An overview of real-world data sources for oncology and considerations for research.

Generating evidence on the use, effectiveness, and safety of new cancer therapies is a priority for researchers, health care providers, payers, and regulators given the rapid pace of change in cancer diagnosis and treatments. The use of real-world data (RWD) is integral to understanding the utilization patterns and outcomes of these new treatments among patients with cancer who are treated in clinical practice and community settings. An initial step in the use of RWD is careful study design to assess the suitability of an RWD source. This pivotal process can be guided by using a conceptual model that encourages predesign conceptualization. The primary types of RWD included are electronic health records, administrative claims data, cancer registries, and specialty data providers and networks. Careful consideration of each data type is necessary because they are collected for a specific purpose, capturing a set of data elements within a certain population for that purpose, and they vary by population coverage and longitudinality. In this review, the authors provide a high-level assessment of the strengths and limitations of each data category to inform data source selection appropriate to the study question. Overall, the development and accessibility of RWD sources for cancer research are rapidly increasing, and the use of these data requires careful consideration of composition and utility to assess important questions in understanding the use and effectiveness of new therapies.

Data linkage in pharmacoepidemiology: A call for rigorous evaluation and reporting.

PURPOSE: The purpose of this paper is to provide guidance on the evaluation of data linkage quality through the development of a checklist for reporting key elements of the linkage process. METHODS: Responding to a call for manuscripts from the International Society for Pharmacoepidemiology (ISPE), a working group including international representation from the academic, industry, and contract research, and regulatory sectors was formed to develop a checklist for evaluation of data linkage performance and reporting data linkage specifically for pharmacoepidemiologic research. This checklist expands on the reporting of studies conducted using observational routinely collected health data specific to pharmacoepidemiology (RECORD-PE) guidelines. RESULTS: A key aspect of data linkage evaluation for pharmacoepidemiology is to articulate how a linkage process was performed and its accuracy in terms of validation and verification of the resulting linked data. This study generates a checklist, which covers domains including data sources, linkage variables, linkage methods, linkage results, and linkage evaluation. For each domain, specific recommendations provide a clear and transparent assessment of the linkage process. CONCLUSIONS: Linking data sources can help to enrich analytic databases to more accurately define study populations, enable adjustment for confounding, and improve the capture of health outcomes. Clear and transparent reporting of data linkage processes will help to increase confidence in the evidence generated from these data by allowing researchers and end users to critically assess the potential for bias owing to the data linkage process.

Development and validation of a 5-year mortality prediction model using regularized regression and Medicare data.

PURPOSE: De-implementation of low-value services among patients with limited life expectancy is challenging. Robust mortality prediction models using routinely collected health care data can enhance health care stakeholders' ability to identify populations with limited life expectancy. We developed and validated a claims-based prediction model for 5-year mortality using regularized regression methods. METHODS: Medicare beneficiaries age 66 or older with an office visit and at least 12 months of pre-visit continuous Medicare A/B enrollment were identified in 2008. Five-year mortality was assessed through 2013. Secondary outcomes included 30-, 90-, and 180-day and 1-year mortality. Claims-based predictors, including comorbidities and indicators of disability, frailty, and functional impairment, were selected using regularized logistic regression, applying the least absolute shrinkage and selection operator (LASSO) in a random 80% training sample. Model performance was assessed and compared with the Gagne comorbidity score in the 20% validation sample. RESULTS: Overall, 183 204 (24%) individuals died. In addition to demographics, 161 indicators of comorbidity and function were included in the final model. In the validation sample, the c-statistic was 0.825 (0.823-0.828). Median-predicted probability of 5-year mortality was 14%; almost 4% of the cohort had a predicted probability greater than 80%. Compared with the Gagne score, the LASSO model led to improved 5-year mortality classification (net reclassification index = 9.9%; integrated discrimination index = 5.2%). CONCLUSIONS: Our claims-based model predicting 5-year mortality showed excellent discrimination and calibration, similar to the Gagne score model, but resulted in improved mortality classification. Regularized regression is a feasible approach for developing prediction tools that could enhance health care research and evaluation of care quality.

Influence of provider factors and race on uptake of breast cancer gene expression profiling.

