Salvage Stereotactic Radiosurgery for Recurrent WHO Grade 2 and 3 Meningiomas: A Multicenter Study (STORM).

PURPOSE: The role of stereotactic radiosurgery (SRS) in the management of grade 2 and 3 meningiomas is not well elucidated. Unfortunately, local recurrence rates are high, and guidelines for management of recurrent disease are lacking. To address this knowledge gap, we conducted STORM, a multicenter retrospective cohort study of patients treated with primary SRS for recurrent grade 2 and 3 meningiomas. METHODS AND MATERIALS: Data on patients with recurrent grade 2 and 3 meningioma treated with SRS at first recurrence were retrospectively collected from eight academic centers in the United States. Patients with multiple lesions at the time of initial diagnosis or more than two lesions at the time of first recurrence were excluded from this analysis. Patient demographics and treatment parameters were extracted at time of diagnosis, first recurrence, and second recurrence. Oncologic outcomes including progression-free survival (PFS) and overall survival (OS) as well as toxicity outcomes were reported at the patient level. RESULTS: From 2000-2022, 108 patients were identified (94% grade 2, 6.0% grade 3). 106 patients (98%) had upfront surgical resection (60% gross-total resection) with 18% receiving adjuvant radiotherapy (RT). Median time to first progression was 2.5 years (IQR 1.34-4.30). At first recurrence, patients were treated with single or fractionated SRS to a median marginal dose of 16 Gy to a maximum of two lesions (87% received single fraction SRS). Median follow-up time after SRS was 2.6 years. 1-, 2-, and 3-year PFS was 90%, 75%, and 57%, respectively after treatment with SRS. 1-, 2-, and 3-year OS was 97%, 94%, and 92%, respectively. On multivariable analysis, grade 3 disease (HR 6.80; 95% CI 1.61-28.6), male sex (HR 3.48; 95% CI 1.47-8.26), and receipt of prior RT (HR 2.69; 95% CI 1.23-5.86) were associated with worse PFS. SRS dose and tumor volume were not correlated with progression. Treatment was well-tolerated, with a 3.0% incidence of grade 2+ radiation necrosis. CONCLUSIONS: This is the largest multi-center study to evaluate salvage SRS in recurrent grade 2 and 3 meningiomas. In this select cohort of patients with primarily grade 2 meningioma with potentially more favorable natural history of delayed, localized first recurrence amenable to salvage SRS, local control rates and toxicity profiles were favorable, warranting further prospective validation.

Access to Benzathine Penicillin G Treatment for Persons With Syphilis, Maricopa County, Arizona, 2021.

BACKGROUND: As the incidence of syphilis continues to increase, examining benzathine penicillin G (BPG) treatment data provides valuable insight for public health strategies. This study analyzed the trends of where BPG is administered relative to the initial clinical site of syphilis diagnosis. Our findings are timely in the context of recent national BPG shortages. METHODS: The analysis included persons diagnosed with any syphilis stage in Maricopa County, Arizona, from January 1, 2021, to December 31, 2021. The Arizona surveillance database (PRISM) was the source of demographic, testing, and treatment data. RESULTS: Of a total of 4028 persons with syphilis, 3038 (75.4%) received at least 1 injection of BPG. Among persons who received an initial BPG injection, only 1719 (56.6%) were diagnosed and treated at the same clinical site type. The Maricopa County Sexually Transmitted Disease Clinic administered BPG to 48.8% (n = 1483) of persons with syphilis who received an initial injection. CONCLUSIONS: Our findings analyze trends in BPG administration that are likely due to treatment referral practices and medication cost. Administration of BPG is not guaranteed at the clinical site of diagnosis, highlighting concerns regarding access to BPG. A burden is placed on patients who are required to leave their diagnosing provider to seek syphilis treatment at other health facilities that administer BPG.

CP110 and CEP135 localize near the proximal and distal centrioles of cattle and human spermatozoa.

Centrosomes play an important role in the microtubule organization of a cell. The sperm's specialized centrosome consists of the canonical barrel-shaped proximal centriole, the funnel-shaped distal centriole, and the pericentriolar material known as striated columns (or segmented columns). Here, we examined the localization of the centriole proteins CEP135 and CP110 in cattle and human spermatozoa. In canonical centrioles, CP110 is a centriole tip protein that controls cilia formation, while CEP135 is a structural protein essential for constructing the centriole. In contrast, we found antibodies recognizing CEP135 and CP110 label near the proximal and distal centrioles at the expected location of the striated columns and capitulum in cattle and humans in an antibody and species-specific way. These findings provide a pathway to understanding the unique functions of spermatozoan centrosome.

