Raising the Bar for Real-World Data in Oncology: Approaches to Quality Across Multiple Dimensions.

PURPOSE: Electronic health record (EHR)-based real-world data (RWD) are integral to oncology research, and understanding fitness for use is critical for data users. Complexity of data sources and curation methods necessitate transparency into how quality is approached. We describe the application of data quality dimensions in curating EHR-derived oncology RWD. METHODS: A targeted review was conducted to summarize data quality dimensions in frameworks published by the European Medicines Agency, The National Institute for Healthcare and Excellence, US Food and Drug Administration, Duke-Margolis Center for Health Policy, and Patient-Centered Outcomes Research Institute. We then characterized quality processes applied to curation of Flatiron Health RWD, which originate from EHRs of a nationwide network of academic and community cancer clinics, across the summarized quality dimensions. RESULTS: The primary quality dimensions across frameworks were relevance (including subdimensions of availability, sufficiency, and representativeness) and reliability (including subdimensions of accuracy, completeness, provenance, and timeliness). Flatiron Health RWD quality processes were aligned to each dimension. Relevancy to broad or specific use cases is optimized through data set size and variable breadth and depth. Accuracy is addressed using validation approaches, such as comparison with external or internal reference standards or indirect benchmarking, and verification checks for conformance, consistency, and plausibility, selected on the basis of feasibility and criticality of the variable to the intended use case. Completeness is assessed against expected source documentation; provenance by recording data transformation, management procedures, and auditable metadata; and timeliness by setting refresh frequency to minimize data lags. CONCLUSION: Development of high-quality, scaled, EHR-based RWD requires integration of systematic processes across the data lifecycle. Approaches to quality are optimized through knowledge of data sources, curation processes, and use case needs. By addressing quality dimensions from published frameworks, Flatiron Health RWD enable transparency in determining fitness for real-world evidence generation.

Evaluating the Impact of Oncology Care Model Reporting Requirements on Biomarker Testing and Treatment.

PURPOSE: The Oncology Care Model (OCM) is Medicare's first alternative payment model program for patients with cancer. As of October 2017, participating practices were required to report biomarker testing of patients with advanced non-small-cell lung cancer (aNSCLC). Our objective was to evaluate the effect of this OCM reporting requirement on quality of care. METHODS: We selected patients with aNSCLC receiving care in practices in a nationwide de-identified electronic health record-derived database. We used an adjusted difference-in-differences (DID) logistic regression model to compare changes in biomarker testing rates (EGFR, ROS1, and ALK) and receipt of biomarker-guided therapy between patients in OCM versus non-OCM practices, before and after OCM implementation. RESULTS: The analysis included 14,048 patients from 45 OCM practices (n = 8,151) and 105 non-OCM practices (n = 5,897). The overall unadjusted rates for biomarker testing and receipt of biomarker-guided therapy increased over the study period (2011-2018) in both OCM (55.5% v 71.6%; 89.8% v 94.6%, respectively) and non-OCM (55.2% v 69.7%; 90.1% v 95.2%, respectively) practices. In the adjusted DID model, the rates of biomarker testing (odds ratio [OR], 1.09 [95% CI, 0.88 to 1.34]; P = .45) and receipt of biomarker-guided therapy (OR, 0.87 [95% CI, 0.52 to 1.45]; P = .58) were similar between OCM and non-OCM practices. CONCLUSION: OCM biomarker documentation and reporting requirements did not appear to increase the proportions of patients with aNSCLC who underwent testing or who received biomarker-guided therapy in OCM versus non-OCM practices.

Impact of patient symptoms and caregiving tasks on psychological distress in caregivers for head and neck cancer (HNC).

OBJECTIVE: To determine the association of caregiving task burden and patient symptom burden with psychological distress among caregivers of head and neck cancer (HNC) patients. METHODS: Adults with HNC and their primary caregivers were included. Patient symptom burden was assessed with the Vanderbilt Head and Neck Symptom Survey-2.0. Caregiving task burden was quantified as task number and task difficulty/distress using the HNC Caregiving Task Inventory. Psychological distress was measured with the Profile of Mood States-Short Form. Two-step clustering analysis was conducted for patient symptom burden, caregiving task burden, and psychological distress. Associations of the resultant clusters of task burden and patient symptoms with caregiver distress were tested using logistic regressions. RESULTS: Eighty-nine HNC caregivers and 84 patients were included. Among patients, two clusters of symptom burden were found (51% mod-high, 49% low). Among caregivers, two clusters of caregiving task burden (40% mod-high, 60% low) and caregiver psychological distress (40% mod-high, 60% low) were found. Caregivers with mod-high task numbers and task difficulty/distress reported higher levels of psychological distress. After controlling for caregiver number of tasks, respective difficulty/distress, and patient symptom burden, caregiver perceived task difficulty/distress had the strongest association with caregiver psychological distress (adjusted OR = 3.83; 95% CI, 1.0-14.64; P = 0.049). CONCLUSIONS: Psychological distress in HNC caregivers is associated with caregiving task burden, with caregivers experiencing high task difficulty/distress at greatest risk. Further study of the caregiver and task characteristics leading to psychological distress should inform supportive interventions for HNC patients and caregivers.