BACKGROUND: Gene expression profiling (GEP) has been rapidly adopted for early breast cancer and can aid in chemotherapy decision making. Study results regarding racial disparities in testing are conflicting, and may reflect different care settings. To the authors' knowledge, data regarding the influence of provider factors on testing are scarce. METHODS: The authors used a statewide, multipayer, insurance claims database linked to cancer registry records to examine the impact of race and provider characteristics on GEP uptake in a cohort of patients newly diagnosed with breast cancer between 2005 and 2012. Incidence proportion models were used to examine the adjusted likelihood of testing. Models were stratified by lymph node status (N0 vs N1). RESULTS: Among 11,958 eligible patients, 23% of black and 26% of non-Hispanic white patients received GEP. Among patients with N0 disease, black individuals were 16% less likely to receive testing after adjustment for clinical factors and the provider's specialty and volume of patients with breast cancer (95% confidence interval, 0.77-0.93). Adjustment for provider characteristics did not attenuate the effect of race on testing. Patients of middle-volume providers were more likely to be tested compared with those with either high-volume or low-volume providers, whereas patients seeing a medical oncologist were more likely to be tested compared with those whose only providers were from surgical specialties. CONCLUSIONS: Provider volume and specialty were found to be significant predictors of GEP use, but did not explain racial disparities in testing. Further research concerning the key contributors to lagging test use among black women is needed to optimize the equitable use of GEPs and support personalized treatment decision making for all patients. Cancer 2018;124:1743-51. © 2018 American Cancer Society.

Endocrine Therapy Initiation and Medical Oncologist Utilization Among Women Diagnosed with Ductal Carcinoma in Situ.

BACKGROUND: Though randomized clinical trials have demonstrated a reduction in second breast events with endocrine therapy among women with ductal carcinoma in situ (DCIS), use of these therapies remains highly variable. The purpose of this study was to evaluate patient and treatment-related factors associated with endocrine therapy initiation and medical oncology specialty utilization after DCIS. MATERIALS AND METHODS: We identified women with a DCIS diagnosis during 2006-2010 in the North Carolina Central Cancer Registry with linked public and private insurance claims in the University of North Carolina Integrated Cancer Information Surveillance System data resource. Multivariable generalized linear regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) for endocrine therapy initiation in the year following DCIS diagnosis. RESULTS: Among 2,090 women with a DCIS diagnosis, 37% initiated endocrine therapy. Initiation was less common among women aged 75+ at diagnosis (RR = 0.79; 95% CI: 0.64-0.97 vs. age 45-54) and women treated with breast-conserving surgery (BCS) who did not receive radiation (RR = 0.63; 95% CI: 0.50-0.78 vs. BCS plus radiation). Consultation with a medical oncologist was strongly associated with endocrine therapy initiation (RR = 1.40; 95% CI: 1.23-1.61). Women who saw a medical oncologist more often had private insurance, higher census tract-level income, hormone receptor positive disease, and treatment with BCS and radiation. CONCLUSION: Treatment strategies for DCIS remain controversial. Our data suggest that endocrine therapy is more often used in addition to standard therapies such as BCS plus radiation, rather than as an alternative to radiation. The Oncologist 2017;22:535-541 IMPLICATIONS FOR PRACTICE: Randomized trials have demonstrated a reduction in second breast cancer events with use of endocrine therapy for ductal carcinoma in situ (DCIS). However, notable variation exists in the uptake of these therapies among DCIS patients. In this study, factors associated with endocrine therapy initiation in the year following a DCIS diagnosis included consultation with a medical oncologist and treatment with breast-conserving surgery with radiation. Our findings help to explain the wide variation in endocrine therapy initiation and suggest the need for clear guidelines in the treatment of DCIS.

Data Linkage to Improve Geriatric Oncology Research: A Feasibility Study.

Older adults (aged 65 years and older) diagnosed with cancer account for most cancer-related morbidity and mortality in the United States but are often underrepresented on clinical trials. Recent attention from a variety of professional, research, regulatory, and patient advocacy groups has centered on data linkage and data sharing as a means to capture patient information and outcomes outside of clinical trials to accelerate progress in the fight against cancer. The development of a more robust observational research data infrastructure would help to address gaps in the evidence base regarding optimal approaches to treating cancer among the growing and complex population of older adults. To demonstrate the feasibility of building such a resource, we linked information from a sample of older adults with cancer in North Carolina using three distinct, but complementary, data sources: (a) the Carolina Senior Registry, (b) the North Carolina Central Cancer Registry, and (c) North Carolina fee-for-service Medicare claims data. A description of the linkage process, metrics, and characteristics of the final cohort is reported. This study highlights the potential for data linkage to improve the characterization of health status among older adults with cancer and the possibility to conduct passive follow-up for outcomes of interest over time. Extensions of these linkage efforts in partnership with other institutions will enhance our ability to generate evidence that can inform the management of older adults with cancer.

