Median Turnaround Time Research Articles

Practical Considerations for Using RNA Sequencing in Management of B-Lymphoblastic Leukemia: Malaysia-Singapore Acute Lymphoblastic Leukemia 2020 Implementation Strategy

Despite the immense genetic heterogeneity of B-lymphoblastic leukemia [or precursor B-cell acute lymphoblastic leukemia (B-ALL)], RNA sequencing (RNA-Seq) could comprehensively interrogate its genetic drivers, assigning a specific molecular subtype in >90% of patients. However, study groups have only started to use RNA-Seq. Forbroader clinical use, technical, quality control, and appropriate performance validation are needed. Wedescribe the development and validation of an RNA-Seq workflow for subtype classification, TPMT/NUDT15/TP53 variant discovery, and immunoglobulin heavy chain (IGH) disease clone identification for Malaysia-Singapore acute lymphoblastic leukemia (ALL) 2020. We validated this workflow in 377 patients in our preceding Malaysia-Singapore ALL 2003/Malaysia-Singapore ALL 2010 studies and proposed the quality control measures for RNA quality, library size, sequencing, and data analysis using the International Organization for Standardization 15189 quality and competence standard for medical laboratories. Compared with conventional methods, we achieved >95% accuracy in oncogene fusion identification, digital karyotyping, and TPMT and NUDT15 variant discovery. We found seven pathogenic TP53 mutations, confirmed with Sanger sequencing, which conferred a poorer outcome. Applying this workflow prospectively to the first 21 patients in Malaysia-Singapore ALL 2020, we identified the genetic drivers and IGH disease clones in >90% of patients with concordant TPMT, NUDT15, and TP53 variants using PCR-based methods. The median turnaround time was 12 days, which was clinically actionable. In conclusion, RNA-Seq workflow could be used clinically in management of B-cell ALL patients.

Pilot experience using tumor-based next generation sequencing increases compliance and reduces barriers for ovarian cancer genetic testing

<h3>Objectives:</h3> Although hereditary risk assessment is advised for all ovarian/tubal/peritoneal (OTP) cancer patients, a variety of barriers limit universal compliance. A workflow using tumor-based next generation sequencing (NGS) germline testing implemented by the pathologist at the time of primary or interval debulking surgery. The objective of this study is to report compliance and turnaround time of a pilot workflow of germline testing via tumor-based NGS in OTP cancer. may reduce some of these barriers. <h3>Methods:</h3> We identified all patients with a new diagnosis of epithelial OTP carcinoma who underwent primary or interval debulking surgery from January to August 2020. All patients were recommended to undergo tumor and germline sequencing, either through our institutional NGS platform or through commercial sequencing. We compared time to results as well as influence of results on maintenance/second-line therapy. <h3>Results:</h3> We identified 35 patients with a median age of 61 (range 29-78) and a median follow-up time of 5 months (range 0-13). Our stage breakdown included 8 Stage I, 4 Stage II, 20 Stage III, and 3 Stage IV patients. A total of 24 patients had high grade serous carcinoma, with 5 endometrioid, 3 clear cell, 2 mucinous, and one high grade NOS tumor. A total of 11 patients underwent interval debulking surgery after neoadjuvant chemotherapy. All but 2 (94.2%) of patients received a genetic counseling referral. A total of 2 patients did not have sequencing performed, while 1 patient did not have enough tumor for sequencing at the time of interval debulking surgery. A total of 10 patients had both tumor and germline sequencing performed at the time of tumor testing, while 20 others had tumor only sequencing. For those patients who did not have a known hereditary germline mutation prior to surgery, the mean turnaround time for germline genetic testing results was 26.5 days (range 19-51) in the NGS + germline group whereas the median turnaround time after commercial testing was 75 days (regardless of primary or interval debulking, range 19-202), p=0.006. A total of 5 patients were identified as germline carriers of the <i>BRCA1</i> or <i>BRCA2</i> mutation, with 1 addition germline finding of a pathogenic variant in ATM. An additional 5 patients had somatic pathogenic mutations in homologous recombination repair pathway genes, all of whom are receiving or being considered for PARP inhibitor maintenance after primary treatment. <h3>Conclusions:</h3> Combining somatic and germline tumor testing at the time of staging/debulking surgery requires upfront coordination with pathology and patient consent, but streamlines the genetic testing process to improve testing rates allow timely results for treatment planning. This approach may also identify additional patients with homologous recombination deficient tumors through simultaneous somatic mutation assessment.

Effectiveness of a Cloud-Based Telepathology System in China: Large-Sample Observational Study.

