Characterizing Cancer Burden in the American Indian Population in North Carolina.

BACKGROUND: The American Indian (AI) population in North Carolina has limited access to the Indian Health Service. Consequently, cancer burden and disparities may differ from national estimates. We describe the AI cancer population and examine AI-White disparities in cancer incidence and mortality. METHODS: We identified cancer cases diagnosed among adult AI and White populations between 2014-2018 from the North Carolina Central Cancer Registry. We estimated incidence and mortality rate ratios (IRR; MRR) by race. Additionally, between the AI and White populations, we estimated relative frequency differences (RRFs, with 95% confidence limits [CL]) of clinical and sociodemographic characteristics. Lastly, we evaluated the geographic distribution of incident diagnoses among AI populations. RESULTS: Our analytic sample included 2,161 AI and 204,613 White individuals with cancer. Compared to the White population, the AI population was more likely to live in rural areas (48% vs 25%; RRF:1.89;CL:1.81,1.97) and to have Medicaid (18% vs 7%; RRF:2.49;CL:2.27,2.71). Among the AI population, the highest age-standardized incidence rates were female breast, followed by prostate and lung and bronchus. Liver cancer incidence was significantly higher among the AI population than White population (IRR:1.27;CL:1.01,1.59). AI patients had higher mortality rates for prostate (MRR:1.72;CL:1.09,2.70), stomach (MRR:1.82;CL:1.15,2.86), and liver (MRR:1.70;CL:1.25,2.33) cancers compared to White patients. CONCLUSIONS: To reduce prostate, stomach, and liver cancer disparities among AI populations in North Carolina, multi-modal interventions targeting risk factors and increasing screening and treatment are needed. IMPACT: This study identifies cancer disparities that can inform targeted interventions to improve outcomes among AI populations in North Carolina.

Simulating the population impact of interventions to reduce racial gaps in breast cancer treatment.

BACKGROUND: Inequities in guideline-concordant treatment receipt contribute to worse survival in Black breast cancer (BCa) patients. Inequity-reduction interventions (eg, navigation, bias training, tracking dashboards) can close such treatment gaps. We simulated the population-level impact of statewide implementation of inequity-reduction interventions on racial BCa inequities in North Carolina. METHODS: Using registry-linked multi-payer claims data, we calculated Black/White inequities in endocrine (ET; n = 12,033) and chemotherapy (CTx; n = 1,819) receipt. We then built cohort- (ET and CTx), and race-stratified Markov models to simulate the potential increase in the proportion of patients receiving ET or CTx and subsequent improvements in BCa outcomes if inequity-reducing intervention were implemented statewide. We report uncertainty bounds representing 95% of simulation results. RESULTS: 75.6% and 72.1% of Black patients received ET and CTx over the 2006-2015 and 2004-2015 periods (vs 79.3 and 78.9% of White patients, respectively). Inequity-reduction interventions could increase ET and CTx receipt among Black patients to 89.9% (85.3, 94.6%) and 85.7% (80.7, 90.9%). Such interventions could also decrease 5-and 10-year BCa mortality gaps from 3.4 to 3.2 (3.0, 3.3) and from 6.7 to 6.1 (5.9, 6.4) percentage points in the ET cohorts and from 8.6 to 8.1 (7.7, 8.4) and from 8.2 to 7.8 (7.3, 8.1) percentage points in the CTx cohorts. CONCLUSIONS: Inequity-focused interventions could improve cancer outcomes for Black patients. However, they would not fully close the racial BCa mortality gap. Addressing other inequities along cancer continuum (eg, screening, pre-and post-diagnosis risk factors) is required to achieve full equity in BCa outcomes.

Characteristics, healthcare utilization, and outcomes of patients with HER2-low breast cancer.

