Survey, Epidemiology, And End Results Research Articles

Excess Mortality in Young Patients with Myeloproliferative Neoplasms

▪Introduction: Myeloproliferative neoplasms (MPNs) - essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) - are associated with significant morbidity and shortened survival, irrespective of age (Srour et al. Br J Hematol. 2016). Despite shortened survival, young MPN patients (pts) are often classified as “low-risk” and managed with aspirin alone, phlebotomy-only (PHL), or observation instead of potentially life-prolonging cytoreductive and/or disease-modifying treatment. Age-biased risk assessment and treatment practices deprive young pts from early intervention and access to clinical trials. Our goal is to highlight the unmet need for identifying and implementing life-prolonging treatment in young MPN pts. Here, we determine and compare the excess mortality from MPNs in young (<60 years) to older pts (≥60 years) in the United States (US).Methods: In this population-based study, demographic (age, sex, race), survival, and cause-of-death data were collected for MPN pts from the US Survey, Epidemiology, and End Results (SEER) registry between 2001-2017; and for the general US population from the Centers for Disease Control and Prevention Wide-ranging OnLine Data for Epidemiologic Research (CDC WONDER) database. SEER reports cancers classified by International Classification of Diseases for Oncology, version 3 (ICD-O-3), which evolved with the WHO classification of myeloid neoplasms in 2001 for ET, PV and PMF. Cause-of-death is reported by ICD-10 codes, which we categorized into cardiovascular (CVE), second cancers (CA), acute leukemia (AL), and others. Excess, or relative mortality was determined by the ratio of observed mortality in MPN pts (Kaplan-Meier estimate) over the expected mortality of the US population matched by age, sex, race, and birth-year (actuarial estimate). A one-sided log-rank test was used. Excess mortality of young compared to older pts was determined from a random-effects model using restricted maximum-likelihood estimator method. All analyses were performed using RStudio software v 1.4.1106.Results: The SEER query identified 40,333 MPN pts (ET: 17,420 (43%), PV: 18,027 (45%), PMF: 4,886 (12%)) diagnosed at a median age of 66 years (ET: 67, PV: 65, PMF: 69) of whom 20,470 (51%) were females (ET: 10,709 (61%), PV: 7,768 (43%), PMF: 1,993 (41%)). The 10-year mortality for ET, PV, and PMF pts <60 was 13%, 18%, and 49% respectively (versus 6% for controls); and ≥60 was 59%, 59%, and 87% respectively (versus 35% for controls) (Figure 1A). Excess all-cause mortality was higher in pts <60 compared to ≥60 with ET (2.75 versus 1.82, p<0.001), PV (3.16 versus 1.92, p<0.001), and PMF (10.6 versus 5.73, p<0.001) (Figure 1B). Excess CVE mortality was higher in PV<60 compared to PV≥60 (3.36 versus 2.55, p=0.036) but not in ET or PMF. Excess CA mortality was higher in PV<60 than PV≥60 (2.36 versus 1.53, p=0.002) but not in ET or PMF. Excess AL mortality was high for all pts, particularly PMF, and was not significantly different in pts <60 compared to ≥60Discussion: Excess or relative mortality emphasizes the burden of MPN-related death with current treatment. In this population-based study, we found excess mortality in young MPN pts (<60), greater than in older pts (≥60). This difference may result from age-biased risk assessment and treatment recommendations that recommend lower intensity therapy for young pts. It may be time to revisit these recommendations since accruing evidence demonstrates long-term safety, efficacy and potential survival benefit of available cytoreductive agents. Certain treatments such as interferon-alpha (IFN) may improve survival in PV (Abu-Zeinah et al. Leukemia. 2021), and a recent randomized clinical trial established superiority of IFN over standard of care PHL in young PV pts (Barbui et al. Lancet Hematol. 2021). These data advocate for early intervention with potentially disease-modifying treatment for all pts regardless of age. These data also call into question age-biased exclusions of many young pts from participation in clinical trials of established or promising drugs.Conclusion: Excess mortality of young MPN pts (<60) is unacceptably high and greater than that of older pts (≥60). Clinical trials testing early intervention with potentially life-prolonging treatments are required. [Display omitted] DisclosuresSilver: Abbvie: Consultancy; PharamEssentia: Consultancy, Speakers Bureau. Scandura: Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Constellation: Research Funding; MPN-RF (Foundation): Research Funding; CR&T (Foudation): Research Funding; European Leukemia net: Honoraria, Other: travel fees . Abu-Zeinah: PharmaEssentia: Consultancy.

The Impact of Radical Cystectomy and Urinary Diversion on Suicidal Death in Patients With Bladder Cancer.

Compared to the general population, suicide is more common in the elderly and in patients with cancer. We sought to examine the incidence of suicide in patients with bladder cancer and evaluate the impact of radical cystectomy in this high-risk population. Patients diagnosed with urothelial carcinoma from 1988 to 2010 were identified in the Survey, Epidemiology, and End Results (SEER) database. Contingency tables of suicide rates and standardized mortality ratios (SMRs) and 95% confidence intervals were calculated. Multivariable logistic regression models were performed to generate odds ratios (ORs) for the identification of factors associated with suicide in this population. There were 439 suicides among patients with bladder cancer observed for 1,178,000 person-years (Standard Morbidity Ratio [SMR] = 2.71). All demographic variables analyzed had a higher SMR for suicide compared to the general population, in particular age ≥80 years (SMR = 3.12), unmarried status (SMR = 3.41), and white race (SMR = 2.60). The incidence of suicide was higher in the general population for patients who underwent radical cystectomy compared to those who did not (SMR = 3.54 vs SMR = 2.66). On multivariate analysis, the strongest predictors of suicide were male gender (vs female; OR = 6.63) and distant disease (vs localized; OR = 5.43). Clinicians should be aware of risk factors for suicide in patients diagnosed with bladder cancer, particularly older, white, unmarried patients with distant disease, and/or those who have undergone radical cystectomy. A multidisciplinary team-based approach, including wound ostomy care trained nursing staff and mental health care providers, may be essential to provide care required to decrease suicide rates in this at-risk population.