Using Procedure Codes to Define Radiation Toxicity in Administrative Data: The Devil is in the Details.

BACKGROUND: Systematic coding systems are used to define clinically meaningful outcomes when leveraging administrative claims data for research. How and when these codes are applied within a research study can have implications for the study validity and their specificity can vary significantly depending on treatment received. SUBJECTS: Data are from the Surveillance, Epidemiology, and End Results-Medicare linked dataset. STUDY DESIGN: We use propensity score methods in a retrospective cohort of prostate cancer patients first examined in a recently published radiation oncology comparative effectiveness study. RESULTS: With the narrowly defined outcome definition, the toxicity event outcome rate ratio was 0.88 per 100 person-years (95% confidence interval, 0.71-1.08). With the broadly defined outcome, the rate ratio was comparable, with 0.89 per 100 person-years (95% confidence interval, 0.76-1.04), although individual event rates were doubled. Some evidence of surveillance bias was suggested by a higher rate of endoscopic procedures the first year of follow-up in patients who received proton therapy compared with those receiving intensity-modulated radiation treatment (11.15 vs. 8.90, respectively). CONCLUSIONS: This study demonstrates the risk of introducing bias through subjective application of procedure codes. Careful consideration is required when using procedure codes to define outcomes in administrative data.

Reducing Racial Disparities in Breast Cancer Care: The Role of 'Big Data'.

Advances in a wide array of scientific technologies have brought data of unprecedented volume and complexity into the oncology research space. These novel big data resources are applied across a variety of contexts-from health services research using data from insurance claims, cancer registries, and electronic health records, to deeper and broader genomic characterizations of disease. Several forms of big data show promise for improving our understanding of racial disparities in breast cancer, and for powering more intelligent and far-reaching interventions to close the racial gap in breast cancer survival. In this article we introduce several major types of big data used in breast cancer disparities research, highlight important findings to date, and discuss how big data may transform breast cancer disparities research in ways that lead to meaningful, lifesaving changes in breast cancer screening and treatment. We also discuss key challenges that may hinder progress in using big data for cancer disparities research and quality improvement.

Cost-Effectiveness Analysis of Four Simulated Colorectal Cancer Screening Interventions, North Carolina.

INTRODUCTION: Colorectal cancer (CRC) screening rates are suboptimal, particularly among the uninsured and the under-insured and among rural and African American populations. Little guidance is available for state-level decision makers to use to prioritize investment in evidence-based interventions to improve their population's health. The objective of this study was to demonstrate use of a simulation model that incorporates synthetic census data and claims-based statistical models to project screening behavior in North Carolina. METHODS: We used individual-based modeling to simulate and compare intervention costs and results under 4 evidence-based and stakeholder-informed intervention scenarios for a 10-year intervention window, from January 1, 2014, through December 31, 2023. We compared the proportion of people living in North Carolina who were aged 50 to 75 years at some point during the window (that is, age-eligible for screening) who were up to date with CRC screening recommendations across intervention scenarios, both overall and among groups with documented disparities in receipt of screening. RESULTS: We estimated that the costs of the 4 intervention scenarios considered would range from $1.6 million to $3.75 million. Our model showed that mailed reminders for Medicaid enrollees, mass media campaigns targeting African Americans, and colonoscopy vouchers for the uninsured reduced disparities in receipt of screening by 2023, but produced only small increases in overall screening rates (0.2-0.5 percentage-point increases in the percentage of age-eligible adults who were up to date with CRC screening recommendations). Increased screenings ranged from 41,709 additional life-years up to date with screening for the voucher intervention to 145,821 for the mass media intervention. Reminders mailed to Medicaid enrollees and the mass media campaign for African Americans were the most cost-effective interventions, with costs per additional life-year up to date with screening of $25 or less. The intervention expanding the number of endoscopy facilities cost more than the other 3 interventions and was less effective in increasing CRC screening. CONCLUSION: Cost-effective CRC screening interventions targeting observed disparities are available, but substantial investment (more than $3.75 million) and additional approaches beyond those considered here are required to realize greater increases population-wide.