BackgroundWhole-slide imaging allows the entire slide to be viewed in a manner that simulates microscopy; therefore, it is widely used in telepathology. However, managing the large digital files needed for whole-slide imaging is difficult. To solve this problem, we set up the Chinese National Cloud-Based Telepathology System (CNCTPS). CNCTPS has been running for more than 4 years and has accumulated a large amount of data.ObjectiveThe main purpose of this study was to comprehensively evaluate the effectiveness of the CNCTPS based on a large sample. The evaluation indicators included service volume, turnaround time, diagnosis accuracy, and economic benefits.MethodsDetails of 23,167 cases submitted to the CNCTPS from January 2016 to December 2019 were collected to analyze the service volume, turnaround time, and economic benefits. A total of 564 patients who visited the First Affiliated Hospital of Zhengzhou University and obtained final diagnoses were followed up to analyze the diagnostic accuracy of the CNCTPS.ResultsFrom 2016 to 2019, the service volume of the CNCTPS increased from 2335 to 9240, and the number of participating hospitals increased from 60 to 74. Consultation requests from county-level hospitals accounted for 86.57% (20,287/23,167). A total of 17,495 of 23,167 cases (75.52%) were confirmed, including 12,088 benign lesions, 5217 malignant lesions, and 190 borderline lesions. Of the cases, 3.85% (893/23,167) failed to be diagnosed for reasons such as poor slice quality and incomplete sampling. The median turnaround time was 16.93 hours and was shortened yearly (between 2018 and 2019: adjusted P=.01; other groups: adjusted P<.001); 82.88% cases were diagnosed in 48 hours. There was a discrepancy between the diagnosis and final diagnosis for 11 cases, including 4 false-positive cases and 7 false-negative cases. The sensitivity and specificity were 97.66% and 98.49%, respectively. The diagnostic accuracy of the system was 98.05%, with no statistical difference from the final diagnosis in the hospital (P=.55). By using this system, a total of US $300,000 was saved for patients every year.ConclusionsThe novel cloud-based telepathology system has the potential to relieve the shortage of pathologists in primary hospitals. It can also simultaneously reduce medical costs for patients in China. It should, therefore, be further promoted to enhance the efficiency, quantity, and quality of telepathology diagnoses.

Abstract 565: A single institutional experience with droplet digital polymerase chain reaction (ddPCR) liquid biopsy for therapeutic decision in avanced solid tumors

Abstract Droplet digital polymerase chain reaction (ddPCR) is a promising method for analyzing minor amounts of cell-free circulating free nucleic acid (DNA and RNA) due to its high sensitivity, low cost, and fast reading, since it dispenses bioinformatics, making it an appropriate alternative to new generation sequencing (NGS) for the detection of biomarkers to guide molecularly targeted cancer therapy. The assay covers main actionable hotspot alterations across many actionable genes: EGFR(mutations), ALK (fusion, mutations), ROS1(fusion), BRAF(mutations), KRAS (mutations), NRAS(mutations), PIK3CA (mutations), ERBB2(CNV- copy number variation), ESR1(mutations), KIT(CNV) and PDGFRA(CNV). Therefore, our genes can be used in panels, both in therapeutically applied genotyping and in detecting molecular responses as well as in secondary resistance to tumors such as NSCLC, breast, cervix. rectal, GIST, melanoma and pancreas. METHODS: dd-PCR was performed using the QX200 system (BIO-RAD®, Hercules). The extraction of DNA and RNA was done using the magnetic beads technique of Thermofisher's MagMAX Kit. All samples were tested in duplicate. Up to now, 108 metastatic cancer patients were tested: NSCLC - 28 (26%), breast - 22 (20%), colorectal - 22(20%), melanoma - 18(17%), pancreas - 8(7%), ovarian - 6(6%), salivary glands - 2 (4%) and GIST 2(4%). RESULTS: Significant genomic alterations were detected in 38(35%) patients: 10 (9%) mutations in the KRAS G12V gene (all in colorectal cancer), 10 (9%) ERBB2 amplification (breast cancer), 4 (3.65%) EGFR L858R mutations (NSCLC), 4 (3.5%) EGFR del19 mutations (NSLC), 4 (3.5%) EGFR T790M mutations (NSCLC), 4 (3.5%) BRAF-V600E mutations (colon and melanoma), 2 (1.8%) ALK-EML4 fusion (NSCLC). The MAF (Mutant Allele Fraction) ranged from 0.9% to 24%. In all cases, the results were decisive for the indication or change of a targeted therapy. Median turnaround time was 36 hours and the average cost of the panels was around 500 USD (median of 4 genes per panel). CONCLUSION: Our results suggest that dd-PCR is a highly sensitive method and could be used for a routine laboratory detection of the important genomic variations to determine the targeted therapy in patients with varied advanced solid tumors. Citation Format: Andre Marcio Murad. A single institutional experience with droplet digital polymerase chain reaction (ddPCR) liquid biopsy for therapeutic decision in avanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 565.

