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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.

PurposeWhile scatter from the patient is assumed to be the primary source of occupational radiation dose associated with fluoroscopically guided interventional procedures, the potential contribution of scatter from the x‐ray collimator assembly is unknown. The purpose of this work was to survey clinical x‐ray angiography systems to assess the potential contribution of collimator assembly scatter on occupational radiation dose.MethodsExperimental methods were designed to measure the relative contributions of scatter originating from within the collimator assembly of the x‐ray tube to total scatter, which included scatter from a patient‐simulating phantom. Measurements were acquired as a function of lateral distance from the x‐ray beam center using a posterior anterior (PA) projection and at a fixed location for variable right anterior oblique to left anterior oblique projections in the range −90º to 90º. For one system, the collimator assembly was partially disassembled to assess the scatter contribution of individual components. For two systems, 0.5 mm Pb was added to the inner surface of the collimator assembly cover and tested for efficacy to block collimator assembly scatter.ResultsConsidering all x‐ray systems and only the PA projection, collimator assembly scatter contributed 20–50% to total scatter. For x‐ray projection angles of −90º to 90º, the relative contribution of collimator assembly to total scatter was dependent on projection angle and ranged from 5% to 56%. X‐ray systems with kerma‐area product meters demonstrated higher collimator assembly scatter than those without. Considering all projection angles, the addition of 0.5 mm Pb to the inside of the collimator assembly cover reduced collimator assembly scatter from 28% to 16% of total scatter for both systems.ConclusionFindings from this work suggest that contemporary radiation safety practices and guidelines should be revised to account for scatter originating from the collimator assembly of angiographic x‐ray tubes.

AbstractAccurate pathologic diagnoses and molecularly informed treatment decisions for a wide variety of cancers depend on robust clinical molecular testing that uses genomic, epigenomic, and transcriptomic-based tools. Nowhere is this more essential than in the workup of brain tumors, as emphasized by the incorporation of molecular criteria into the 2016 World Health Organization classification of central nervous system tumors and the updated official guidelines of the National Comprehensive Cancer Network. Despite the medical necessity of molecular testing in brain tumors, access to and utilization of molecular diagnostics is still highly variable across institutions, and a lack of reimbursement for such testing remains a significant obstacle. The objectives of this review are (i) to identify barriers to adoption of molecular testing in brain tumors, (ii) to describe the current molecular tools recommended for the clinical evaluation of brain tumors, and (iii) to summarize how molecular data are interpreted to guide clinical care, so as to improve understanding and justification for their coverage in the routine workup of adult and pediatric brain tumor cases.

Abstract Rationale Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings. Objectives To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), β-d-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis). Methods Studies were selected and appraised by pairs of reviewers. Bivariate random effects meta-analysis was used to generate pooled sensitivity, specificity, and diagnostic likelihood ratios. Results Serum GM in patients with impaired immunity suspected of having IA had sensitivity of 0.71 (95% confidence interval [CI], 0.64–0.78) and specificity of 0.89 (95% CI, 0.84–0.92). A cutoff of 1 optical density index yielded optimal sensitivity and specificity. BAL GM in patients with impaired immunity suspected of having IA had sensitivity of 0.84 (95% CI, 0.73–0.91) and specificity of 0.88 (95% CI, 0.81–0.91). Serum or whole-blood PCR in immunocompromised patients with suspected IA had sensitivity of 0.81 (95% CI, 0.73–0.86) and specificity of 0.79 (95% CI, 0.68–0.86). BAL PCR in patients at high risk for IA had high sensitivity of 0.90 (95% CI, 0.77–0.96) and specificity of 0.96 (95% CI, 0.93–0.98) for diagnosing IA. β-d-glucan assay in patients in the intensive care unit at risk for invasive candidiasis or candidemia had sensitivity of 0.81 (95% CI, 0.74–0.86) and specificity of 0.60 (95% CI, 0.49–0.71). Data on diagnostic accuracy of antigen detection and serology testing for endemic mycoses were limited and heterogeneous (varied according to test, patient immunity, and suspected endemic disease). Conclusions The diagnosis of invasive fungal infections remains a challenge. Various serum and BAL markers can aid in diagnosis. This evidence supports the development of clinical practice recommendations by the American Thoracic Society.

Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin’s lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.

