Clinical Characteristics, Treatment Patterns, and Healthcare Costs and Utilization for Hepatocellular Carcinoma (HCC) Patients Treated at a Large Referral Center in Washington State 2007-2018.

INTRODUCTION: Though the treatment landscape for hepatocellular carcinoma (HCC) has evolved significantly with the refinement of liver-directed therapy techniques and the introduction of new drugs, few studies have investigated the impact of the changing treatment landscape on lifetime treatment costs, particularly in Barcelona Clinic Liver Cancer (BCLC) stage C disease. We sought to investigate real-world clinical characteristics, treatment patterns, and healthcare costs in a cohort of HCC patients treated at a single high-volume institution in Washington (WA) state. METHODS: We conducted a retrospective cohort study of patients diagnosed with HCC between 2007 and 2018 using abstracted electronic medical record (EMR) data linked to cancer registry data and health claims from commercial plans, Medicare, and Medicaid. We described clinical and treatment characteristics, including BCLC stage and Child Pugh score. We investigated median survival and mean lifetime treatment costs by BCLC stage using Kaplan-Meier cost estimator methods. A multivariate Cox proportional hazards model was used to investigate factors associated with overall survival. RESULTS: The final cohort included 215 patients, the majority of whom were white (71%), male (68%), and with underlying hepatitis C (61%). Mean per patient lifetime costs were highest in BCLC A and BCLC C patients. Mean lifetime costs in BCLC A patients ($292,134) was driven by surgery, hospital, pharmacy, imaging, and outpatient costs. Chemotherapy costs were highest in BCLC C patients, though not the predominant area of spending. Median survival was highest in patients with BCLC 0 and A disease; BCLC stage C and higher area deprivation index (ADI) were associated with poorer survival. CONCLUSION: In a cohort of WA state HCC patients, mean lifetime costs were highest in patients with BCLC A disease, attributable to surgery and hospital costs. As increased utilization of newer and less toxic therapies improves survival in BCLC C patients, mean lifetime costs in this group may also rise.

Effect of Clinical Trial Participation on Costs to Payers in Metastatic Non-Small-Cell Lung Cancer.

PURPOSE: The costs associated with clinical trial enrollment remain uncertain. We hypothesized that trial participation is associated with decreased total direct medical costs to health care payers in metastatic non-small-cell lung cancer. METHODS: In this retrospective cohort study, we linked clinical data from electronic medical records to sociodemographic data from a cancer registry and claims data from Medicare and two private insurance plans. We used a difference-in-difference analysis to estimate mean per patient per month total direct medical costs for patients enrolled on a second-line (2L) trial versus patients receiving standard-of-care 2L systemic therapy. RESULTS: Among 70 eligible patients, the difference-in-difference of mean per patient per month total direct medical costs between 2L trial participants and nonparticipants was -$6,663 (P = .01), for a mean savings of $45,308 per patient for the duration of 2L trial therapy. In a secondary analysis by primary insurance payer, this difference-in-difference was -$5,526 (P = .26) for patients with commercial insurance and -$7,432 (P = .01) for patients with Medicare. CONCLUSION: Participation in a 2L trial was associated with a $6,663 per month cost savings to health care payers for the duration of trial participation. Further studies are necessary to elucidate differences in cost savings from trial participation for Medicare and commercial payers. If confirmed, these results support health care payer investment in programs to improve clinical trial access and enrollment.

Receipt of Screening Mammography by Insured Women Diagnosed With Breast Cancer and Impact on Outcomes.

