Testing for EGFR Variants in Pleural and Pericardial Effusion Cell-Free DNA in Patients With Non-Small Cell Lung Cancer.

Importance: Molecular testing in non-small cell lung cancer (NSCLC) is commonly limited by inadequate tumor sample. Plasma cell-free DNA (cfDNA) genotyping as a complementary test is specific but only moderately sensitive. Genotyping of cfDNA in pleural and pericardial effusion (PE-cfDNA) can further optimize molecular diagnostic yield and reduce the need for repeated biopsies. Objective: To prospectively validate droplet digital polymerase chain reaction (ddPCR) for detection of sensitizing EGFR variants and acquired Thr790Met variant (T790M) from PE-cfDNA in patients with NSCLC. Design, Setting, and Participants: This prospective diagnostic validation study was conducted between September 6, 2016, and January 21, 2021 at 2 major Hong Kong cancer centers. Patients with advanced NSCLC with both wild-type and variant EGFR status and exudative PE who underwent thoracocentesis or pericardiocentesis were randomly enrolled. Patients were either EGFR-tyrosine kinase inhibitor (TKI) naive (cohort 1) or EGFR-TKI treated but osimertinib naive (cohort 2). Enrolled patients underwent pleural- or pericardial-fluid and blood sampling for ddPCR EGFR testing. EGFR status results with ddPCR testing of PE-cfDNA and blood were compared with EGFR status in matched tumor biopsy or PE cell block samples. Main Outcomes and Measures: Specificity, sensitivity, and concordance of PE-cfDNA for detection of sensitizing EGFR variants and acquired T790M variation. Results: Among 171 patients (54% female) enrolled, there were 104 in cohort 1 and 67 in cohort 2. In cohort 1, 37% (38/102) were EGFR-variant positive; PE-cfDNA showed 97% sensitivity (95% CI, 92%-100%), 97% specificity (95% CI, 93%-100%), and 97% concordance (ĸ = 0.94, P < .001) for the detection of sensitizing EGFR variants. It was more sensitive than plasma in detecting sensitizing EGFR variants (97% vs 74%, P < .001). In cohort 2, 38% (15 of 40) were positive for the EGFR T790M variant; PE-cfDNA showed 87% sensitivity (95% CI, 69%-100%), 60% specificity (95% CI, 41%-79%), and 70% concordance (ĸ = 0.42, P = .004) for acquired T790M. The EGFR T790M variant was detected in 51% of PE-cfDNA vs 25% of PE cell block samples. Conclusions and Relevance: In this diagnostic study, EGFR variants could be accurately detected from PE-cfDNA in patients with NSCLC. More EGFR T790M was detected in PE-cfDNA than in guideline-recommended PE cell block preparations. These results suggest that PE-cfDNA can complement plasma and tumor genotyping for detecting EGFR variants in patients with advanced NSCLC.

Speaking of values: the ethics of communication.

The patient-doctor relationship is central to medicine. From this relationship, duties and obligations are derived; within this relationship, hopes and expectations are set. Communication is essential in this relationship and evidence-based efforts directed at improving it are a key element in improving care. At an even deeper level, critical reflection reveals fundamental values operating within and beneath this discourse that must be addressed if the goals of improving communication are to be achieved in a meaningful way. This is the stuff of the ethics of patient-physician communication. Because these values are so deeply embedded in the speech and actions of physicians, insights are best provided by those who are observers of the discourse rather than by participants. Observations from the history and sociology of physician communication, literary analysis and reflections on the illness experience by women provide important insights into the values and attitudes underlying physician communication, which must be taken into account in the education of physicians if the outcome is to benefit all participants.

Codes and character: the pillars of professional ethics.

Historically, the ethics of a professional were the ethics of a gentleman. The social changes in the 1960s, where citizens asked for a greater voice in all affairs that affected them gave rise to formal approaches to ethics in the health fields. Principle-based and case-based reasoning have been dominant. Neither codes nor approaches based on virtue (the character of the professional) are perfect solutions in all cases, but professions are strengthened through the development and discussion of statements about ethical conduct.

Bioethics and Canadian dentistry.