Deep-Learning-Based Screening and Ancillary Testing for Thyroid Cytopathology.

Thyroid cancer is the most common malignant endocrine tumor. The key test to assess preoperative risk of malignancy is cytologic evaluation of fine-needle aspiration biopsies (FNABs). The evaluation findings can often be indeterminate, leading to unnecessary surgery for benign post-surgical diagnoses. We have developed a deep-learning algorithm to analyze thyroid FNAB whole-slide images (WSIs). We show, on the largest reported data set of thyroid FNAB WSIs, clinical-grade performance in the screening of determinate cases and indications for its use as an ancillary test to disambiguate indeterminate cases. The algorithm screened and definitively classified 45.1% (130/288) of the WSIs as either benign or malignant with risk of malignancy rates of 2.7% and 94.7%, respectively. It reduced the number of indeterminate cases (N = 108) by reclassifying 21.3% (N = 23) as benign with a resultant risk of malignancy rate of 1.8%. Similar results were reproduced using a data set of consecutive FNABs collected during an entire calendar year, achieving clinically acceptable margins of error for thyroid FNAB classification.

Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.

Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-α in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.

Practical Considerations During Brachytherapy Applicator Placement for Locally Advanced Cervical Cancer.

Brachytherapy is an integral part of the definitive treatment for locally advanced cervical cancer following external beam radiation therapy. Placement of brachytherapy applicators is an important skill for radiation oncologists and care must be taken to place applicators appropriately to limit complications associated with the procedure and ensure that the radiation dose sufficiently covers the target while sparing the surrounding organs at risk. Using example cases, we discuss strategies for the placement of brachytherapy applicators in patients with anatomical considerations such as large obstructing uterine fibroids and the retroverted uterus. We also discuss the management of uterine perforation during applicator placement and approaches to patients with a poor response to external beam radiation therapy before brachytherapy delivery. We draw upon the available literature and our clinical experience to suggest approaches to these challenging scenarios.

Delineation of recurrent glioblastoma by whole brain spectroscopic magnetic resonance imaging.

BACKGROUND: Glioblastoma (GBM) cellularity correlates with whole brain spectroscopic MRI (sMRI) generated relative choline to N-Acetyl-Aspartate ratio (rChoNAA) mapping. In recurrent GBM (rGBM), tumor volume (TV) delineation is challenging and rChoNAA maps may assist with re-RT targeting. METHODS: Fourteen rGBM patients underwent sMRI in a prospective study. Whole brain sMRI was performed to generate rChoNAA maps. TVs were delineated by the union of rChoNAA ratio over 2 (rChoNAA > 2) on sMRI and T1PC. rChoNAA > 2 volumes were compared with multiparametric MRI sequences including T1PC, T2/FLAIR, diffusion-restriction on apparent diffusion coefficient (ADC) maps, and perfusion relative cerebral blood volume (rCBV). RESULTS: rChoNAA > 2 (mean 27.6 cc, range 6.6-79.1 cc) was different from other imaging modalities (P ≤ 0.05). Mean T1PC volumes were 10.7 cc (range 1.2-31.4 cc). The mean non-overlapping volume of rChoNAA > 2 and T1PC was 29.2 cm3. rChoNAA > 2 was 287% larger (range 23% smaller-873% larger) than T1PC. T2/FLAIR volumes (mean 111.7 cc, range 19.0-232.7 cc) were much larger than other modalities. rCBV volumes (mean 6.2 cc, range 0.2-19.1 cc) and ADC volumes were tiny (mean 0.8 cc, range 0-3.7 cc). Eight in-field failures were observed. Three patients failed outside T1PC but within rChoNAA > 2. No grade 3 toxicities attributable to re-RT were observed. Median progression-free and overall survival for re-RT patients were 6.5 and 7.1 months, respectively. CONCLUSIONS: Treatment of rGBM may be optimized by sMRI, and failure patterns suggest benefit for dose-escalation within sMRI-delineated volumes. Dose-escalation and radiologic-pathologic studies are underway to confirm the utility of sMRI in rGBM.

Treatment Completion With Three-Dose Series of Benzathine Penicillin Among People Diagnosed With Late Latent and Unknown Duration Syphilis, Maricopa County, Arizona.