Racial disparities in colon cancer survival: a matched cohort study.

Differences in colon cancer survival by race are a recognized problem among Medicare beneficiaries. To determine to what extent the racial disparity in survival is due to disparity in presentation characteristics at diagnosis or disparity in subsequent treatment. Black patients with colon cancer were matched with 3 groups of white patients: a "demographic characteristics" match controlling for age, sex, diagnosis year, and Survey, Epidemiology, and End Results (SEER) site; a "presentation" match controlling for demographic characteristics plus comorbid conditions and tumor characteristics, including stage and grade; and a "treatment" match, including presentation variables plus details of surgery, radiation, and chemotherapy. 16 U.S. SEER sites. 7677 black patients aged 65 years or older diagnosed between 1991 and 2005 in the SEER-Medicare database and 3 sets of 7677 matched white patients, followed until 31 December 2009. 5-year survival. The absolute difference in 5-year survival between black and white patients was 9.9% (95% CI, 8.3% to 11.4%; P<0.001) in the demographic characteristics match. This disparity remained unchanged between 1991 and 2005. After matching for presentation characteristics, the difference decreased to 4.9% (CI, 3.6% to 6.1%; P<0.001). After additional matching for treatment, this difference decreased to 4.3% (CI, 2.9% to 5.5%; P<0.001). The disparity in survival attributed to treatment differences made up only an absolute 0.6% of the overall 9.9% survival disparity. An observational study limited to elderly Medicare fee-for-service beneficiaries living in selected geographic areas. Racial disparities in colon cancer survival did not decrease among patients diagnosed between 1991 and 2005. This persistent disparity seemed to be more related to presentation characteristics at diagnosis than to subsequent treatment differences. Agency for Healthcare Research and Quality and National Science Foundation.

Abstract A31: Identifying barriers to breast cancer screening guideline adherence among minority women residing in rural geographical regions: Final analysis

Abstract Background: Minority women residing in rural geographic communities bear a disproportionate burden of mortality due to invasive breast cancer compared to other racial/ethnic majority groups. Despite this heightened rate of mortality, preventative screening in African American (AA) and Hispanic (H) women is significantly lower than that of Non-Hispanic White (NHW) women. The purpose of this study is to identify and validate the barriers associated with non-compliance to recommended breast cancer screening guidelines in AA and H women in rural geographic regions. Methods: A prior observational analysis conducted by RHEAI using data from the Texas Cancer Registry (TCR), U.S. Census Bureau, and Survey Epidemiology and End Results (SEER) Database identified Cherokee County, Texas as having significant disparity in breast cancer screening and mortality rates when comparing AA, H, and NHW women. To gauge this disparity, we collected opinions about breast cancer screening and mortality incidence by surveying 13 local stakeholders (including breast cancer survivors, religious leaders, community leaders, local hospital employees and educators) within the minority community. Based on stakeholder survey results and health disparity literature reviews, a relevant and culturally sensitive survey was developed using the 5-point Likert scale to identify the perceived barriers to breast cancer screening in the general minority community. A total of 115 surveys of AA and H women were planned. The sample size was calculated based on the percentage of AA and H women residing in Cherokee County with a 95% level of confidence and a +5% margin of error. Results: 115 surveys were completed online via Facebook Survey (n=62) and in printed form (n=53) between 06/2012 and 05/2013. Median age of participants was 49 years (range 28-64), 73% were AA women and 27% were H women residing in rural Cherokee County. Lack of breast cancer educational/awareness programs, limited transportation access, and lack of mammography facilities were identified as barriers associated with decreased adherence to breast cancer screening guidelines. Identified barriers varied based on participant age, familial breast cancer history, and education level. Conclusions: The results of this study demonstrate that minority women in rural areas are willing to comply with recommended screening guidelines if they have access to appropriate educational tools and screening facilities. RHEAI is currently working with community stakeholders to design and initiate a region-wide culturally relevant breast cancer screening and prevention educational/awareness program. Citation Format: Monique J. Carter. Identifying barriers to breast cancer screening guideline adherence among minority women residing in rural geographical regions: Final analysis. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr A31. doi:10.1158/1538-7755.DISP13-A31

Survival Patterns in United States (US) Medicare Enrollees with Non-CML Myeloproliferative Neoplasms (MPN)

PurposeNon-CML myeloproliferative neoplasms (MPN) include essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Reported median overall survival (OS) ranges from a few to several years for MF, a decade or more for ET and PV. The study objective was to compare US survival rates of ET, PV, and MF patients with matched non-MPN/non-cancer controls in a nationally representative database.Patients and MethodsData were taken retrospectively from the Survey, Epidemiology, and End Results (SEER)-Medicare linked database. Medicare enrollees with a new SEER MPN diagnosis between Jan 1, 2001 and Dec 31, 2007 were eligible. First MPN diagnosis was required at or after Medicare enrollment to allow for continuous follow-up. Non-MPN/non-cancer control groups were selected from Medicare separately for each MPN subtype and demographically matched to cases at a ratio of 5∶1. Survival was determined starting from the case diagnosis date using the Kaplan-Meier method.ResultsA total of 3,364 MPN patients (n = 1,217 ET; 1,625 PV; 522 MF) met the inclusion criteria and were matched to controls. Mean age was 78.4, 76.1, and 77.4 years for ET, PV, and MF, respectively, and percent female was 63, 50, and 41. Median OS was significantly (p<0.05) lower for MPN cases vs. controls (ET: 68 vs. 101 months; PV: 65 vs. 104; MF: 24 vs. 106).ConclusionsIn the US Medicare population, survival in MF patients was worse than that of patients with ET or PV and significantly worse than matched controls. Survival of patients with ET or PV was substantially inferior to matched controls. These findings have implications for the clinical management of MPN patients and underscore the need for effective therapies in all MPN subtypes.