Association Between Choice of Radical Prostatectomy, External Beam Radiotherapy, Brachytherapy, or Active Surveillance and Patient-Reported Quality of Life Among Men With Localized Prostate Cancer.

Importance: Patients diagnosed with localized prostate cancer have to decide among treatment strategies that may differ in their likelihood of adverse effects. Objective: To compare quality of life (QOL) after radical prostatectomy, external beam radiotherapy, and brachytherapy vs active surveillance. Design, Setting, and Participants: Population-based prospective cohort of 1141 men (57% participation among eligible men) with newly diagnosed prostate cancer were enrolled from January 2011 through June 2013 in collaboration with the North Carolina Central Cancer Registry. Median time from diagnosis to enrollment was 5 weeks, and all men were enrolled with written informed consent prior to treatment. Final follow-up date for current analysis was September 9, 2015. Exposures: Treatment with radical prostatectomy, external beam radiotherapy, brachytherapy, or active surveillance. Main Outcomes and Measures: Quality of life using the validated instrument Prostate Cancer Symptom Indices was assessed at baseline (pretreatment) and 3, 12, and 24 months after treatment. The instrument contains 4 domains-sexual dysfunction, urinary obstruction and irritation, urinary incontinence, and bowel problems-each scored from 0 (no dysfunction) to 100 (maximum dysfunction). Propensity-weighted mean domain scores were compared between each treatment group vs active surveillance at each time point. Results: Of 1141 enrolled men, 314 pursued active surveillance (27.5%), 469 radical prostatectomy (41.1%), 249 external beam radiotherapy (21.8%), and 109 brachytherapy (9.6%). After propensity weighting, median age was 66 to 67 years across groups, and 77% to 80% of participants were white. Across groups, propensity-weighted mean baseline scores were 41.8 to 46.4 for sexual dysfunction, 20.8 to 22.8 for urinary obstruction and irritation, 9.7 to 10.5 for urinary incontinence, and 5.7 to 6.1 for bowel problems. Compared with active surveillance, mean sexual dysfunction scores worsened by 3 months for patients who received radical prostatectomy (36.2 [95% CI, 30.4-42.0]), external beam radiotherapy (13.9 [95% CI, 6.7-21.2]), and brachytherapy (17.1 [95% CI, 7.8-26.6]). Compared with active surveillance at 3 months, worsened urinary incontinence was associated with radical prostatectomy (33.6 [95% CI, 27.8-39.2]); acute worsening of urinary obstruction and irritation with external beam radiotherapy (11.7 [95% CI, 8.7-14.8]) and brachytherapy (20.5 [95% CI, 15.1-25.9]); and worsened bowel symptoms with external beam radiotherapy (4.9 [95% CI, 2.4-7.4]). By 24 months, mean scores between treatment groups vs active surveillance were not significantly different in most domains. Conclusions and Relevance: In this cohort of men with localized prostate cancer, each treatment strategy was associated with distinct patterns of adverse effects over 2 years. These findings can be used to promote treatment decisions that incorporate individual preferences.

Statewide geographic variation in outcomes for adults with acute myeloid leukemia in North Carolina.

BACKGROUND: Population-based studies have demonstrated survival disparities related to socioeconomic factors for patients with acute myeloid leukemia (AML). The objective of the current study was to determine whether the local health care infrastructure, represented by Area Health Education Centers (AHEC) region, or treating center experience, represented by National Cancer Institute Comprehensive Cancer Center (NCICCC) designation, were associated with outcomes among patients with AML in North Carolina. METHODS: Patients who were diagnosed with AML from 2003 to 2009 were identified using the University of North Carolina Lineberger Integrated Cancer Information and Surveillance System, a database linking insurance claims to the North Carolina Cancer Registry. A Cox proportional-hazards model was used to explore survival based on AHEC region. A subset of patients who received inpatient chemotherapy was examined to evaluate the impact of treatment at an NCICCC. RESULTS: Nine hundred patients were identified in the study period, 553 of whom received inpatient chemotherapy therapy within 30 days of diagnosis. Almost one-half of these patients (n = 294) received chemotherapy at a non-NCICCC. Among the patients who received intensive inpatient therapy, residence in 3 of 9 AHEC regions was associated with a higher risk of mortality (hazard ratio: range, 1.97-4.03; P < .01) at 1 year in multivariate analysis. Treatment at a non-NCICCC was not associated with an increased risk of mortality at 1 year (hazard ratio, 1.25; 95% confidence interval, 0.95-1.65). CONCLUSIONS: Survival among patients with AML in North Carolina varies according to geographic region. Further examination of local practice and referral patterns may inform strategies to improve AML outcomes across the state. Cancer 2016;122:3041-3050. © 2016 American Cancer Society.