BACKGROUND: Syphilis is a public health concern as cases are rising each year. If untreated, syphilis is associated with significant morbidity and risk of vertical transmission during pregnancy. For people with late latent and unknown duration stages, 3 injections of benzathine penicillin G (BPG) at 1-week intervals are recommended. Our study quantified treatment for people diagnosed with late latent and unknown duration syphilis in Maricopa County, Arizona with a secondary analysis of pregnant women to assess completion of 3 injections of BPG in multiple time intervals. METHODS: Maricopa County syphilis case data were extracted from the state-run database (PRISM). Records were reviewed for people with late latent and unknown duration syphilis during January 1, 2016, to December 31, 2021. Treatment types and time intervals between treatments were analyzed. RESULTS: Of a total of 14,924 people with syphilis reported in Maricopa County, 5372 (36.0%) were staged as late latent or unknown duration syphilis. Completion of 3 BPG injections in the time frame of 7 to 9 days was 42.9% (n = 2302). Completion among pregnant women (n = 406) with 3 injections was 68.7% (n = 279). CONCLUSIONS: The completion rate of 3 BPG injections for people with late latent or unknown duration syphilis is low. An unmet need exists to identify barriers to treatment including access to BPG and public health follow-up after the first injection. Prioritized effort is needed to identify and classify patients as having earlier stages of syphilis that require only 1 BPG injection.

Highly selective α-aryloxyalkyl C-H functionalisation of aryl alkyl ethers.

We report highly selective photocatalytic functionalisations of alkyl groups in aryl alkyl ethers with a range of electron-poor alkenes using an acridinium catalyst with a phosphate base and irradiation with visible light (456 nm or 390 nm). Experiments indicate that the reaction operates via direct single-electron oxidation of the arene substrate ArOCHRR' to its radical cation by the excited state organic photocatalyst; this is followed by deprotonation of the ArOC-H in the radical cation to yield the radical ArOC˙RR'. This radical then attacks the electrophile to form an intermediate alkyl radical that is reduced to complete the photocatalytic cycle. The oxidation step is selective for activated arenes (ArOR) over their non-activated counterparts and the subsequent deprotonation of the methoxy group affords the α-aryloxyalkyl radical that leads to a wide range of functionalised products in good to excellent yield.

Interleukin-22 regulates neutrophil recruitment in ulcerative colitis and is associated with resistance to ustekinumab therapy.

The function of interleukin-22 (IL-22) in intestinal barrier homeostasis remains controversial. Here, we map the transcriptional landscape regulated by IL-22 in human colonic epithelial organoids and evaluate the biological, functional and clinical significance of the IL-22 mediated pathways in ulcerative colitis (UC). We show that IL-22 regulated pro-inflammatory pathways are involved in microbial recognition, cancer and immune cell chemotaxis; most prominently those involving CXCR2+ neutrophils. IL-22-mediated transcriptional regulation of CXC-family neutrophil-active chemokine expression is highly conserved across species, is dependent on STAT3 signaling, and is functionally and pathologically important in the recruitment of CXCR2+ neutrophils into colonic tissue. In UC patients, the magnitude of enrichment of the IL-22 regulated transcripts in colonic biopsies correlates with colonic neutrophil infiltration and is enriched in non-responders to ustekinumab therapy. Our data provide further insights into the biology of IL-22 in human disease and highlight its function in the regulation of pathogenic immune pathways, including neutrophil chemotaxis. The transcriptional networks regulated by IL-22 are functionally and clinically important in UC, impacting patient trajectories and responsiveness to biological intervention.

Survival and Yield of Surveillance Imaging in Long-Term Survivors of Brain Metastasis Treated with Stereotactic Radiosurgery.