PURPOSE: Treatment for HER2-low [defined as ImmunoHistoChemistry (IHC) 1 + or 2 + and negative/normal in Situ Hybridization (ISH)] breast cancer patients is rapidly evolving, yet we lack critical information about the HER2-low population. METHODS: We conducted a retrospective cohort study of women aged 18 years or older diagnosed with breast cancer between 2010 and 2016 in North Carolina. Analyses were conducted for the overall cohort and a stage IV sub-cohort. We examined demographic and clinical characteristics, and characterized prevalence of HER2-low disease and healthcare utilization. We estimated adjusted rate ratios for the association between HER2 classifications and utilization outcomes, and hazard ratios for 3-year all cause mortality (stage IV only). RESULTS: The overall and stage IV cohorts included 12,965 and 635 patients, respectively. HER2-low patients represented more than half of both cohorts (59% overall, 53% stage IV). HER2-low patients were more likely than IHC 0 patients to have hormone receptor (HR)-positive disease. In the stage IV cohort, HER2-low patients were more likely to be Black (26% vs. 16% IHC 0, p = 0.0159). In both cohorts, rates of hospitalizations were slightly higher among HER2-low patients. There were no survival differences between HER2-low and IHC 0 among stage IV patients. CONCLUSION: New treatment options for HER2-low breast cancer may have potential for significant impact at the population level particularly for patients with stage IV disease. In light of racial differences between HER2-low and IHC 0 patients observed in our cohort, research- and practice-based efforts to ensure equitable adoption of new treatment guidelines for patients with HER2-low metastatic breast cancer will be essential.

Medications for Opioid Use Disorder and Mortality and Hospitalization Among People With Opioid Use-related Infections.

BACKGROUND: Severe skin and soft tissue infections related to injection drug use have increased in concordance with a shift to heroin and illicitly manufactured fentanyl. Opioid agonist therapy medications (methadone and buprenorphine) may improve long-term outcomes by reducing injection drug use. We aimed to examine the association of medication use with mortality among people with opioid use-related skin or soft tissue infections. METHODS: An observational cohort study of Medicaid enrollees aged 18 years or older following their first documented medical encounters for opioid use-related skin or soft tissue infections during 2007-2018 in North Carolina. The exposure was documented medication use (methadone or buprenorphine claim) in the first 30 days following initial infection compared with no medication claim. Using Kaplan-Meier estimators, we examined the difference in 3-year incidence of mortality by medication use, weighted for year, age, comorbidities, and length of hospital stay. RESULTS: In this sample, there were 13,286 people with opioid use-related skin or soft tissue infections. The median age was 37 years, 68% were women, and 78% were white. In Kaplan-Meier curves for the total study population, 12 of every 100 patients died during the first 3 years. In weighted models, for every 100 people who used medications, there were four fewer deaths over 3 years (95% confidence interval = 2, 6). CONCLUSION: In this study, people with opioid use-related skin and soft tissue infections had a high risk of mortality following their initial healthcare visit for infections. Methadone or buprenorphine use was associated with reductions in mortality.

Association of Receipt of Systemic Treatment for Melanoma With Insurance Type in North Carolina.

BACKGROUND: Previous studies of hospital-based patients with metastatic melanoma suggest sociodemographic factors, including insurance type, may be associated with the receipt of systemic treatments. OBJECTIVES: To examine whether insurance type is associated with the receipt of systemic treatment among patients with melanoma in a broad cohort of patients in North Carolina. METHODS: We conducted a retrospective cohort study between 2011 and 2017 of patients with stages III-IV melanoma using data from the North Carolina Central Cancer Registry linked to Medicare, Medicaid, and private health insurance claims across the state. The primary outcome was the receipt of any systemic treatment, and the secondary outcome was the receipt of immunotherapy. RESULTS: A total of 372 patients met the inclusion criteria. The average age was 68 years old (interquartile range: 56-76) and 61% were male. Within the cohort 48% had Medicare only, 29% had private insurance, 12% had both Medicare and Medicaid, and 11% had Medicaid only. A total of 186 (50%) patients received systemic treatment for melanoma, 125 (67%) of whom received immunotherapy. The use of systemic therapy, including immunotherapy, increased significantly over time. Having Medicaid-only insurance was independently associated with a 45% lower likelihood of receiving any systemic treatment [0.55 (95% CI: 0.35, 0.85)] and a 43% lower likelihood of receipt of immunotherapy [0.57 (95% CI: 0.34, 0.95)] compared with private insurance. CONCLUSIONS: Stage III-IV melanoma patients with Medicaid-only insurance were less likely to receive systemic therapy or immunotherapy than patients with private insurance or Medicare insurance. This finding raises concerns about insurance-based disparities in treatment access.