Referral patterns between high- and low-volume centers and associations with uterine cancer treatment and survival: a population-based study of Medicare, Medicaid, and privately insured women.

BACKGROUND: High-volume center surgery and gynecologic oncology care are associated with improved outcomes for women with uterine cancer. Referral patterns, from biopsy through to chemotherapy, may have patients interacting with high-volume centers for all, a portion, or none of their care. The relative frequency, the underlying factors that contribute to referral, and the potential impact of these referral patterns on treatment outcomes are unknown. OBJECTIVE: We sought to analyze the referral patterns and subsequent impact of care sites on treatment for women with high- and low-risk uterine cancer. STUDY DESIGN: This is a population-based retrospective cohort study of uterine cancer cases from 2004 through 2009 in North Carolina. Using state cancer registry files linked to Medicare, Medicaid, and private payer insurance claims, we analyzed referral and treatment patterns by annual surgical volume (high ≥12/y). We examined clinical and demographic factors associated with referral and used modified Poisson regression to evaluate risk of referral, lymphadenectomy, and chemotherapy. Stratified Kaplan-Meier plots and Cox proportional hazard models were used to examine survival. RESULTS: A total of 2053 women were analyzed, including 34% (n = 677) with grade 3 histology. Of 1630 (80%) women with preoperative biopsies, referral patterns (biopsy to surgery) were: low volume to high volume (n = 652, 40%), followed by high volume to high volume (n = 605, 37%), then low volume to low volume (n = 318, 20%), and the rare high volume to low volume (n = 50, 3%). Women retained in low-volume centers after biopsy were older, were less likely to have private insurance, and had more comorbidities. High-risk histology (aRR, 1.14; 95% confidence interval, 1.04-1.25) was positively associated with referral, while Medicaid insurance was negatively associated with referral (aRR, 0.64; 95% confidence interval, 0.42-0.96). Most women (74%, n = 1557) had surgery at high-volume centers. Lymphadenectomy was less likely at low-volume centers (aRR, 0.71; 95% confidence interval, 0.64-0.77). Similarly, for high-risk patients, the relationship between low-volume center surgery and subsequent chemotherapy was aRR, 0.71 (95% confidence interval, 0.48-1.02). Of 290 women who received chemotherapy, the referral patterns (surgery to chemotherapy) were: high volume-all (high volume to high volume), high volume-hybrid (high volume to low volume, or low volume to high volume), and high volume-none (low volume to low volume). In all, 36% (n = 104/290) received chemotherapy at a low-volume center, the majority (68%, n = 71/104) of whom were referred from high-volume centers after surgery. Crude, unadjusted mortality risk of chemotherapy recipients differed by referral pattern (surgery to chemotherapy): high volume-all patients (hazard ratio, 1.0; referent), followed by high volume-hybrid (hazard ratio, 1.33; 95% confidence interval, 0.93-1.91) then high volume-none patients (RR, 1.95; 95% confidence interval, 1.24-3.08). CONCLUSION: Most women with uterine cancer treated at high-volume centers arrive through referral, which is affected by age and type of insurance, in addition to histology. For high-risk women who require chemotherapy, survival may be related to the extent of treatment received at high-volume centers.

Gynecologic cancer outcomes in the elderly poor: A population-based study.