OBJECTIVES: The optimal frequency of surveillance brain magnetic resonance imaging (MRI) in long-term survivors with brain metastases after stereotactic radiosurgery (SRS) is unknown. Our aim was to identify the optimal frequency of surveillance imaging in long-term survivors with brain metastases after SRS. METHODS: Eligible patients were identified from a cohort treated with SRS definitively or postoperatively at our institution from 2014 to 2019 with no central nervous system (CNS) failure within 12 months from SRS. Time to CNS disease failure diagnosis and cost per patient were estimated using theoretical MRI schedules of 2, 3, 4, and 6 months starting 1 year after SRS until CNS failure. Time to diagnosis was calculated from the date of CNS progression to the theoretical imaging date on each schedule. RESULTS: This cohort included 55 patients (median follow-up from SRS: 2.48 years). During the study period, 20.0% had CNS disease failure (median: 2.26 years from SRS treatment). In this cohort, a theoretical 2-month, 3-month, 4-month, and 6-month MRI brain surveillance schedule produced a respective estimated time to diagnosis of CNS disease failure of 1.11, 1.74, 1.65, and 3.65 months. The cost of expedited diagnosis for the cohort (dollars/month) for each theoretical imaging schedule compared with a 6-month surveillance schedule was $6600 for a 2-month protocol, $4496 for a 3-month protocol, and $2180 for a 4-month protocol. CONCLUSIONS: Based on cost-benefit, a 4-month MRI brain schedule should be considered in patients with metastatic disease to the brain treated definitively or postoperatively with SRS without evidence of CNS recurrence at 1 year.

AACR Project GENIE: 100,000 Cases and Beyond.

The American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) is an international pan-cancer registry with the goal to inform cancer research and clinical care worldwide. Founded in late 2015, the milestone GENIE 9.1-public release contains data from >110,000 tumors from >100,000 people treated at 19 cancer centers from the United States, Canada, the United Kingdom, France, the Netherlands, and Spain. Here, we demonstrate the use of these real-world data, harmonized through a centralized data resource, to accurately predict enrollment on genome-guided trials, discover driver alterations in rare tumors, and identify cancer types without actionable mutations that could benefit from comprehensive genomic analysis. The extensible data infrastructure and governance framework support additional deep patient phenotyping through biopharmaceutical collaborations and expansion to include new data types such as cell-free DNA sequencing. AACR Project GENIE continues to serve a global precision medicine knowledge base of increasing impact to inform clinical decision-making and bring together cancer researchers internationally. SIGNIFICANCE: AACR Project GENIE has now accrued data from >110,000 tumors, placing it among the largest repository of publicly available, clinically annotated genomic data in the world. GENIE has emerged as a powerful resource to evaluate genome-guided clinical trial design, uncover drivers of cancer subtypes, and inform real-world use of genomic data. This article is highlighted in the In This Issue feature, p. 2007.

Pharmacological Management of Saddle Pulmonary Embolism in a High-Risk Patient With COVID-19.

A pulmonary embolism (PE) that is located in the main pulmonary artery is known as a saddle pulmonary embolism. Individuals at high risk who become unstable often require surgical intervention or more aggressive management with thrombolytic therapy. COVID-19 is a known risk factor for a hypercoagulable state and therefore increases the risk of PE and its associated complications. Individuals hospitalized with the COVID-19 virus and who have evidence of right ventricular dysfunction with PE are found to have a significantly higher risk of mortality. We present a case of an individual with several high-risk factors for PE as well as COVID-19 infection and evidence of cardiac strain, making the decision for treatment less clear. He was, however, treated successfully with heparin and enoxaparin alone. Furthermore, our case hadresolving symptoms of COVID-19, highlighting the importance of high clinical suspicion for PE in those diagnosed with COVID-19.

Use of Machine Learning-Based Software for the Screening of Thyroid Cytopathology Whole Slide Images.

CONTEXT.­: The use of whole slide images (WSIs) in diagnostic pathology presents special challenges for the cytopathologist. Informative areas on a direct smear from a thyroid fine-needle aspiration biopsy (FNAB) smear may be spread across a large area comprising blood and dead space. Manually navigating through these areas makes screening and evaluation of FNA smears on a digital platform time-consuming and laborious. We designed a machine learning algorithm that can identify regions of interest (ROIs) on thyroid fine-needle aspiration biopsy WSIs. OBJECTIVE.­: To evaluate the ability of the machine learning algorithm and screening software to identify and screen for a subset of informative ROIs on a thyroid FNA WSI that can be used for final diagnosis. DESIGN.­: A representative slide from each of 109 consecutive thyroid fine-needle aspiration biopsies was scanned. A cytopathologist reviewed each WSI and recorded a diagnosis. The machine learning algorithm screened and selected a subset of 100 ROIs from each WSI to present as an image gallery to the same cytopathologist after a washout period of 117 days. RESULTS.­: Concordance between the diagnoses using WSIs and those using the machine learning algorithm-generated ROI image gallery was evaluated using pairwise weighted κ statistics. Almost perfect concordance was seen between the 2 methods with a κ score of 0.924. CONCLUSIONS.­: Our results show the potential of the screening software as an effective screening tool with the potential to reduce cytopathologist workloads.

