Oncologic Errors in Diagnostic Radiology: A 10-Year Analysis Based on Medical Malpractice Claims.

PURPOSE: To retrospectively analyze the nature and extent of oncology-related errors accounting for malpractice allegations in diagnostic radiology. METHODS: The Comparative Benchmarking System of the Controlled Risk Insurance Company, a database containing roughly 30% of medical malpractice claims in the United States, was searched retrospectively for the period 2008 to 2017. Claims naming radiology as a primary service were identified and were stratified and compared by oncologic versus nononcologic status, allegation type (diagnostic versus nondiagnostic), and imaging modality. RESULTS: Over the 10-year period, radiology was the primary responsible service for 3.9% of all malpractice claims (2,582 of 66,061) and 12.8% of claims with diagnostic allegations (1,756 of 13,695). Oncology (neoplasms) accounted for 44.0% of radiology cases with diagnostic allegations, a larger share than any other category of medical condition. Among radiology cases with diagnostic allegations, high-severity harm occurred in 79% of oncologic but just 42% of nononcologic cases. Of all oncologic radiology cases, 97.4% had diagnostic allegations, and just 55.0% of nononcologic radiology cases had diagnostic allegations. Imaging misinterpretation was a contributing factor for a large majority (80.7% [623 of 772]) of oncologic radiology cases with diagnostic allegations. The modalities most commonly used in oncologic radiology cases with diagnostic allegations involving misinterpretation were mammography and CT. CONCLUSION: Oncology represents the largest source of radiology malpractice cases with diagnostic allegations. Oncologic radiology malpractice cases are more likely than nononcologic radiology cases to be due to diagnostic errors. Furthermore, compared with those that are nononcologic, oncologic radiology cases with diagnostic allegations are more likely to be associated with high-severity harm. Efforts are warranted to reduce misinterpretations of oncologic imaging.

National Trends in Oncologic Diagnostic Imaging.

OBJECTIVE: To characterize national trends in oncologic imaging (OI) utilization. METHODS: This retrospective cross-sectional study used 2004 and 2016 CMS 5% Carrier Claims Research Identifiable Files. Radiologist-performed, primary noninvasive diagnostic imaging examinations were identified from billed Current Procedural Terminology codes; CT, MRI, and PET/CT examinations were categorized as "advanced" imaging. OI examinations were identified from imaging claims' primary International Classification of Diseases-9 and International Classification of Diseases-10 codes. Imaging services were stratified by academic practice status and place of service. State-level correlations of oncologic advanced imaging utilization (examinations per 1,000 beneficiaries) with cancer prevalence and radiologist supply were assessed by Spearman correlation coefficient. RESULTS: The national Medicare sample included 5,051,095 diagnostic imaging examinations (1,220,224 of them advanced) in 2004 and 5,023,115 diagnostic imaging examinations (1,504,608 of them advanced) in 2016. In 2004 and 2016, OI represented 4.3% and 3.9%, respectively, of all imaging versus 10.8% and 9.5%, respectively, of advanced imaging. The percentage of advanced OI done in academic practices rose from 18.8% in 2004 to 34.1% in 2016, leaving 65.9% outside academia. In 2016, 58.0% of advanced OI was performed in the hospital outpatient setting and 23.9% in the physician office setting. In 2016, state-level oncologic advanced imaging utilization correlated with state-level radiologist supply (r = +0.489, P < .001) but not with state-level cancer prevalence (r = -0.139, P = .329). DISCUSSION: OI usage varied between practice settings. Although the percentage of advanced OI done in academic settings nearly doubled from 2004 to 2016, the majority remained in nonacademic practices. State-level oncologic advanced imaging utilization correlated with radiologist supply but not cancer prevalence.

Clinical Application of Computational Methods in Precision Oncology: A Review.