Initial Clinical Findings of a Mathematical Model to Predict Survival of Head and Neck Cancer

(1) Identify clinical features that impact survival for head and neck cancer. (2) Determine the individual contribution to mortality of significant clinical features. (3) Develop a web-based calculator to integrate clinical features and predict survival outcome for individual patients. Analysis of a national cancer database. We fit patient data to the binary-biological model of cancer lethality, a mathematical model designed to predict cancer outcome. The model predicts the risk of cancer death, using information on tumor size, nodal status, and other prognostic factors. Analysis was carried out on a cohort of ~50,000 patients with head and neck cancer from the Survey, Epidemiology and End-Results (SEER) 2009 data set and validated with a cohort of ~1300 patients from an institutional Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary database. We developed a web-based calculator written in JavaScript, PHP, and HTML. The risk of death due to head and neck cancer increases monotonically with tumor size. Each positive lymph node is associated with ~14% extra risk of death. Anatomical site, age, race, tumor extension, N stage, and extracapsular spread contribute to mortality. The lethal impact of these prognostics factors can be accurately estimated by the Size + Nodes + PrognosticMarkers (SNAP) method. This predictive cancer model and web-based calculator provide a basis for estimating the risk of death for head and neck cancer patients by assigning values to the lethal contributions of tumor size, number of positive nodes, anatomical site, tumor extension, N stage, extracapsular spread, age at diagnosis, and race.

Abstract 172: Predictors of breast cancer clinical trial participation by logistic regression analysis in minority women residing in medically underserved regions.

Abstract Background Enrollment investigation literature estimates that 3% of newly diagnosed breast cancer patients participate in clinical trials annually in the United States. Participation levels decrease significantly when varied by race and geographic location. African American women, specifically those residing in medically underserved regions, are historically underrepresented in clinical trials as compared to their white/non-Hispanic counterparts. The focus of this study is to capture characteristics of African American women who would participate in a breast cancer trial. Significant trial participation factors were identified using logistic regression analysis. Methods Using data from the Texas Cancer Registry (TCR), U.S. Census Bureau, and Survey Epidemiology and End Results (SEER) Database, Cherokee County, Texas was identified as a medically underserved region. We collected opinions about breast cancer clinical trial participation by surveying 13 local stakeholders (including breast cancer survivors, religious leaders, community leaders, local hospital employees and educators) within the minority community. On the basis of stakeholder survey results and health disparities literature review, a relevant and culturally sensitive survey was developed to identify the different demographic, economic and social characteristics in the general minority female population. A total of 115 surveys of African American women were planned. The sample size was calculated based on the percentage of African American women residing in Cherokee County with a 95% level of confidence and a +/-5% margin of error. Logistic regression analysis revealed the association of characteristics with trial participation. Results At the time of this analysis, 44 surveys were completed between 06/2012 and 10/2012. Median age of participants was 43 years (range 31-65), 100% were African American women residing in rural Cherokee County. Age, cancer diagnosis of a relative, education level, and religious institution affiliation were associated with trial participation in unadjusted analyses. Multi-variative analyses indicate that patient age was the strongest independent predictor of trial participation. Insurance coverage and income level were also observed interaction effects. The most common reason reported for trial participation was altruism. Conclusion Interim results of this study reveal correlation between the potential of African American women to participate in clinical trials and the following factors: age, family history of cancer, and religious institution affiliation. Further understanding of this relationship will possibly contribute to the development of intervention initiatives and policies to influence those who are adverse to such participation. Citation Format: Monique J. Carter, Tracy A. Davis. Predictors of breast cancer clinical trial participation by logistic regression analysis in minority women residing in medically underserved regions. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 172. doi:10.1158/1538-7445.AM2013-172

Survival Patterns in Patients with Non-CML Myeloproliferative Neoplasms: Evidence From a United States SEER/Medicare Population

