Biospecimens acquired during routine medical practice are the primary sources of molecular information about patients and their diseases that underlies precision medicine and translational research. In cancer care, molecular analysis of biospecimens is especially common because it often determines treatment choices and may be used to monitor therapy in real time. However, patient specimens are collected, handled, and processed according to routine clinical procedures during which they are subjected to factors that may alter their molecular quality and composition. Such artefactual alteration may skew data from molecular analyses, render analysis data uninterpretable, or even preclude analysis altogether if the integrity of a specimen is severely compromised. As a result, patient care and safety may be affected, and medical research dependent on patient samples may be compromised. Despite these issues, there is currently no requirement to control or record preanalytical variables in clinical practice with the single exception of breast cancer tissue handled according to the guideline jointly developed by the American Society of Clinical Oncology and College of American Pathologists (CAP) and enforced through the CAP Laboratory Accreditation Program. Recognizing the importance of molecular data derived from patient specimens, the CAP Personalized Healthcare Committee established the Preanalytics for Precision Medicine Project Team to develop a basic set of evidence-based recommendations for key preanalytics for tissue and blood specimens. If used for biospecimens from patients, these preanalytical recommendations would ensure the fitness of those specimens for molecular analysis and help to assure the quality and reliability of the analysis data.
Context.— Cancer immunotherapy provides unprecedented rates of durable clinical benefit to late-stage cancer patients across many tumor types, but there remains a critical need for biomarkers to accurately predict clinical response. Although some cancer immunotherapy tests are associated with approved therapies and considered validated, other biomarkers are still emerging and at various states of clinical and translational exploration. Objective.— To provide pathologists with a current and practical update on the evolving field of cancer immunotherapy testing. The scientific background, clinical data, and testing methodology for the following cancer immunotherapy biomarkers are reviewed: programmed death ligand-1 (PD-L1), mismatch repair, microsatellite instability, tumor mutational burden, polymerase δ and ε mutations, cancer neoantigens, tumor-infiltrating lymphocytes, transcriptional signatures of immune responsiveness, cancer immunotherapy resistance biomarkers, and the microbiome. Data Sources.— Selected scientific publications and clinical trial data representing the current field of cancer immunotherapy. Conclusions.— The cancer immunotherapy field, including the use of biomarker testing to predict patient response, is still in evolution. PD-L1, mismatch repair, and microsatellite instability testing are helping to guide the use of US Food and Drug Administration–approved therapies, but there remains a need for better predictors of response and resistance. Several categories of tumor and patient characteristics underlying immune responsiveness are emerging and may represent the next generation of cancer immunotherapy predictive biomarkers. Pathologists have important roles and responsibilities as the field of cancer immunotherapy continues to develop, including leadership of translational studies, exploration of novel biomarkers, and the accurate and timely implementation of newly approved and validated companion diagnostics.
A B S T R AC T This study investigated the role of concurrent musical parts in pitching ability in sight-singing, concentrating on the effects of melodic and harmonic coherence. Twenty-two experienced singers sang their part twice in each of four novel chorales. The chorales contained either original or altered melody and original (tonal) or altered (atonal) harmony. Participants also performed an interval-singing task. Alterations from the original in both melody and harmony increased pitching errors in sight-singing. These results indicate respectively that pattern recognition and harmonic prediction are integral to sight-singing ability. Singers made fewer errors on the second reading, showing the role of familiarity. Error rate correlated with interval-singing performance. Less skilled sight-singers were significantly more affected by a disruption in harmony than were better sight-singers. The results suggest an increasing role for internal auditory representations with increasing expertise.
reviewed retrospectively. UroVysion testing was used at the beginning and end of each IVT cycle, and cytology and cystoscopy 6 weeks after completing each cycle. KaplanMeier actuarial survival was analysed, stratified by the UroVysion result after IVT. Univariate and multivariate Cox regression analyses were used to identify significant predictors of recurrence.
RESULTSIn all, 42 patients had induction IVT with bacille Calmette-Guérin (BCG), BCG + interferon, or mitomycin. The median follow-up was 21 months. Recurrent disease was detected in 18 patients. In a univariate analysis, chronic renal insufficiency (hazard ratio 12.1, P = 0.03), positive cytology after IVT (2.7, P = 0.05), and a positive UroVysion test after IVT (8.3, P < 0.01) were predictive of failure. In the multivariate analysis, high grade disease (5.3, P = 0.05), a risk score of > 6 (4.7, P = 0.02) and a positive UroVysion test after IVT (6.7, P < 0.01) were significant predictors of recurrence.
Objectives: Nodular fasciitis (NF) is a self-limited, mass-forming, fibrous proliferation that can occur in the head and neck and may mimic malignancy. Fine-needle aspiration biopsy (FNAB) is a minimally invasive, rapid, accurate method of obtaining diagnostic material from head and neck masses. In this study, we verify the usefulness of FNAB in obtaining a definitive diagnosis of NF. Methods: Cases were identified from our laboratory information system. Cytology slides were reviewed to note morphologic features and confirm diagnoses. Clinical history was obtained to document the case presentations and outcomes. Results: All 9 cases were found to have clinical presentations and common distinguishing morphologic features consistent with NF. Two cases were excised surgically, and the remainder regressed spontaneously. There were no recurrences. Conclusions: FNAB can produce a definitive diagnosis of NF, providing an opportunity to avoid surgical excision in patients with a typical clinical presentation.
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