A Hybrid Human-Machine Learning Approach for Screening Prostate Biopsies Can Improve Clinical Efficiency Without Compromising Diagnostic Accuracy.

CONTEXT.­: Prostate cancer is a common malignancy, and accurate diagnosis typically requires histologic review of multiple prostate core biopsies per patient. As pathology volumes and complexity increase, new tools to improve the efficiency of everyday practice are keenly needed. Deep learning has shown promise in pathology diagnostics, but most studies silo the efforts of pathologists from the application of deep learning algorithms. Very few hybrid pathologist-deep learning approaches have been explored, and these typically require complete review of histologic slides by both the pathologist and the deep learning system. OBJECTIVE.­: To develop a novel and efficient hybrid human-machine learning approach to screen prostate biopsies. DESIGN.­: We developed an algorithm to determine the 20 regions of interest with the highest probability of malignancy for each prostate biopsy; presenting these regions to a pathologist for manual screening limited the initial review by a pathologist to approximately 2% of the tissue area of each sample. We evaluated this approach by using 100 biopsies (29 malignant, 60 benign, 11 other) that were reviewed by 4 pathologists (3 urologic pathologists, 1 general pathologist) using a custom-designed graphical user interface. RESULTS.­: Malignant biopsies were correctly identified as needing comprehensive review with high sensitivity (mean, 99.2% among all pathologists); conversely, most benign prostate biopsies (mean, 72.1%) were correctly identified as needing no further review. CONCLUSIONS.­: This novel hybrid system has the potential to efficiently triage out most benign prostate core biopsies, conserving time for the pathologist to dedicate to detailed evaluation of malignant biopsies.

The Reliability and Accuracy of Endoscopic Items and Scores Used in the Assessment of the Ileoanal Pouch and Cuff.

BACKGROUND AND AIMS: Currently used endoscopic items for the assessment of pouchitis and cuffitis have deficiencies in reliability and validation. We assessed the reliability and accuracy of new endoscopic items for pouchitis and of the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] for cuffitis. METHODS: Three new endoscopic items were assessed and included in the Monash pouchitis endoscopic subscore: bleeding [absent/contact/spontaneous]; erosions [absent/<10/≥10]; and ulceration [absent/<10%/≥10%]. Three raters evaluated 44 pouchoscopy videos in duplicates, in random order. Intra- and inter-rater reliability of all endoscopic items and UCEIS were assessed. Clinical and histological pouchitis disease activity index [PDAI] subscores were also assessed and faecal calprotectin was measured. RESULTS: All three Monash endoscopic items had substantial intra-rater reliability with intraclass correlation coefficients [ICCs] >0.61 [95% CI >0.61], compared with only ulcers from the currently used PDAI endoscopic subscore, but inter-rater reliability was only substantial for ulceration and no better than those of the currently used endoscopic items. The Monash endoscopic subscore had a strong positive correlation with the reference standard global endoscopic lesion severity r = 0.80 [95% CI 0.80-0.80] and the reference standard PDAI endoscopic subscore r = 0.70 [95% CI 0.67-0.73], which was higher than the correlation observed for the currently used PDAI endoscopic subscore. The UCEIS had substantial intra-rater reliability, but only fair inter-rater reliability and poor diagnostic performance for cuffitis. CONCLUSIONS: The Monash endoscopic items, and endoscopic subscore they generate, have enhanced overall performance compared with the currently used PDAI items and subscore. Further validation and responsiveness to change in disease state are indicated.

Deep learning segmentation of glomeruli on kidney donor frozen sections.