AbstractAbstract 428 Background:Non-CML myeloproliferative neoplasms (MPNs) include essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF) and MPN not otherwise specified (MPN-NOS), and are characterized by activation of JAK2 signaling and abnormal blood cell production. Reported median overall survival (OS) for MF ranges from a few (Cervantes et al. J Clin Oncol epub 2012;42:0240) to several years (Hultcrantz et al. J Clin Oncol epub 2012;42:1925). ET and PV median OS is reported to be a decade or more, although recent findings based on the Swedish cancer registry indicate that PV and ET patients may experience shorter survival than previously understood (Hultcrantz et al. J Clin Oncol epub 2012;42:1925; Barbui et al. 2011;29:3179–3184). Survival of MPN-NOS patients is not well characterized in the literature. MPN patients experience multiple comorbidities that can increase the risk of disability and death. However, survival rates of MPN patients from a nationally representative US population have not been recently described. MPN is more prevalent in the elderly; therefore, Medicare enrollees are a highly relevant source for US-based survival estimates in these diseases. Objective:To compare survival rates of MPN patients (ET, PV, MF and MPN-NOS) with matched non-MPN/non-cancer controls. Methods:In this retrospective study, data were taken from the Survey, Epidemiology, and End Results (SEER)-Medicare linked database in the US. SEER-Medicare combines clinical information from the SEER cancer registry with medical and pharmacy claims for Medicare enrollees. Codes for reporting MPN cases to SEER have been available since 2001. In our study, Medicare enrollees with a new SEER MPN diagnosis between Jan 1, 2001 and Dec 31, 2007 were selected and evaluated for survival. Patients were classified into MPN subtypes as indicated by their SEER registry diagnosis. First MPN diagnosis was required to occur at or before Medicare enrollment to allow for continuous follow-up. Non-MPN/non-cancer control groups were selected from Medicare for each MPN subtype and matched to cases 5:1 based on year of birth, gender, race, geographic location, and reason for Medicare eligibility. Survival for both case and matching controls was determined starting from the case diagnosis date. Survival was estimated using the Kaplan-Meier method. Results:A total of 4,274 MPN patients (n = 1217 ET, 1625 PV, 522 MF and 910 MPN-NOS) were identified for inclusion and assigned matching controls.Demographic results and survival findings are presented in Table 1. Kaplan-Meier survival curves are shown in Figure 1.Table 1Patient Characteristics and SurvivalETPVMFMPN-NOS(N=1217)(N=1625)(N=522)(N=910)Age at MPN Diagnosis (years)Mean Age78.476.177.479SD8.210.57.98.2Age Groupn%n%n%n%<4560.5251.530.640.445 - 54151.2694.361.270.855 - 64413.4905.5132.5262.965 - 7430525.144227.216331.22182475 - 8460850.073044.927151.945650.1≥8524219.926916.66612.619921.9GenderMale45737.680849.730658.645750.2Female76062.581750.321641.445349.8RaceWhite105987145089.24709080288.1Black967.9925.7315.9808.8Other171.4211.320.4111.2Asian292.4422.691.791Hispanic141.2181.1101.980.9North American Native20.220.1....Patient SurvivalCasesControlsCasesControlsCasesControlsCasesControlsMean OS (months)65.278.762.280.032.281.042.275.5Median OS (months)67.9101.164.9103.923.5106.328.493.9 [Display omitted] Conclusions:Survival in MF and MPN-NOS patients was worse than that of patients with ET or PV and significantly worse than matched controls. Contrary to the commonly held thought that PV and ET patients experience near-normal life expectancy, survival of patients with ET or PV was substantially inferior to matched controls. These findings have implications for the clinical management of MPN patients and underscore the need for effective therapies in all MPN subtypes. Disclosures:Price:Eli Lilly and Company: Employment, Equity Ownership. Davis:Eli Lilly, Merck, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, Eisai, Sanof-Aventis, Gilead Sciences, MedImmune: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Karve:RTI Health Solutions: Consultancy, Research Funding. Pohl:Eli Lilly and Company: Employment, Equity Ownership. Walgren:Eli Lilly and Company: Employment, Equity Ownership.

Health Care Utilization and Associated Costs in Elderly Persons with Non-CML Myeloproliferative Neoplasms: Real-World Evidence From a United States Medicare Population

AbstractAbstract 4273 Background:Non-CML myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF) and MPN not otherwise specified (MPN-NOS), are characterized by activation of JAK2 signaling and abnormal blood cell production. Median survival ranges from months to years for MF and up to a decade or more for PV and ET. Some symptomatic treatment options exist, but with the exception of hematopoietic stem cell transplant, none are curative. Although MPN incidence is highest in persons aged ≥65 years, little is known about overall health care utilization and costs in elderly persons with these diseases. MPNs are more prevalent in the elderly and therefore Medicare enrollees are a highly relevant source for US-based resource utilization and cost data for these diseases. Objective:To compare all-cause health care utilization and costs from four subtypes of elderly MPN patients (ET, PV, MF and MPN-NOS) with matched non-MPN/non-cancer controls. Methods:Retrospective data were taken from the Survey, Epidemiology, and End Results (SEER)-Medicare linked database in the US, which combines clinical information from the SEER cancer registry (MPN reporting has been required since 2001) with medical and pharmacy claims for Medicare enrollees. Patients with a new MPN diagnosis between Jan 1, 2001 and Dec 31, 2007 were selected and evaluated for all-cause health care utilization and costs from Jan 1, 2008 (index date) through Dec 31, 2008 (follow-up end date). Patients were classified by MPN subtype based on the most recent diagnosis information (ICD-O-3 from the SEER registry or ICD-9-CM from Medicare claims) before the index date. Patients who died before follow-up end, had HMO or discontinuous Medicare enrollment during the follow-up year, had enrollment based on end stage renal disease, or a diagnosis of a non-MPN malignancy before follow-up end were excluded from the study. Separate non-MPN/non-cancer control groups were selected for each MPN subtype and matched (5:1) on birth year, gender, ethnicity, geography, and reason for Medicare eligibility. Per patient health care utilization and costs during the follow-up year were aggregated and stratified by care setting. Costs were adjusted to 2010 US$ and represent amounts reimbursed by Medicare to providers. Costs were compared between MPN cases and controls using univariate t-tests. Results:A total of 1,355 MPN patients (n = 445 ET, 684 PV, 81 MF, 145 MPN-NOS) were identified for study inclusion and assigned matching controls. For ET, PV, MF and MPN-NOS cases, respectively, mean [SD] age at index was 75.5 [9.7], 70.8 [11.3], 70.8 [10.4] and 74.1 [8.9] years and % female was 69.0, 43.9, 54.3, and 55.2. Mean [SD] years between first MPN diagnosis and study index date was 3.1 [2.0], 3.4[1.9], 2.7 [2.0], and 3.1 [2.1] for ET, PV, MF and MPN-NOS cases, respectively. A significantly (p<0.05) higher proportion of MPN cases, regardless of subtype, had ≥1 hospitalization during follow-up vs. controls (ET vs. control: 22% vs. 16%, PV vs. control: 27% vs. 15%, MF vs. control: 31% vs. 12%, MPN-NOS vs. control: 36% vs. 17%). Mean [SD] total days of hospital care were similarly higher in MPN cases (ET vs. control: 2.7 [12.8] vs. 1.6 [6.6], PV vs. control: 2.6 [7.0] vs. 1.7 [9.5], MF vs. control: 2.5 [6.2] vs. 1.2 [5.9], MPN-NOS vs. control: 4.0 [10.0] vs. 2.1 [13.7]), although the PV vs. control difference was not statistically significant. The ER visit rate during follow-up was also significantly (p<0.05) higher in MPN cases (ET vs. control: 34% vs. 24%, PV vs. control: 38% vs. 25%, MF vs. control: 46% vs. 21%, MPN-NOS vs. control: 44% vs. 29%). All-cause costs for MPN cases vs. matched controls are presented in the figure. Mean total costs per patient, driven equally by inpatient and outpatient services, were significantly (p<0.001) higher in MPN cases (ET vs. control: $11,259 vs. $8,897, PV vs. control: $13,337 vs. $8,530, MF vs. control: $20,917 vs. $7,367, MPN-NOS vs. control: $20,174 vs. $9,800). Conclusions:Total health care costs during a given year for elderly patients with MPNs are 1.3 to 3 times higher (depending on subtype) than those of matched controls. These findings may help inform future cost effectiveness evaluations of novel MPN treatments, as well as decision making in the provision of optimal MPN care within a Medicare system in which resources are finite and must be allocated ethically and efficiently. [Display omitted] Disclosures:Karve:RTI Health Solutions: Consultancy, Research Funding. Price:Eli Lilly and Company: Employment, Equity Ownership. Davis:Eli Lilly, Merck, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, Eisai, Sanof-Aventis, Gilead Sciences, MedImmune: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Pohl:Eli Lilly and Company: Employment, Equity Ownership. Walgren:Eli Lilly and Company: Employment, Equity Ownership.