Patient Protection and Affordable Care Act Medicaid expansion and gains in health insurance coverage and access among cancer survivors.

BACKGROUND: The Patient Protection and Affordable Care Act extends Medicaid coverage to millions of low-income adults, including many survivors of cancer who were unable to purchase affordable health insurance coverage in the individual health insurance market. METHODS: Using data from the 2011 to 2015 Behavioral Risk Factor Surveillance System, the authors compared changes in coverage and health care access measures for low-income cancer survivors in states that did and did not expand Medicaid. RESULTS: The study population of 17,381 individuals included adults aged 18 to 64 years, and was predominantly female, white, and unmarried. The authors found a relative reduction in the uninsured rate of 11.7 percentage points and a relative increase in the probability of having a personal physician of 5.8 percentage points. Stratifying by whether states expanded Medicaid by 2015, the authors found that relative gains in coverage and access were larger among those individuals residing in states with expanded Medicaid compared with those residing in nonexpansion states. CONCLUSIONS: The results of the current study suggest that the Patient Protection and Affordable Care Act Medicaid expansion has improved coverage and access for cancer survivors. Cancer 2018;124:2645-52. © 2018 American Cancer Society.

Financial and socio-economic factors influencing pre- and post-cancer therapy oral care.

PURPOSE: The primary objective of this study is to evaluate how attendance at dental visits may change as cancer patients move through pre-diagnosis, diagnosis, and into survivorship. METHODS: The Health and Retirement Study consists of longitudinal survey data collected biannually detailing financial and health information in subjects over 51 years old. We assessed a subset of 4195 patients who received a new cancer diagnosis during the study period. The odds of reporting a dental visit were examined using a mixed effects logistic regression model. A propensity score weighted analysis of the association between dental attendance and survival was also undertaken. RESULTS: The odds of attending a dental visit were substantially lower in the peri-diagnosis period OR = 0.784 (0.700, 0.876) and the post-diagnosis period OR = 0.734 (0.655, 0.823) compared to pre-diagnosis. This effect persisted in patients who survived for at least 2 years indicating that the decline in oral health visits was not due to low expected survival. After propensity score weighting, patients who attended a dental visit in the peri-diagnosis period demonstrated a reduced hazard of all-cause mortality HR = 0.825 (0.681, 0.979) compared with those with no attendance. CONCLUSIONS: Dental attendance decreases by a statistically and clinically significant amount both during and after cancer therapy despite guideline recommendations encouraging dental referral and monitoring for many types of cancer therapy. Attendance at dental appointments during cancer therapy is associated with improved survival, which is likely due to a combination of direct and indirect effects.

Immunotherapy in Lung Cancer.

Lung cancer has not traditionally been viewed as an immune-responsive tumor. However, it is becoming evident that tumor-induced immune suppression is vital to malignant progression. Immunotherapies act by enhancing the patient's innate immune response and hold promise for inducing long-term responses in select patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Immune checkpoint inhibitors, in particular, inhibitors to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have shown promise in early studies and are currently in clinical trials in both small cell lung cancer and non-small cell lung cancer patients. Two large randomized phase III trials recently demonstrated superior overall survival (OS) in patients treated with anti-PD-1 therapy compared to chemotherapy in the second-line setting.

Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

UNLABELLED: : The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. IMPLICATIONS FOR PRACTICE: The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease.

Making the Grade: The Impact of Low-Grade Toxicities on Patient Preference for Treatment With Novel Agents.