Mortality associated with bacterial and fungal infections and overdose among people with drug use diagnoses.

PURPOSE: Hospital visits for drug use-related bacterial and fungal infections have increased alongside overdose deaths. The incidence of mortality from these infections and the comparison to overdose mortality is not established. METHODS: This cohort study examined mortality outcomes among adults with drug use diagnoses who were insured by public and private plans during 2007 through 2018 in North Carolina. We examined bacterial- and fungal infection-related mortality and overdose mortality using cumulative incidence functions. RESULTS: Among 131,522 people with drug use diagnoses, the median age was 45 years (interquartile range: 31-57), 58% were women and 65% had an opioid use disorder diagnosis. The 1-year incidence of bacterial and fungal infection-associated mortality was progressively higher as age increased (35-49 years: 9 per 10,000 people, 50-64 years: 23 per 10,000, 65+ years: 50 per 10,000 people). Conversely, the 1-year incidence of overdose mortality was markedly lower among older adults compared to those under the age of 65 (18-34 years: 34 deaths per 10,000 people; 35-49 years: 47 per 10,000; 50-64 years: 41 per 10,000; 65+ years: 9 per 10,000). CONCLUSIONS: Bacterial and fungal infections and overdose were notable causes of death among adults with drug use diagnoses, and varied by age group.

Evaluating Nurses' Time to Response by Severity and Cancer Stage in a Remote Symptom Monitoring Program for Patients With Breast Cancer.

PURPOSE: Remote symptom monitoring (RSM) using electronic patient-reported outcomes enables patients with cancer to communicate symptoms between in-person visits. A better understanding of key RSM implementation outcomes is crucial to optimize efficiency and guide implementation efforts. This analysis evaluated the association between the severity of patient-reported symptom alerts and time to response by the health care team. METHODS: This secondary analysis included women with stage I-IV breast cancer who received care at a large academic medical center in the Southeastern United States (October 2020-September 2022). Symptom surveys with at least one severe symptom alert were categorized as severe. Response time was categorized as optimal if the alert was closed by a health care team member within 48 hours. Odds ratios (ORs), predicted probabilities, and 95% CIs were estimated using a patient-nested logistic regression model. RESULTS: Of 178 patients with breast cancer included in this analysis, 63% of patients identified as White and 85% of patients had a stage I-III or early-stage cancer. The median age at diagnosis was 55 years (IQR, 42-65). Of 1,087 surveys included, 36% reported at least one severe symptom alert and 77% had an optimal response time by the health care team. When compared with surveys that had no severe symptom alerts, surveys with at least one severe symptom alert had similar odds of having an optimal response time (OR, 0.97; 95% CI, 0.68 to 1.38). The results were similar when stratified by cancer stage. CONCLUSION: Response times to symptom alerts were similar for alerts with at least one severe symptom compared with alerts with no severe symptoms. This suggests that alert management is being incorporated into routine workflows and not prioritized based on disease or symptom alert severity.

Hepatocellular Carcinoma Surveillance among Individuals with Cirrhosis: Trends by Payer, Etiology, and Calendar Year, from a Statewide, Multi-Payer Dataset, 2010-2018.