BACKGROUND: The purpose of this study was to determine factors associated with receipt of screening mammography by insured women before breast cancer diagnosis, and subsequent outcomes. PATIENTS AND METHODS: Using claims data from commercial and federal payers linked to a regional SEER registry, we identified women diagnosed with breast cancer from 2007 to 2017 and determined receipt of screening mammography within 1 year before diagnosis. We obtained patient and tumor characteristics from the SEER registry and assigned each woman a socioeconomic deprivation score based on residential address. Multivariable logistic regression models were used to evaluate associations of patient and tumor characteristics with late-stage disease and nonreceipt of mammography. We used multivariable Cox proportional hazards models to identify predictors of subsequent mortality. RESULTS: Among 7,047 women, 69% (n=4,853) received screening mammography before breast cancer diagnosis. Compared with women who received mammography, those with no mammography had a higher proportion of late-stage disease (34% vs 10%) and higher 5-year mortality (18% vs 6%). In multivariable modeling, late-stage disease was most associated with nonreceipt of mammography (odds ratio [OR], 4.35; 95% CI, 3.80-4.98). The Cox model indicated that nonreceipt of mammography predicted increased risk of mortality (hazard ratio [HR], 2.00; 95% CI, 1.64-2.43), independent of late-stage disease at diagnosis (HR, 5.00; 95% CI, 4.10-6.10), Charlson comorbidity index score ≥1 (HR, 2.75; 95% CI, 2.26-3.34), and negative estrogen receptor/progesterone receptor status (HR, 2.09; 95% CI, 1.67-2.61). Nonreceipt of mammography was associated with younger age (40-49 vs 50-59 years; OR, 1.69; 95% CI, 1.45-1.96) and increased socioeconomic deprivation (OR, 1.05 per decile increase; 95% CI, 1.03-1.07). CONCLUSIONS: In a cohort of insured women diagnosed with breast cancer, nonreceipt of screening mammography was significantly associated with late-stage disease and mortality, suggesting that interventions to further increase uptake of screening mammography may improve breast cancer outcomes.

Utilization of Systemic Therapy in Patients With Cancer Near the End of Life in the Pre- Versus Postimmune Checkpoint Inhibitor Eras.

PURPOSE: Systemic therapy use in the last 30 days of life (DOL) for patients with advanced cancer is a low-value medical practice. We hypothesized that systemic therapy use in the last 30 DOL increased after approval of antiprogrammed cell death protein 1 immune checkpoint inhibitors (ICIs) and has contributed to increased health care utilization and spending. METHODS: We investigated the change in prevalence of any systemic therapy use in the last 30 DOL among patients with advanced solid tumors in the 4 years before and after antiprogrammed cell death protein 1 ICI approval in 2014. We used cases from the Western Washington Cancer Surveillance System linked to commercial and Medicare insurance. We calculated the difference in prevalence between the pre- and post-ICI periods. We also calculated the annual prevalence of any systemic therapy and ICI use in the last 30 DOL and measured health care utilization (emergency department visits and hospitalizations) and costs during the last 30 DOL. RESULTS: Eight thousand eight hundred seventy-one patients (median age 73 years) were included; 34% and 66% in the pre-and post-ICI period, respectively. Systemic therapy use in the last 30 DOL was lower in the post-ICI versus pre-ICI period (12.4% v 14.4%; difference -2.0% [95% CI, -3.5 to -0.5]). The annual prevalence of systemic therapy use in the last 30 DOL also declined, although ICI use rose. Patients treated with ICIs in last 30 DOL had more emergency department visits, hospitalizations, and higher costs. CONCLUSION: Systemic therapy use in the last 30 DOL was lower in the period after ICI approval. However, ICI use rose over time and had higher utilization and costs in the last 30 DOL. Systemic therapy use in the last 30 DOL warrants monitoring, especially as more ICI indications are approved.

Access to Tyrosine Kinase Inhibitors and Survival in Patients with Advanced EGFR+ and ALK+ Positive Non-small-cell Lung Cancer Treated in the Real-World.

INTRODUCTION: We assessed the proportion of patients with advanced epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer (NSCLC) who receive tyrosine kinase inhibitors (TKIs) in the real-world, predictors of TKI use, and impact of TKI therapy on overall survival (OS). MATERIALS AND METHODS: We identified patients diagnosed with stage IV EGFR+ and ALK+ positive NSCLC from January 1, 2010 to December 31, 2018, in the Cancer Surveillance System registry and linked their records to Medicare and commercial insurance claims. We reported the proportions of patients with 1 or more TKI claims versus no TKI claims and used logistic regression to identify predictors of TKI use. We evaluated the effect of TKI use on OS by applying extended Cox proportional hazard models with TKI use as a time-dependent exposure and landmark analysis in a subcohort (N = 105). We adjusted Cox models for confounding patient characteristics. RESULTS: Of 117 eligible patients (median age = 69; 62% women; 88% EGFR+), 21 (17.9%) had no TKI claims. Diagnosis in 2015 to 2018 was independently associated with lower likelihood of TKI therapy compared with 2010 to 2014 (adjusted odds ratio, 0.29; P = .020). TKI use was associated with longer OS in a multivariate extended Cox model and in the landmark analysis (adjusted hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.33; 0.99; P = .048; adjusted HR, 0.55; 95% CI, 0.30; 1.00; P = .050). CONCLUSION: Approximately 18% of patients with advanced EGFR+ and ALK+ positive NSCLC do not receive TKIs and have inferior survival. Further studies need to investigate barriers of access to TKIs in biomarker-selected patients.

