Median Turnaround Time Research Articles

Point-of-Care Brain MRI: Preliminary Results from a Single-Center Retrospective Study.

Background Point-of-care (POC) MRI is a bedside imaging technology with fewer than five units in clinical use in the United States and a paucity of scientific studies on clinical applications. Purpose To evaluate the clinical and operational impacts of deploying POC MRI in emergency department (ED) and intensive care unit (ICU) patient settings for bedside neuroimaging, including the turnaround time. Materials and Methods In this preliminary retrospective study, all patients in the ED and ICU at a single academic medical center who underwent noncontrast brain MRI from January 2021 to June 2021 were investigated to determine the number of patients who underwent bedside POC MRI. Turnaround time, examination limitations, relevant findings, and potential CT and fixed MRI findings were recorded for patients who underwent POC MRI. Descriptive statistics were used to describe clinical variables. The Mann-Whitney U test was used to compare the turnaround time between POC MRI and fixed MRI examinations. Results Of 638 noncontrast brain MRI examinations, 36 POC MRI examinations were performed in 35 patients (median age, 66 years [IQR, 57-77 years]; 21 women), with one patient undergoing two POC MRI examinations. Of the 36 POC MRI examinations, 13 (36%) occurred in the ED and 23 (64%) in the ICU. There were 12 of 36 (33%) POC MRI examinations interpreted as negative, 14 of 36 (39%) with clinically significant imaging findings, and 10 of 36 (28%) deemed nondiagnostic for reasons such as patient motion. Of 23 diagnostic POC MRI examinations with comparison CT available, three (13%) demonstrated acute infarctions not apparent on CT scans. Of seven diagnostic POC MRI examinations with subsequent fixed MRI examinations, two (29%) demonstrated missed versus interval subcentimeter infarctions, while the remaining demonstrated no change. The median turnaround time of POC MRI was 3.4 hours in the ED and 5.3 hours in the ICU. Conclusion Point-of-care (POC) MRI was performed rapidly in the emergency department and intensive care unit. A few POC MRI examinations demonstrated acute infarctions not apparent at standard-of-care CT examinations. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Anzai and Moy in this issue.

Emergency triage of brain computed tomography via anomaly detection with a deep generative model

Triage is essential for the early diagnosis and reporting of neurologic emergencies. Herein, we report the development of an anomaly detection algorithm (ADA) with a deep generative model trained on brain computed tomography (CT) images of healthy individuals that reprioritizes radiology worklists and provides lesion attention maps for brain CT images with critical findings. In the internal and external validation datasets, the ADA achieved area under the curve values (95% confidence interval) of 0.85 (0.81–0.89) and 0.87 (0.85–0.89), respectively, for detecting emergency cases. In a clinical simulation test of an emergency cohort, the median wait time was significantly shorter post-ADA triage than pre-ADA triage by 294 s (422.5 s [interquartile range, IQR 299] to 70.5 s [IQR 168]), and the median radiology report turnaround time was significantly faster post-ADA triage than pre-ADA triage by 297.5 s (445.0 s [IQR 298] to 88.5 s [IQR 179]) (all p < 0.001).

Clinical Performance Characteristics of the Swift Normalase Amplicon Panel for Sensitive Recovery of Severe Acute Respiratory Syndrome Coronavirus 2 Genomes

Amplicon-based sequencing methods are central in characterizing the diversity, transmission, and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but need to be rigorously assessed for clinical utility. Herein, we validated the Swift Biosciences' SARS-CoV-2 Swift Normalase Amplicon Panels using remnant clinical specimens. High-quality genomes meeting our established library and sequence quality criteria were recovered from positive specimens, with 95% limit of detection of 40.08 SARS-CoV-2 copies/PCR. Breadth of genome recovery was evaluated across a range of CT values (11.3 to 36.7; median, 21.6). Of 428 positive samples, 413 (96.5%) generated genomes with <10% unknown bases, with a mean genome coverage of 13,545× ± SD 8382×. No genomes were recovered from PCR-negative specimens (n = 30) or from specimens positive for non–SARS-CoV-2 respiratory viruses (n = 20). Compared with whole-genome shotgun metagenomic sequencing (n = 14) or Sanger sequencing for the spike gene (n = 11), pairwise identity between consensus sequences was 100% in all cases, with highly concordant allele frequencies (R2 = 0.99) between Swift and shotgun libraries. When samples from different clades were mixed at varying ratios, expected variants were detected even in 1:99 mixtures. When deployed as a clinical test, 268 tests were performed in the first 23 weeks, with a median turnaround time of 11 days, ordered primarily for outbreak investigations and infection control.