Rapid identification of bacteria from respiratory samples of patients hospitalized in intensive care units, with FilmArray Pneumonia Panel Plus

ObjectivesThis study aimed to evaluate the performance of FilmArray Pneumonia Panel Plus (FA-PP) for the detection of typical bacterial pathogens in respiratory samples from patients hospitalized in intensive care units (ICUs). MethodsFA-PP was implemented for clinical use in the microbiology laboratory in March 2020. A retrospective analysis on a consecutive cohort of adult patients hospitalized in ICUs between March 2020 and May 2020 was undertaken. The respiratory samples included sputum, blind bronchoalveolar lavage (BBAL) and protected specimen brush (PSB). Conventional culture and FA-PP were performed in parallel. ResultsIn total, 147 samples from 92 patients were analysed; 88% had coronavirus disease 2019 (COVID-19). At least one pathogen was detected in 46% (68/147) of samples by FA-PP and 39% (57/147) of samples by culture. The overall percentage agreement between FA-PP and culture results was 98% (93–100%). Bacteria with semi-quantitative FA-PP results ≥105 copies/mL for PSB samples, ≥106 copies/mL for BBAL samples and ≥107 copies/mL for sputum samples reached clinically significant thresholds for growth in 90%, 100% and 91% of cultures, respectively. FA-PP detected resistance markers, including mecA/C, blaCTX-M and blaVIM. The median turnaround time was significantly shorter for FA-PP than for culture. ConclusionsFA-PP may constitute a faster approach to the diagnosis of bacterial pneumonia in patients hospitalized in ICUs.

A single institution experience with droplet digital polymerase chain reaction (dd-PCR) liquid biopsy (LB) for therapeutic decision in advanced solid tumors.

3038 Background: Droplet digital polymerase chain reaction (ddPCR) is a promising method for analyzing minor amounts of cell-free circulating free nucleic acid (DNA and RNA) due to its high sensitivity, low cost, and fast reading, since it dispenses bioinformatics, making it an appropriate alternative to new generation sequencing (NGS) for the detection of biomarkers to guide molecularly targeted cancer therapy. The assay covers main actionable hotspot alterations across many actionable genes: EGFR(mutations), ALK (fusion, mutations), ROS1(fusion), BRAF(mutations), KRAS (mutations), NRAS(mutations), PIK3CA (mutations), ERBB2(CNV- copy number variation), ESR1(mutations), KIT(CNV) and PDGFRA(CNV). Therefore, our genes can be used in panels, both in therapeutically applied genotyping and in detecting molecular responses as well as in secondary resistance to tumors such as NSCLC, breast, cervix. rectal, GIST, melanoma and pancreas. Methods: dd-PCR was performed using the QX200 system (BIO-RAD, Hercules). The extraction of DNA and RNA was done using the magnetic beads technique of Thermofisher's MagMAX Kit. All samples were tested in duplicate. Up to now, 108 metastatic cancer patients were tested: NSCLC - 28 (26%), breast - 22 (20%), colorectal - 22(20%), melanoma - 18(17%), pancreas - 8(7%), ovarian - 6(6%), salivary glands - 2 (4%) and GIST 2(4%). Results: Significant genomic alterations were detected in 38(35%) patients: 10 (9%) mutations in the KRAS G12V gene (all in colorectal cancer), 10 (9%) ERBB2 amplification (breast cancer), 4 (3.65%) EGFR L858R mutations (NSCLC), 4 (3.5%) EGFR del19 mutations (NSLC), 4 (3.5%) EGFR T790M mutations (NSCLC), 4 (3.5%) BRAF-V600E mutations (colon and melanoma), 2 (1.8%) ALK-EML4 fusion (NSCLC). The MAF (Mutant Allele Fraction) ranged from 0.9% to 24%. In all cases, the results were decisive for the indication or change of a targeted therapy. Median turnaround time was 36 hours and the average cost of the panels was around 500 USD (median of 4 genes per panel). Conclusions: Our results suggest that dd-PCR is a highly sensitive method and could be used for a routine laboratory detection of the important genomic variations to determine the targeted therapy in patients with varied advanced solid tumors.

Blood-based tumor mutational burden from circulating tumor DNA (ctDNA) across advanced solid malignancies using a commercially available liquid biopsy assay.