BACKGROUND: Hepatocellular carcinoma (HCC) surveillance is underutilized, with <25% of individuals with cirrhosis receiving surveillance exams as recommended. The epidemiology of cirrhosis and HCC in the United States has also shifted in recent years, but little is known about recent trends in surveillance utilization. We characterized patterns of HCC surveillance by payer, cirrhosis etiology, and calendar year in insured individuals with cirrhosis. METHODS: We conducted a retrospective cohort study of individuals with cirrhosis using claims data from Medicare, Medicaid, and private insurance plans in North Carolina. We included individuals ≥ 18 years with a first occurrence of an ICD-9/10 code for cirrhosis between January 1, 2010, and June 30, 2018. The outcome was HCC surveillance by abdominal ultrasound, CT, or MRI. We estimated 1- and 2-year cumulative incidences for HCC surveillance and assessed longitudinal adherence to surveillance by computing the proportion of time covered (PTC). RESULTS: Among 46,052 individuals, 71% were enrolled through Medicare, 15% through Medicaid, and 14% through private insurance. The overall 1-year cumulative incidence of HCC surveillance was 49% and the 2-year cumulative incidence was 55%. For those with an initial screen in the first 6 months of their cirrhosis diagnosis, the median 2-year PTC was 67% (Q1, 38%; Q3, 100%). CONCLUSIONS: HCC surveillance initiation after cirrhosis diagnosis remains low, though it has improved slightly over time, particularly among individuals with Medicaid. IMPACT: This study provides insight into recent trends in HCC surveillance and highlights areas to target for future interventions, particularly among patients with nonviral etiologies.

Race, geography, and risk of breast cancer treatment delays: A population-based study 2004-2015.

BACKGROUND: Treatment delays affect breast cancer survival and constitute poor-quality care. Black patients experience more treatment delay, but the relationship of geography to these disparities is poorly understood. METHODS: We studied a population-based, retrospective, observational cohort of patients with breast cancer in North Carolina between 2004 and 2017 from the Cancer Information and Population Health Resource, which links cancer registry and sociodemographic data to multipayer insurance claims. We included patients >18 years with Stage I-III breast cancer who received surgery or chemotherapy as their first treatment. Delay was defined as >60 days from diagnosis to first treatment. Counties were aggregated into nine Area Health Education Center regions. Race was dichotomized as Black versus non-Black. RESULTS: Among 32,626 patients, 6190 (19.0%) were Black. Black patients were more likely to experience treatment delay >60 days (15.0% of Black vs. 8.0% of non-Black). Using race-stratified modified Poisson regression, age-adjusted relative risk of delay in the highest risk region was approximately twice that in the lowest risk region among Black (relative risk, 2.1; 95% CI, 1.6-2.6) and non-Black patients (relative risk, 1.9; 95% CI, 1.5-2.3). Adjustment for clinical and sociodemographic features only slightly attenuated interregion differences. The magnitude of the racial gap in treatment delay varied by region, from 0.0% to 9.4%. CONCLUSIONS: Geographic region was significantly associated with risk of treatment delays for both Black and non-Black patients. The magnitude of racial disparities in treatment delay varied markedly between regions. Future studies should consider both high-risk geographic regions and high-risk patient groups for intervention to prevent delays.

End-of-Life Care for Patients With Metastatic Renal Cell Carcinoma in the Era of Oral Anticancer Therapy.

PURPOSE: New therapies including oral anticancer agents (OAAs) have improved outcomes for patients with metastatic renal cell carcinoma (mRCC). However, little is known about the quality of end-of-life (EOL) care and systemic therapy use at EOL in patients receiving OAAs or with mRCC. METHODS: We retrospectively analyzed EOL care for decedents with mRCC in two parallel cohorts: (1) patients (RCC diagnosed 2004-2015) from the University of North Carolina's Cancer Information and Population Health Resource (CIPHR) and (2) patients (diagnosed 2007-2015) from SEER-Medicare. We assessed hospice use in the last 30 days of life and existing measures of poor-quality EOL care: systemic therapy, hospital admission, intensive care unit admission, and > 1 ED visit in the last 30 days of life; hospice initiation in the last 3 days of life; and in-hospital death. Associations between OAA use, patient and provider characteristics, and EOL care were examined using multivariable logistic regression. RESULTS: We identified 410 decedents in the CIPHR cohort (53.4% received OAA) and 1,508 in SEER-Medicare (43.5% received OAA). Prior OAA use was associated with increased systemic therapy in the last 30 days of life in both cohorts (CIPHR: 26.5% v 11.0%; P < .001; SEER-Medicare: 23.4% v 11.7%; P < .001), increased in-hospital death in CIPHR, and increased hospice in the last 30 days in SEER-Medicare. Older patients were less likely to receive systemic therapy or be admitted in the last 30 days or die in hospital. CONCLUSION: Patients with mRCC who received OAAs and younger patients experienced more aggressive EOL care, suggesting opportunities to optimize high-quality EOL care in these groups.