BACKGROUND: Adults aged ≥65 years who are dually enrolled in Medicare and Medicaid are an at-risk group in health care. However, to the best of the authors' knowledge, the outcomes of women with gynecologic cancers in this population are unknown. METHODS: The current study was a population-based cohort study of North Carolina state cancer registry cases of uterine, ovarian, cervical, and vulvar/vaginal cancers (2003-2009), with linked enrollment in Medicare and state Medicaid. Outcomes of all-cause mortality and stage of disease at the time of diagnosis were analyzed as a function of enrollment status using multivariate analysis and survival curves. RESULTS: Of 4522 women aged ≥65 years (3702 of whom were enrolled in Medicare [82%] and 820 of whom were dually enrolled [18%]), there were 2286 cases of uterine (51%), 1587 cases of ovarian (35%), 302 cases of cervical (7%), and 347 cases of vulvar/vaginal (8%) cancers. Dual enrollees had increased all-cause mortality overall (adjusted hazard ratio [aHR], 1.34; 95% confidence interval [95% CI], 1.19-1.49), and within each cancer site (uterine: aHR, 1.22 [95% CI, 1.02-1.47]; ovarian: aHR, 1.25 [95% CI, 1.05-1.49]; cervical: aHR, 1.34 [95% CI, 0.96-1.87]; and vulvar/vaginal: aHR, 1.93 [95% CI, 1.36-2.72]). Increased odds of advanced-stage disease at the time of diagnosis among dual enrollees was only present in patients with uterine cancer (adjusted odds ratio, 1.38; 95% CI, 1.06-1.79). Stratified survival curves demonstrated the strongest disparities among women with early-stage uterine and early-stage vulvar/vaginal cancers. CONCLUSIONS: Women aged ≥65 years who were dually enrolled in Medicare and Medicaid were found to have an overall 34% increase in all-cause mortality after diagnosis with a gynecologic cancer compared with the non-dually enrolled Medicare population. Women with early-stage uterine and vulvar/vaginal cancers appeared to have the most disparate outcomes. Because these malignancies are generally curable, they have the most potential for benefit from targeted interventions.

Provider-based research networks and diffusion of surgical technologies among patients with early-stage kidney cancer.

BACKGROUND: Provider-based research networks such as the National Cancer Institute's Community Clinical Oncology Program (CCOP) have been shown to facilitate the translation of evidence-based cancer care into clinical practice. This study compared the utilization of laparoscopy and partial nephrectomy among patients with early-stage kidney cancer according to their exposure to CCOP-affiliated providers. METHODS: With linked Surveillance, Epidemiology, and End Results-Medicare data, patients with T1aN0M0 kidney cancer who had been treated with nephrectomy from 2000 to 2007 were identified. For each patient, the receipt of care from a CCOP physician or hospital and treatment with laparoscopy or partial nephrectomy were determined. Adjusted for patient characteristics (eg, age, sex, and marital status) and other organizational features (eg, community hospital and National Cancer Institute-designated cancer center), multivariate logistic regression was used to estimate the association between each surgical innovation and CCOP affiliation. RESULTS: During the study interval, 1578 patients (26.8%) were treated by a provider with a CCOP affiliation. Trends in the utilization of laparoscopy and partial nephrectomy remained similar between affiliated and nonaffiliated providers (P ≥ .05). With adjustments for patient characteristics, organizational features, and clustering, no association was noted between CCOP affiliation and the use of laparoscopy (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.81-1.53) or partial nephrectomy (OR, 1.04; 95% CI, 0.82-1.32) despite the more frequent receipt of these treatments in academic settings (P < .05). CONCLUSIONS: At a population level, patients treated by providers affiliated with CCOP were no more likely to receive at least 1 of 2 surgical innovations for treatment of their kidney cancer, indicating perhaps a more limited scope to provider-based research networks as they pertain to translational efforts in cancer care.

Provider-based research networks may improve early access to innovative colon cancer treatment for African Americans treated in the community.

BACKGROUND: African American (AA) patients with colon cancer (CC) experience worse outcomes than whites partly due to differential treatment. The National Cancer Institute's Community Clinical Oncology Program (CCOP), a provider-based research network, adopts and diffuses innovative CC treatments quickly. The authors hypothesized that CCOP participation would lessen racial differences in the receipt of oxaliplatin, an innovative treatment for CC, among patients with stage III CC in the community. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, the authors performed a population-based retrospective cohort study of AA and white individuals aged ≥66 years who were diagnosed with AJCC stage III CC from 2003 through 2005. Generalized estimating equations were used to calculate the odds of receiving an oxaliplatin-containing regimen. Predicted probabilities of oxaliplatin receipt for race-CCOP combinations were calculated. The absolute difference in oxaliplatin receipt between races was estimated using the interaction contrast ratio. RESULTS: Of 2971 included individuals, 36% received oxaliplatin, 29.5% were CCOP-affiliated, and 7.6% were AA. On multivariate analysis, early diffusion of oxaliplatin was not found to be associated with race or CCOP participation. The probability of receiving oxaliplatin for AAs participating in a CCOP (0.46) was nearly double that of AAs who were not participating in a CCOP (0.25; P <.05). For white individuals, the probabilities of receiving oxaliplatin did not differ by CCOP participation. For oxaliplatin receipt, the joint effects assessment suggested a greater benefit of CCOP participation among AAs (interaction contrast ratio, 1.7). CONCLUSIONS: Among older patients with stage III CC, there is a differential impact of race on oxaliplatin receipt depending on CCOP participation. AAs treated by CCOPs were more likely to receive oxaliplatin than AAs treated elsewhere. Provider-based research networks may facilitate early access to innovative treatment for AAs with stage III CC.