Health Care Cost Associated With Contemporary Chronic Myelogenous Leukemia Therapy Compared With That of Other Hematologic Malignancies.

PURPOSE: Given the widespread introduction of tyrosine kinase inhibitors (TKIs), we evaluated the cost associated with chronic myelogenous leukemia (CML) care compared with the cost of care for patients with hematologic malignancies (HEM) and for patients without cancer (GEN), to aid with resource allocation and clinical decision making. METHODS: A retrospective cohort was constructed from the OptumLabs Data Warehouse using claims from 2000 to 2016. Eligible patients had ≥ 2 CML claims and were enrolled continuously for ≥ 6 months before diagnosis and ≥ 1 year afterward (n = 1,909). Patients with CML were frequency matched 4:1 with HEM and GEN cohorts and were observed through October 2017. We used generalized linear models to assess the variation in total mean annualized health care costs in the 3 cohorts and to examine the influence of factors associated with costs. RESULTS: Mean annualized costs for CML were $82,054 (ie, $25,471 [95% CI, $20,808 to $30,133] more than those for HEM and $74,993 [95% CI, $70,818 to $79,167] more than those for GEN); these differences were driven by pharmacy costs in the CML group. The cost of CML care exceeded that for HEM and GEN for all index years in this study and increased over each diagnostic interval until 2015, peaking at $91,990. The mean annual cost of all TKIs increased. Imatinib's mean annualized cost was $41,546 in the period 2000-2004 but increased to $105,069 in the period 2015-2017. In multivariable analysis, percent days on TKIs had the greatest influence on cost: ≥ 75% of the time versus none showed a difference in cost of $108,716 (95% CI, $99,193 to $118,239). CONCLUSION: Contemporary CML costs exceeded the cost of treatment of other hematologic malignancies. Cost was primarily driven by TKIs, whose cost continued to increase over time.

Adverse events among chronic myelogenous leukemia patients treated with tyrosine kinase inhibitors: a real-world analysis of health plan enrollees.

With tyrosine kinase inhibitor (TKI) therapy, chronic myelogenous leukemia (CML) is now a chronic disease. CML patients treated with TKIs (n = 1200) were identified from the OptumLabs® Data Warehouse (de-identified claims and electronic health records) between 2000 and 2016 and compared with a non-cancer cohort (n = 7635). The 5-year cumulative incidence of all organ system outcomes was significantly greater for the TKI versus non-cancer group. In the first year, compared with imatinib, later generation TKIs were associated with primary infections (hazard ratios [HR] 1.43, 95% CI 1.02-2.00), circulatory events (HR 1.15, 95% CI 1.01-1.31), and skin issues (HR 1.43, 95% CI 1.13-1.80); musculoskeletal and nervous system/sensory issues were less common (HRs 0.83-0.84, p < 0.05). Increased risk of infections, cardiopulmonary and skin issues associated with later generation TKIs persisted in subsequent years. In this real-world population, TKI therapy was associated with a high burden of adverse events. Later generation TKIs may have greater toxicity than imatinib.

Out-of-Pocket Costs for Tyrosine Kinase Inhibitors and Patient Outcomes in EGFR- and ALK-Positive Advanced Non-Small-Cell Lung Cancer.