Adaptation of Remote Symptom Monitoring Using Electronic Patient-Reported Outcomes for Implementation in Real-World Settings.

PURPOSE: Despite evidence of clinical benefits, widespread implementation of remote symptom monitoring has been limited. We describe a process of adapting a remote symptom monitoring intervention developed in a research setting to a real-world clinical setting at two cancer centers. METHODS: This formative evaluation assessed core components and adaptations to improve acceptability and fit of remote symptom monitoring using Stirman's Framework for Modifications and Adaptations. Implementation outcomes were evaluated in pilot studies at the two cancer centers testing technology (phase I) and workflow (phase II and III) using electronic health data; qualitative evaluation with semistructured interviews of clinical team members; and capture of field notes from clinical teams and administrators regarding barriers and recommended adaptations for future implementation. RESULTS: Core components of remote symptom monitoring included electronic delivery of surveys with actionable symptoms, patient education on the intervention, a system to monitor survey compliance in real time, the capacity to generate alerts, training nurses to manage alerts, and identification of personnel responsible for managing symptoms. In the pilot studies, while most patients completed > 50% of expected surveys, adaptations were identified to address barriers related to workflow challenges, patient and clinician access to technology, digital health literacy, survey fatigue, alert fatigue, and data visibility. CONCLUSION: Using an implementation science approach, we facilitated adaptation of remote symptom monitoring interventions from the research setting to clinical practice and identified key areas to promote effective uptake and sustainability.

The Timing, the Treatment, the Question: Comparison of Epidemiologic Approaches to Minimize Immortal Time Bias in Real-World Data Using a Surgical Oncology Example.

BACKGROUND: Studies evaluating the effects of cancer treatments are prone to immortal time bias that, if unaddressed, can lead to treatments appearing more beneficial than they are. METHODS: To demonstrate the impact of immortal time bias, we compared results across several analytic approaches (dichotomous exposure, dichotomous exposure excluding immortal time, time-varying exposure, landmark analysis, clone-censor-weight method), using surgical resection among women with metastatic breast cancer as an example. All adult women diagnosed with incident metastatic breast cancer from 2013-2016 in the National Cancer Database were included. To quantify immortal time bias, we also conducted a simulation study where the "true" relationship between surgical resection and mortality was known. RESULTS: 24,329 women (median age 61, IQR 51-71) were included, and 24% underwent surgical resection. The largest association between resection and mortality was observed when using a dichotomized exposure [HR, 0.54; 95% confidence interval (CI), 0.51-0.57], followed by dichotomous with exclusion of immortal time (HR, 0.62; 95% CI, 0.59-0.65). Results from the time-varying exposure, landmark, and clone-censor-weight method analyses were closer to the null (HR, 0.67-0.84). Results from the plasmode simulation found that the time-varying exposure, landmark, and clone-censor-weight method models all produced unbiased HRs (bias -0.003 to 0.016). Both standard dichotomous exposure (HR, 0.84; bias, -0.177) and dichotomous with exclusion of immortal time (HR, 0.93; bias, -0.074) produced meaningfully biased estimates. CONCLUSIONS: Researchers should use time-varying exposures with a treatment assessment window or the clone-censor-weight method when immortal time is present. IMPACT: Using methods that appropriately account for immortal time will improve evidence and decision-making from research using real-world data.

Patient- And Provider-Level Predictors of Survival Among Patients With Metastatic Renal Cell Carcinoma Initiating Oral Anticancer Agents.