Application value of metagenomic next-generation sequencing for pathogen detection in childhood agranulocytosis with fever

To study the application value of metagenomic next-generation sequencing (mNGS) for pathogen detection in childhood agranulocytosis with fever. A retrospective analysis was performed on the mNGS results of pathogen detection of 116 children with agranulocytosis with fever who were treated from January 2020 to December 2021. Among these children, 38 children with negative mNGS results were enrolled as the negative group, and 78 children with positive results were divided into a bacteria group (n=22), a fungal group (n=23), and a viral group (n=31). Clinical data were compared between groups. For the 116 children with agranulocytosis and fever, the median age was 8 years at diagnosis, the median turnaround time of mNGS results was 2 days, and the positive rate of mNGS testing was 67.2% (78/116). Compared with the negative group, the bacterial group had a higher procalcitonin level (P<0.05), the fungal group had higher level of C-reactive protein and positive rate of (1,3)-β-D glucan test/galactomannan test (P<0.05), and the fungal group had a longer duration of fever (P<0.05). Among the 22 positive microbial culture specimens, 9 (41%) were consistent with the mNGS results. Among the 17 positive blood culture specimens, 8 (47%) were consistent with the mNGS results. Treatment was adjusted for 28 children (36%) with the mNGS results, among whom 26 were cured and discharged. The mNGS technique has a shorter turnaround time and a higher sensitivity for pathogen detection and can provide evidence for the pathogenic diagnosis of children with agranulocytosis and fever.

Rapid exome sequencing in critically ill children impacts acute and long-term management of patients and their families: A retrospective regional evaluation

IntroductionGenetic disorders are a significant cause of paediatric morbidity and mortality. Rapid exome sequencing was introduced by the National Health Service (NHS) in England on 1st October 2019 for acutely unwell children with a likely monogenic disorder, or to inform current pregnancy management where there was a previously affected child or fetus. We present results of a 12-month patient cohort from one large clinical genetics centre in England. MethodsPatients were identified through local genetics laboratory records. We included all cases which underwent rapid exome sequencing between 1st October 2020 and 30th September 2021. DNA was extracted, quality checked and exported to the Exeter Genomic laboratory where library preparation, exome sequencing of all known human genes, gene-agnostic bioinformatic analysis, variant interpretation, MDT discussions and reporting were performed. ResultsNinety-five probands were included. Trio analysis was performed in 90% (85), duo in 8% (8), singleton in 2% (2). The median turnaround time for preliminary reports was 11 days. The overall diagnostic yield was 40% (38 patients); 36% (34 patients) made solely on exome with a further 4% on concomitant exome and microarray analysis. Highest diagnostic rates were seen in patients with neuro-regression, skeletal dysplasia, neuromuscular and neurometabolic conditions.Where the diagnosis was made solely through exome sequencing, management was altered for the proband or family in 97% (33/34). For the proband, this was most commonly that the diagnosis was able to inform current management and prognosis (20 patients, 59%), as well as direct specialist referrals (10 patients, 29%). For families, the exome sequencing results provided accurate recurrence risk counselling in 88% (30/34) with cascade testing offered if indicated in some families. ConclusionsIn the majority of cases, the genetic diagnoses influenced acute and long-term management for critically ill children and their families. Paediatric and neonatal clinicians in the NHS now have direct access to exome sequencing for their patients. The rapid turnaround time was particularly helpful to alter the management in acute clinical settings and is a powerful tool for diagnosing monogenic conditions. This study is an example of a highly successful integration of a national rapid exome sequencing service with diagnostic rates comparable to previously reported literature.

Resting 12‑lead ECG tests performed by patients at home amid the COVID-19 pandemic — Results from the first 1000 patients

BackgroundThere were surges in the demand for telehealth and home care in the COVID-19 pandemic. A new home ECG testing model was developed and used in the real-world clinical practice. MethodsSince June 2020, QT Medical, Inc. (Diamond Bard, California) has been providing home ECG testing service by mail. Upon receiving the order from a clinician, an ECG testing kit was sent to the patient by mail. The kit included an ECG recorder, a prepositioned electrode strip of proper size for the patient (determined by the ordering clinician), printed instructions for performing the test, and a return envelope. We reviewed and analyzed the de-identified administrative dataset of the first 1000 ECG tests ordered by 37 medical practices. ResultsOf the 1000 patients served by this mail delivery home ECG testing service, 77.3% were female and 22.7% were male. Their ages ranged from 1 year old to 96 years old, mean 49.5 ± 13.4 years (median 52). 92.9% patients completed their tests with clinical quality ECGs uploaded to their ordering clinician's online accounts. Of those who did not complete the tests, the main reason was they “no longer needed the test”. Failure to complete the test due to technical issues was 1.4%. Only one patient had to repeat the test due to inadequate ECG quality as judged by the ordering physician. The median turnaround time, from the kit being mailed out to the recorder being returned, was 10 days. Overall, 2.2% of the ECG devices were lost in shipping or unreturned by patients. ConclusionOf the first 1000 patients who had their ECG tests at homes, it was found that this home ECG testing platform and care model could be reliably used by patients with no training to acquire clinical grade ECG. The current study proved that medical standard, resting 12‑lead ECG can be performed by the majority of patients at home.