3040 Background: Pembrolizumab was recently FDA approved across solid tumors for TMB scores ≥ 10mut/Mb as assessed by next-generation sequencing (NGS) of tissue (tTMB). A prior study of advanced cancer patients treated with immunotherapy found that higher somatic TMB, as defined by the 80th percentile in each histology, was associated with better overall survival. Previously, bTMB assessed by ctDNA from patients with newly diagnosed advanced NSCLC at a score of 16 mut/MB correlated with a tTMB score of 10 mut/MB. TMB levels vary by cancer type, line of treatment, and therapy received; the distribution of bTMB scores across solid tumor types has not been well characterized. Here we report the distribution of bTMB scores in patients with advanced malignancies. Methods: We queried 5,610 samples from patients with different cancer types undergoing clinical cell-free DNA testing (Guardant360; Redwood City, CA) and assessed bTMB scores from October 2020 - January 2021. bTMB score was derived via a previously described computational algorithm examining the total number of synonymous and non-synonymous SNVs and indels across a 1.0MB genomic footprint. We assessed the success rate of bTMB evaluation, overlap with microsatellite instability (MSI) status, and defined the distribution of bTMB levels across indications in this dataset. Results: bTMB score was successfully assessed in 4,275/5,610 (76.3%) samples (Table). The majority of samples (58%) were tested at disease progression as compared to initial diagnosis (42%). The median turnaround time from sample receipt to clinical reporting was 11 days and decreased to 9 days over the course of the study. For the majority of cancer types the 80th percentile TMB was ≥ 16 mut/MB tissue equivalency. Conclusions: Our analysis demonstrates the feasibility of measuring bTMB using a commercially available liquid biopsy assay. bTMB scores trended higher than tTMB previously reported in these cancer types, reflecting the ability of ctDNA to better capture tumor heterogeneity. cfDNA may allow for exploration of bTMB evolution throughout treatment. TMB should be interpreted in the context of disease, treatment, and method; these data establish a pan-cancer benchmark for bTMB which will serve as a resource for further studies.[Table: see text]

A cancer organogram test as a guide for oncology treatments in SOLID tumors: An analysis of 628 tests in 419 patients.

2602 Background: A CLIA-certified organoid based drug sensitivity assay (a cancer organogram) has been developed for all solid tumors. An actionable report of organogram sensitivities to endocrine, chemotherapy and targeted agents, produced a drug sensitivity score as a tool to inform therapy decision making. Objectives: To evaluate the success rate of organoid derivation, the organogram drug responses across cancer types and to analyze the impact of the organogram report on therapeutic decision making. Methods: From 2016 to 2020, 628 cancer organograms were performed, with 513 tumor samples from 419 cancer patients. Within 48 hours of collection, fresh samples of tumor cells obtained from core biopsies, surgical excisions, or fluids were cultured, the majority as 3D organoids. Drug screens were performed with a library of up to 220 drugs, and dose-response was evaluated across a range of concentrations for each drug. Organogram sensitivity was ranked as response in five categories based on SPM Score: Exceptional (SPM15/14), Good (13/12), Moderate to Low (11/9), and None( &lt; 9). 118 drugs on average were tested per screen (range: 68-152), so in a total of 628 organograms, more than 70,000 individual drug trials have been performed. The median turnaround time was 28 days (range: 19.5-51.5). Results: Of the 513 collected samples, 314 were fresh specimens: 96 core biopsies, 151 surgical specimens, and 67 fluids (pleural effusions or ascites), with an organoid derivation success rate of 58.3%, 78%, and 88%, respectively. Overall success rate in organoid derivation was 70.2%. Samples with poor viability and low tumor cell count (22%) were rejected. The primary cancer types tested were ovarian (n = 92, 17.9%), breast (n = 73, 14.2%), colorectal (n = 70, 13.6%), pancreatic (n = 51, 9.9%), cholangiocarcinoma (n = 42, 8.1%), and other solid tumors (n = 185, 36%). Median age of patients was 56 years old (range: 5-83), most of them heavily pretreated. 20.45% of drugs screened had exceptional and good responses (SPM score 15-12) (SD: 17.92%). We reviewed genomic data from 374 third-party genomic reports. The most frequent genomic alterations found were TP53 (n = 143, 38.2%), BRCA1 and BRCA2 (n = 47, 12.5%) CDKN2A (n = 42, 11.2%), FGFR1/2/3/4 (n = 41, 10.9%), and PIK3CA (n = 38, 10.1%). Post-test treatment information is available for a subset of 61 patients. The treating physician made an organogram-guided therapeutic decision in 32/44 patients with post test treatment drugs scored (72%). Conclusions: The cancer organogram test has a high rate of success in generating an actionable report that identifies therapies for patients with limited therapeutic options, including those with no known genomic biomarkers. The organogram guided selection of therapeutics for a significant subset of patients, nearly 4 times the rate reported with genomic testing alone.

