Pharmacoepidemiology: A time for a new multidisciplinary approach to precision medicine.

The advent of the genomic age has created a rapid increase in complexity for the development and selection of drug treatments. A key component of precision medicine is the use of genetic information to improve therapeutic effectiveness of drugs and prevent potential adverse drug reactions. Pharmacoepidemiology, as a field, uses observational methods to evaluate the safety and effectiveness of drug treatments in populations. Pharmacoepidemiology by virtue of its focus, tradition, and research orientation can provide appropriate study designs and analysis methods for precision medicine. The objective of this manuscript is to demonstrate how pharmacoepidemiology can impact and shape precision medicine and serve as a reference for pharmacoepidemiologists interested in contributing to the science of precision medicine. This paper depicts the state of the science with respect to the need for pharmacoepidemiology and pharmacoepidemiological methods, tools and approaches for precision medicine; the need for and how pharmacoepidemiologists use their skills to engage with the precision medicine community; and recommendations for moving the science of precision medicine pharmacoepidemiology forward. We propose a new integrated multidisciplinary approach dedicated to the emerging science of precision medicine pharmacoepidemiology.

Organ Dysfunction in Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Real-world data enables evaluation of immune checkpoint inhibitor (ICI) use in advanced melanoma management. We examined characteristics and outcomes of ICI-treated patients with advanced melanoma and organ dysfunction (baseline and emergent). MATERIALS AND METHODS: This retrospective observational study used electronic health records derived from a nationwide data set to examine advanced melanoma patients treated with first-line ICIs (2011-2018). Clinical characteristics, real-world time to treatment discontinuation (rwTTD), and overall survival (OS) were analyzed for patients with normal organ function and those with organ dysfunction prior to ICI initiation. Patients with emergent dysfunction in the 90 days following ICI initiation were identified, and potentially associated characteristics were explored. RESULTS: Of 2,407 patients included, 1,884 and 1,717 had evaluable renal and hepatic laboratory values, respectively. Patients with baseline renal dysfunction (2.4%) were older and more frequently male, and less frequently treated with ICI combinations, than patients with normal renal function. Patients with baseline hepatic dysfunction (2.8%) were similar to patients with normal hepatic function regarding demographics and treatments received. Patients with baseline organ dysfunction displayed shorter rwTTD and OS. Among patients with normal baseline organ function, 4.6% and 7.4% developed renal and hepatic dysfunction within 90 days of ICI initiation, respectively; this was associated with combination ICI treatment. CONCLUSION: Patients with advanced melanoma and baseline organ dysfunction frequently receive ICI treatment but have poorer clinical outcomes than patients with normal organ function. Among patients with normal renal and hepatic function at ICI initiation, emergent organ dysfunction rates in this real-world cohort are similar to those reported in clinical trials. IMPLICATIONS FOR PRACTICE: Real-world data provide an opportunity to understand treatment patterns, toxicity, and clinical outcomes among patients treated outside of clinical trials. This study confirms that patients with advanced melanoma and baseline renal or hepatic dysfunction are being treated with ICI therapy more frequently as monotherapy than in combination therapy. For those real-world patients with normal baseline organ function, emergent renal and hepatic dysfunction are both more common in patients treated with combination versus ICI monotherapy.

Risk of diabetes complications among those with diabetes receiving androgen deprivation therapy for localized prostate cancer.