First experience of implementing Candida auris real-time PCR for surveillance in the UK: detection of multiple introductions with two international clades and improved patient outcomes

Candida auris has been associated with rapid transmission and high mortality. A novel PCR-based surveillance programme was initiated at a London teaching hospital from January 2018. The results of this implementation until March 2019 are presented along with the clinical, transmission and phylogenetic characteristics encountered in that setting. A real-time PCR assay for C.auris was developed, validated, and implemented for direct use on skin swabs and urine. Environmental swabs were also tested by PCR as an emergency outbreak-control measure. Clinical risk factors and outcomes of patients were determined. Environmental dispersal was assessed using 24h settle plate cultures around nine colonized patients followed by air sampling around one colonized patient during high- and low-turbulence activities. Sequencing was performed using Illumina HiSeq and maximum likelihood phylogenies were constructed using rapid bootstrap analysis. Twenty-one C.auris colonized patients were identified. Median turnaround time of colonization detection reduced from 141h (5.8 days) to approximately 24h enabling rapid infection-control precautions. Settle plates detected 70-600cfu/m2 around colonized patients over 24h and air sampling suggested dispersal during turbulent activities. C.auris DNA was detected from 35.7% environmental swabs. Despite being in a high-risk setting, no patients developed invasive infection. Sequencing analysis of isolates from this centre identified two introductions of the South Asian (Clade I) and one of the South African (Clade III) strain. The PCR offers a rapid, scalable method of screening and supports clinical risk reduction in settings likely to encounter multiple introductions.

Impact of Xpert MTB/RIF on Outcomes of Adults Hospitalized With Spinal Tuberculosis: Findings From a Comparative Cohort in Beijing, China.

BackgroundSpinal tuberculosis (TB) is one of the most common forms of extrapulmonary tuberculosis, causing increased morbidity and lifelong disabilities. Here, we conducted a retrospective study to determine the impact on patient outcomes of the Xpert MTB/RIF test vs. phenotypical drug susceptibility testing for spinal TB.MethodsIn-patients with spinal TB were enrolled in 2013 and 2017 at Beijing Chest Hospital. Data were collected from an electronic patient record system that documented demographic and clinical characteristics. All the patients were routinely followed-up at 1, 3, 6, 9, and 12 months after surgery during outpatient treatment.ResultsA total of 361 patients affected by spinal TB were enrolled in our analysis, including 178 patients in 2013 and 183 patients in 2017. In 2013, the cumulative postoperative recurrence rate of patients with spinal TB was 23% (41/178), which was significantly higher than that in 2017 (8.2%, 15/183, P < 0.001). Additionally, the patients with spinal TB diagnosed in 2013 relapsed significantly sooner than those in 2017 (P < 0.001). In the multivariate analysis, rifampicin (RIF) resistance was associated with the recurrence of spinal TB. The turnaround time of Xpert ranged from 1 to 3 days, with a median of 1 day (IQR: 1–2). For the phenotypic drug susceptibility test (pDST)-based algorithm, the median turnaround time was 67 days, considerably longer than that of the Xpert-based algorithm (P < 0.001).ConclusionThe RIF resistance is an independent risk factor for postoperative recurrence in patients with spinal TB. Early detection of RIF resistance due to the application of Xpert is an effective strategy to reduce spinal TB recurrence.

Feasibility of a multifaceted intervention to improve treatment initiation among patients diagnosed with TB using Xpert MTB/RIF testing in Uganda.

BackgroundOne in five patients diagnosed with TB in Uganda are not initiated on TB treatment within two weeks of diagnosis. We evaluated a multifaceted intervention for improving TB treatment initiation among patients diagnosed with TB using Xpert® MTB/RIF testing in Uganda.MethodsThis was a pre-post interventional study at one tertiary referral hospital. The intervention was informed by the COM-B model and included; i) medical education sessions to improve healthcare worker knowledge about the magnitude and consequences of pretreatment loss to follow-up; ii) modified laboratory request forms to improve recording of patient contact information; and iii) re-designed workflow processes to improve timeliness of sputum testing and results dissemination. TB diagnostic process and outcome data were collected and compared from the period before (June to August 2019) and after (October to December 2019) intervention initiation.ResultsIn September 2019, four CME sessions were held at the hospital and were attended by 58 healthcare workers. During the study period, 1242 patients were evaluated by Xpert® MTB/RIF testing at the hospital (679 pre and 557 post intervention). Median turnaround time for sputum test results improved from 12 hours (IQR 4–46) in the pre-intervention period to 4 hours (IQR 3–6) in the post-intervention period. The proportion of patients started on treatment within two weeks of diagnosis improved from 59% (40/68) to 89% (49/55) (difference 30%, 95% CI 14%-43%, p<0.01) while the proportion of patients receiving a same-day diagnosis increased from 7.4% (5/68) to 25% (14/55) (difference 17.6%, 95% CI 3.9%-32.7%, p<0.01).ConclusionThe multifaceted intervention was feasible and resulted in a higher proportion of patients initiating TB treatment within two weeks of diagnosis.