Preoperatively misclassified, surgically removed benign renal masses: a systematic review of surgical series and United States population level burden estimate.

PURPOSE: A significant proportion of renal masses removed for suspected malignancy are histologically benign with the probability inversely proportional to lesion size. To our knowledge the number of preoperatively misclassified benign renal masses treated with nephrectomy is currently unknown. Given the increasing incidence and decreasing average size of renal cell carcinoma, this burden is likely increasing. We estimated the population level burden of surgically removed, preoperatively misclassified benign renal masses in the United States. MATERIALS AND METHODS: We systematically reviewed the literature for studies of pathological findings of renal masses removed for suspected renal cell carcinoma based on preoperative imaging through July 1, 2014. We excluded studies that did not describe benign pathology and with masses not stratified by size, and in which pathology results were based on biopsy. SEER data were queried for the incidence of surgically removed renal cell carcinomas in 2000 to 2009. RESULTS: A total of 19 studies of tumor pathology based on size met criteria for review. Pooled estimates of the proportion of benign histology in our primary analysis (American studies only and 1 cm increments) were 40.4%, 20.9%, 19.6%, 17.2%, 9.2% and 6.4% for tumors less than 1, 1 to less than 2, 2 to less than 3, 3 to less than 4, 4 to 7 and greater than 7, respectively. The estimated number of surgically resected benign renal masses in the United States from 2000 to 2009 increased by 82% from 3,098 to 5,624. CONCLUSIONS: These estimates suggest that the population level burden of preoperatively misclassified benign renal masses is substantial and increasing rapidly, paralleling increases in surgically resected small renal cell carcinoma. This study illustrates an important and to our knowledge previously unstudied dimension of overtreatment that is not directly quantified in contemporary surveillance data.

Comparative Effectiveness of Oxaliplatin Versus 5-flourouricil in Older Adults: An Instrumental Variable Analysis.

BACKGROUND: Oxaliplatin was rapidly adopted for treatment of stage III colon cancer after FDA approval in November 2004, thus providing an opportunity to use calendar time as an instrumental variable in nonexperimental comparative effectiveness research. Assuming instrument validity, instrumental variable analyses account for unmeasured confounding and are particularly valuable in sub-populations of unresolved effectiveness, such as older individuals. METHODS: We examined stage III colon cancer patients ages 65+ years initiating chemotherapy between 2003 and 2008 using US population-based cancer registry data linked with Medicare claims (N = 3,660). Risk differences for all-cause mortality were derived from Kaplan-Meier survival curves. We examined instrumental variable strength and compared risk differences with propensity score estimates. RESULTS: Calendar time greatly affected oxaliplatin receipt. The calendar time instrument compared patients treated from January 2003 through September 2004 (N = 1,449) with those treated from March 2005 through May 2007 (N = 1,432), resulting in 54% compliance. The 1-, 2-, and 3-year local average treatment effect of the risk differences per 100 patients in the "compliers" (95% confidence intervals) were -4.6 (-8.2, -0.44), -6.3 (-12, -0.16), and -9.2 (-15, -2.5), respectively. Corresponding propensity score-matched results were -1.9 (-4.0, 0.2), -3.4 (-6.2, -0.05), and -4.3 (-7.5, -0.96). CONCLUSIONS: Instrumental variable and propensity score analyses both indicate better survival among patients treated with oxaliplatin. As these results are based on different populations and assumptions, the instrumental variable analysis adds to evidence of oxaliplatin's effectiveness in older adults, who bear the greatest burden of colon cancer yet were underrepresented in clinical trials. In nonexperimental comparative effectiveness research of rapidly emerging therapies, the potential to use calendar time as an instrumental variable is worth consideration.