PURPOSE: Androgen deprivation therapy (ADT), used increasingly in the treatment of localized prostate cancer, is associated with substantial long-term adverse consequences, including incident diabetes. While previous studies have suggested that ADT negatively influences glycemic control in existing diabetes, its association with diabetes complications has not been investigated. In this study, we examined the association between ADT use and diabetes complications in prostate cancer patients. METHODS: A retrospective cohort study was conducted among men with newly diagnosed localized prostate cancer between 1995 and 2008, enrolled in three integrated health care systems. Men had radical prostatectomy or radiotherapy (curative intent therapy), existing type II diabetes mellitus (T2DM), and were followed through December 2010 (n = 5,336). Cox proportional hazards models were used to examine associations between ADT use and diabetes complications (any complication), and individual complications (diabetic neuropathy, diabetic retinopathy, diabetic amputation or diabetic cataract) after prostate cancer diagnosis. RESULTS: ADT use was associated with an increased risk of any diabetes complication after prostate cancer diagnosis (adjusted hazard ratio, AHR, 1.12, 95% CI 1.03-1.23) as well as an increased risk of each individual complication compared to non-use. CONCLUSION: ADT use in men with T2DM, who received curative intent therapy for prostate cancer, was associated with an increased risk of diabetes complications. These findings support those of previous studies, which showed that ADT worsened diabetes control. Additional, larger studies are required to confirm these findings and to potentially inform the development of a risk-benefit assessment for men with existing T2DM, before initiating ADT.

Prediagnostic aspirin use and mortality in women with stage I to III breast cancer: A cohort study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: There is a body of evidence indicating that aspirin may reduce the risk of cancer mortality. However, to the authors' knowledge, the optimal exposure timing and mechanism of action remain unclear. In the current study, the authors investigated associations between prediagnostic aspirin use and breast cancer-specific mortality in a US population. METHODS: Postmenopausal women diagnosed with stage I to III breast cancer (1993-2009) were identified (2925 women with a total of 18,073 person-years) from the National Cancer Institute's Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Prediagnostic aspirin use (1274 women) was identified from study questionnaires. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) for associations between aspirin use and breast cancer-specific mortality. Effect modification by lymph node status was evaluated. RESULTS: Prediagnostic aspirin use was not found to be associated with lower breast cancer-specific mortality (HR, 0.95; 95% CI, 0.68-1.31 [P = .74]). In analyses stratified by lymph node status, aspirin use was found to be associated with lower breast cancer-specific mortality among women with lymph node-negative tumors (HR, 0.54; 95% CI, 0.32-0.93 [P = 0.02]), but not those with lymph node-positive tumors (HR, 1.41; 95% CI, 0.92-2.16 [P = 0.11]). Tests for interaction were found to be statistically significant (P for interaction =.006). No association was noted between aspirin use and lymph node status. CONCLUSIONS: Prediagnostic aspirin use was not found to be associated with a reduction in breast cancer-specific mortality overall. However, effect modification by lymph node status was observed and mortality was found to be reduced by approximately one-half among aspirin users with lymph node-negative disease. This represents a clinically significant reduction in breast cancer mortality. These findings contribute to the understanding of aspirin's mechanism of action in breast cancer. However, further etiologic research to understand this association is warranted. Cancer 2016;122:2067-75. © 2016 American Cancer Society.

Cardiovascular toxicity after antiangiogenic therapy in persons older than 65 years with advanced renal cell carcinoma.

BACKGROUND: Sorafenib and sunitinib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) approved in 2005 and 2006, respectively, for the treatment of patients with renal cell carcinoma (RCC). A population-based, observational cohort study of the cardiovascular risk of VEGFR TKI therapy in elderly RCC patients was conducted. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, this study analyzed patients who were 66 years old or older and were diagnosed with RCC from 2000 to 2009. The incidence of cardiovascular adverse events, including congestive heart failure and cardiomyopathy (CHF/CM), acute myocardial infarction (AMI), stroke, and cardiovascular deaths, was examined through December 2010. A Cox proportional hazards model was created to calculate the hazard ratio (HR), and adjustments were made for age, sex, comorbidity, and the use of other systemic therapy. RESULTS: A total of 171 of 670 patients who received sunitinib or sorafenib had cardiovascular events. The incidence rates for CHF/CM, AMI, and stroke were 0.87, 0.14, and 0.14 per 1000 person-days, respectively. Sunitinib or sorafenib use was associated with an increased risk of cardiovascular events (HR, 1.38; 95% confidence interval [CI], 1.02-1.87) and especially stroke (HR, 2.84; 95% CI, 1.52-5.31) in comparison with 788 patients diagnosed with advanced RCC from 2007 to 2009 who were eligible for Part D but did not receive either agent. In subgroup analyses, patients who were 66 to 74 years old at diagnosis had the highest increased risk of stroke associated with the use of either or both drugs. CONCLUSIONS: Sunitinib and sorafenib might be associated with an increased risk of cardiovascular events and particularly stroke.