Abstract 2267: Biomarker testing and treatment (tx) patterns in a large community oncology network

Abstract Introduction: Biomarker testing identifies actionable mutations to inform targeted tx for personalized healthcare. This study examined biomarker testing and tx patterns ≤ 90 days (d) after advanced (adv) or metastatic (met) diagnosis (Dx) at the OneOncology (OneOnc) network. Methods: A retrospective observational study using the nationwide Flatiron Health electronic health record-derived de-identified database from selected OneOnc practices included patients (pts) ≥ 18 y, who had Dx between 1/1/18 - 4/30/21 with adv non-small cell lung cancer (aNSCLC), met breast cancer (mBC), met colorectal cancer (mCRC) or adv melanoma (aMel), with ≥ 1 visit ≤ 90 d after adv or met Dx, and who had ≥ 90 d follow-up. Descriptive analyses were conducted. Results: Of the pts who met the inclusion criteria, 91% of 2,391 aNSCLC, 100% of 1,043 mBC, 92% of 1,344 mCRC and 84% of 358 aMel had ≥ 1 biomarker test at any time, where 78% aNSCLC, 82% mBC, 70% mCRC and 67% aMel were tested ≤ 90 d after adv or met Dx. Testing rates varied by biomarker (Table). Across indications, ≥ 70% commercial health insured vs. ≥ 50% Medicaid insured pts were tested. Commercial labs were used in 91% aNSCLC, 86% mBC, 80% mCRC and 93% aMel. Amongst treated pts, 14% of 1,693 aNSCLC, 2% of 725 mBC, 22% of 881 mCRC and 25% of 169 aMel received tx before test results were available. NGS was tested in 69% aNSCLC, 29% mBC, 70% mCRC, and 57% aMel. The median turnaround time (TAT) from adv or met Dx to 1st test result from NGS vs other biomarker tests was 26 vs 13 d in aNSCLC, 14 vs 5 d in mBC, 35 vs 10 d in mCRC and 44 vs 21 d in aMel. Conclusions: The majority of testing occurred ≤ 90 d after adv or met Dx, while 18% - 33% of pts were not tested. The varying testing rates across indications reflect the intended use of biomarker tests to guide 1st line therapies. More than 75% pts treated after testing result available signal community oncologist recognizing the importance of biomarker testing in guiding tx decisions. Improvements in TAT for NGS may reduce the issue of tx decisions made prior to test results. Table. Biomarker testing rate by indication amongst pts tested ≤ 90 d after adv or met Dx aNSCLCn=1,858 mBCn=859 mCRCn=936 aMeln=239 EGFR 89% ALK 87% BRAF 81% 80% 98% KRAS 67% 82% ROS1 86% PD-L1 85% 18% 27% ER 93% PR 93% HER2 92% BRCA 20% PIK3CA 28% MMR/MSI 93% NRAS 77% 49% KIT 50% ER, estrogen receptor; MMR, mismatch repair; MSI, microsatellite instability; PR, progesterone receptor. Citation Format: Esprit Ma, Elaine Yu, Tania Szado, Richard Price, Craig S. Meyer, Anuj Shah, Baiyu Yang, Daniel Vaena, Davey Daniel, Dennis Slater, Harry Staszewski, Bruno Fang, Lasika Seneviratne, Lee Schwartzberg. Biomarker testing and treatment (tx) patterns in a large community oncology network [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2267.

Expert clinical pharmacological advice may make an antimicrobial TDM program for emerging candidates more clinically useful in tailoring therapy of critically ill patients

BackgroundTherapeutic drug monitoring (TDM) may represent an invaluable tool for optimizing antimicrobial therapy in septic patients, but extensive use is burdened by barriers. The aim of this study was to assess the impact of a newly established expert clinical pharmacological advice (ECPA) program in improving the clinical usefulness of an already existing TDM program for emerging candidates in tailoring antimicrobial therapy among critically ill patients.MethodsThis retrospective observational study included an organizational phase (OP) and an assessment phase (AP). During the OP (January–June 2021), specific actions were organized by MD clinical pharmacologists together with bioanalytical experts, clinical engineers, and ICU clinicians. During the AP (July–December 2021), the impact of these actions in optimizing antimicrobial treatment of the critically ill patients was assessed. Four indicators of performance of the TDM-guided real-time ECPA program were identified [total TDM-guided ECPAs July–December 2021/total TDM results July–December 2020; total ECPA dosing adjustments/total delivered ECPAs both at first assessment and overall; and turnaround time (TAT) of ECPAs, defined as optimal (< 12 h), quasi-optimal (12–24 h), acceptable (24–48 h), suboptimal (> 48 h)].ResultsThe OP allowed to implement new organizational procedures, to create a dedicated pathway in the intranet system, to offer educational webinars on clinical pharmacology of antimicrobials, and to establish a multidisciplinary team at the morning bedside ICU meeting. In the AP, a total of 640 ECPAs were provided for optimizing 261 courses of antimicrobial therapy in 166 critically ill patients. ECPAs concerned mainly piperacillin–tazobactam (41.8%) and meropenem (24.9%), and also other antimicrobials had ≥ 10 ECPAs (ceftazidime, ciprofloxacin, fluconazole, ganciclovir, levofloxacin, and linezolid). Overall, the pre–post-increase in TDM activity was of 13.3-fold. TDM-guided dosing adjustments were recommended at first assessment in 61.7% of ECPAs (10.7% increases and 51.0% decreases), and overall in 45.0% of ECPAs (10.0% increases and 35.0% decreases). The overall median TAT was optimal (7.7 h) and that of each single agent was always optimal or quasi-optimal.ConclusionsMultidisciplinary approach and timely expert interpretation of TDM results by MD Clinical Pharmacologists could represent cornerstones in improving the cost-effectiveness of an antimicrobial TDM program for emerging TDM candidates.