Importance: There is an enormous and growing amount of data available from individual cancer cases, which makes the work of clinical oncologists more demanding. This data challenge has attracted engineers to create software that aims to improve cancer diagnosis or treatment. However, the move to use computers in the oncology clinic for diagnosis or treatment has led to instances of premature or inappropriate use of computational predictive systems. Objective: To evaluate best practices for developing and assessing the clinical utility of predictive computational methods in oncology. Evidence Review: The National Cancer Policy Forum and the Board on Mathematical Sciences and Analytics at the National Academies of Sciences, Engineering, and Medicine hosted a workshop to examine the use of multidimensional data derived from patients with cancer and the computational methods used to analyze these data. The workshop convened diverse stakeholders and experts, including computer scientists, oncology clinicians, statisticians, patient advocates, industry leaders, ethicists, leaders of health systems (academic and community based), private and public health insurance carriers, federal agencies, and regulatory authorities. Key characteristics for successful computational oncology were considered in 3 thematic areas: (1) data quality, completeness, sharing, and privacy; (2) computational methods for analysis, interpretation, and use of oncology data; and (3) clinical infrastructure and expertise for best use of computational precision oncology. Findings: Quality control was found to be essential across all stages, from data collection to data processing, management, and use. Collecting a standardized parsimonious data set at every cancer diagnosis and restaging could enhance reliability and completeness of clinical data for precision oncology. Data completeness refers to key data elements such as information about cancer diagnosis, treatment, and outcomes, while data quality depends on whether appropriate variables have been measured in valid and reliable ways. Collecting data from diverse populations can reduce the risk of creating invalid and biased algorithms. Computational systems that aid clinicians should be classified as software as a medical device and thus regulated according to the potential risk posed. To facilitate appropriate use of computational methods that interpret high-dimensional data in oncology, treating physicians need access to multidisciplinary teams with broad expertise and deep training among a subset of clinical oncology fellows in clinical informatics. Conclusions and Relevance: Workshop discussions suggested best practices in demonstrating the clinical utility of predictive computational methods for diagnosing or treating cancer.

Challenges and Opportunities to Updating Prescribing Information for Longstanding Oncology Drugs.

A number of important drugs used to treat cancer-many of which serve as the backbone of modern chemotherapy regimens-have outdated prescribing information in their drug labeling. The Food and Drug Administration is undertaking a pilot project to develop a process and criteria for updating prescribing information for longstanding oncology drugs, based on the breadth of knowledge the cancer community has accumulated with the use of these drugs over time. This article highlights a number of considerations for labeling updates, including selecting priorities for updating; data sources and evidentiary criteria; as well as the risks, challenges, and opportunities for iterative review to ensure prescribing information for oncology drugs remains relevant to current clinical practice.

Improving Cancer Diagnosis and Care: Patient Access to High-Quality Oncologic Pathology.

Drawing on discussions at a workshop hosted by the National Cancer Policy Forum, current challenges in pathology are reviewed and practical steps to facilitate high­quality cancer diagnosis and care through improved patient access to expertise in oncologic pathology are highlighted.

Accelerating anticancer drug development - opportunities and trade-offs.

The traditional approach to drug development in oncology, with discrete phases of clinical testing, is becoming untenable owing to expansion of the precision medicine paradigm, whereby patients are stratified into multiple subgroups according to the underlying cancer biology. Seamless approaches to drug development in oncology hold great promise of accelerating the accessibility of novel therapeutic agents to the public but are also accompanied by important trade-offs, including the limited availability of information on the clinical benefit and safety of novel agents at the time of market entry. In this Perspectives article, we describe several opportunities, in the form of novel trial designs or modelling strategies, to improve the efficiency of drug development in oncology, as well as new mechanisms to obtain information about anticancer therapies throughout their life cycle, such as innovative functional imaging techniques or the use of real-world clinical data.

Weight management and physical activity throughout the cancer care continuum.

Mounting evidence suggests that weight management and physical activity (PA) improve overall health and well being, and reduce the risk of morbidity and mortality among cancer survivors. Although many opportunities exist to include weight management and PA in routine cancer care, several barriers remain. This review summarizes key topics addressed in a recent National Academies of Science, Engineering, and Medicine workshop entitled, "Incorporating Weight Management and Physical Activity Throughout the Cancer Care Continuum." Discussions related to body weight and PA among cancer survivors included: 1) current knowledge and gaps related to health outcomes; 2) effective intervention approaches; 3) addressing the needs of diverse populations of cancer survivors; 4) opportunities and challenges of workforce, care coordination, and technologies for program implementation; 5) models of care; and 6) program coverage. While more discoveries are still needed for the provision of optimal weight-management and PA programs for cancer survivors, obesity and inactivity currently jeopardize their overall health and quality of life. Actionable future directions are presented for research; practice and policy changes required to assure the availability of effective, affordable, and feasible weight management; and PA services for all cancer survivors as a part of their routine cancer care. CA Cancer J Clin 2018;68:64-89. © 2017 American Cancer Society.

Commentary on the Consensus Statement of the American Society of Breast Surgeons on Contralateral Prophylactic Mastectomy.

The increasing rate of contralateral prophylactic mastectomy (CPM) led the American Society of Breast Surgeons (ASBrS) to issue an evidence-based consensus statement on CPM, as well as a discussion guide that health care providers can use to facilitate shared decision making with patients considering CPM for unilateral breast cancer. This article suggests several ways to improve the discussion guide by eliciting patient values and preferences and by providing more current, detailed, and balanced information about the potential risks and benefits of CPM.