PURPOSE: In an era of rapid expansion of FDA approvals for oral anticancer agents (OAAs), it is important to understand the factors associated with survival among real-world populations, which include groups not well-represented in pivotal clinical trials of OAAs, such as the elderly, racial minorities, and medically complex patients. Our objective was to evaluate patient- and provider-level characteristics' associations with mortality among a multi-payer cohort of metastatic renal cell carcinoma (mRCC) patients who initiated OAAs. METHODS: This retrospective cohort study was conducted using data from the North Carolina state cancer registry linked to multi-payer claims data for the years 2004 to 2015. Provider data were obtained from North Carolina Health Professions Data System and the National Plan & Provider Enumeration System. Included patients were individuals with mRCC who initiated an OAA and survived ≥90 days after beginning treatment. We estimated hazard ratios (HR) and corresponding 95% confidence limits (CL) using Cox hazard models for associations between patient demographics, patient clinical characteristics, provider-level factors, and 2-year all-cause mortality. RESULTS: The cohort included 207 patients with mRCC who received OAAs. In multivariable models, clinical variables such as frailty (HR: 1.36, 95% CL: 1.11-1.67) and de novo metastatic diagnosis (HR: 2.63, 95%CL: 1.67-4.16) were associated with higher all-cause mortality. Additionally, patients solely on Medicare had higher adjusted all-cause mortality compared with patients with any private insurance (HR: 2.35, 95% CL: 1.32-4.18). No provider-level covariates investigated were associated with all-cause mortality. CONCLUSIONS: Within a real-world population of mRCC patients taking OAAs, survival differed based on patient characteristics. In an era of rapid expansion of FDA approvals for OAAs, these real-world data underscore the continued importance of access to high-quality care, particularly for medically complex patients with limited resources.

Evaluating the implementation and impact of navigator-supported remote symptom monitoring and management: a protocol for a hybrid type 2 clinical trial.

BACKGROUND: Symptoms in patients with advanced cancer are often inadequately captured during encounters with the healthcare team. Emerging evidence demonstrates that weekly electronic home-based patient-reported symptom monitoring with automated alerts to clinicians reduces healthcare utilization, improves health-related quality of life, and lengthens survival. However, oncology practices have lagged in adopting remote symptom monitoring into routine practice, where specific patient populations may have unique barriers. One approach to overcoming barriers is utilizing resources from value-based payment models, such as patient navigators who are ideally positioned to assume a leadership role in remote symptom monitoring implementation. This implementation approach has not been tested in standard of care, and thus optimal implementation strategies are needed for large-scale roll-out. METHODS: This hybrid type 2 study design evaluates the implementation and effectiveness of remote symptom monitoring for all patients and for diverse populations in two Southern academic medical centers from 2021 to 2026. This study will utilize a pragmatic approach, evaluating real-world data collected during routine care for quantitative implementation and patient outcomes. The Consolidated Framework for Implementation Research (CFIR) will be used to conduct a qualitative evaluation at key time points to assess barriers and facilitators, implementation strategies, fidelity to implementation strategies, and perceived utility of these strategies. We will use a mixed-methods approach for data interpretation to finalize a formal implementation blueprint. DISCUSSION: This pragmatic evaluation of real-world implementation of remote symptom monitoring will generate a blueprint for future efforts to scale interventions across health systems with diverse patient populations within value-based healthcare models. TRIAL REGISTRATION: NCT04809740 ; date of registration 3/22/2021.

Provider- and patient-level predictors of oral anticancer agent initiation and adherence in patients with metastatic renal cell carcinoma.

