICD-9 and HCPCS codes were used to pool the claims for Trastuzumab use, chemotherapy, comorbidities and CHF claims. Statistical analysis including comparison of characteristics, Kaplan-Meier survival estimates of CHF rates for long term follow up, and Multivariable Cox regression model using Trastuzumab as a time-dependent variable were performed. Out of 17,684 selected cohort, 2,037 (12%) received Trastuzumab. Among them, 35% (714 out of 2037) were diagnosed with CHF, compared to 31% (4784 of 15647) of CHF rate in other chemotherapy recipients (p<.0001). After 10 years of follow-up, 65% of Trastuzumab users developed CHF, compared to 47% in their counterparts. After adjusting for patient demographic, tumor and clinical characteristics, older breast cancer patients who used Trastuzumab showed a significantly higher risk in developing CHF than other chemotherapy recipients (HR 1.69, 95% CI 1.54 - 1.85). And this risk is increased along with the increment of age (p-value < .0001). Among Trastuzumab users, these covariates also significantly increased the risk of CHF: older age, stage IV, Non-Hispanic black race, unmarried, comorbidities, Anthracyclin use, Taxane use, and lower educational level. It is concluded that, Trastuzumab users in older breast cancer patients had 69% higher risk in developing CHF than non-Trastuzumab users, much higher than the 27% increase reported in younger clinical trial patients. Older age, Non-Hispanic black race, unmarried, comorbidity, combined use with Anthracycline or Taxane also significantly increase the risk of CHF development in older patients treated with Trastuzumab. ^

Geographic variation in the utilization and survival associated with oxaliplatin chemotherapy in patients with stage III colon cancer

Background: Overall objectives of this dissertation are to examine the geographic variation and socio-demographic disparities (by age, race and gender) in the utilization and survival of newly FDA-approved chemotherapy agents (Oxaliplatin-containing regimens) as well as to determine the cost-effectiveness of Oxaliplatin in a large nationwide and population-based cohort of Medicare patients with resected stage-III colon cancer. Methods: A retrospective cohort of 7,654 Medicare patients was identified from the Surveillance, Epidemiology and End Results – Medicare linked database. Multiple logistic regression was performed to examine the relationship between receipt of Oxaliplatin-containing chemotherapy and geographic regions while adjusting for other patient characteristics. Cox proportional hazard model was used to estimate the effect of Oxaliplatin-containing chemotherapy on the survival variation across regions using 2004-2005 data. Propensity score adjustments were also made to control for potential bias related to non-random allocation of the treatment group. We used Kaplan-Meier sample average estimator to calculate the cost of disease after cancer-specific surgery to death, loss-to follow-up or censorship. Results: Only 51% of the stage-III patients received adjuvant chemotherapy within three to six months of colon-cancer specific surgery. Patients in the rural regions were approximately 30% less likely to receive Oxaliplatin chemotherapy than those residing in a big metro region (OR=0.69, p=0.033). The hazard ratio for patients residing in metro region was comparable to those residing in big metro region (HR: 1.05, 95% CI: 0.49-2.28). Patients who received Oxalipaltin chemotherapy were 33% less likely to die than those received 5-FU only chemotherapy (adjusted HR=0.67, 95% CI: 0.41-1.11). KMSA-adjusted mean payments were almost 2.5 times higher in the Oxaliplatin-containing group compared to 5-FU only group ($45,378 versus $17,856). When compared to no chemotherapy group, ICER of 5-FU based regimen was $12,767 per LYG, and ICER of Oxaliplatin-chemotherapy was $60,863 per LYG. Oxaliplatin was found economically dominated by 5-FU only chemotherapy in this study population. Conclusion: Chemotherapy use varies across geographic regions. We also observed considerable survival differences across geographic regions; the difference remained even after adjusting for socio-demographic characteristics. The cost-effectiveness of Oxaliplatin in Medicare patients may be over-estimated in the clinical trials. Our study found 5-FU only chemotherapy cost-effective in adjuvant settings in patients with stage-III colon cancer.^

Using spatial linear models with SAR and CAR structure to examine Texas lung cancer incidence rates

Scholars have found that socioeconomic status was one of the key factors that influenced early-stage lung cancer incidence rates in a variety of regions. This thesis examined the association between median household income and lung cancer incidence rates in Texas counties. A total of 254 individual counties in Texas with corresponding lung cancer incidence rates from 2004 to 2008 and median household incomes in 2006 were collected from the National Cancer Institute Surveillance System. A simple linear model and spatial linear models with two structures, Simultaneous Autoregressive Structure (SAR) and Conditional Autoregressive Structure (CAR), were used to link median household income and lung cancer incidence rates in Texas. The residuals of the spatial linear models were analyzed with Moran's I and Geary's C statistics, and the statistical results were used to detect similar lung cancer incidence rate clusters and disease patterns in Texas.^