Purpose: Recent advances in computational image analysis offer the opportunity to develop automatic quantification of histologic parameters as aid tools for practicing pathologists. We aim to develop deep learning (DL) models to quantify nonsclerotic and sclerotic glomeruli on frozen sections from donor kidney biopsies. Approach: A total of 258 whole slide images (WSI) from cadaveric donor kidney biopsies performed at our institution ( n = 123 ) and at external institutions ( n = 135 ) were used in this study. WSIs from our institution were divided at the patient level into training and validation datasets (ratio: 0.8:0.2), and external WSIs were used as an independent testing dataset. Nonsclerotic ( n = 22767 ) and sclerotic ( n = 1366 ) glomeruli were manually annotated by study pathologists on all WSIs. A nine-layer convolutional neural network based on the common U-Net architecture was developed and tested for the segmentation of nonsclerotic and sclerotic glomeruli. DL-derived, manual segmentation, and reported glomerular count (standard of care) were compared. Results: The average Dice similarity coefficient testing was 0.90 and 0.83. And the F 1 , recall, and precision scores were 0.93, 0.96, and 0.90, and 0.87, 0.93, and 0.81, for nonsclerotic and sclerotic glomeruli, respectively. DL-derived and manual segmentation-derived glomerular counts were comparable, but statistically different from reported glomerular count. Conclusions: DL segmentation is a feasible and robust approach for automatic quantification of glomeruli. We represent the first step toward new protocols for the evaluation of donor kidney biopsies.

Impact of COVID-19 Lockdowns on Sexual Health Care Utilization and STD Reporting, Maricopa County.

The Maricopa County Department of Public Health (MCDPH) Sexually Transmitted Disease (STD) Clinic remained operational during a 6-week statewide Coronavirus Disease 2019 (COVID-19) Stay-at-Home Order. The present study sought to evaluate the effect of the Stay-at-Home Order on countywide STD reporting and uptake of sexual health services. We compared countywide daily median STD reporting and MCDPH STD clinic attendance across 3 timeframes; (1) Pre-Lockdown (01/01/2020-03/30/2020); (2) Lockdown (03/31/2020-05/15/2020); and (3) Post-Lockdown (05/16/2020-12/31/2020). STD reporting was characterized as incident chlamydia, gonorrhea, and primary and secondary syphilis. Clinic attendance was characterized as clients visiting through express testing or provider visits. Differences in STD reporting and clinic attendance were evaluated using non-parametric testing. Comparing Pre-Lockdown to Lockdown, we observed significant declines in the daily median chlamydia case reporting (-22%) and clinic express testing attendance (-29%). Comparing Lockdown to Post-Lockdown, we observed significant increases in daily median chlamydia and gonorrhea case reporting (+20%, +15%; respectively) and clinic express testing and provider visits (+42%, +20%; respectively). No significant difference was observed in countywide syphilis reporting across the 3 timeframes. Declines in STD reporting were observed countywide during the lockdown and were concurrent with declines in attendance observed at the MCDPH STD Clinic. Maintenance of clinic operations during the lockdown allowed for continued uptake of STD testing, diagnosis, treatment, and partner services. This study of sexual health care utilization at the public STD clinic in Maricopa County, Arizona, found reduced testing and provider visits contributed to lower countywide STD reporting during the Arizona COVID-19 Stay-at-Home Order.

Implementation of a Molecular Tumor Registry to Support the Adoption of Precision Oncology Within an Academic Medical Center: The Duke University Experience.

Comprehensive genomic profiling to inform targeted therapy selection is a central part of oncology care. However, the volume and complexity of alterations uncovered through genomic profiling make it difficult for oncologists to choose the most appropriate therapy for their patients. Here, we present a solution to this problem, The Molecular Registry of Tumors (MRT) and our Molecular Tumor Board (MTB). PATIENTS AND METHODS: MRT is an internally developed system that aggregates and normalizes genomic profiling results from multiple sources. MRT serves as the foundation for our MTB, a team that reviews genomic results for all Duke University Health System cancer patients, provides notifications for targeted therapies, matches patients to biomarker-driven trials, and monitors the molecular landscape of tumors at our institution. RESULTS: Among 215 patients reviewed by our MTB over a 6-month period, we identified 176 alterations associated with therapeutic sensitivity, 15 resistance alterations, and 51 alterations with potential germline implications. Of reviewed patients, 17% were subsequently treated with a targeted therapy. For 12 molecular therapies approved during the course of this work, we identified between two and 71 patients who could qualify for treatment based on retrospective MRT data. An analysis of 14 biomarker-driven clinical trials found that MRT successfully identified 42% of patients who ultimately enrolled. Finally, an analysis of 4,130 comprehensive genomic profiles from 3,771 patients revealed that the frequency of clinically significant therapeutic alterations varied from approximately 20% to 70% depending on the tumor type and sequencing test used. CONCLUSION: With robust informatics tools, such as MRT, and the right MTB structure, a precision cancer medicine program can be developed, which provides great benefit to providers and patients with cancer.