Identifying and addressing the needs of adolescents and young adults with cancer: summary of an Institute of Medicine workshop.

Cancer is the leading disease-related cause of death in adolescents and young adults (AYAs). This population faces many short- and long-term health and psychosocial consequences of cancer diagnosis and treatment, but many programs for cancer treatment, survivorship care, and psychosocial support do not focus on the specific needs of AYA cancer patients. Recognizing this health care disparity, the National Cancer Policy Forum of the Institute of Medicine convened a public workshop to examine the needs of AYA patients with cancer. Workshop participants identified many gaps and challenges in the care of AYA cancer patients and discussed potential strategies to address these needs. Suggestions included ways to improve access to care for AYAs, to deliver cancer care that better meets the medical and psychosocial needs of AYAs, to develop educational programs for providers who care for AYA cancer survivors, and to enhance the evidence base for AYAs with cancer by facilitating participation in research.

Expanding public-private collaborations to enhance cancer drug development: a report of the Institute of Medicine's workshop series, "Implementing a National Cancer Clinical Trials System for the 21st Century".

Since their inception in the 1950s, the National Cancer Institute-funded cancer cooperative groups have been important contributors to cancer clinical and translational research. In 2010, a committee appointed by the Institute of Medicine (IOM) of the National Academy of Sciences completed a consensus review on the status of the U.S. publicly funded cancer clinical trials system. This report identified a need to reinvigorate the cooperative groups and provided recommendations for improving their effectiveness. Follow-up workshops to monitor progress were conducted by the IOM's National Cancer Policy Forum and the American Society of Clinical Oncology (ASCO) in 2011 and 2013. One of the key recommendations of the IOM report was a call for greater collaboration among stakeholders in cancer research. In particular, more active engagement and better alignment of incentives among the cooperative groups, the National Cancer Institute, the U.S. Food and Drug Administration, and the biopharmaceutical industry were identified as essential to achieving the promise of oncology drug development. This review, based on presentations and discussion during the IOM-ASCO workshops, outlines the progress and remaining challenges of these collaborations.

Reducing tobacco-related cancer incidence and mortality: summary of an institute of medicine workshop.

Tobacco use remains a serious and persistent national problem. Recognizing that progress in combating cancer will never be fully achieved without addressing the tobacco problem, the National Cancer Policy Forum of the Institute of Medicine convened a public workshop exploring current issues in tobacco control, tobacco cessation, and implications for cancer patients. Workshop participants discussed potential policy, outreach, and treatment strategies to reduce tobacco-related cancer incidence and mortality, and highlighted a number of potential high-value action items to improve tobacco control policy, research, and advocacy.

Practice-Changing Strategies to Deliver Affordable, High-Quality Cancer Care: Summary of an Institute of Medicine Workshop.

The authors summarize presentations and discussion from the Delivering Affordable Cancer Care in the 21st Century workshop and focus on proposed strategies to improve the affordability of cancer care while maintaining or improving the quality of care.

Accelerating cancer therapy development: the importance of combination strategies and collaboration. Summary of an Institute of Medicine workshop.

Cancer cells contain multiple genetic changes in cell signaling pathways that drive abnormal cell survival, proliferation, invasion, and metastasis. Unfortunately, patients treated with single agents inhibiting only one of these pathways--even if showing an initial response--often develop resistance with subsequent relapse or progression of their cancer, typically via the activation of an alternative uninhibited pathway. Combination therapies offer the potential for inhibiting multiple targets and pathways simultaneously to more effectively kill cancer cells and prevent or delay the emergence of drug resistance. However, there are many unique challenges to developing combination therapies, including devising and applying appropriate preclinical tests and clinical trial designs, prioritizing which combination therapies to test, avoiding overlapping toxicity of multiple agents, and overcoming legal, cultural, and regulatory barriers that impede collaboration among multiple companies, organizations, and/or institutions. More effective strategies to efficiently develop combination cancer therapies are urgently needed. Thus, the Institute of Medicine's National Cancer Policy Forum recently convened a workshop with the goal of identifying barriers that may be impeding the development of combination investigational cancer therapies, as well as potential solutions to overcome those barriers, improve collaboration, and ultimately accelerate the development of promising combinations of investigational cancer therapies.

Patient-centered cancer treatment planning: improving the quality of oncology care. Summary of an Institute of Medicine workshop.