BRAF testing timelines and impact on the starting of systemic treatment.

e21575 Background: Targeted therapy with BRAF and MEK inhibitors constitute part of the standard treatment for BRAF V600 mutated melanoma. Timely detection of BRAF mutation is necessary for clinicians and patients to make treatment decisions. We aimed to map the BRAF testing timelines from the time of request until the reported result in order to assess obstacles to timely BRAF reporting in our community, and its impact on the initiation of systemic therapy. Methods: In this single-center retrospective study, we included adult patients referred to the Medical Oncology Department at the Princess Margaret Cancer Centre (PM) from January 2019 to August 2019 with histologically confirmed cutaneous or mucosal melanoma and BRAF molecular testing performed in 2019. The Log-Rank method was applied to detect differences in BRAF turnaround time and time to treatment initiation in specified subgroups. A p value &lt; 0.05 was considered statistically significant. Results: Sixty-six cases were identified. The median age was 64 (24-88), and 42 (64%) were male. At the time of BRAF request, 10 (15%) patients had stage II, 33 (50%) had stage III, and 23 (35%) had stage IV disease. Twenty-eight (43%) were positive for the BRAF V600E/K mutation by ARMS assay and 4 (6%) for other variants by NGS test. Thirty-three (50%) patients had the BRAF test available at their first PM Medical Oncology visit. Median time between BRAF request and result was 17 days; when a reflex BRAF test was ordered by the Pathology Department, the median turnaround time was 12 days (95% CI 8-15), compared to 20 days (95% CI 16-23) if the order was requested by another specialist ( p &lt; 0.001). Median time to transfer samples between institutions was 6 days. If the BRAF test was processed within the institution where the biopsy was performed, the BRAF median turnaround time was 13 days (95% CI 6-19) compared to 19 days (95% CI 16-21) if a sample was transferred to another institution ( p = 0.02). In total, 49 patients had systemic therapy. Median time between the first visit with Medical Oncology and treatment initiation was 29 days and was not statistically different if the BRAF result was available or not (28 vs. 34 days; p = 0.09). In the subgroup with stage IV disease (Table), 20 patients received systemic therapy; the median time to treatment initiation was 24 days and differed with BRAF result availability (20 vs. 31 days, p = 0.03). Conclusions: The current BRAF testing timeline at the PM varies from days to weeks. A major factor impacting this timeline is transfer time, which can be streamlined by pathology reflex testing. Delays in turnaround time appears to impact subsequent timing and type of therapeutic interventions, especially in patients with stage IV disease.[Table: see text]

Biomarker tissue journey among patients (pts) with untreated metastatic non-small cell lung cancer (mNSCLC) in the U.S. Oncology Network community practices.

9004 Background: Given the importance of molecular testing and targeted therapy for mNSCLC, the MYLUNG (Molecularly Informed Lung Cancer Treatment in a Community Cancer Network) consortium pragmatic study assessed real-world biomarker testing rates and turnaround times (TAT) within The US Oncology Network of over 1,000 providers across the United States. Methods: This was a retrospective observational chart review study of pts with mNSCLC initiating first-line (1L) systemic therapy between 04/01/2018 and 03/31/2020. iKnowMed electronic health records were used to examine timing of biomarker testing: before 1L therapy (cohort 1), after 1L therapy (cohort 2) or no testing (cohort 3). We assessed testing rates for ALK, BRAF, EGFR, ROS1, and PD-L1; use of full next-generation sequencing panel (NGS); time from mNSCLC diagnosis (dx) to 1L therapy; TAT from biomarker orders to results; and time from mNSCLC dx to test results. Results: We identified 3474 adults. Median age was 69 years (range 23-90), 51% female, 74% with adenocarcinoma and 76% with a documented ECOG performance status of 0 or 1. Testing rates are shown in table: 90% of pts had at least one biomarker test and 46% received all 5 biomarker tests. Changes in testing rates from 2018 to 2020 were 51% to 59% for BRAF, 71% to 71% for EGFR, 71% to 70% for ALK, 69% to 67% for ROS1, 82% to 84% for PD-L1, and 42% to 49% for pts tested for all 5 biomarkers. NGS testing increased from 33% to 44% (p&lt;0.0001). The median (interquartile range [IQR]) time from mNSCLC dx to 1L therapy for all pts was 35 (22, 55) days. Median (IQR) TAT from biomarker testing orders to results ranged from 10 (6, 17) to 15 (10, 22) days for the individual biomarkers; and time from mNSCLC dx to biomarker results ranged from 14 (7, 26) to 21 (12, 36) days by biomarker. Conclusions: This real-world study showed that most pts received at least one biomarker test prior to 1L, but &lt;50% received all 5 tests. NGS testing occurred in &lt;50% of pts but increased over the periods examined. Median time from dx to 1L therapy was about 5 weeks and TAT from orders to results about 2 weeks. Analyses by histology and other trends will be reported. These data will be compared to the next phase of the MYLUNG study, which will evaluate contemporary ordering practices and TATs prospectively[Table: see text]

Impact of rapid multigene assays with short turnaround time (TAT) on the development of precision medicine for non-small cell lung cancer (NSCLC).