Newly implemented community CD4 service in Tshwaragano, Northern Cape province, South Africa, positively impacts result turn-around time.

BackgroundThe Northern Cape is South Africa’s largest province with an HIV prevalence of 7.1% versus a 13.5% national prevalence. CD4 testing is provided at three of five National Health Laboratory Service district laboratories, each covering a 250 km precinct radius. Districts without a local service report prolonged CD4 turn-around times (TAT).ObjectiveThis study documented the impact of a new CD4 laboratory in Tshwaragano in the remote John Taolo Gaetsewe district of the Northern Cape, South Africa.MethodsCD4 test volumes and TAT (total, pre-analytical, analytical, and post-analytical) data for the Northern Cape province were extracted for June 2018 to October 2019. The percentage of CD4 results within the stipulated 40-h TAT cut-off and the median and 75th percentiles of all TAT parameters were calculated. Pre-implementation, samples collected at Tshwaragano were referred to Kimberley or Upington, Northern Cape, South Africa.ResultsPre-implementation, 95.4% of samples at Tshwaragano were referred to Kimberley for CD4 testing (36.3% of Kimberley’s test volumes). Only 7.5% of Tshwaragano’s total samples were referred post-implementation. The Tshwaragano laboratory’s CD4 median total TAT decreased from 24.7 h pre-implementation to 12 h post-implementation (p = 0.003), with > 95.0% of results reported within 40 h. The Kimberley laboratory workload decreased by 29.0%, and testing time significantly decreased from 10 h to 4.3 h.ConclusionThe new Tshwaragano CD4 service significantly decreased local TAT. Upgrading existing community laboratories to include CD4 testing can alleviate provincial service load and improve local access, TAT and efficiency in the centralised reference laboratory.

Clinical laboratory mutation analysis performed on aggressive B cell non-Hodgkin lymphoma patient biopsies.

e19561 Background: Results from comprehensive genomic analysis performed on aggressive B cell non-Hodgkin lymphomas (aBNHL) patient (pt) biopsies (bx) have identified mutations (mut) which may be predictive of pt survival. However, results from mut analysis (MA) performed on aBNHL pt bx in clinical laboratories are not well-described. Methods: Bx diagnostic of non-Burkitt aBNHL obtained from 7/2015-2/2021 with MA performed in the Penn Center for Personalized Diagnostics clinical laboratory using 3 consecutive versions of lymphoma sequencing panels were retrospectively analyzed. Mut tested varied by panel. Mut detected with variant allele frequency (VAF) ≥10% were included. Results: MA was performed on 293 aBNHL pt bx with a successful assay for 270 (7.8% failure rate). Request for MA was made by interpreting hematopathologist 93% and treating clinician 7%. Median turnaround time (TAT) from receipt of bx to result report was 18 (range 8-53) days. Notable pt characteristics included prior/concurrent indolent lymphoma (IL) 31% and prior systemic therapy received for IL and/or aBNHL 38%. Notable bx characteristics included bx type paraffin-embedded tissue 85% and bone marrow 12%, histologic classification diffuse large B cell lymphoma 86% and high grade B cell lymphoma 13%, cell of origin (COO) by Hans algorithm non-germinal center B (non-GCB) 51% and GCB 44%, known double expressor lymphoma 30%, known MYC rearrangement 18%, known double hit lymphoma 9% and any mut detected with VAF ≥10% 82%. Number and percentage of mut occurring in ≥10% of bx (minimum tested bx for mut ≥92) with associated COO are listed in the table. Subset analysis of 147 bx obtained from pts with newly-diagnosed aBNHL (15% with previously-untreated IL) had similar bx characteristics to the entire population were analyzed for the presence of mut reported in poor-prognosis COO-associated classifications: Cluster 5 for non-GCB and Cluster 3 for GCB (PMID: 29713087), double-hit signature (DHITsig) for GCB (PMID: 30523716) and molecular high grade (MHG) for GCB (PMID: 30523719). For 77 non-GCB bx, 19% had Cluster 5 mut. For 59 GCB bx, 56% had at least one of Cluster 3, DHITsig or MHG mut. Conclusions: Clinical laboratory MA performed on nearly 300 aBNHL pt bx was highly successful with a short TAT and demonstrated recurrent gene mut associated with aBNHL development. In the subset of bx from previously-untreated pts, MA identified mut associated with poor-prognosis genetic subtypes of aBNHL.[Table: see text]

Use of Merlin Assay to identify patients with a low-risk for SN metastasis in a prospective multicenter Dutch study of a primary melanoma gene-signature (CP-GEP model) to predict sentinel node status during COVID-19.