PURPOSE: We investigated the association of out-of-pocket (OOP) costs for tyrosine kinase inhibitors (TKIs) with overall survival (OS) in epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC). We secondarily investigated associations of TKI OOP costs with TKI adherence, duration of therapy (DOT), and TKI discontinuation. METHODS: We used the Hutchinson Institute for Cancer Outcomes Research registry-claims database to identify patients with stage IV EGFR- or ALK-positive NSCLC; ≥ 1 claims for EGFR or ALK TKIs; and ≥ 3-month survival from TKI initiation. We estimated the average monthly TKI OOP costs per patient up to 3 months from TKI initiation, categorizing patients into quartiles of TKI OOP costs (Q1 < Q2 < Q3 < Q4). We conducted landmark analysis at 3 months from TKI initiation to compare Q1-3 v Q4 TKI OOP costs with respect to OS, TKI DOT, TKI adherence, and TKI discontinuation. RESULTS: Seventy-eight and twenty-seven patients comprised the Q1-3 and Q4 groups, respectively. Median monthly TKI OOP costs were $1,431 (Q1-3) v $2,888 (Q4). Compared with Q1-3, Q4 patients had inferior OS (adjusted hazard ratio [HR], 1.85; [95% CI, 1.11 to 3.10], similar TKI DOT (adjusted HR, 1.06; 95% CI, 0.53 to 2.15), decreased TKI adherence (adjusted odds ratio [OR], 0.28; 95% CI, 0.10 to 0.76), and higher TKI discontinuation rate (adjusted OR, 8.75; 95% CI, 2.59 to 29.52). CONCLUSION: Among patients with advanced EGFR- and ALK-positive NSCLC, higher TKI OOP costs are associated with decreased TKI adherence, a higher likelihood of TKI discontinuation, and inferior survival.

Comparison of Treatment, Cost, and Survival in Patients With Metastatic Colorectal Cancer in Western Washington, United States, and British Columbia, Canada.

PURPOSE: Few studies have directly compared health care utilization, costs, and outcomes between patients treated in the US multipayer health system and Canada's single-payer system. Using cancer registry and claims data, we assessed treatment types, costs, and survival for patients with metastatic colorectal cancer (mCRC) in Western Washington State (WW) and British Columbia (BC). MATERIALS AND METHODS: Patients age ≥ 18 years diagnosed with mCRC in 2010 and later were identified from the BC Cancer database and a regional database linking WW SEER to claims from Medicare and two large commercial insurers. Demographics, treatment characteristics, costs of systemic therapy, and survival data were obtained from these databases and compared between the two regions. RESULTS: A total of 1,592 patients from BC and 901 from WW were included in the study. Median age was similar (BC, 66 years; WW, 63 years), but patients in BC were more likely to be male (57.1% v 51.2%; P ≤ .01) and to have de novo metastatic disease (61.0% v 38.3%; P ≤ .01). The use of radiation therapy was similar between regions (BC, 31.2%; WW, 33.9%; P = .18), but primary tumor resection was more common in BC (74.1% v 66.3%; P ≤ .01) as was hepatic metastasectomy (12.4% v 2.3%; P ≤ .01). Similar percentages of patients received systemic therapy (BC, 68.8%; WW, 67.1%; P = .40), but costs were significantly higher for first-line systemic therapy in WW ($6,226 v $15,792 per patient per month; P ≤ .01). Median overall survival was similar (BC, 16.9 months; WW, 18 months). CONCLUSION: Cost of systemic therapy for mCRC was significantly higher for patients in WW than in BC, but this did not translate to a difference in overall survival.

Association of Financial Burden With Self-Rated and Mental Health in Older Adults With Cancer.

Objective: Financial problems in cancer survivors are associated with distress and reduced quality of life. Most studies have been cross-sectional, and a longitudinal study is needed to guide clinical interventions. Method: We used data from two surveys of the National Health and Aging Trends Study (NHATS). Participants (n = 307) reported whether they experienced six indicators of financial burden. The Patient Health Questionnaire 4 assessed depressive symptoms and general anxiety. Cross-lagged panel analyses assessed whether financial burden predicted distress and health or vice versa. Results: In the total sample, financial burden at the first survey predicted depressive symptoms (p < .01), general anxiety (p < .01), and self-rated health (p < .01) at the second survey. Depressive symptoms, general anxiety, and self-rated health at the first survey did not predict later financial burden (ps > .05). Discussion: Results suggest financial problems predict later distress and poor health. This study highlights the need to address financial burden in cancer survivors.

Improving socioeconomic status may reduce the burden of malaria in sub Saharan Africa: A systematic review and meta-analysis.