Dosing recommendations for pharmacogenetic interactions related to drug metabolism.

OBJECTIVE: Pharmacogenomic studies have established the important contribution of drug-metabolizing enzyme genotype toward drug toxicity and treatment failure; however, clinical implementation of pharmacogenomics has been slow. The aim of this study was to systematically review the information on drug-metabolizing enzyme pharmacogenomics available in the US drug labeling, practice guidelines, and recommendations. METHODS: Drug-metabolizing enzyme genotype and phenotype information was assessed in US FDA drug labeling, clinical practice guidelines, and independent technology assessors to evaluate the consistency in information sources for healthcare providers. RESULTS: Eighty four gene-drug pairs were identified as having drug-metabolizing enzyme genotype or phenotype information within the label. The manner in which pharmacogenomic information was presented was heterogeneous both within the label and between clinical practice recommendations. CONCLUSION: For proper implementation of pharmacogenomics in clinical practice, information sources for healthcare providers should relay consistent and clear information for the appropriate use of biomarkers.

Implementation of the 21-gene recurrence score test in the United States in 2011.

PURPOSE: We examined hospital use of the 21-gene breast cancer test in the United States. We report state-level differences in utilization and propose a model for predicting implementation of guideline-recommended genomic testing. METHODS: Genomic Health provided test orders for calendar year 2011.We summarized utilization at the hospital and state levels. Using logistic regression, we analyzed the association between the likelihood to order the test and the hospital's institutional and regional characteristics. RESULTS: In 2011, 45% of 4,712 acute-care hospitals ordered the test, which suggests that 25% of newly diagnosed invasive female breast cancer cases were tested. Significant predictors of testing included participation in National Cancer Institute (NCI) clinical research cooperative groups (odds ratio (OR) 3.73; 95% confidence interval, 2.96-4.70), advanced imaging (OR, 2.19; CI, 1.78-2.68), high-complexity laboratory (OR, 2.15; CI, 1.24-3.70), affiliation with a medical school (OR, 1.57; CI, 1.31-1.88), and reconstructive surgery (OR, 1.23; CI, 1.01-1.50). Significant regional predictors included metropolitan county (OR, 3.77; CI, 2.83-5.03), above-mean income (OR, 1.37; CI, 1.11-1.69), and education (OR, 1.26; CI, 1.03-1.54). Negative predictors included designation as a critical-access hospital (OR, 0.10; CI, 0.07-0.14) and distance from an NCI cancer center (OR, 0.998; CI, 0.997-0.999), with a 15% decrease in likelihood for every 100 miles. CONCLUSION: Despite considerable market penetration of the test, there are significant regional and site-of-care differences in implementation, particularly in rural states.Genet Med 18 10, 982-990.

Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population.

PURPOSE: The objective of this study was to describe trends in the prevalence of regular aspirin and nonsteroidal anti-inflammatory drug (NSAID) use among adults in the United States during 2005 and 2010, and to identify characteristics of regular users. METHODS: Data from the 2005 and 2010 National Health Interview Survey (NHIS) were analyzed to estimate the prevalence of regular use of aspirin and NSAIDs among U.S. adults aged 18 years and older. Results were stratified by demographics and self-reported medical conditions and extrapolated to provide U.S. population estimates. RESULTS: In 2010, around 43 million adults (19.0%) took aspirin at least three times per week for more than 3 months (i.e. regular users), and more than 29 million adults (12.1%) were regular users of NSAIDs. Compared with 2005, this was an overall increase of 57% in aspirin use and 41% in NSAID use. These increases were consistent across the strata of age, sex, race, and selected medical conditions, including cardiovascular disease (CVD), arthritis, peptic ulcers, cancer, and severe headache, except for Asian Americans. CONCLUSION: Large increases in the use of both aspirin and NSAIDs were observed over a 5 year period. The increase may be the result of increasing media attention reporting that regular aspirin use lowers the risk of CVD and related deaths, and may also prevent cancer. Moreover, safety concerns related to alternative medications such as acetaminophen and selective COX-2 inhibitors may influence users of these drugs to switch to aspirin and NSAIDs.