9571 Background: Approximately 70%-85% of patients who undergo sentinel lymph node biopsy (SLNb) show no nodal metastasis in the sentinel node (SN). The clinicopathological and gene expression profile (CP-GEP) model ( Merlin Assay) was developed and validated to identify patients that may forgo the SLNb surgery due to their low risk for for nodal metastasis This study was initiated during the first wave of Covid-19 pandemic to allow for surgical triage on SLNb and evaluate the implementation of the Merlin assay in clinical practice. Methods: This study was conducted in four designated melanoma centers in the Netherlands. Patients (age &gt; 18y) with newly diagnosed melanoma of the skin, eligible to undergo SLNb were screened for study inclusion. Main exclusion criteria was prior history of primary melanoma ( &gt; T1b) in the past 5 years. After enrollment, tissue sections of the primary melanoma were centrally reviewed at the Erasmus MC Cancer Institute to determine Breslow thickness at primary diagnosis. FFPE tumor tissue was dispatched for molecular analysis of eight target genes known to play a role in cancer development. In combination with age, Breslow thickness, and GEP outcome, risk of having nodal metastasis was calculated. Results were binary presented as 'CP-GEP low risk' and 'CP-GEP high risk'. SLNb status was used as gold standard for comparison. Results: A total of 177 patients were analyzed using the CP-GEP model. Median age was 64 years (IQR 52-73) Median Breslow thickness was 1.4mm (IQR 1.0-2.4). Of all patients 28.2% was diagnosed with T1, 40.7% with T2 and 20.9% with T3 melanoma. Corresponding positivity rate was 7%, 14% and 29% respectively. A total of 24 out of 177 patients had a positive SLNb. Median turn-around time from inclusion to CP-GEP result was 15 days. Overall 37.1.% of patients had a CP-GEP low risk profile. The CP-GEP model had a NPV of 94.6%. Conclusions: This is the first prospective multicenter implementation study for the Merlin assay. Results are in line with previous validation studies. The CP-GEP model could accurately identify patients at low risk for SN metastasis. Implementation in clinical practice is feasible based on current turn-around time. In the future, using the Merlin assay to deselect patients for SLNB may allow for a reduction of surgery in patients with melanoma.

Plasma first: Accelerating lung cancer diagnosis through liquid biopsy.

3039 Background: Molecular profiling of tumor tissue is the gold standard for treatment decision making in advanced non-small cell lung cancer. Results may be delayed or unavailable due to insufficient tissue samples or prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma molecular testing as part of the initial diagnostic work-up for patients with suspected advanced lung cancer (NCT04863924). Methods: Patients with radiologic evidence of advanced lung cancer referred to the lung rapid diagnostic program underwent plasma circulating tumor DNA (ctDNA) testing using InVisionFirst-Lung, a next-generation sequencing (NGS) assay targeting 37 genes. Standard tissue testing was performed with comprehensive NGS (Oncomine). The primary endpoint was time to treatment in stage IV NSCLC patients compared to an historical pre-COVID-19 cohort (2018-9). Secondary endpoints included actionable targets identified in plasma, % of patients starting targeted therapy based on liquid biopsy and result turnaround time (TAT). Results: Between July 1 to December 31, 2021, 60 patients were enrolled. Median age was 70 years (range 33-91), 52% were female, 57% Caucasian, 48% never smokers. Of these, 73% had NSCLC, 12% small cell, 10% non-lung pathology and 5% declined tissue biopsy. Of 44 NSCLC patients, 5 (11%) had early-stage disease and underwent curative therapy. Most stage IV patients (79%) had systemic treatment. Median time to treatment initiation in the study cohort was 34 days (n = 31, range 10-90) versus 62 days (n = 101, range 13-159) in the historical cohort (p&lt;0.0001). Two thirds (N = 23) of stage IV NSCLC patients had actionable alterations identified, (30% in current/ex-smokers); 18 started targeted therapy including 10 based on plasma results before tissue results were available. Median TAT was 7 days for plasma from blood draw to reporting (range 4-14) and 26 days for tissue molecular testing (range 11-42), p&lt;0.0001. Concordance was high between plasma and tissue testing (70%). Liquid biopsy identified actionable alterations for 3 patients not identified by tissue NGS. In 4 cases, plasma testing failed to identify actionable alterations detected in tissue, due to undetectable plasma ctDNA. Conclusions: Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC leads to faster molecular results and shortens time to treatment compared to tissue testing alone. Supplementing the current standard of tissue molecular testing with a plasma-first approach during the diagnostic work up of patients with suspected advanced lung cancer may increase access to precision medicine and improve patient outcomes. Clinical trial information: NCT04863924. [Table: see text]

Rapid access to biomarker data in a community setting: Integration of next-generation sequencing into routine pathologic workflow.