Comorbidity Burden in Elderly Persons with Non-CML Myeloproliferative Neoplasms: Real-World Evidence From a United States Medicare Population

AbstractAbstract 1734 Background:Non-CML myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF) and MPN not otherwise specified (MPN-NOS), are characterized by activation of JAK2 signaling and abnormal blood cell production. MPN patients, especially those aged ≥65 years (in whom MPN incidence is highest), are at increased risk for cardiovascular and other comorbidities (Vannucchi et al. Blood 2007;110:840-6, Marchioli et al. J Clin Oncol 2005;23:2224-32). However, comorbidity rates in elderly MPN patients as compared with non-MPN controls have not been described in previous literature. MPNs are more prevalent in the elderly and therefore Medicare enrollees are a highly relevant source for US-based epidemiological data for these diseases. Objective:To compare comorbidity rates from four subtypes of elderly MPN patients (ET, PV, MF and MPN-NOS) with matched non-MPN/non-cancer controls. Methods:Retrospective data were taken from the Survey, Epidemiology, and End Results (SEER)-Medicare linked database in the US, which combines clinical information from the SEER cancer registry (MPN reporting has been required since 2001) with medical and pharmacy claims for Medicare enrollees. Patients with a new MPN diagnosis between Jan 1, 2001 and Dec 31, 2007 were selected and evaluated for comorbidities from Jan 1, 2008 (index date) through Dec 31, 2008 (follow-up end date). Patients were classified by MPN subtype based on the most recent diagnosis information (ICD-O-3 from the SEER registry or ICD-9-CM from Medicare claims) before the index date. Patients who died before follow-up end, had HMO or discontinuous Medicare enrollment during the follow-up year, had enrollment based on end stage renal disease, or were diagnosed with a non-MPN malignancy before follow-up end were excluded. Comorbidities were defined by ICD-9-CM diagnosis codes comprising the Charlson Comorbidity Index (CCI) (Charlson et al. J Chron Dis 1987;40:373–83; Deyo et al. J Clin Epidemiol 1992;45:613-9) as well as other adverse conditions. Separate non-MPN/non-cancer control groups were selected for each MPN subtype and matched (5:1) on birth year, gender, ethnicity, geography, and reason for Medicare eligibility. The proportion of patients with individual comorbidities and mean CCI during the follow-up year were compared between MPN cases and controls using univariate chi-square tests and t-tests. Results:A total of 1,355 MPN patients (n = 445 ET, 684 PV, 81 MF, 145 MPN-NOS) were identified for inclusion and assigned matching controls. For ET, PV, MF and MPN-NOS cases, respectively, mean [SD] age at index was 75.5 [9.7], 70.8 [11.3], 70.8 [10.4] and 74.1 [8.9] years and % female was 69.0, 43.9, 54.3, and 55.2. Mean [SD] years between first MPN diagnosis and study index date was 3.1 [2.0], 3.4[1.9], 2.7 [2.0], and 3.1 [2.1] for ET, PV, MF and MPN-NOS cases, respectively. Comorbidity rates during the follow-up period for MPN cases and matched controls are shown in the figure. Compared with controls, ET, PV and MPN-NOS cases had significantly (p<0.05) higher rates of serious cardiovascular events and comorbidities during the follow-up year, including myocardial infarction (ET vs. control: 8.1% vs. 4.0%, PV vs. control: 8.6% vs. 4.3%, MPN-NOS vs. control: 9.7% vs. 5.0%), congestive heart failure (CHF) (ET vs. control: 16.4% vs. 12.7%, PV vs. control: 18.4% vs. 10.1%, MPN-NOS vs. control: 22.1% vs. 12.4%), peripheral vascular disease (PVD) (ET vs. control: 20.0% vs. 15.4%, PV vs. control: 19.4% vs. 13.6%, MPN-NOS vs. control: 27.6% vs. 15.7%), and stroke (ET vs. control: 17.8% vs. 13.4%, PV vs. control: 17.8% vs. 13.1%, MPN-NOS vs. control: 22.1% vs. 13.9%). MF cases also had higher rates of CHF, PVD and stroke, but due to small sample size, only congestive heart failure was significant. Other comorbidities were significantly higher in all MPN subtypes, notably thromboembolism, renal disease, moderate-to-severe liver disease, and infections. Conclusions:Medicare enrollees with MPNs generally experienced significantly higher comorbidity rates and overall comorbidity burden (based on mean CCI scores) than matched controls. These findings have implications for both the clinical management of MPN patients as well as for health economic assessments, since a substantial portion of the cost of care for MPNs may reside in treatment of comorbidities not directly coded to MPNs. [Display omitted] Disclosures:Davis:Eli Lilly, Merck, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, Eisai, Sanof-Aventis, Gilead Sciences, MedImmune: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Price:Eli Lilly and Company: Employment, Equity Ownership. Karve:RTI Health Solutions: Consultancy, Research Funding. Pohl:Eli Lilly and Company: Employment, Equity Ownership. Walgren:Eli Lilly and Company: Employment, Equity Ownership.