Utilization of bevacizumab in US elderly patients with colorectal cancer receiving chemotherapy.

OBJECTIVE: Bevacizumab, the first FDA-approved anti-angiogenesis agent, has been used for metastatic colorectal cancer since 2004. This study evaluated the utilization of bevacizumab among elderly metastatic colorectal cancer patients in the United States. METHODS: Using Surveillance and Epidemiology and End Results (SEER)-Medicare data, this retrospective cohort study consisted of individuals aged 65 years or older with a colorectal cancer diagnosis between 2005 and 2009, who received chemotherapy any time through 2010. This included patients with newly diagnosed metastatic colorectal cancer and patients who progressed from initially diagnosed earlier-stage disease. We ascertained comorbid conditions using ICD-9 codes and conducted logistic regression to identify patients' characteristics associated with bevacizumab use. RESULTS: A total of 8645 patients were identified (mean age 74 years; 52% male); 57% of patients received bevacizumab with initially diagnosed metastatic colorectal cancer and 44% of patients with treated progressive or recurrent disease. After adjusting for other covariates, we found that patients aged ≥80 years were less likely to receive bevacizumab compared with those aged 65-69 years (odds ratio (OR), 0.64 (95% confidence interval (CI): 0.57-0.73)), or if they had evidence of comorbid cardiomyopathy/congestive heart failure (OR, 0.82 (CI: 0.70-0.95)) or arrhythmic disorder (OR, 0.85 (CI: 0.75-0.96)). Adoption of bevacizumab into practice was rapid following its approval, and the use increased from 36% to 40% from 2005 to 2010 (p = 0.013). There were significant regional variations in bevacizumab use. CONCLUSIONS: Despite rapid uptake since its original approval, there appears to be low use of bevacizumab in elderly metastatic colorectal cancer patients in the United States. Regional variations and the strong effects of age and comorbidity suggest lack of consensus among oncologists regarding benefits and risks of bevacizumab in elderly patients.

Importance of Patient Health Insurance Coverage and Out-of-Pocket Costs for Genomic Testing in Oncologists' Treatment Decisions.

PURPOSE: Use of genomic testing, especially multimarker panels, is increasing in the United States. Not all tests and related treatments are covered by health insurance, which can result in substantial patient out-of-pocket (OOP) costs. Little is known about oncologists' treatment decisions with respect to patient insurance coverage and OOP costs for genomic testing. METHODS: We identified 1,049 oncologists who used multimarker tumor panels from the 2017 National Survey of Precision Medicine in Cancer Treatment. Separate multivariable ordinal logistic regressions examined associations of oncologist-, practice-, and area-level characteristics and oncologists' ratings of importance (very, somewhat, or a little/not important) of insurance coverage and OOP costs for genomic testing in treatment decisions, adjusting for oncologist years of experience, sex, race and ethnicity, specialty, use of next-generation sequencing (NGS) tests, region, tumor boards, patient insurance mix, and area-level socioeconomic characteristics. RESULTS: Among oncologists, 47.3%, 32.7%, and 20.0% reported that patient insurance coverage for genomic testing was very, somewhat, or a little/not important, respectively, in treatment decisions. In addition, 56.9%, 28.0%, and 15.2% reported that OOP costs for testing were very, somewhat, or a little/not important, respectively. In adjusted analyses, oncologists who used NGS tests were more likely to report patient insurance and OOP costs as important (odds ratio [OR], 2.00 [95% CI, 1.16 to 3.45] and OR, 2.12 [95% CI, 1.22 to 3.68], respectively) in treatment decisions compared with oncologists who did not use these tests, as were oncologists who treated solid tumors, rather than only hematological cancers. More years of experience and higher percentages of Medicaid or self-paid/uninsured patients in the practice were associated with reporting insurance coverage (OR, 1.43 [95% CI, 1.09 to 1.89]) and OOP costs (OR, 1.51 [95% CI, 1.13 to 2.01]) as important. Oncologists in practices with molecular tumor boards for genomic tests were less likely to report coverage (OR, 0.63 [95% CI, 0.47 to 0.85]) and OOP costs (OR, 0.72 [95% CI, 0.53 to 0.97]) as important than their counterparts in practices without these tumor boards. CONCLUSION: Most oncologists rate patient health insurance and OOP costs for genomic tests as important considerations in subsequent treatment recommendations. Modifiable factors associated with these ratings can inform interventions to support patient-physician decision making about care.

Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010.

Two selective estrogen receptor modulators, tamoxifen and raloxifene, have been shown in randomized clinical trials to reduce the risk of developing primary invasive breast cancer in high-risk women. In 1998, the U.S. Food and Drug Administration (FDA) used these studies as a basis for approving tamoxifen for primary breast chemoprevention in both premenopausal and postmenopausal women at high risk. In 2007, the FDA approved raloxifene for primary breast cancer chemoprevention for postmenopausal women. Data from the year 2010 National Health Interview Survey were analyzed to estimate the prevalence of tamoxifen and raloxifene use for chemoprevention of primary breast cancers among U.S. women. Prevalence of use of chemopreventive agents for primary tumors was 20,598 (95 % CI, 518-114,864) for U.S. women aged 35-79 for tamoxifen. Prevalence was 96,890 (95 % CI, 41,277-192,391) for U.S. women aged 50-79 for raloxifene. Use of tamoxifen and raloxifene for prevention of primary breast cancers continues to be low. In 2010, women reporting medication use for breast cancer chemoprevention were primarily using the more recently FDA approved drug raloxifene. Multiple possible explanations for the low use exist, including lack of awareness and/or concern about side effects among primary care physicians and patients.

Building the evidence base for decision making in cancer genomic medicine using comparative effectiveness research.

The clinical utility is uncertain for many cancer genomic applications. Comparative effectiveness research (CER) can provide evidence to clarify this uncertainty. The aim of this study was to identify approaches to help stakeholders make evidence-based decisions and to describe potential challenges and opportunities in using CER to produce evidence-based guidance. We identified general CER approaches for genomic applications through literature review, the authors' experiences, and lessons learned from a recent, seven-site CER initiative in cancer genomic medicine. Case studies illustrate the use of CER approaches. Evidence generation and synthesis approaches used in CER include comparative observational and randomized trials, patient-reported outcomes, decision modeling, and economic analysis. Significant challenges to conducting CER in cancer genomics include the rapid pace of innovation, lack of regulation, and variable definitions and evidence thresholds for clinical and personal utility. Opportunities to capitalize on CER methods in cancer genomics include improvements in the conduct of evidence synthesis, stakeholder engagement, increasing the number of comparative studies, and developing approaches to inform clinical guidelines and research prioritization. CER offers a variety of methodological approaches that can address stakeholders' needs and help ensure an effective translation of genomic discoveries.

Strengthening the reporting of genetic risk prediction studies (GRIPS): explanation and elaboration.

• The rapid and continuing progress in gene discovery for complex diseases is fuelling interest in the potential application of genetic risk models for clinical and public health practice. • The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality. • Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction. • A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by prior reporting guidelines. • These recommendations aim to enhance the transparency, quality and completeness of study reporting and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct or analysis.