3143 Background: Biomarker data in the form of next generation sequencing (NGS) are critical to the delivery of precision cancer care. Onsite testing is often limited to large academic centers, requiring smaller community centers to rely on samples send outs. Turnaround time for biomarkers can be lengthy and can adversely affect the delivery of optimal therapy in many tumor types. This study aims to evaluate the feasibility of rapidly delivered comprehensive NGS in a community center using a novel workflow in the laboratory by integrating NGS into the routine immunohistochemistry (IHC) service. Methods: An automated NGS workflow utilizing the Genexus integrated sequencer with the Oncomine precision assay GX (OPA, Thermofisher Scientific), was validated for clinical use and integrated into the routine diagnostic IHC service. During the study period (Oct 2020 – Oct 2021), NGS biomarker data was generated and reported alongside IHC biomarkers where applicable. A retrospective chart review was performed to assess the early experience and performance characteristics of this novel approach to biomarker testing. Results: A total of 578 solid tumor samples underwent genomic profiling. Median turnaround time for biomarker results was 3 business days (IQR 2-5). The majority (n = 481, 83%) of cases were resulted in fewer than 5 business days. Tumor types included lung cancer (n = 310, 54%), melanoma (n = 97, 17%), and colorectal cancer (n = 68, 12%). Specimen types included surgical resections (n = 104, 18%), core biopsies (n = 411, 71%), and cytology specimens (n = 63, 11%). NGS testing detected key driver alterations at expected prevalence rates in respective tumor types; lung EGFR (16%), ALK (3%), RET (1%), melanoma BRAF (43%), colorectal RAS/RAFwild-type (33%), among others. Conclusions: This is the first study demonstrating the clinical feasibility and turnaround time statistics of automated comprehensive NGS performed and interpreted in parallel with diagnostic histopathology and immunohistochemistry in a community setting. This novel approach of integrating biomarkers, IHC, and morphology offers rapid turnaround by removing the need for outsourcing biomarker data. This model could be adopted by other community centers to improve rapid access to biomarker data and therapeutic decision making.

Impact of turnaround time (TAT) of molecular testing on initial treatment (Tx) in newly diagnosed stage 4 non-small cell lung cancer (NSCLC 4): An Integra Connect (IC) retrospective observational study.

e13510 Background: Broad molecular profile-based initiation of Tx in newly diagnosed NSCLC 4 (KF Mileham, Cancer Med, 2022) is advocated by NCCN guidelines. Despite this, Tx is often started prior to, and without knowledge of, an actionable oncogenic driver (AOD), and often without subsequent switch to appropriate tyrosine kinase inhibitor (TKI). In this study we sought to assess the impact of TAT of genomic testing on Tx in patients harboring a potentially actionable EGFR mutation. Methods: By interrogating the IC curated database, we identified 2,357 newly diagnosed NSCLC 4 patients (pts) who started an initial line of therapy (LOT 1) between 1/1/2019 and 12/31/2021. Squamous carcinoma pts were excluded unless documented to be never smokers or &lt;age 40. We assessed testing across all sample types and performed the analysis on solid tumor tissue next-generation sequence (NGS) tested patients. We used an order for EGFR as a surrogate for AOD evaluation and collected date of order and reporting of EGFR test results, and date of 1st Tx start. From this, we calculated TAT and whether Tx was initiated after genomic results. In addition, we captured whether testing was in-house or by reference lab (RL). We looked at the RLs that comprise of the top 85% of NGS test sources, where the testing source was known. We removed records where test order dates and results dates were the same date, where test order dates or results dates were unknown, and where TAT &gt; 90 days. EGFR Effective Testing Rate (EETR) is defined as EGFR result prior to line 1 Tx start. Results: Median age was 70 (range 40 - 89) and 50% male. Pts with TAT of ≤7 days had an 82% EETR vs. Pts with TAT of &gt;29 days had a 61% EETR. Overall, RLs had a median TAT of 19 days with a 72% EETR, whereas in-house labs had a median TAT of 15 days with a EETR of 80%. Conclusions: When providers and patients can obtain test results within 21 days of test order there is a higher likelihood of waiting for the test result to start Tx. Many community oncology practices are contemplating implementing in-house testing solutions to improve rates of testing and turnaround time of testing. This may prove to be an effective strategy given the better TAT for in-house testing. When there is faster TAT, patients and providers wait to start initial Tx. Getting patients on appropriate therapy based on their biomarker status can improve overall survival.[Table: see text]

Personalised selection of experimental treatment in patients with advanced solid cancer is feasible using whole-genome sequencing