BACKGROUND: Improving oral anticancer agent (OAA) initiation and adherence is the important quality-of-care issues, particularly since one fourth of anticancer agents being developed will be administered orally. Our objective was to identify provider- and patient-level characteristics associated with OAA initiation and adherence among individuals with metastatic renal cell carcinoma (mRCC). METHODS: We used state cancer registry data linked to multi-payer claims data to identify patients with mRCC diagnosed in 2004-2015. Provider data were obtained from North Carolina Health Professions Data System and the National Plan & Provider Enumeration System. We estimated risk ratios (RRs) and corresponding 95% confidence limits (CLs) using modified Poisson regression to evaluate factors associated with OAA initiation and adherence. RESULTS: Among the 207 (out of 687) patients who initiated an OAA following mRCC diagnosis and survived 90 days, median proportion of days covered was 0.91. Patients with a modal provider specializing in hematology/medical oncology were much more likely to initiate OAAs than those seen by other specialties. Additionally, patients with a female provider were more likely to initiate OAAs than those with a male provider. Compared to patients treated by providers practicing in both urban and rural areas, patients with providers practicing solely in urban areas were more likely to initiate OAAs, after controlling for patient-level factors (RR = 1.37; 95% CL: 1.09-1.73). Medicare patients were less likely to be adherent than those with private insurance (RR = 0.61; 95% CL: 0.42-0.87). CONCLUSIONS: Our results suggest that provider- and patient-level factors influence OAA initiation in patients with mRCC but only insurance type was associated with adherence.

Patterns and Predictors of Oral Anticancer Agent Use in Diverse Patients With Metastatic Renal Cell Carcinoma.

PURPOSE: Availability of targeted oral anticancer agents (OAAs) has transformed care for patients with metastatic renal cell carcinoma (mRCC). Our objective was to identify patterns and predictors of OAA use within 12 months after mRCC was detected to understand real-world adoption of OAAs. METHODS: We used a novel, North Carolina cancer registry-linked multipayer claims data resource to examine patterns of use of five oral therapies among patients with mRCC diagnosed in 2006-2015, with claims through 2016. Patients were required to have 12 months of continuous enrollment before metastatic index date. Log-Poisson models estimated unadjusted and adjusted risk ratios (RRs) for associations between patient characteristics and OAA use. In sensitivity analyses, we used a competing risk framework to estimate adjusted risk differences in OAA use. RESULTS: Our population-based study of 713 patients demonstrated low (37%) OAA use during the first year after metastatic index date among both publicly and privately insured patients, with shifting patterns of use consistent with regulatory approvals over time. Compared with patients age 18-49 years, patients age 70-74 years were half likely to use OAAs (95% confidence limit [CL], 0.34 to 0.78) and patients age 80+ years were 71% less likely to use OAAs (95% CL, 0.17 to 0.50). Patients with two comorbidities (RR, 0.73; 95% CL, 0.55 to 0.98) and those with 3+ comorbidities (RR, 0.68; 95% CL, 0.50 to 0.91) were less likely to receive OAA than those without comorbidities. Patients with higher frailty also had lower OAA utilization (RR, 0.67; 95% CL, 0.52 to 0.85). CONCLUSION: These findings suggest a need to better understand the system-level and provider-level drivers of OAA underuse, as well as OAA adherence and associated survival.

Understanding and identifying immortal-time bias in surgical health services research: An example using surgical resection of stage IV breast cancer.

Surgical health services researchers are increasingly utilizing observational data to assess associations between treatments and outcomes, especially since some procedures are unable to be evaluated through randomized controlled trials. However, the results of many of these studies may be affected by the presence of immortal-time bias, which exists when treatment does not occur on Day 0 of the study. This bias can result in researchers overestimating a treatment benefit, or even observe a treatment benefit when none exists. In this paper, we describe what immortal-time bias is, the challenges it presents, and how to recognize and address it using the real-world example of surgical resection of the primary tumor for stage IV breast cancer throughout. In our example, we guide researchers and illustrate how the early studies, which did not account for immortal-time bias, suggested a protective benefit of surgery, and how these results were supplanted by more recent studies through identifying and addressing immortal-time bias in their design and analyses.

Association of surgical interval and survival among hospital and non-hospital based patients with melanoma in North Carolina.