Strengthening the reporting of genetic risk prediction studies (GRIPS): explanation and elaboration.

The rapid and continuing progress in gene discovery for complex diseases is fuelling interest in the potential application of genetic risk models for clinical and public health practice. The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality. Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction. A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by prior reporting guidelines. These recommendations aim to enhance the transparency, quality and completeness of study reporting, and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct or analysis.

Correlates of unrealistic risk beliefs in a nationally representative sample.

Unrealistically optimistic or pessimistic risk perceptions may be associated with maladaptive health behaviors. This study characterized factors associated with unrealistic optimism (UO) and unrealistic pessimism (UP) about breast cancer. Data from the 2005 National Health Interview Survey were analyzed (N = 14,426 women). After accounting for objective risk status, many (43.8%) women displayed UO, 12.3% displayed UP, 34.5% had accurate risk perceptions (their perceived risk matched their calculated risk), and 9.5% indicated "don't know/no response." Multivariate multinomial logistic regression indicated that UO was associated with higher education and never smoking. UP was associated with lower education, lower income, being non-Hispanic Black, having ≥3 comorbidities, current smoking, and being overweight. UO was more likely to emerge in younger and older than in middle-aged individuals. UO and UP are associated with different demographic, health, and behavioral characteristics. Population segments that are already vulnerable to negative health outcomes displayed more UP than less vulnerable populations.

Distribution of Genomic Testing Resources by Oncology Practice and Rurality: A Nationally Representative Study.

PURPOSE: Oncologists are increasingly using molecular profiling to inform personalized patient treatment decisions. Despite its promising utility, the integration of genomic testing into diverse clinical health care settings across geographic settings has been understudied. METHODS: We used data from the National Survey of Precision Medicine in Cancer Treatment, a nationally representative sample of practicing US oncologists, to assess the availability of six genomic testing resources, including on-site pathology, contracts with outside laboratories, on-site genetic counselors, internal policies or protocols for using genomic and biomarker testing, electronic medical record alerts, and genomic or molecular tumor boards. We used multivariate logistic regression models to examine differences in the availability of each genomic testing resource by practice type and rurality while adjusting for payer mix and patient volume. RESULTS: A larger proportion of multispecialty group and academic practices had genomic testing resources available compared with solo and nonacademic practices. Electronic medical record alerts were the least available resource, whereas contracts with outside laboratories were the most available resource. Compared with urban practices, there were significantly fewer practices located in rural areas that had on-site pathology, on-site genetic counselors, protocols for genomic tests, and molecular tumor boards. CONCLUSION: Genomic testing resources varied by practice type and geography among a nationally representative sample of practicing oncologists. This variation has important implications for the development of interventions and policies to support the more equitable delivery of precision oncology to patients with cancer.

The National Cancer Institute and Cannabis and Cannabinoids Research.

The landscape of both recreational and medicinal cannabis use has changed dramatically over the past decade; however, research examining the risks and benefits of cannabis and cannabinoid use has lagged significantly behind the increased media promotion and their use by the general public and cancer patients. The National Cancer Institute (NCI) has supported cannabis-related research projects and funding opportunity announcements. In addition, NCI organized a virtual symposium on December 15-18, 2020, to discuss recent research findings on the use of cannabis and cannabinoids in relationship to cancer risk, prevention, and care. Specifically, the symposium sought to highlight the state of the science regarding cannabis, including the chemical constituents of cannabis (eg, cannabinoids), and cancer research involving cannabis, including cancer epidemiology, use in cancer patients, cancer biology and prevention, and preclinical and clinical cancer symptom and treatment side effect management with cannabis and cannabinoids as therapeutics. The symposium identified promising areas of future study, current barriers to conducting the research, and strategies to overcome those barriers. The series of papers in this special edition provide a summary of the symposium sessions as well as a synopsis of opportunities and challenges related to conducting research in this area.

Oncologist-Reported Reasons for Not Ordering Multimarker Tumor Panels: Results From a Nationally Representative Survey.