BACKGROUND: A clear understanding of the effects of housing structure, education, occupation, income, and wealth on malaria can help to better design socioeconomic interventions to control the disease. This literature review summarizes the relationship of housing structure, educational level, occupation, income, and wealth with the epidemiology of malaria in sub-Saharan Africa (SSA). METHODS: A systematic review and meta-analysis was conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines. The protocol for this study is registered in PROSPERO (ID=CRD42017056070), an international database of prospectively registered systematic reviews. On January 16, 2016, available literature was searched in PubMed, Embase, CINAHL, and Cochrane Library. All but case studies, which reported prevalence or incidence of Plasmodium infection stratified by socioeconomic status among individuals living in SSA, were included without any limits. Odds Ratio (OR) and Relative Risk (RR), together with 95% CI and p-values were used as effect measures. Heterogeneity was assessed using chi-square, Moran's I2, and tau2 tests. Fixed (I2<30%), random (I2≥30%) or log-linear dose-response model was used to estimate the summary OR or RR. RESULTS: After removing duplicates and screening of titles, abstracts, and full text, 84 articles were found eligible for systematic review, and 75 of them were included in the meta-analyses. Fifty-seven studies were cross-sectional, 12 were prospective cohort, 10 were case-control, and five were randomized control trials. The odds of Plasmodium infection increased among individuals who were living in poor quality houses (OR 2.13, 95% CI 1.56-3.23, I2 = 27.7), were uneducated (OR 1.36, 95% CI 1.19-1.54, I2 = 72.4.0%), and were farmers by occupation (OR 1.48, 95% CI 1.11-1.85, I2 = 0.0%) [p<0.01 for all]. The odds of Plasmodium infection also increased with a decrease in the income (OR 1.02, 95% CI 1.01-1.03, tau2<0.001), and wealth index of individuals (OR 1.25, 95% CI 1.18-1.35, tau2 = 0.028) [p<0.001 for both]. Longitudinal studies also showed an increased risk of Plasmodium infection among individuals who were living in poor quality houses (RR 1.86, 95% CI 1.47-2.25, I2 = 0.0%), were uneducated (OR 1.27, 1.03-1.50, I2 = 0.0%), and were farmers (OR 1.36, 1.18-1.58) [p<0.01 for all]. CONCLUSIONS: Lack of education, low income, low wealth, living in poorly constructed houses, and having an occupation in farming may increase risk of Plasmodium infection among people in SSA. Public policy measures that can reduce inequity in health coverage, as well as improve economic and educational opportunities for the poor, will help in reducing the burden of malaria in SSA.

Comorbidity is associated with higher risk of financial burden in Medicare beneficiaries with cancer but not heart disease or diabetes.

The aim of the study was to examine how multimorbidity influences the prevalence of financial burden among older adults with heart disease, diabetes, or cancer.The study was a cross-sectional analysis of prospective observational cohort survey study.Older adults (age 65 or older) who did not report 1/6 major chronic illnesses (n = 2773; reference group), reported 1/3 major chronic illnesses without comorbidity (heart disease n = 206; diabetes n = 460; cancer n = 417), and reported 1/3 major chronic illnesses with comorbidity (heart disease n = 232; diabetes n = 202; cancer n = 109).The measures were presence of chronic diseases (heart disease, diabetes, cancer), comorbid chronic diseases (stroke, lung disease, dementia), medical-related financial burden (credit card debt due to medical costs, paying medical bills over time), and overall financial burden (financial help from family, credit card debt, help with food, utilities, and other necessities).The proportion reporting financial burden ranged from 15% to 27% across samples. Heart disease was unrelated to medical or overall financial burden, regardless of comorbidity. Diabetes was unrelated to financial burden except diabetes without comorbidity was associated with lower odds of overall financial burden compared to healthy older adults (odds ratio [OR] = 0.655, 95% confidence interval [CI]: 0.468-0.917). Cancer with comorbidity, but not cancer without comorbidity, was associated with greater odds of medical related (OR = 1.678, 95% CI: 1.057-2.664) and overall financial burden (OR = 1.748, 95% CI: 1.064-2.872).The association of multimorbidity with financial burden likely varies based on specific diseases. Future research on financial burden should focus on specific disease combinations such as cancer with comorbidity.