Surgical excision is important for melanoma treatment. Delays in surgical excision after diagnosis of melanoma have been linked to decreased survival in hospital-based cohorts. This study was aimed at quantifying the association between the timeliness of surgical excision and overall survival in patients diagnosed with melanoma in hospital- and non-hospital-based settings, using a retrospective cohort study of patients with stage 0-III melanoma and using data linked between the North Carolina Central Cancer Registry to Medicare, Medicaid, and private health insurance plan claims across the state. We identified 6,496 patients diagnosed between 2004 and 2012 with follow-up through 2017. We categorized the time from diagnostic biopsy to surgical excision as < 6 weeks after diagnosis, 6 weeks to 90 days after diagnosis, and > 90 days after melanoma diagnosis. Multivariable Cox regression was used to estimate differences in survival probabilities. Five-year overall survival was lower for those with time to surgery over 90 days (78.6%) compared with those with less than 6 weeks (86%). This difference appeared greater for patients with Stage 1 melanoma. This study was retrospective, included one state, and could not assess melanoma specific mortality. Surgical timeliness may have an effect on overall survival in patients with melanoma. Timely surgery should be encouraged.

Hypofractionated radiation in older women with breast cancer.

BACKGROUND: American Society of Radiation Oncology Choosing Wisely campaign recommends hypofractionated radiation and against routine use of intensity-modulated radiation therapy (IMRT) in early-stage estrogen receptor-positive breast cancer. We analyzed guideline recommendation adherence and financial implications in a modern Medicare cohort of women treated across the southeastern United States. METHODS: Our study population comprised Medicare patients over 65 years of age with breast cancer diagnosis from 12 cancer centers in the Southeast United States with stage 0-II breast treated with lumpectomy from 2012 to 2015. Hypofractionation was defined as 4 or fewer weeks of radiation treatments. Factors associated with utilization of hypofractionation and IMRT were identified using Poisson regression. Median costs during radiation treatments were compared for hypofractionation and IMRT. RESULTS: In older women (median age 71), 75% were treated with conventional fractionation, and 20% received IMRT. Hypofractionated women were more likely to have a positive estrogen(ER) or progestorone(PR) receptor status, lower comorbidity scores, and be treated at a high volume center (all P < 0.05). IMRT was utilized in 20% of patients and was more common in women treated with conventional fractionation (P < 0.001). Positive ER/PR status (P < 0.001) and utilization of hormonal blockade (P = 0.02) were associated with increased utilization of IMRT. CONCLUSION: In an older cohort of patients with early-stage breast cancer, a majority were treated with conventional fractionated radiation, while approximately 20% were treated with IMRT. Both of which were associated with increased cost relative to hypofractionation.

Affordable Care Act and cancer stage at diagnosis in an underserved population.

The Patient Protection and Affordable Care Act (ACA) has increased insurance coverage among underserved individuals, but the effect of ACA on cancer diagnosis is currently debated, particularly in Medicaid non-expansion states. Therefore, we aimed to assess the effect of ACA implementation on stage at diagnosis among underserved cancer patients in Texas, a Medicaid non-expansion state. We used data from the institutional registry of the JPS Center for Cancer Care, which serves an urban population of underserved cancer patients. Eligible individuals were aged 18 to 64 years and diagnosed with a first primary invasive solid tumor between 2008 and 2015. We used a natural experiment framework and interrupted time-series analysis to assess level (i.e. immediate) and slope (over time) changes in insurance coverage and cancer stage at diagnosis between pre- and post-ACA periods. Our study population comprised 4808 underserved cancer patients, of whom 51% were racial/ethnic minorities. The prevalence of uninsured cancer patients did not immediately change after ACA implementation but modestly decreased over time (PR = 0.94; 95% CL: 0.90, 0.98). The prevalence of early- and advanced-stage diagnosis did not appreciably change overall or when stratified by screen-detectable cancers. Our results suggest that ACA implementation decreased the prevalence of uninsured cancer patients but had little effect on cancer stage at diagnosis in an underserved population. Given that Texas is a Medicaid non-expansion state, Medicaid expansion and alternative approaches may need to be further explored to improve earlier cancer diagnosis among underserved individuals.