The Relationship Between Socioeconomic Status and Clinical Outcomes in African Americans with Chronic Lymphocytic Leukemia

Abstract 3912 Background:Epidemiologic data compiled by the Survey Epidemiology and End Results (SEER) identifies important differences in incidence and survival for African Americans with chronic lymphocytic leukemia (CLL). Although the incidence of CLL is lower among African Americans (AA) than Caucasians (Cauc) (4.4 and 6.1 per 100,000 men, respectively), age adjusted survival is inferior. The overall 5-year relative survival for 1999–2006 from 17 SEER geographic areas by race and sex was: 77.0% for Cauc men, 81.1% for Cauc women, 62.4% for AA men, and 68.3% for AA women; hence, AA CLL patients have an approximate 15% greater absolute risk of CLL-related death in the first 5 years after diagnosis. We have undertaken biologic and genetic investigations to identify factors that contribute to poorer outcomes among AA patients with CLL. A central unanswered question is whether the differences in biology and genetics are the primary cause of inferior overall survival, or whether differences in socioeconomic status (SES) also play a significant role in clinical outcomes. Methods:The Duke University CLL database contains information on greater than 550 CLL patients at Duke University Hospital and the Durham Veterans Affairs Medical Center. We performed a detailed retrospective analysis of this cohort, using average income by ZIP code as a surrogate marker for SES. This was compared with survival data abstracted from the Social Security Outcomes Database. The primary outcome measure was overall survival, and secondary outcome measure was time to treatment (TTT). These outcome measures were compared against average income by ZIP code in addition to other standard validated clinical risk parameters such as race, gender, age, and Rai stage. Statistical analyses were performed using JMP software, version 9.0.1 (SAS, Cary, NC). Average income by ZIP code is publicly available information via IRS tax returns; we used the average adjusted gross income from 2007. Results:Mean household income, as estimated by ZIP code, was $43,255/year for AA (n= 37) and $55,353/year for Cauc (n= 363) (p<0.0001). For univariate analyses, Kaplan-Meier survival curves were generated for age, race, gender, and average income by ZIP code. Mean survival was 8.5 years for AA, and 17.9 years for Cauc (p<0.0001, Log-Rank). Mean survival was 18.5 years for those under the age of 60, and 14.8 years for those 60 and above (p<0.0001, Log-Rank). Mean survival was 18.6 years for females, and 15.9 years for males (p= 0.25, Log-Rank). For univariate analysis, average income by ZIP code was divided into quintiles, and mean survival was 16.0, 13.4, 16.2, 18.0, and 13.9 years, in order of ascending incomes (p= 0.73, Log-Rank). Mean TTT was 2.7 years for AA, and 4.5 years for Cauc (p= 0.0004, t-test). A multivariable analysis using a Cox proportional hazards model showed that the following prognostic variables (followed by respective hazard ratios (HR) and p value) were independent predictors of shorter overall survival: AA race (versus Cauc race; HR= 3.6, p= 0.0005), age (examined as a continuous variable; HR= 1.07, per unit change in regressor, HR= 41.1 per change in regressor over entire range, p= <0.0001), Rai stage (HR varies depending on stages under comparison, p= 0.003), and male gender (versus female; HR= 1.9, p= 0.015). Mean income by ZIP code was not an independent predictor of shorter overall survival (examined as a continuous variable; HR= 0.99, per unit change in regressor, HR= 0.53 per change in regressor over entire range, p= 0.39). Conclusions:AA patients with CLL have poorer overall survival than Cauc. We have examined whether SES plays a role in these inferior outcomes. While the AA patients in our cohort have lower average household incomes, this was not an independent predictor of survival in a multivariable model. We conclude that clinical and biologic, rather than socioeconomic, factors are primary determinants of inferior clinical outcomes. However, SES is intrinsically a difficult construct to measure, and it is possible that using average incomes by ZIP code does not accurately approximate socioeconomic status. Disclosures:No relevant conflicts of interest to declare.

Abstract B01: Identifying barriers to breast cancer screening guideline adherence among minority women residing in rural geographic regions.