Background:The pivotal FIRST trial, the largest study conducted in transplant‐ineligible (TNE) patients (pts) with newly diagnosed multiple myeloma (NDMM), examined lenalidomide plus low‐dose dexamethasone until disease progression (Rd continuous), Rd for 18 cycles (Rd18), and melphalan, prednisone, and thalidomide (MPT). The study, conducted in 18 countries in Europe, North America, and Asia Pacific, demonstrated that Rd continuous significantly improved progression‐free survival (PFS) vs MPT (median 26.0 vs 21.9 mos; HR, 0.69; 95% CI, 0.59‐0.79; P < .00001). PFS was similarly extended for Rd continuous vs Rd18 (median 21.0 mos; HR, 0.70; 95% CI, 0.60‐0.81). Furthermore, median overall survival (OS) was significantly longer with Rd continuous vs MPT (median 59.1 vs 49.1 mos; HR, 0.78; 95% CI, 0.67‐0.92; P = .0023). These results support the use of frontline oral, alkylator‐free continuous therapy for TNE NDMM pts and established Rd continuous as a standard of care as reflected by clinical guidelines in Canada, the US, and Europe.Aims:To report outcomes in the subset of patients from Canada and the US.MethodsPts with TNE NDMM were randomized 1:1:1 to Rd continuous (with lenalidomide given on days 1‐21 of 28‐day cycles until disease progression), Rd18 (with lenalidomide given on days 1‐21 of eighteen 28‐day cycles), or MPT (twelve 42‐day cycles). Rd18 and MPT were both 72 weeks in duration. Stratification factors included country and Rd continuous vs MPT was the primary comparison. The primary endpoint was PFS and secondary endpoints included OS, time to next therapy (TTNT) and safety. Time from randomization to second progression or death (PFS2) was an exploratory analysis. Response assessment used for PFS and PFS2 analysis was determined by investigators based on International Myeloma Working Group criteria. Data is presented as of the January 21, 2016 cutoff used for the final OS analysis.Results:A total of 312 pts from Canada (n = 252) and the US (n = 60) were enrolled (104 in each arm). Consistent with results from the intent‐to‐treat (ITT) analysis, the Canada/US subgroup also demonstrated a significant improvement in PFS with Rd continuous vs MPT (median 29.3 vs 20.2 mos; HR, 0.69; 95% CI, 0.49‐0.97; P = .03326) and an improvement vs Rd18 (median 21.9 mos; HR, 0.72; 95% CI, 0.51‐1.02; Table). Median OS was 56.9 vs 46.8 mos for Rd continuous vs MPT (HR, 0.77; 95% CI, 0.53‐1.11; P = .15346). Median PFS2 was longer for Rd continuous vs MPT (median 39.3 vs 35.1 mos; HR, 0.69; 95% CI 0.50‐0.95) as was TTNT (median 39.1 vs 24.6 mos; HR, 0.54; 95% CI, 0.37‐0.78). Additional details, including safety data, will be presented at the meeting.Summary/Conclusion:In the Canada/US subpopulation of pts from FIRST, Rd continuous extended median PFS by 9 mos vs MPT and > 7 mos vs Rd18. Rd continuous also delayed median TTNT > 14 mos and resulted in a longer PFS2 vs MPT, suggesting that the benefit from frontline Rd continuous is maintained at relapse. These results are consistent with that from the ITT population confirming the advantage of Rd continuous vs MPT in the Canada/US subgroup and supporting the role of Rd continuous as a standard of care for TNE pts with NDMM. The efficacy observed with Rd continuous raises the question on the role of immunostimulatory effects by the immunomodulatory agents in NDMM.image

2009 Background: NRG CC001, a phase III trial of WBRT plus memantine (WBRT+M) with or without HA, sought to evaluate the neuro-protective effects of lowering the hippocampal radiation dose. Methods: Patients (pts) with BM were stratified by RPA class and prior radiosurgery/surgery and randomized to WBRT+M or HA-WBRT+M (30Gy/10 fractions). Standardized NCF tests were performed at baseline, 2, 4, 6, and 12 months (mos). The primary endpoint was NCF failure, defined as decline using the reliable change index on Hopkins Verbal Learning Test-Revised, Trail Making Test, or Controlled Oral Word Association. Cumulative incidence estimated NCF failure (death without NCF failure was competing risk); between-arms differences tested using Gray’s test. Deterioration at each collection time point was tested using a chi-square test. Patient-reported symptoms were assessed using the MD Anderson Symptom Inventory Brain Tumor module and analyzed using mixed effects models and t-tests. Results: From 7/2016 to 3/2018, 518 pts were randomized. Median follow-up was 7.9 mos. HA-WBRT+M was associated with lower NCF failure risk (adjusted hazard ratio (HR) = 0.74, p = 0.02) due to lower risk of deterioration in executive function at 4 mos (p = 0.01) and encoding (p = 0.049) and consolidation (p = 0.02) at 6 mos. Age≤61 predicted lower NCF failure risk (HR = 0.60, p = 0.0002); non-significant test for interaction indicated independent effects of HA and age. Patient-reported fatigue (p = 0.036), difficulty speaking (p = 0.049) and problems remembering things (p = 0.013) at 6 mos favored the HA-WBRT+M arm. Imputation models accounting for missing data also favored the HA-WBRT+M arm for patient-reported cognition (p = 0.011) and symptom interference (p = 0.008) at 6 mos. Treatment arms did not differ in toxicity, overall survival, or intracranial progression. Conclusions: HA during WBRT+M for BM better preserves NCF and patient-reported symptoms, while achieving similar intracranial control and survival. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute. Clinical trial information: NCT02360215.