9094 Background: A variety of oncogene drivers have been identified in NSCLC and molecularly-stratified precision medicine has led to improved survival in advanced NSCLC. Next-generation sequencing (NGS)-based testing is utilized to detect actionable gene alterations; however, the TAT of NGS is often too long to translate into clinical decision making. Thus, rapid multi-gene testing alternatives are needed. Methods: A lung cancer genomic screening project (LC-SCRUM-Asia) capturing clinical outcome was established in 2013 to identify patients with oncogene drivers and to support the development of novel targeted therapies. Since February 2013 to May 2019 (LC-SCRUM-Asia 1st-phase), single gene testing and/or a targeted NGS assay, Oncomine Comprehensive Assay (OCA), were used for the genomic screening. Since June 2019 to December 2020 (2nd-phase), a multi-gene PCR assay (Amoy 9-in-1 test) and a rapid NGS assay (Genexus/Oncomine Precision Assay [OPA]) were also implemented as rapid multi-gene testing. Results: A total of 10667 Japanese NSCLC patients, including 6826 in the 1st-phase and 3841 in the 2nd-phase, were enrolled in the LC-SCRUM-Asia. Success rate for OCA: 93%, for 9-in-1 test: 98%, for Genexus/OPA: 96%. Median TAT for OCA: 21 days, for 9-in-1 test: 3 days, for Genexus/OPA: 4 days. The frequencies of genetic alterations detected in the 1st-/2nd-phase were EGFR: 17/24%, KRAS: 15/16%, HER2 ex20ins: 4/3%, ALK fusions: 3/3%, RET fusions: 3/2%, ROS1 fusions: 3/2%, MET ex14skip: 2/2%, BRAF V600E: 1/1%, NRG1 fusions: 0/0.2% and NTRK3 fusions: 0.05/0.04%. Overall percent agreement of 9-in-1 test compared with OCA for EGFR/KRAS/HER2/BRAF/MET/ALK/ROS1/RET/NTRK3 alterations was 98%, and that of OPA compared with OCA was 95%. The rate of patients who received targeted therapies as 1st-line treatment was significantly elevated in the 2nd-phase compared with the 1st-phase (510/3841 [13%] vs. 567/6826 [8%], p &lt; 0.001). Through the genomic screening, 1410 (37%) and 1269 (18%) candidate patients for clinical trials of KRAS, HER2, BRAF, MET, ALK, ROS1, RET or TRK-targeted drugs were identified in the 2nd-phase and in the 1st-phase, respectively. The rate of patients who were actually enrolled into the genotype-matched clinical trials were also significantly higher in the 2nd-phase than in the 1st-phase (222 [6%] vs. 186 [3%], p &lt; 0.001). In 1st-line treatments for advanced NSCLC patients, the median progression-free survival was 8.5 months (95% CI, 7.7−9.4) in the 2nd-phase (n = 1839) versus 6.1 months (95% CI, 5.9−6.3) in the 1st-phase (n = 4262) (p &lt; 0.001). Conclusions: Both the 9-in-1 test and Genexus/OPA had short TATs (3−4 days), high success rates (96−98%) and good concordance (95−98%) compared with another NGS assay (OCA). These rapid multi-gene assays highly contributed to enabling precision medicine and the development of targeted therapies for advanced NSCLC.

Impact of different SARS-CoV-2 assays on laboratory turnaround time.

IntroductionClinical microbiology laboratories have had to cope with an increase in the volume of tests due to the emergence of the SARS-CoV-2 virus. Short turnaround times (TATs) are important for case tracing and to help clinicians in patient management. In such a context, high-throughput systems are essential to process the bulk of the tests. Rapid tests are also required to ensure shorter TATs for urgent situations. In our laboratory, SARS-CoV-2 assays were initially implemented on our custom platform using a previously published method. The commercial cobas 6800 (Roche diagnostics) assay and the GeneXpert Xpress (Cepheid) SARS-CoV-2 assay were implemented on 24 March and 8 April 2020, respectively, as soon as available.Hypothesis/Gap StatementDespite the abundant literature on SARS-CoV-2 assays, the articles focus mainly on the diagnostic performances. This is to our knowledge the first article that specifically studies the TAT of different assays.AimWe aimed to describe the impact of various SARS-CoV-2 assays on the TAT at the beginning of the outbreak.MethodologyIn this study, we retrospectively analysed the TAT of all SARS-CoV-2 assays performed in our centre between 24 February and 9 June, 2020.ResultsWe retrieved 33 900 analyses, with a median TAT of 6.25 h. TATs were highest (6.9 h) when only our custom platform was used (24 February to 24 March, 2020). They were reduced to 6.1 h when the cobas system was introduced (24 March to 8 April, 2020). The implementation of the GeneXpert further reduced the median TAT to 4.8 h (8 April to 9 June, 2020). The GeneXpert system had the shortest median TAT (1.9 h), followed by the cobas (5.5 h) and by our custom platform (6.9 h).ConclusionThis work shows that the combination of high-throughput systems and rapid tests allows the efficient processing of a large number of tests with a short TAT. In addition, the use of a custom platform allowed the quick implementation of an in-house test when commercial assays were not yet available.