BACKGROUND: Targeted therapies have shown clinical benefit in the treatment of solid tumors. The toxicity profiles and treatment duration and schedule of these agents differ considerably from those of traditional chemotherapy. Many studies of targeted therapies report sizeable numbers of grade 1 or 2 toxicities. We sought to determine whether anticipation of low-grade toxicities and treatment logistics impact patient willingness to undergo therapy. PATIENTS AND METHODS: A total of 209 patients with cancer (101 lung and 108 breast) were surveyed at the Vanderbilt-Ingram Cancer Center regarding willingness to comply with treatment based on anticipated efficacy, dosing convenience, and toxicity profiles. All toxicities were Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 1 and 2. Willingness to comply with treatment depending on toxicity, anticipated benefit, cancer type, and dosing convenience was compared. RESULTS: A substantial number of patients (2.9%-48.8%, depending on the toxicity described) professed unwillingness to undergo treatment because of anticipated grade 1 and 2 toxicities. Gastrointestinal and constitutional toxicities had a stronger negative impact on patient willingness to undergo therapy than dermatologic toxicity. Patients with lung cancer were significantly more likely to accept dermatologic and gastrointestinal toxicities than those with breast cancer. Willingness to tolerate toxicities correlated with expected benefit in terms of life expectancy and chance of cure. Lengthy travel distance for treatment negatively impacted willingness to undergo treatment. CONCLUSIONS: Anticipation of low-grade toxicities and dosing inconvenience negatively impacts patient willingness to be treated, which may affect adherence and therapeutic outcomes from therapy. Long-term tolerability should be considered when developing and assessing the impact of novel agents.

Generations of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Perils and Progress.

OPINION STATEMENT: Epidermal growth factor receptor (EGFR) mutations have been detected in approximately 10 % of North American patients diagnosed with non-small cell lung cancer (NSCLC). Approximately 90 % of these mutations are exon 19 deletions or exon 21 L858R point mutations. First- and second-generation EGFR tyrosine kinase inhibitors (TKIs) are approved as first-line therapy based on clinical trials demonstrating superior response rates, progression free survival (PFS), and overall survival (OS) compared to chemotherapy in patients with EGFR mutation-positive NSCLC treated with an EGFR TKI prior to chemotherapy. However, the majority of patients treated with an EGFR TKI develop resistance to therapy within about 12 months, approximately 50 % of patients due to a second site mutation, the T790M mutation occurring within exon 20. At the time of progression, the EGFR TKI is most commonly discontinued and a different systemic therapy is initiated. However, oncogene addiction persists and recent exciting data with third-generation EGFR TKIs suggests that acquired resistance may be surmountable. The newest EGFR TKIs have shown activity against EGFR-mutant NSCLC after progression on first-generation TKIs, including those with T90M, while sparing wild-type EGFR and hence appear to be both well tolerated and efficacious. At this time, it appears that third-generation EGFR TKIs are effective following first-generation therapy, and determining the most appropriate sequence to maximize overall survival is a matter of ongoing investigation. As the arsenal of active agents in EGFR mutant NSCLC grows, future research into potential combinations, optimal timing, and resistance mechanisms of these new treatments, as well as their possible role in the adjuvant, post-chemoradiation, and neoadjuvant settings holds great promise for this group of patients.

Sodium thiosulfate in the treatment of non-uremic calciphylaxis.

Calciphylaxis is a metastatic calcification-induced vasculopathy that results in the occlusion of small blood vessels. Although calciphylaxis is normally associated with end-stage renal disease, calciphylaxis from non-uremic origin occurs as well. While the number of reports continues to increase, a standard treatment for non-uremic calciphylaxis has yet to be established. Sodium thiosulfate (STS), which has been proven to be effective in the treatment of uremic calciphylaxis, shows promise; however, reports of its use in non-uremic cases are limited. We describe a case of non-uremic calciphylaxis in a patient with normal renal and parathyroid function who had complete resolution of disease after treatment with STS, and we review similar cases in the published work. Based on the successful outcomes detailed in this case series, STS appears to be an effective therapy for non-uremic calciphylaxis.

Treatment of early-stage pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer death, and it is estimated that over 43,000 people would be diagnosed with and over 36,000 people would die of pancreatic cancer in the United States in 2010. Surgical resection remains the only chance for possible cure, but only 15% to 20% of patients newly diagnosed with pancreatic cancer are considered for surgical resection. Of these, the median five-year survival rate is still less than 20%, with most resections resulting in recurrent disease. This suggests that even seemingly resectable pancreatic cancer has microscopic systemic spread before operative intervention occurs. Both adjuvant and neoadjuvant therapies have been studied in an effort to improve survival for patients with resectable pancreatic cancer.