Developing the follow-up schedules for women with breast cancer

Background: The follow-up care for women with breast cancer requires an understanding of disease recurrence patterns and the follow-up visit schedule should be determined according to the times when the recurrence are most likely to occur, so that preventive measure can be taken to avoid or minimize the recurrence. Objective: To model breast cancer recurrence through stochastic process with an aim to generate a hazard function for determining a follow-up schedule. Methods: We modeled the process of disease progression as the time transformed Weiner process and the first-hitting-time was used as an approximation of the true failure time. The women's "recurrence-free survival time" or a "not having the recurrence event" is modeled by the time it takes Weiner process to cross a threshold value which represents a woman experiences breast cancer recurrence event. We explored threshold regression model which takes account of covariates that contributed to the prognosis of breast cancer following development of the first-hitting time model. Using real data from SEER-Medicare, we proposed models of follow-up visits schedule on the basis of constant probability of disease recurrence between consecutive visits. Results: We demonstrated that the threshold regression based on first-hitting-time modeling approach can provide useful predictive information about breast cancer recurrence. Our results suggest the surveillance and follow-up schedule can be determined for women based on their prognostic factors such as tumor stage and others. Women with early stage of disease may be seen less frequently for follow-up visits than those women with locally advanced stages. Our results from SEER-Medicare data support the idea of risk-controlled follow-up strategies for groups of women. Conclusion: The methodology we proposed in this study allows one to determine individual follow-up scheduling based on a parametric hazard function that incorporates known prognostic factors.^

Impact of racial differences in medical care on breast cancer survival: Findings from a large nationwide and retrospective cohort study

Background: No studies have attempted to determine whether nodal surgery utilization, time to initiation and completion of chemotherapy or surveillance mammography impact breast cancer survival. ^ Objectives and Methods: To determine whether receipt of nodal surgery, initiation and completion of chemotherapy, and surveillance mammography impact of racial disparities in survival among breast cancer patients in SEER areas, 1992-2005. ^ Results: Adjusting for nodal surgery did not reduce racial disparities in survival. Patients who initiated chemotherapy more than three months after surgery were 1.8 times more likely to die of breast cancer (95% CI 1.3-2.5) compared to those who initiated chemotherapy less than a month after surgery, even after controlling for known confounders or controlling for race. Despite correcting for chemotherapy initiation and completion and known predictors of outcome, African American women still had worse disease specific survival than their Caucasian counterparts. We found that non-whites underwent surveillance mammography less frequently compared with whites and mammography use during a one- or two-year time interval was associated with a small reduced risk of breast-cancer-specific and all-cause mortality. Women who received a mammogram during a two-year interval could expect the same disease-specific survival benefit or overall survival benefit as women who received a mammogram during a one-year interval. We found that while adjustment for surveillance mammography receipt and physician visits reduced differences in mortality between blacks and whites, these survival disparities were eliminated after adjusting for the number of surveillance mammograms received. ^ Conclusions: The disparities in survival among African American and Hispanic women with breast cancer are not explained by nodal surgery utilization or chemotherapy initiation and chemotherapy completion. Surveillance mammograms, physician visits and number of mammograms received may play a major role in achieving equal outcomes for breast cancer-specific mortality for women diagnosed with primary breast cancer. Racial disparities in all-cause mortality were explained by racial differences in surveillance mammograms to certain degree, but were no longer significant after controlling for differences in comorbidity. Focusing on access to quality care and post treatment surveillance might help achieve national goals to eliminate racial disparities in healthcare and outcomes. ^

Challenges, Strengths and Opportunities Related to Implementing Comprehensive Evidence-Based Guidelines on Breast Cancer Survivorship Care by Primary Care Physicians and Nurse Practitioners in Southeastern Ontario

Background Many breast cancer survivors continue to have a broad range of physical and psychosocial problems after breast cancer treatment. As cancer centres move forward with earlier discharge of stable breast cancer survivors to primary care follow-up it is important that comprehensive evidence-based breast cancer survivorship care is implemented to effectively address these needs. Research suggests primary care providers are willing to provide breast cancer survivorship care but many lack the knowledge and confidence to provide evidence-based care. Purpose The overall purpose of this thesis was to determine the challenges, strengths and opportunities related to implementing comprehensive evidence-based breast cancer survivorship guidelines by primary care physicians and nurse practitioners in southeastern Ontario. Methods This mixed-methods research was conducted in three phases: (1) synthesis and appraisal of clinical practice guidelines relevant to provision of breast cancer survivorship care within the primary care practice setting; (2) a brief quantitative survey of primary care providers to determine actual practices related to provision of evidence-based breast cancer survivorship care; and (3) individual interviews with primary care providers about the challenges, strengths and opportunities related to provision of comprehensive evidence-based breast cancer survivorship care. Results and Conclusions In the first phase, a comprehensive clinical practice framework was created to guide provision of breast cancer survivorship care and consisted of a one-page checklist outlining breast cancer survivorship issues relevant to primary care, a three-page summary of key recommendations, and a one-page list of guideline sources. The second phase identified several knowledge and practice gaps, and it was determined that guideline implementation rates were higher for recommendations related to prevention and surveillance aspects of survivorship care and lowest related to screening for and management of long-term effects. The third phase identified three major challenges to providing breast cancer survivorship care: inconsistent educational preparation, provider anxieties, and primary care burden; and three major strengths or opportunities to facilitate implementation of survivorship care guidelines: tools and technology, empowering survivors, and optimizing nursing roles. A better understanding of these challenges, strengths and opportunities will inform development of targeted knowledge translation interventions to provide support and education to primary care providers.

Biologic therapies and non-melanoma skin cancer rates in three chronic immune-mediated diseases

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

A retrospective survey of cancer in relation to occupation /

"Contract no. HSM 99-73-5."

Cancer statistics review.

Data derived from the Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics.

The impact of depression on patient outcomes among older adults with lung cancer

Thesis (Ph.D.)--University of Washington, 2016-06

Racial Disparities in the Utilization of Preventive Health Services among Older Women with Early Stage Endometrial Cancer Enrolled in Medicare

Thesis (Master's)--University of Washington, 2016-06