Evaluation of the Barricor Tube in 28 Routine Chemical Tests and Its Impact on Turnaround Time in an Outpatient Clinic.

BackgroundWe recently introduced the Barricor (BD, Franklin Lakes, NJ, USA) plasma separation tube, which uses a mechanical separator instead of a gel. We evaluated the effects of using the Barricor tube in a stat (statin) laboratory on the results and turnaround time (TAT) of routine chemical tests. We verified the impact of Barricor tube on reducing TAT and providing results similar to those obtained using serum separator tubes (SSTs).MethodsWe collected venous blood samples from 166 outpatients in Barricor tubes and SSTs and measured 28 routine analytes using an AU5800 instrument (Beckman Coulter, Brea, CA, USA). TAT indexes were compared before and after using Barricor tube.ResultsMean percent differences were <5%, except for alanine aminotransferase , total CO2, high-density lipoprotein, phosphate, total protein, and direct bilirubin. The median TAT decreased from 45 to 38 minutes, and the rate of a TAT >60 minutes decreased from 7.84% to 2.66%, which was approximately one-third of that for SST. The reduction in TAT was attributable to a decrease in centrifugation time. Incomplete clotting and repeated centrifugation, which occurred frequently when using SST, also decreased after using the Barricor tubes.ConclusionsThe Barricor tube is an alternative to SST for routine chemical tests in institutions aiming to reduce TAT, with clinically allowable differences in test results.

In-depth investigation of turn-around time of full blood count tests requested from a clinical haematology outpatient department in Cape Town, South Africa.

BackgroundThe performance of laboratories can be objectively assessed using the overall turn-around time (TAT). However, TAT is defined differently by the laboratory and clinicians; therefore, it is important to determine the contribution of all the different components making up the laboratory test cycle.ObjectiveWe carried out a retrospective analysis of the TAT of full blood count tests requested from the haematology outpatient department at Tygerberg Academic Hospital in Cape Town, South Africa, with an aim to assess laboratory performance and to identify critical steps influencing TAT.MethodsA retrospective audit was carried out, focused on the full blood count tests from the haematology outpatient department within a period of 3 months between 01 February and 30 April 2018. Data was extracted from the National Health Laboratory Service laboratory information system. The time intervals of all the phases of the test cycle were determined and total TAT and within-laboratory (intra-lab) TAT were calculated.ResultsA total of 1176 tests were analysed. The total TAT median was 275 (interquartile range [IQR] 200.0–1537.7) min with the most prolonged phase being from authorisation to review by clinicians (median 114 min; IQR: 37.0–1338.5 min). The median intra-lab TAT was 55 (IQR 40–81) min and 90% of the samples were processed in the laboratory within 134 min of registration.ConclusionOur findings showed that the intra-lab TAT was within the set internal benchmark of 3 h. Operational phases that were independent of the laboratory processes contributed the most to total TAT.

Metastatic NSCLCs With Limited Tissues: How to Effectively Identify Driver Alterations to Guide Targeted Therapy in Chinese Patients

IntroductionMolecular diagnostics of newly diagnosed patients with metastatic NSCLC (mNSCLC) with limited tissue samples often face several obstacles in routine practice using next-generation sequencing (NGS), mainly owing to insufficient tissue or DNA; thus, how to effectively identify the molecular profiling of these cases to accurately guide targeted therapy remains elusive. We evaluated whether an optimized workflow with the combined use of multiple technologies could be helpful. MethodsTissue NGS was used as the frontline method. Amplification refractory mutation system polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, and plasma NGS were used as supplements. ResultsAmong 208 mNSCLC cases with limited tissue (cohort 1), molecular genotyping using single-tissue NGS failed in 42 (20.2%) and actionable alterations were identified in only 112 of 208 cases (53.8%). In comparison, the optimized workflow in 1184 additional mNSCLC cases with limited tissue (cohort 2) increased the discovery rate of actionable alterations from 59.7% detected by tissue NGS to 70.4%. It was because that driver alterations were identified using amplification refractory mutation system polymerase chain reaction plus immunohistochemistry or fluorescence in situ hybridization in 53 of 78 (67.9%) tissue NGS-failed cases, and using plasma NGS in 73 of 143 (51.0%) tissue NGS-failed cases, which led to matched targeted therapies in 57 cases with clinical response. Moreover, the median turnaround time of the optimized workflow was significantly shorter than that of repeated biopsy for tissue NGS (p < 0.001). ConclusionsThe optimized workflow can improve mutation detection and may avoid repeated biopsy, thus allowing the timely initiation of targeted therapies for patients with newly diagnosed mNSCLC.