Abstract Background: Minority women residing in rural geographic communities bear a disproportionate burden of mortality due to invasive breast cancer compared to other racial/ethnic majority groups. Despite this heightened rate of mortality, preventive screening in African American (AA) and Hispanic (H) women is significantly lower than that of Non-Hispanic White (NHW) women. The purpose of this study is to identify and validate the barriers associated with non-compliance to recommended breast cancer screening guidelines in AA and H women in rural geographic regions. Methods: A prior observational analysis conducted by RHEAI using data from the Texas Cancer Registry (TCR), U.S. Census Bureau, and Survey Epidemiology and End Results (SEER) Database identified Cherokee County, Texas as having a significant disparity in breast cancer screening and mortality rates when comparing AA, H, and NHW women. To gauge this disparity, we collected opinions about breast cancer screening and mortality incidence by surveying 13 local stakeholders (including breast cancer survivors, religious leaders, community leaders, local hospital employees, and educators) within the minority community. Based on stakeholder survey results and health disparity literature reviews, a relevant and culturally sensitive survey was developed using the 5-point Livert scale to identify the perceived barriers to breast cancer screening in the general minority population. A total of 115 surveys of AA and H women were planned. The sample size was calculated based on the percentage of AA and H women residing in Cherokee County with a 95% level of confidence and a +/- 5% margin of error. Results: At the time of this analysis, 24 of 115 (Response Rate=20.87%) surveys were completed online via electronic survey (n=20) and in printed form (n=4) between 05/2012 and 07/2012. The median age of participants was 42 years (range 30-62), 100% were AA women residing in rural Cherokee County. Lack of breast cancer educational/awareness programs, limited transportation access, and lack of local mammography facilities were identified as statistically significant barriers associated with decreased adherence to breast cancer screening guidelines. These barriers varied based on participant age, familial breast cancer history, and level of education. Conclusions: The interim results of this study demonstrate that minority women in rural areas encounter unique barriers to breast cancer screening access. Upon completion of accrual and data analysis for this study, RHEAI is committed to addressing the identified barriers through effective interventions. Our ultimate goal is to improve health care accessibility for underserved minority groups through collaborative efforts within the community. Note: This abstract was not presented at the conference. Citation Format: Monique J. Carter, Arturo A. Pizaña, Scharri E. Walker, Tracy A. Davis. Identifying barriers to breast cancer screening guideline adherence among minority women residing in rural geographic regions. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B01.

Medicare Fee-for-Service Enrollees with Acute Myelogenous Leukemia: An Analysis of Treatment Patterns and Patient Survival

Abstract 505 Background:Acute myelogenous leukemia (AML) is the most common type of leukemia among adults in the US. The incidence of AML increases with age. Older AML patients, constituting the majority of the AML population, generally have poor outcomes with median survival less than 3 months. Published information on treatment patterns and survival trends in elderly patients with AML is outdated and newer information on treatment patterns and survival is lacking. Objective:The goal of this retrospective database analysis is to examine treatment patterns, overall patient survival, predictors of which patients are likely to receive chemotherapy, and predictors of mortality among Medicare fee-for-service enrollees diagnosed with AML in the most recent available database. Methods:Medicare patients aged 65+ years in the SEER (Survey, Epidemiology, and End Results) cancer registry with a new AML diagnosis between 1/1/1997 and 12/31/2007 were selected for study inclusion. Patients were required to have at least 6 months of pre-AML Medicare Part A and B benefits and no evidence of managed care (Medicare Part C) enrollment post-AML diagnosis. Patients were excluded from the analysis if they had evidence of another tumor (either solid or hematological) in the SEER registry before the first AML diagnosis. Health care claims in the 6 months pre-index were examined, and patients with any diagnosis of a solid tumor (not specified in SEER) were also excluded. Patients were followed until their date of death or end of observation period (i.e., 12/31/2007). Study measures included AML-directed treatments (i.e., chemotherapy, radiation therapy, hematopoietic stem-cell/bone marrow transplants [HSCT/BMT]), best supportive care received, and post-AML diagnosis survival time. Patient survival time was assessed overall and for patients receiving chemotherapy during follow-up versus patients receiving best supportive care only. Temporal changes in treatment utilization and survival were assessed by evaluating these measures separately for AML cases diagnosed in 1997–1999, 2000–2003, and 2004–2007. Multivariate logistic regressions were undertaken to assess predictors of receipt of chemotherapy, including patient demographics, comorbidities, and year of AML diagnosis. Results:6,888 patients met the study inclusion criteria. Mean (SD) and median age were 78.3 (7.2) and 78.0 years respectively. Over 43% of patients received chemotherapy at any point post-diagnosis. Chemotherapy use increased slightly over time: 40.7%, 42.3%, and 46.0% of patients diagnosed with AML in the periods in 1997–1999, 2000–2003, and 2004–2007, respectively. Fifty-six percent of patients received only best supportive care post-diagnosis, and the percentage slightly decreased over time. Among patients receiving only best supportive care, rates of hospice care increased substantially over time: 32.9%, 42.7%, and 49.1% in each of the respective time periods. Rates of HSCT/BMT procedures were low with an increase over time: 0.67%, 2.06%, and 2.49%. Nearly all patients (97.1%) died during the observable follow-up, and median survival time was 2.6 months. Among patients who received chemotherapy, 93.9% died during follow-up and the median survival was 6.5 months with 5.7, 6.4, and 7.0 months among patients diagnosed in 1997–1999, 2000–2003, and 2004–2007, respectively. Among patients who received only best-supportive care, 99.5% died during follow-up and median survival was 1.5 months with little change over time. Younger patients (65–74 years vs >= 75 years), patients with fewer comorbidities (Charlson Comorbidity Index [CCI] ≤1 vs > CCI >1), patients with a post-AML secondary cancer diagnosis, and patients diagnosed with AML in more recent years were found to be more likely to receive chemotherapy. Conclusions:Findings from our analysis showed an increasing trend in rates of chemotherapy treatment and utilization of hospice care among Medicare patients with AML. However, a large portion of elderly patients remain untreated. Median survival among patients who received chemotherapy was found to increase over time. Patients who received chemotherapy, when compared to those who did not, had a lower mortality rate and an over 3-fold longer median survival. Disclosures:Yu:Boehringer Ingelheim Pharmaceuticals, Inc.: Employment.