BackgroundBiomarker-guided therapy in an experimental setting has been suggested to improve patient outcomes. However, trial-specific pre-screening tests are time and tissue consuming and complicate the personalised treatment of patients eligible for early-phase clinical trials. In this study the feasibility of whole-genome sequencing (WGS) as a one-test-for-all for guided inclusion in early-phase trials was investigated.MethodsPhase I Molecular Tumor Board (MTB) at the Erasmus MC Cancer Institute reviewed patients with advanced cancer without standard-of-care treatment (SOC) options for a ‘fresh-frozen’ (FF) tumour biopsy for WGS based on clinical-pathological features. Clinical grade WGS was performed by Hartwig Medical Foundation. MTB matched the patient with a trial, if available.ResultsFrom September 2019–March 2021, 31 patients with highly diverse tumour types underwent a tumour biopsy for WGS. The median turnaround time (TAT) was 15 days [10–42 days]. At least one actionable event was found in 84% of the patients (26/31). One-third of the patients (11/31) received matched experimental treatment.ConclusionsWGS on fresh FF biopsies is a feasible tool for the selection of personalised experimental therapy in patients with advanced cancer without SOC options. WGS is now possible in an acceptable TAT and thus could fulfil the role of a universal genomic pre-screening test.

Research and implementation of a whole-genome sequencing surveillance system for outbreak detection

Background: Traditional infection prevention (IP) methods for outbreak detection often rely on geotemporal clustering confined to single locations. We recently developed the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), which combines whole-genome sequencing (WGS) surveillance and machine learning of the electronic health record (EHR). Our retrospective research findings show potential transmissions averted and cost savings using EDS-HAT in real time. Here, we describe the process and initial findings from EDS-HAT real-time implementation. Methods: Real-time whole-genome sequencing surveillance began on November 1, 2021. Patient cultures positive for select bacterial pathogens who were hospitalized for ≥3 days or had a recent healthcare exposure in the prior 30-days were collected. Isolates were deemed genetically related if ≤15 single-nucleotide polymorphisms (SNPs) were identified for all organisms except Clostridioides difficile (≤2 SNPs). Clusters were manually investigated by both research and IP teams, and interventions were performed by the IP team. Data on collection, analysis, notification, and intervention dates were gathered. Results: As of January 11, 2022, 413 isolates had undergone whole-genome sequencing. Among them, 18 unique patient isolates were genetically related to ≥1 other isolate, comprising 7 clusters (range, 2–6 patients). Notable findings include a Pseudomonas aeruginosa cluster possibly related to a shared bronchoscope, a pseudo-outbreak of Serratia marcescens related to autopsy blood culture practice, and a cluster of vancomycin-resistant Enterococcus faecium on a shared transplant unit. Only 1 cluster of 2 isolates of Klebsiella pneumoniae had no known possible transmission routes. The median turnaround time from patient’s culture date to IP notification was 19 days (range, 13–28), with noted delays over the winter holiday. Concusions: Real-time WGS can identify small clusters including potentially interruptible transmission routes. Rapid turnaround time, coordination between clinical and genomic laboratories, and a robust IP team are key factors in implementing a WGS surveillance program. Real-time WGS surveillance has the potential to reduce costs for hospitals, improve patient safety, and save lives.Funding: NoneDisclosures: None

Clinical utility of comprehensive circulating tumor DNA genotyping compared with standard of care tissue testing in patients with newly diagnosed metastatic colorectal cancer

BackgroundComprehensive biomarker testing is essential in selecting optimal treatment for patients with metastatic colorectal cancer (mCRC); however, incomplete genotyping is widespread, with most patients not receiving testing for all guideline-recommended biomarkers, in part due to reliance on burdensome sequential tissue-based single-biomarker tests with long waiting times or availability of only archival tissue samples. We aimed to demonstrate that liquid biopsy, associated with rapid turnaround time (TAT) and lower patient burden, effectively identifies guideline-recommended biomarkers in mCRC relative to standard of care (SOC) tissue testing.Patients and methodsProspectively enrolled patients with previously untreated mCRC undergoing physician discretion SOC tissue genotyping submitted pretreatment blood samples for comprehensive circulating tumor DNA (ctDNA) analysis with Guardant360 and targeted RAS and BRAF analysis with OncoBEAM.ResultsAmong 155 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 82 patients, versus 88 identified with comprehensive ctDNA (52.9% versus 56.8%, noninferiority demonstrated down to α = 0.005) and 69 identified with targeted PCR ctDNA analysis (52.9% versus 44.5%, noninferiority rejected at α = 0.05). Utilizing ctDNA in addition to tissue increased patient identification for a guideline-recommended biomarker by 19.5% by rescuing those without tissue results either due to tissue insufficiency, test failure, or false negatives. ctDNA median TAT was significantly faster than tissue testing when the complete process from sample acquisition to results was considered (median 10 versus 27 days, P < 0.0001), resulting in accelerated biomarker discovery, with 52.0% biomarker-positive patients identified by ctDNA versus 10.2% by SOC tissue 10 days after sample collection (P < 0.0001).ConclusionsComprehensive ctDNA genotyping accurately identifies guideline-recommended biomarkers in patients with mCRC at a rate at least as high as SOC tissue genotyping, in a much shorter time. Based on these findings, the addition of ctDNA genotyping to clinical practice has significant potential to improve the care of patients with mCRC.