Samba II PCR testing for COVID-19 in pregnant women: a retrospective cohort study and literature review

BackgroundAsymptomatic carriage of COVID-19 in pregnant women has been reported and could lead to outbreaks in maternity units. We sought to ascertain the impact of rapid isothernal nucleic acid based testing for COVID-19 in an unselected cohort of pregnant women attending our maternity unit. We also assessed the correlation between community prevalence and asymptomatic carriage.MethodsData for the retrospective cohort study were collected from a large UK tertiary maternity unit over a 4-week period using computerised hospital records. Literature searches were performed across multiple repositories. COVID-19 prevalence was extracted from online repositories.ResultsNasopharyngeal and oropharyngeal swabs were obtained from 457/465 (98%) women during the study period. The median turnaround time for results was 5.3 h (interquartile range (IQR) 2.6–8.9 h), with 92% of the results returned within 24 h. In our cohort, only one woman tested positive, giving a screen positive rate of 0.22% (1/457; 95% CI: 0.04–1.23%). One woman who tested negative developed a fever postnatally following discharge but was lost to follow-up. From our literature review, we did not find any correlation between asymptomatic carriage in pregnant women and the reported regional prevalence of COVID-19.ConclusionsTesting using the SAMBA-II machine was acceptable to the vast majority of pregnant women requiring admission and had a low turnaround time. Asymptomatic carriage is low, but not correlated to community prevalence rates. Screening pregnant women on admission will remain an important component in order to minimise nosocomial infection.

Am I Ready to Be an Independent Neuroradiologist? Objective Trends in Neuroradiology Fellows' Performance during the Fellowship Year.

Aside from basic Accreditation Council for Graduate Medical Education guidelines, few metrics are in place to monitor fellows' progress. The purpose of this study was to determine objective trends in neuroradiology fellowship training on-call performance during an academic year. We retrospectively reviewed the number of cross-sectional neuroimaging studies dictated with complete reports by neuroradiology fellows during independent call. Monthly trends in total call cases, report turnaround times, relationships between volume and report turnaround times, and words addended to preliminary reports by attending neuroradiologists were evaluated with regression models. Monthly variation in frequencies of call-discrepancy macros were assessed via χ2 tests. Changes in frequencies of specific macro use between fellowship semesters were assessed via serial 2-sample tests of proportions. From 2012 to 2017, for 29 fellows, monthly median report turnaround times significantly decreased during the academic year: July (first month) = 79 minutes (95% CI, 71-86 minutes) and June (12th month) = 55 minutes (95% CI, 52-60 minutes; P value = .023). Monthly report turnaround times were inversely correlated with total volumes for CT (r = -0.70, F = 9.639, P value = .011) but not MR imaging. Words addended to preliminary reports, a surrogate measurement of report clarity, slightly improved and discrepancy rates decreased during the last 6 months of fellowship. A nadir for report turnaround times, discrepancy errors, and words addended to reports was seen in December and January. Progress through fellowship correlates with a decline in report turnaround times and discrepancy rates for cross-sectional neuroimaging call studies and slight improvement in indirect quantitative measurement of report clarity. These metrics can be tracked throughout the academic year, and the midyear would be a logical time point for programs to assess objective progress of fellows and address any deficiencies.

Embedding an Advanced Pharmacy Technician in an Adult Specialty Pulmonary Clinic to Complete Prior Authorizations Improves Efficiency and Provider Satisfaction

Purpose: The purpose of this study is to assess the impact of a clinic embedded Medication Assistance Program (MAP) specialist on the prescription benefit prior authorization (PA) process and provider satisfaction in an adult pulmonary clinic. Methods: In this mixed methods study, a retrospective cohort analysis was done to determine the turnaround time for the PA process from initial referral to approval or final denial in an adult pulmonary clinic. Additionally, a pre- and post-implementation survey to providers was conducted to assess provider satisfaction and perceptions around the prescription benefit PA process. The first study aim assessed PA efficiency by summarizing PA approval rate and PA turnaround time using descriptive statistics. Any prescriptions written by a clinic provider requiring a PA during the timeframe of June 2018 through August 2018 were included. The second study aim assessed change in provider satisfaction, analyzed via the Mann-Whitney U test. Results: The MAP specialist completed 110 PAs over 3 months for 110 unique patients. Median turnaround time was 3 hours, with 76% of PAs approved in less than 24 hours. Initial approval rate was 82.7%, and overall approval rate following the appeals process was 87.3%. A significant difference between the pre- and post-survey responses were identified in 2 of the 17 questions. Conclusion: Implementation of a clinic embedded MAP specialist to complete PAs demonstrated an efficient process while also improving provider satisfaction.

Reasons for delay in timely administration of adjuvant chemotherapy for patients with stage III colon cancer: a multicentre cohort study from the McGill University Department of Oncology

PurposeAdjuvant chemotherapy within 56 or 84 days following curative resection is globally accepted as the standard of care for stage III colon cancer as it has been associated with improved...

Status of the Journal of Wildlife Management, 2020; the Times They are A‐Changing

Status of the <i>Journal of Wildlife Management</i>, 2020; the Times They are A‐Changing