Building the evidence for decision-making: the relationship between local public health capacity and community mortality.

OBJECTIVES: We examined associations between local health department (LHD) spending, staffing, and services and community health outcomes in North Carolina. METHODS: We analyzed LHD investments and community mortality in North Carolina from 2005 through 2010. We obtained LHD spending, staffing, and services data from the National Association of City and County Health Officials 2005 and 2008 profile surveys. Five mortality rates were constructed using Centers for Disease Control and Prevention mortality files, North Carolina vital statistics data, and census data for LHD service jurisdictions: heart disease, cancer, diabetes, pneumonia and influenza, and infant mortality. RESULTS: Spending, staffing, and services varied widely by location and over time in the 85 North Carolina LHDs. A 1% increase in full-time-equivalent staffing (per 1000 population) was associated with decrease of 0.01 infant deaths per 1000 live births (P < .05). Provision of women and children's services was associated with a reduction of 1 to 2 infant deaths per 1000 live births (P < .05). CONCLUSIONS: Our findings, in the context of other studies, provide support for investment in local public health services to improve community health.

Trends in stage-specific incidence rates for urothelial carcinoma of the bladder in the United States: 1988 to 2006.

BACKGROUND: Bladder cancer is notable for a striking heterogeneity of disease-specific risks. Among the approximately 75% of incident cases found to be superficial to the muscularis propria at the time of presentation (non-muscle-invasive bladder cancer), the risk of progression to the lethal phenotype of muscle-invasive disease is strongly associated with stage and grade of disease. Given the suggestion of an increasing percentage of low-risk cases in hospital-based registry data in recent years, the authors hypothesized that population-based data may reveal changes in the stage distribution of early-stage cases. METHODS: Surveillance, Epidemiology, and End Results (SEER) data were used to examine trends for the stage-specific incidence of bladder cancer between 1988 and 2006, adjusted for age, race, and sex, using Joinpoint and nonparametric tests. RESULTS: The adjusted incidence rate of papillary noninvasive (Ta) predominantly low grade (77%) disease was found to increase from 5.52 to 9.09 per 100,000 population (P < .0001), with an average annual percentage change of +3.3. Over the same period, concomitant, albeit smaller, decreases were observed for flat in situ (Tis) and lamina propria-invasive (T1) disease (2.57 to 1.19 and 6.65 to 4.61 per 100,000 population [both P < .0001]; average annual percent change of -5.0 and -1.6, respectively). The trend was most dramatic among patients in the oldest age strata, suggesting a previously unappreciated cohort phenomenon. CONCLUSIONS: The findings of the current study should motivate further epidemiological investigations of differential associations of genetic and environmental factors with different bladder cancer phenotypes as well as further scrutiny of clinical practice guideline recommendations for the growing subgroup of predominantly older patients with lower-risk disease.

Racial disparities in initiation of adjuvant endocrine therapy of early breast cancer.

Endocrine therapy (ET) is the cornerstone of adjuvant therapy for hormone-receptor positive (HR+) breast cancer. The survival gap between African-American (AA) and white women with breast cancer is most pronounced in HR+ subtypes, and could be related to differences in ET use. The relationship between race and initiation of ET is not well defined. We investigated patterns of ET initiation by race in a diverse cohort of women covered by commercial health insurance. We identified 2,640 women with incident HR+ breast cancer in the North Carolina Central Cancer Registry whose records linked to commercial insurance claims using the Integrated Cancer Information and Surveillance System (ICISS) database. The sample included women age <65 years diagnosed with stage I-III HR+ cancers between 2004 and 2009. We used multivariate Poisson regression to examine the effect of race on likelihood of initiating ET. 14 % of women did not initiate ET within 12 months of diagnosis. AA women were 17 % less likely to initiate ET than whites (aRR 0.83, 95 % CI 0.74-0.93). When analyzed by subset, racial disparities persisted among women who received chemotherapy (aHR 0.67, 95 % CI 0.56-0.80) but not among women who did not receive chemotherapy (aHR 0.96, 95 % CI 0.76-1.21). AA women in our sample were less likely to initiate ET than whites, and this disparity was concentrated among chemotherapy-treated women. ET under-utilization may contribute to the racial survival gap in HR+ breast cancer, and represents an opportunity for intervention to reduce breast cancer disparities.