Papillary Carcinomas of the Gallbladder: Analysis of Noninvasive and Invasive Types

Although papillary carcinomas have been recognized as distinct morphologic variants of gallbladder neoplasms, they have been lumped together in a single group despite the recognition of noninvasive and invasive types. As a result, the biologic behavior of each type remains undescribed. To compare the biologic behavior of noninvasive and invasive papillary carcinomas of the gallbladder. The clinical and morphologic features of 16 noninvasive papillary carcinomas (>1 cm) of the gallbladder were analyzed, and their clinical behavior was compared with that of 370 invasive papillary carcinomas recorded in the Survey Epidemiology and End Results (SEER) Program of the National Cancer Institute from 1973 through 2001. The biologic behavior of invasive papillary carcinomas was compared with that of invasive nonpapillary carcinomas of the gallbladder recorded in SEER. Hematoxylin-eosin-stained sections were available for review in the 16 noninvasive papillary carcinomas. The number of slides examined per case varied from 3 to 16, with an average of 7. The 16 patients with noninvasive papillary carcinomas included 11 women and 5 men, aged 34 to 83 years (mean age, 61 years). Thirteen patients had cholelithiasis. Laparoscopic cholecystectomy was performed on 12 patients and open cholecystectomy on 4. The tumors measured from 1.3 to 8.6 cm and were well to moderately differentiated. Fourteen noninvasive papillary carcinomas showed biliary phenotype, and 2 showed intestinal phenotype. Follow-up was obtained in 11 patients; 6 were asymptomatic 5 to 11 years after surgery, 2 were symptom free 9 months to 4 years following cholecystectomy, and 3 died of unrelated causes 2 to 3 years after surgery. Three hundred seventy cases of invasive papillary carcinomas were recorded in SEER. The 10-year relative survival rate for 225 patients with invasive papillary carcinomas confined to the gallbladder wall was 52%, while the 10-year relative survival rate for 83 patients with papillary carcinomas that had spread to the lymph nodes was less than 10%. Of the remaining 62 invasive papillary carcinomas, 58 had distant metastases and 4 were not staged. The 10-year relative survival rate for invasive nonpapillary carcinomas confined to the gallbladder wall was 30%. Noninvasive papillary carcinomas of the gallbladder-regardless of size, cell phenotype, and degree of differentiation-do not metastasize, and a simple cholecystectomy appears to be a curative procedure. In contrast, invasive papillary carcinomas do metastasize and are associated with a poor prognosis (10-year relative survival rate for tumors confined to the gallbladder wall was 52%, while the 10-year relative survival rate for tumors with lymph node metastasis was <10%). The separation of papillary carcinomas into noninvasive and invasive types is clinically relevant and therefore fully justified.

Papillary Carcinomas of the Gallbladder: Analysis of Noninvasive and Invasive Types

Abstract Context.—Although papillary carcinomas have been recognized as distinct morphologic variants of gallbladder neoplasms, they have been lumped together in a single group despite the recognition of noninvasive and invasive types. As a result, the biologic behavior of each type remains undescribed. Objective.—To compare the biologic behavior of noninvasive and invasive papillary carcinomas of the gallbladder. Design.—The clinical and morphologic features of 16 noninvasive papillary carcinomas (>1 cm) of the gallbladder were analyzed, and their clinical behavior was compared with that of 370 invasive papillary carcinomas recorded in the Survey Epidemiology and End Results (SEER) Program of the National Cancer Institute from 1973 through 2001. The biologic behavior of invasive papillary carcinomas was compared with that of invasive nonpapillary carcinomas of the gallbladder recorded in SEER. Hematoxylin-eosin–stained sections were available for review in the 16 noninvasive papillary carcinomas. The num...

Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients.

The risk of lymphoma is increased in patients with rheumatoid arthritis (RA), and spontaneous reporting suggests that methotrexate (MTX) and anti-tumor necrosis factor (anti-TNF) therapy might be associated independently with an increased risk of lymphoma. However, data from clinical trials and clinical practice do not provide sufficient evidence concerning these issues because of small sample sizes and selected study populations. The objective of this study was to determine the rate of and standardized incidence ratio (SIR) for lymphoma in patients with RA and in RA patient subsets by treatment group. Additionally, we sought to determine predictors of lymphoma in RA. We prospectively studied 18,572 patients with RA who were enrolled in the National Data Bank for Rheumatic Diseases (NDB). Patients were surveyed biannually, and potential lymphoma cases received detailed followup. The SEER (Survey, Epidemiology, and End Results) cancer data resource was used to derive the expected number of cases of lymphoma in a cohort that was comparable in age and sex with the RA cohort. The overall SIR for lymphoma was 1.9 (95% confidence interval [95% CI] 1.3-2.7). The SIR for biologic use was 2.9 (95% CI 1.7-4.9) and for the use of infliximab (with or without etanercept) was 2.6 (95% CI 1.4-4.5). For etanercept, with or without infliximab, the SIR was 3.8 (95% CI 1.9-7.5). The SIR for MTX was 1.7 (95% CI 0.9-3.2), and was 1.0 (95% CI 0.4-2.5) for those not receiving MTX or biologics. Lymphoma was associated with increasing age, male sex, and education. Lymphomas are increased in RA. Although the SIR is greatest for anti-TNF therapies, differences between therapies are slight, and confidence intervals for treatment groups overlap. The increased lymphoma rates observed with anti-TNF therapy may reflect channeling bias, whereby patients with the highest risk of lymphoma preferentially receive anti-TNF therapy. Current data are insufficient to establish a causal relationship between RA treatments and the development of lymphoma.