This study examines oncologist-reported reasons for not using multimarker tumor panel testing and the association between these reasons and oncologist-level, facility-level, and patient-mix characteristics. METHODS: We used data collected from a nationally representative sample (N = 1,281) of medical oncologists participating in the National Cancer Institute's National Survey of Precision Medicine in Cancer Treatment. RESULTS: In addition to testing not being seen as relevant (87%) and no evidence of test utility (77%), the most frequently reported reasons for not ordering a multimarker tumor panel test was difficulty in obtaining sufficient tissue (57%) and using individual gene tests (72%). These reasons were more likely to be reported by oncologists practicing in rural clinics and less likely to be reported by oncologists with an academic affiliation or with access to genetic services such as on-site genetic counselors and internal genetic testing policies. CONCLUSION: Modifiable, organizational factors were associated with ordering multimarker tumor panels. Receipt of genomics training and organizational policies related to the use of genomics were associated with lower reporting of barriers to ordering multimarker tumor panels, pointing to potential targets for future studies aimed at increasing appropriate multimarker tumor panel testing in cancer treatment management.

Involving patients and their families in deciding to use next generation sequencing: Results from a nationally representative survey of U.S. oncologists.

OBJECTIVE: Next generation sequencing (NGS) may aid in tumor classification and treatment. Barriers to shared decision-making may influence use of NGS. We examined, from oncologists' perspectives, whether barriers to involving patients/families in decision-making were associated with NGS use. METHODS: Using data from the first national survey of medical oncologists' perspectives on precision medicine (N = 1281), we approached our analyses in two phases. Bivariate analyses initially evaluated associations between barriers to involving patients/families in deciding to use NGS and provider- and organizational-level characteristics. Modified Poisson regressions then examined associations between patient/family barriers and NGS use. RESULTS: Approximately 59 % of oncologists reported at least one barrier to involving patients/families in decision-making regarding NGS use. Those reporting patient/family barriers tended to have fewer genomic resources at their practices, to be in rural or suburban areas, and to have a higher proportion of Medicaid patients. However, these barriers were not associated with NGS use. CONCLUSIONS: Oncologists encounter barriers to involving patients/families in NGS testing decisions. Organizational barriers may also potentially play a role in testing decisions. PRACTICE IMPLICATIONS: To foster patient-centered care, strategies to support patient involvement in genomic testing decisions are needed, particularly among practices in low-resource settings.

Epidemiologic Research of Rare Cancers: Trends, Resources, and Challenges.

BACKGROUND: The goals of this project were to assess the status of NCI's rare cancer-focused population science research managed by the Division of Cancer Control and Population Sciences (DCCPS), to develop a framework for evaluation of rare cancer research activities, and to review available resources to study rare cancers. METHODS: Cancer types with an overall age-adjusted incidence rate of less than 20 cases per 100,000 individuals were identified using NCI Surveillance, Epidemiology and End Results (SEER) Program data. SEER data were utilized to develop a framework based on statistical commonalities. A portfolio analysis of DCCPS-supported active grants and a review of three genomic databases were conducted. RESULTS: For the 45 rare cancer types included in the analysis, 123 active DCCPS-supported rare cancer-focused grants were identified, of which the highest percentage (18.7%) focused on ovarian cancer. The developed framework revealed five clusters of rare cancer types. The cluster with the highest number of grants (n = 43) and grants per cancer type (10.8) was the cluster that included cancer types of higher incidence, average to better survival, and high prevalence (in comparison with other rare cancers). Resource review revealed rare cancers are represented in available genomic resources, but to a lesser extent compared with more common cancers. CONCLUSIONS: This article provides an overview of the rare cancer-focused population sciences research landscape as well as information on gaps and opportunities. IMPACT: The findings of this article can be used to develop efficient and comprehensive strategies to accelerate rare cancer research.See related commentary by James V. Lacey Jr, p. 1300.