Formal ethical reflection and analysis have become expected components of clinical decision making for all health professionals. The implicit acceptance of professional ethics as the sole determinant of "the right and the good" has been replaced by an expectation for more broadly-based understanding of ethical issues. Dentists, like physicians, must be clear about professional ethics and competent in interdisciplinary and interprofessional discussions of the right and good. Modern bioethics is providing approaches to these issues to help practitioners make ethical clinical decisions. These approaches may not be appropriate for dentistry, especially as practised in Canada. Clearly, there are fundamental questions concerning dentistry as a profession, patient-dentist interactions and dental health that must be addressed to form a basis for an ethic relevant to professional practice. The answers to these questions have profound implications for the initial and continuing education of Canadian dentists and for dentistry itself. Some possible starting points for a truly Canadian ethic for dentistry are suggested from a non-dentist, physician ethicist.

Values, health, and health care.

The National Forum on Health was established to provide advice to the federal government on future directions for health and health care in Canada. The forum was committed to base its assessments on the twin pillars of values and evidence. To clarify the value base for policy recommendations, the values committee of the forum reviewed all available data from opinion polls, surveys, and values research relating to Canadians and health issues for the last 25 years. Original research was developed using the focus-group method to analyse a structured set of questions presented in video format such as Stories of Choice. The results of the retrospective review and contemporary research confirmed the endurance of basic values such as equity, equality in accessibility, quality, effectiveness, efficiency, and compassion. It further identified emerging values regarding personal and public accountability, and broadening visions of health.

Bioethics for clinicians: 9. Involving children in medical decisions.

Medical decisions involving children raise particular ethical issues for physicians and other members of the health care team. Although parents and physicians have traditionally made most medical decisions on behalf of children, the developing autonomy of children is increasingly being recognized in medical decision-making. This poses a challenge for physicians, who must work with the child's family and with other health care practitioners to determine the child's role in decision-making. A family-centred approach respects the complex nature of parent-child relationships, the dependence and vulnerability of the child and the child's developing capacity for decision-making.

Ethics teaching and learning in pediatric training: development of a curriculum.

The Royal College of Physicians and Surgeons of Canada has stated that residency programs "must provide opportunities for residents to gain an understanding of the basic principles of biomedical ethics as it relates to the specialty." This article presents the steps taken to develop a curriculum for teaching and learning biomedical ethics in Canadian pediatric residency programs, and to provide a model for teaching ethics in this context. Using literature reviews, and opinion surveys of departmental chairpersons, pediatric residents, and practising pediatricians across Canada, we have developed a teachers' handbook to help faculty members in teaching ethics. It can also be used as a tool to enhance faculty development in ethics. The manual is to be distributed to all pediatric training programs throughout Canada in 1997, and its use will be evaluated over the subsequent year. It offers a prototype that is adaptable to Royal College programs other than pediatrics.

The CMA Code of Ethics: more room for reflection.

Codes of ethics stand as a promise to society about the integrity of a profession in return for the power and authority given to that profession by society. The revised CMA Code of Ethics (see pages 1176A to 1176B) is timely and significant and should be applauded and supported by all physicians. It speaks clearly to competence, high standards of practice and communication, and the importance of informed patient choice. Nonetheless, the code provides no systematic justification for the principles it asserts. Although these principles are helpful tools, they are insufficient to resolve major ethical dilemmas. The code provides no means of ordering ethical priorities and fails to address issues such as peer review and conflict of interest. It is deafeningly silent on both abortion and euthanasia. In view of these limitations, the code must be seen as an important but unfinished reflection on the essence of being a good physician.

Shaping a preferred future: Catholic healthcare beyond the year 2000.

The Catholic Health Association of Canada recognizes that the Canadian healthcare system is changing. In a special supplement to the summer edition of the Review, we explored the forces at play within our healthcare environment and identified significant emerging trends. In Part II of this review, we look at the role for Catholic healthcare in Canada beyond the year 2000 by presenting the perspectives of four key spokespersons. These spokespersons outline the valuable contribution Catholic healthcare make within the Canadian healthcare system.