The Institute of Medicine's National Cancer Policy Forum recently convened a workshop on patient-centered cancer treatment planning, with the aim of raising awareness about this important but often overlooked aspect of cancer treatment. A primary goal of patient-centered treatment planning is to engage patients and their families in meaningful, thorough interactions with their health care providers to develop an accurate, well-conceived treatment plan, using all available medical information appropriately while also considering the medical, social, and cultural needs and desires of the patient and family. A cancer treatment plan can be shared among the patient, family, and care team in order to facilitate care coordination and provide a roadmap to help patients navigate the path of cancer treatment. There are numerous obstacles to achieving patient-centered cancer treatment planning in practice. Some of these challenges stem from the patient and include patients' lack of assertiveness, health literacy, and numeracy, and their emotional state and concurrent illnesses. Others are a result of physician limitations, such as a lack of time to explain complex information and a lack of tools to facilitate treatment planning, as well as insensitivity to patients' informational, cultural, and emotional needs. Potential solutions to address these obstacles include better training of health care providers and patients in optimal communication and shared decision making, and greater use of support services and tools such as patient navigation and electronic health records. Other options include greater use of quality metrics and reimbursement for the time it takes to develop, discuss, and document a treatment plan.

A National Cancer Clinical Trials Network: recommendations from the Institute of Medicine.

Oncology has become one of the most active areas of drug discovery, with >800 cancer therapeutics in development. This not only presents an unprecedented opportunity to improve the outcome for patients with cancer but also requires an effective and efficient clinical trials network to generate the evidence necessary for regulatory approval and optimal integration of new treatments into clinical care. The Clinical Trials Cooperative Group Program supported by the National Cancer Institute has been instrumental in establishing standards of care in oncology over the last 50 years, but it currently faces numerous challenges that threaten its ability to undertake the large-scale, multi-institutional trials that advance patient care. The Institute of Medicine recently appointed a consensus study committee to assess the organization and operation of the Cooperative Group Program and recommend ways to improve the quality of cancer clinical trials conducted by the Groups and others. The committee developed a set of recommendations, summarized here, that aim to improve the speed and efficiency of trials; incorporate innovative science and trial design; improve prioritization, selection, and support of trials; and increase participation by patients and physicians.

Opening up to precompetitive collaboration.

In order to enhance biomedical research and development efficiency and innovation, nontraditional research collaborations have emerged that feature the sharing of information, resources, and capabilities. Although many of these so-called precompetitive collaborations are in the field of oncology, the lessons they offer are broadly applicable to other subfields of translational medicine.

Strategies to facilitate the development of new contraceptives.

Contraception is not readily accessible to much of the world's population and, in any case, no method is 100% effective or appropriate for all users. There is a pressing need for new methods to address the diverse requirements of the global community of men and women at all stages of their reproductive lives. This article will look at some of the new opportunities in contraceptive research and highlight strategies to overcome old challenges for the development of novel contraceptives.

Specific inhibition of DNMT1 by antisense oligonucleotides induces re-expression of estrogen receptor-alpha (ER) in ER-negative human breast cancer cell lines.

Recent studies have shown that changes in epigenetic regulation, such as DNA methylation and histone acetylation, are associated with silencing of the estrogen receptor a (ER) gene in ER-negative human breast cancer cells. Treatment of these cells with the general DNMT inhibitor, 5-aza-2'deoxycytidine, led to reactivation of functional ER protein. This study addresses the hypothesis that specific inhibition of the maintenance DNA methyltransferase, DNMT1, by antisense oligonucleotides (DNMT1 ASO) is sufficient to re-express the ER gene in ER-negative human breast cancer cell lines. MDA-MB-231 and Hs578t cells were transfected with 100 nM and 150 nM DNMT1 ASO respectively for three consecutive days and evidence of DNMT1 downregulation and functional ER re-expression was sought. Significant growth reduction was observed within 48 hr and persisted after 96 hr. DNMT1 expression was blocked after exposure to DNMT1 ASO as detected by RT-PCR, Western blot and enzymatic assay whereas a mutant DNMT1 ASO had little effect. This was associated with enhanced ER mRNA and protein expression and restoration of estrogen responsiveness in MDA-MB-231 cells as demonstrated by the ability of the induced ER protein to elicit ERE-regulated reporter activity from a luciferase reporter construct. Methylation specific PCR showed that the ER CpG island was minimally demethylated, suggesting that other epigenetic events, introduced by specific DNMT1 inhibition, might also be involved in ER re-expression. Our results suggest that specific inhibition of DNMT1 expression alone is sufficient to re-express ERa in human breast cancer cell lines.